อายุรศาสตร์โรคไต

Nephrology
GLOMERULAR
DISEASES
APPROACH TO THE
PATIENTS WITH
SUSPECTED OF
GLOMERULAR DISEASES
Clinical presentations of
glomerular diseases
Differentiate between glomerular syndromes

Nephritic syndrome versus nephrotic syndrome
Proteinuria: varying in degree

of proteinuria, more specific in
proteinuria > 2 g/day
Nephritic syndrome
Glomerular hematuria
Decreased GFR: oliguria,
anuria, uremic symptoms
Salt and water retention:
edema, hypertension
Decreased of GFR: edema, oliguria,

hypertension, azotemia
Active urine sediments: dysmorphic RBC, RBC
cast
Subnephrotic-ranged proteinuria
Nephrotic-ranged proteinuria
Hyperlipidemia
Nephrotic syndrome Hypoalbuminemia
Edema
Lipiduria: oval fat body, fatty cast
Asymptomatic versus symptomatic
Define onset of disease: history of urine volume and characters
change, nocturia, edema, broad cast in urine (subacute to chronic onset), ultrasound kidney
Acute onset: days to week
Subacute onset: weeks to month
Chronic onset: 3 months
3
Isomorphic RBC from light microscope
Broad cast
Classify glomerular syndromes
Evaluation of secondary causes of glomerular disease

Predict pathological findings by clinical manifestations
Asymptomatic urinary abnormalities

Asymptomatic proteinuria
Nephrotic
features
Nephritic
features
Minimal change disease (MCD)
++++
Membranous nephropathy (MN)
++++
Focal segmental glomerulosclerosis (FSGS)
+++
++
Fibrillary glomerulonephritis
+++
++
Mesangioproliferative glomerulonephritis
++
++
Membranoproliferative glomerunephritis
(MPGN)
++
+++
Proliferative glomerulonephritis
++
+++
Acute diffuse proliferative glomerulonephritis
++++
Crescentic glomerulonephritis
++++
Asymptomatic hematuria
Nephrotic syndrome
Acute glomerulonephritis
(AGN): acute onset
Rapidly progressive glomerulonephritis (RPGN): subacute
onset
Chronic glomerunephritis
(CGN): chronic onset
Evaluation of secondary causes according to predicted pathological

findings
5
Renal biopsy
Indication
Significant proteinuria: urine protein > 1 g/day
(or equivalent)
Unexplained renal impairment
Renal manifestation of systemic disease
Contraindication
Absolute
contraindication
Relative
contraindication
Complication: incidence 3-9% (majority are minor complication), <7% of bleeding required intervention, > 90% occurs in 24 hours
Gross hematuria
Perinephric hematoma
Arteriovenous fistula
Sepsis
Uncontrolled hypertension
Bleeding diathesis
Widespread cystic disease
Renal malignancy
Hydronephrosis
Uncooperative patient
Renal vein thrombosis
Single kidney
Antiplatelet or anticoagulant therapy
Anatomic abnormalities
Small kidneys
Active urinary or skin sepsis
Obesity
Death: due to undiagnosed hematoma

0.2%
Prepare the patients for treatment: evaluation of
occult infection (chest x-ray, dental examination, stool concentrate for parasite)
Select the treatment regimen according to type
of glomerular disease
References
Emmett M, Fenves AZ, and Schwartz JC. Approach to the patient with kidney disease. In: Taal MW, et al.
editor. Brenner & Rectors The Kidney. 9th ed. Philadephia: Elsevier Saunders; 2012. p 844-867.
Salama AD, and Cook HT. The renal biopsy. In: Taal MW, et al. editor. Brenner & Rectors The Kidney. 9th
ed. Philadephia: Elsevier Saunders; 2012. P 1006-1016.
ASYMPTOMATIC
PROTEINURIA
DEFINITION
Total protein excretion
Normal
< 150 mg/day
Proteinuria
150 mg/day
mg/day
> 3,500
Albumin excretion
Normal
2 30 mg/day
Microalbuminuria
30 300 mg/day
Pathogenesis and etiologies

Overflow proteinuria
Large amount of small molecular weight protein filter through normal glomerulus and exceeds the capacity of normal tubular cells for
complete reabsorption
Causes: monoclonal gammopthies (e.g. multiple myeloma), intravascular hemolysis (hemoglobinuria), rhabdomyolysis (myoglobinuria)
Tubular proteinuria
Tubular cells injury results in increase secretion of Tamm-Horsfall protein, increase secretion of other brush border components, and
decrease reabsorption of small molecular
weight protein in urine
- Infections: pyeolonephritis, tuberculosis

- Metabolic: DM, hyperuricemia, uricosuria, hypercalcemia, hypercalciuria, hypokalemia, oxalosis, cystinosis
- Immunologic: Sjgrenss syndrome, renal transplant rejection, drug hypersensitivity, sarcoidosis
- Toxic: analgesic abuse, radiation nephritis, lithium, heavy metals (lead, cadmium, mercury), Balkan nephropathy, cyclosporine, cisplatin, aminoglycoside
- Anatomic: obstruction, ureterovesical reflux, medullary sponge kidney
- Miscellaneous: multiple myeloma, amyloidosis, sickle cell disease, medullary
sponge kidney
Urine protein usually < 2 g/day

Urine albumin : 2 microglobulin ratio 10:1
Causes
- Hereditary: polycystic kidney disease,
medullary cystic disease
10
Glomerular proteinuria
Glomerular injuries result in loss charge- and/
or size-selectivity properties of glomerular
basement membrane, and subsequently abnormally increase in clearance of urine protein
Urine protein usually < 2 g/day
Urine albumin : 2 microglobulin ratio >
1,000:1
Causes: primary and secondary glomerulonephritis and nephrotic syndrome (see in
Etiologies of nephrotic syndrome), hereditary nephritis (Alports syndrome, thin basement membrane disease)
Benign orthostatic proteinuria

Commonly found in tall adolescents
Protenuria occurs only in the morning after
ambulation, but not in the nighttime
Urine protein < 1 g/day, and no any abnormal
urine sediment
Half of patients spontaneous recovery in 10
years, but small number progress to overt renal disease
Functional and transient proteinuria
Proteinuria which occurs associated with
non-renal cause and disappear after resolution of disease process
Heart failure, fever, or heavy exercise
11
Approach to the patients with asymptomatic proteinuria
12
Indications for renal biopsy

Urine protein > 2 g/day
Urine protein < 2 g/day with any of the followings: microscopic hematuria, hypertension, low serum complement, or family history of hereditary nephritis
References
Kashif W, et al. Proteinuria: How to evaluate an important finding. Cleve Clin J Med 2003;70:535-547.
Adler SG and Kairley K. The patient with hematuria, proteinuria, or both, and abnormal findings on urinary microscopy. In: Schrier RW. editor. Manual of nephrology. 7th ed. Phiadephia: Lippincott Williams & Wilkins;
2009. P 122-139.
13
ASYMPTOMATIC
HEMATURIA
14
DEFINITION AND
ETIOLOGIES
Bed rest
Analgesics
Hydration: to increase urine flow rate to 2 3 L/
day
Avoid sports which at a risk of abdominal
trauma: such as rugby, boxing
15
APPROACH TO THE
PATIENTS WITH
ASYMPTOMATIC
HEMATURIA
16
17
Indications for renal biopsy

Impaired renal function
Urine protein > 2 g/day
Any of the followings: hypertension, low serum complement, or family history of hereditary nephritis
References
Adler SG and Kairley K. The patient with hematuria, proteinuria, or both, and abnormal findings on urinary microscopy. In: Schrier RW. editor. Manual of nephrology. 7th ed. Phiadephia: Lippincott Williams & Wilkins;
2009. P 122-139.
Emmett M, Fenves AZ, and Schwartz JC. Approach to the patient with kidney disease. In: Taal MW, et al. editor. Brenner & Rectors The Kidney. 9th ed. Philadephia: Elsevier Saunders; 2012. p 844-867.
18
NEPHRITIC SYNDROMES
19
DEFINITION
Inflammatory process occurred in glomeruli
20
ETIOLOGIES
21
Immune complex glomerulonephritis

Lupus nephritis (LN)
Post-infectious glomerulonephritis (PIGN)
IgA nephropathy (IgAN) and Henoch-Schnlein
purpura (HSP)
Subacute bacterial endocarditis
Membranoproliferative glomerulonephritis
(MPGN)
Cryoglobulinemia
Anti-glomerular basement membrane
Pauci-immune glomerulonephritis
ANCA-associated glomerulonephritis
Granulomatosis with polyangitis (GPA) or
Wegners granulomatosis
Eosinophilic granulomatosis with polyangitis
(EGPA) or Churg-Strauss syndrome
Microscopic polyangiitis (MPA)
Renal limited pauci-immune glomerulonephritis
Double positive disease
(GBM)
Anti-GBM disease
Goodpastures syndrome
22
CLASSIFICATION
By onset of disease
Acute glomerulonephritis (AGN)
Rapidly progressive glomerulonephritis
(RPGN) or crescentic glomerulonephritis
Chronic glomerulonephritis (CGN)
By etiologies: see Etiologies
23
CLINICAL
MANIFESTATIONS
Active urine sediment: dysmorphic RBCs, RBC
casts, and often WBCs and WBC casts
Hematuria
Sporadic, intermittent, or persistent hematuria
Microscopic, or gross hematuria
Reduced GFR
Subnephrotic-ranged to nephrotic-ranged proteinuria
Variable degree of hypertension, oliguria, and
edema
24
APPROACH TO THE
PATIENTS WITH NEPHRITIC
SYNDROME
Differentiate onset of disease
AGN: most common and prototype is postinfectious GN
RPGN: can caused by any disease in all three
groups (immune complex GN, anti-GBM, and
pauci-immune GN)
CGN: can result from any diseases that causes
nephritic or nephrotic syndrome
Differential diagnosis by using data from history taking and physical examination
(See Approach to the patients suspected glomerular diseases)
Investigations: depend on the differential diagnosis
e.g. serum complement, ANA, ANCA, anti-GBM,
HBsAg, anti-HCV, and renal biopsy
25
References
26
NEPHROTIC SYNDROME
(NS)
27
DEFINITION
Nephrotic-ranged proteinuria: urine protein
> 3 3.5 g/day or equivalent
Hypoalbuminemia
Edema
Hperlipidemia
28
ETIOLOGIES
29
Secondary NS
Infections: HBV, HCV, HIV, tuberculosis, infective
endocarditis, visceral abscess, shunt nephritis
Secondary causes of NS
MCD
Hodgkins lymphoma, NSAIDs
FSGS
HIV, nephron loss, familial, obesity,

hypertension, reflux nephropathy,
heroin, analgesic nephropathy
MN
HBV, HCV, solid tumors, Dpenicillamine, NSAIDs, gold, SLE,

non-Hodgkins lymphoma,
amyloidosis
MPGN
Chronic infection (infective

endocarditis, tuberculosis, HCV,
HBV, visceral abscess, shunt
nephritis), chronic inflammation
(rheumatoid arthritis, SLE), light
chain disease
Autoimmune diseases: SLE, rheumatoid arthritis,

Sjgren syndrome
Medications: NSAIDs, gold, D-penicillamine, heroin
Malignancies: hematologic malignancy (Hodgkons and non Hodgkins lymphoma, plasma cell
dyscrasia), solid tumors
Metabolic abnormalities: DM, hypertension, obesity
Miscellaneous diseases: reflux nephropathy, analgesic, nephron loss, amyloidosis
30
Primary NS
Primary NS: diagnosis can be made after exclude secondary causes
Minimal change disease (MCD)
Focal segmental glomerulonephritis (FSGS)
Membranous nephropathy (MN)
Membranoproliferative glomerulonephritis (MPGN)
IgM nephropathy (IgMN)
31
CLINICAL
MANIFESTATIONS
Severity of diseases in primary NS are more severe than in secondary NS
32
Clinical manifestation of primary nephrotic syndrome
Age
Hypertension
Hematuria
Response to steroid
therapy
MCD
Very young
Good
FSGS
Young
1/3 of patients
2/3 of patients
1/3 response
MN
Aging
1/3 of patients
2/3 of patients
None, but 1/3 of patients

have spontaneous
remission
MPGN
Young
1/3 of patients
80% of patients
Poor
IgMN
Middle age
10% of patients
<5% of patients
80% response
33
References
34
COMMON
GLOMERULAR DISEASES
35
LUPUS NEPHRITIS
36
Epidemiology
Incidence 1.8 7.6 cases / 100,000 people, prevalence 40 200 cases / 100,000 people
Age of onset: peak 15 45 years, 85% are younger than 55 years
Female:male ratio 10:1
More than 60% of adults with SLE have renal involvement
50% of adults with SLE have renal involvement at presentation
Same incidence of renal involvement in male and female
Pathogenesis
Genetic, environmental, immunoregulatory, hormonal, and epigenetic factors contribute sequentially or simultaneously on the immune system result in loss of self-tolerance and generation of autoantibodies, immune complexes, autoreactive or inflammatory T cells and cytokines which damage to various organ, including kidneys.
37
Classification
International society of nephrology/renal pathology society (ISN/RPS) 2003 classification of LN
Class I
Minimal mesangial lupus nephritis

Normal glomeruli by light microscopy, but mesangial immune deposits by immunofluorescence
Class II
Mesangial proliferative lupus nephritis
Purely mesangial hypercellularity of any degree or mesangial matrix expansion by light
microscopy, with mesangial immune deposits
May be a few isolated subepithelial or subendothelial deposits visible by immunofluorescence or
electron microscopy, but not by light microscopy
Class III
Focal lupus nephritisa
Active or inactive focal, segmental or global endo- or extracapillary glomerulonephritis involving
<50% of all glomeruli, typically with focal subendothelial immune deposits, with or without
mesangial alterations
Active lesions: focal proliferative lupus nephritis
Class III (A)
Active and chronic lesions: focal proliferative and sclerosing lupus nephritis
Class III (A/C)
Chronic inactive lesions with glomerular scars: focal sclerosing lupus nephritis
Class III (C)
Class IV
Diffuse lupus nephritisb
Active or inactive diffuse, segmental or global endo- or extracapillary glomerulonephritis
involving >50% of all glomeruli, typically with diffuse subendothelial immune deposits, with or
without mesangial alterations. This class is divided into diffuse segmental(IV-S) lupus nephritis
when > 50% of the involved glomeruli have segmental lesions, and diffuse global (IV-G) lupus
nephritis when >50% of the involved glomeruli have golbal lesions. Segmental is defined as a
glomerular lesion that involves less than half of the glomerular tuft. This class includes cases
with diffuse wire loop deposits but with little or no glomerular proliferation
38
Class IV-S (A)

Class IV-G (A)
Class IV-S (A/C)
Class IV-S (C)
Class IV-G (C)
Class V
Class VI
Active lesions: diffuse segmental proliferative lupus nephritis

Active lesions: diffuse global proliferative lupus nephritis
Active and chronic lesions: diffuse segmental proliferative and sclerosing lupus nephritis
Active and chronic lesions: diffuse global proliferative and sclerosing lupus nephritis
Chronic inactive lesions with scars: diffuse segmental sclerosing lupus nephritis
Chronic inactive lesions with scars: diffuse global sclerosing lupus nephritis
Membranous lupus nephritis
Global or segmental subepithelial immune deposits or their morphologic sequelae by light
microscopy and by immunofluorescence or electron microscopy, with or without mesangial
alterations
Class V lupus nephritis may occur in combination with class III or IV in which case both will be
diagnosed
Class V lupus nephritis show advanced sclerosis
Advanced sclerosis lupus nephritis
>90% of glomeruli globally sclerosed without residual activity
aIndicate
the proportion of glomeruli with active and with sclerotic lesions.

bIndicate the proportion of glomeruli with fibrinoid necrosis and/or cellular crescents.
Indicate and grade (mild, moderate, severe) tubular atrophy, interstitial inflammation and fibrosis,
severity of arteriosclerosis or other vascular lesions.
39
Abbreviated international society of

nephrology/renal pathology society
(ISN/RPS) 2003 classification of LN
Class I
Minimal mesangial lupus nephritis

a
Class II
Mesangial proliferative lupus nephritis
Indicate the proportion of glomeruli with active and

with sclerotic lesions
b Indicate
Class III
Focal lupus nephritisa
the proportion of glomeruli with fibrinoid necrosis and cellular crescents

c Class
Class IV
Class V
Diffuse segmental (IV-S) or global (IV-G)

lupus nephritisb
Membranous lupus nephritisc
V may occur in combination with class III or IV

in which case both will be diagnosed
Indicate and grade (mild, moderate, severe) tubular atrophy, interstitial inflammation and fibrosis, severity of
arteriosclerosis or other vascular lesions
Class VI Advanced sclerosing lupus nephritis
40
Clinical manifestations
Class I
No clinical renal manifestation
Class II
Proteinuria: usually < 1 g/day,

no hematuria, normal blood pressure,
normal renal function
Class III
Hematuria,
subnephrotic-ranged proteinuria,
mild renal impairment,
mild hypertension
Class IV
Hematuria,
subnephrotic-ranged to nephrotic-ranged proteinuria, mild to severe renal
impairment,
mild to severe hypertension
Class V
Nephrotic syndrome,
no hematuria,
usually normal blood pressure, normal renal function
Class VI
Chronic kidney disease, depend of severity of disease
41
Investigations
Low complement in class IV, but variable in
class V
Extra-renal manifestations as in the criteria for diagnosis
Renal pathology
Light microscope
see in classification
Immunofluoresence
Immunofluoresence: positive staining in glomeruli, tubules, interstitium, and blood vessels
Predominant IgG, with co-deposits of IgM and
IgA in most specimens
Presence of fibrin, fibrinogen, C3 and C1q
staining are common
Electron microscope
Class I and II: mesangial EDD
Class III, IV and V: subendothelial and subepithelial EDD
Tubulorecticular inclusions (TRIs): intracellular
branching tubular structures, 24 nm in diameter
located within dilated cisternae of the endoplasmic reticulum of glomerular nad vascular endothelial cells, can be found in patients with HIV infection, other viral infections, and who receive
INF-
Diagnosis
Definite diagnostic tool for LN is renal biopsy
Presumptive diagnosis of LN can be done in the
patients with renal manifestations who meet the
criteria for diagnosis of SLE
Full house staining: presence of IgG, IgM,

IgA, C3 and C1q staining, highly suggestive
of LN
42
Criteria for diagnosis SLE

SLICC
SLICC (systemic lupus international collaborating clinics) criteria (2012)
Diagnosis can be made if
Presence of at least 4 of the followings, including at least one clinical criterion and one
immunologic criterion, or
Presence of biopsy-proven nephritis compatible with SLE, and presence of ANAs or antidsDNA antibodies
Clinical criteria
1. Acute cutaneous lupus, including:
Lupus malar rash (do not count if malar
discoid)
Bullous lupus
Toxic epidermal necrolysis variant of SLE
Maculopapular lupus rash
Photosensitivity lupus rash
In the absence of dermatomyositis
OR
subacute cutaneous lupus (nonindurated
psoriaform and/or annular polycyclic lesions
that resolve without scarring, although
occasionally with postinflammatory
dyspigmentation or telangiectasias)
2. Chronic cutaneous lupus, including:
Classic discoid rash
Localized (above the neck)
Generalized (above and below the neck)
Hypertrophic (verrucous) lupus
Lupus panniculitis (profundus)
Mucosal lupus
Lupus erythematosus tumidus
Chillblains lupus
Discoid lupus/lichen plannus overlap
43
Clinical criteria
Clinical criteria
3. Oral ulcers
Palate
Buccal
Tongue
OR
Nalsal ulcers
in the absence of other causes, such as
vasculitis, Behets disease, infection
(herpesvirus), inflammatory bowel disease,
reactive arthritis, and acidic foods
6. Serositis
Typical pleurisy for more than 1 day OR pleural
effusion OR pleural rub
Typical pericardial pain (pain with recumbency
improved by sitting forward) for more than 1
day OR pericardial effusion OR pericardial rub
OR pericarditis by EKG in the absence of other
causes, such as infection, uremia, and
Dresslers pericarditis
4. Nonscarring alopecia (diffuse thinning or hair

fragility with visible broken hairs) in the absence of
other causes such as alopecia areata, drugs, iron
deficiency, and androgenic alopecia
7. Renal
Urine protein-to-creatinine ratio (or 24-hour urine
protein) representing 500 mg protein/24 horurs OR red
blood cell casts
5. Synovitis involving 2 or more joints, characterized by

swelling or effusion
OR tenderness in 2 or more joints and at least 30
minutes of morning stiffness
44
Clinical criteria
8. Neurologic
Seizures
Psychosis
Mononeuritis multiplex
in the absence of other known causes such as
primary vasculitis
Peripheral or cranial neuropathy
primary vasculitis, infection, and diabetes
mellitus
Acute confusional state in the absence of other
causes, including toxic/metabolic, uremia,
drugs
9. Hemolytic anemia
Clinical criteria
10. Leukopemia (< 4,000/mm3 at least once)

in the absence of other known causes such as Feltys
syndrome, drugs, and portal hypertension
OR
Lymphopenia (< 1,000/mm3 at least once)
corticosteroids, drugs, and infection
11. Thrombocytopenia (< 100,000/mm3 at least once)

in the absence of other known causes such as drugs,
portal hypertension, and thrombotic thrombocytopenic
purpura
45
Immunologic criteria
Immunologic criteria
1. Immunologic criteria
5. Low complement
Low C3
Low C4
Low CH50
2. Anti-dsDNA antibody level above laboratory

reference range (or > 2-fold the reference range if
tested by ELISA)
3. Anti-Sm: presence of antibody to Sm nuclear

antigen
6. Direct Coombs test in the absence of hemolytic

anemia
4. Antiphospholipid antibody positivity as determined

by any of the following:
Positive test result for lupus anticoagulant
False-positive test result for rapid plasma
regain
Medium- or high-titer anticardiolipin antibody
level (IgA, IgG, or IgM)
Positive test result for anti-2-glycoprotein I
(IgA, IgG, or IgM)
46
ACR (American college of rheumatology)

criteria (1997)
4 of the 11 criteria are needed for the diagnosis
Criterion
Definition
Malar rash
Fixed erythema, flat or raised,

over the malar eminences,
tending to spare the nasolabial
folds
Discoid rash
Erythematous raised patches with

adherent keratotic scaling and
follicular plugging; atrophic
scarring may occur in older
lesions
Skin rash as a result of unusual

Photosensitivity reaction to sunlight, by patient
history or physician observation
Oral ulcers
Oral or nasopharyngeal
ulceration, usually painless,
observed by physician
Nonerosive
arthritis
Involving 2 or more peripheral

joints, characterized by
tenderness, swelling, or effusion
Criterion
Definition
Pleuritis or
pericarditis
1. Pleuritis convincing history of

pleuritic pain or rubbing heard by
physician or evidence of pleural
effusion, or
2. Pericarditis documented by
EKG or rub or evidence of
pericardial effusion
Renal disorder
1. Persistent proteinuria > 0.5 g/

day or more than 3+ if quantitation
not performed, or
2. Cellular casts may be red
cell, hemoglobin, granular,
tubular, or mixed
47
Criterion
Definition
Neurologic
disorder
1. Seizures in the absence of

offending drugs or known
metabolic derangements; e.g.,
uremia, ketoacidosis, or
electrolyte imbalance, or
2. Psychosis in the absence of
offending drugs or known
metabolic derangements, e.g.,
uremia, ketoacidosis, or
electrolyte imbalance
Hematologic
disorder
1. Hemolytic anemia with

recticulocytosis, or
2. Leukepenia < 4,000/mm3 on 2
occasions, or
3. Lymphopenia <1,500/mm3 on
2 occasions, or
4. Thrombocytopenia <100,000/
mm3 in the absence of offending
drugs
Criterion
Definition
1. Anti-DNA: antibody to native DNA in

abnormal titer, or
2. Anti-Sm: presence of antibody to Sm
nuclear antigen, or
3. Positive finding of antiphospholipid
antibodies on:
3.1 an abnormal serum level of IgG
Immunologic
or IgM anticardiolipin antibodies,
disorder
3.2 a positive test result for lupus
anticoagulant using a standard method,
or
3.3 a false positive test result for at
least 6 months confirmed by Treponema
pallidum immobilization or fluorescent
treponemal antibody absorption test
Antinuclear
antibodies
An abnormal titer of antinuclear

antibody by immunofluoresence or an
equivalent assay at any point in time
and in the absence of drugs
48
Treatment
Specific treatment
Specific treatment
Class I: treat extrarenal manifestations
Class II: treat extrarenal manifestations
In case of proteinuria > 3 g/day, treat as MCD
Class III and IV
Initial therapy
- Calcineurin inhibitors (CNIs): alternative therapy for patients who intolerance to azathioprine or MMF
Class V
In case of persistent nephrotic-ranged proteinuria: corticosteroid plus cyclophosphamide, or
CNIs, or MMF, or azathioprine
Class VI: treat extrarenal manifestations
Hydroxychloroquine: maximum dosage 6 6.5
mg/kg/day, in all LN patients unless contraindicate
- Corticosteroid plus cyclophosphamide or

MMF
- In case of worsening LN during first 3
months of treatment, change to alternative
treatment, or repeat renal biopsy to guide the
treatment
Maintenance therapy: continue after complete
remission for at least 1 year before tapering the
dosage
- Corticosteroid 10 mg/d plus azathioprine
1.5 -2.5 mg/kg/day or MMF 1 2 g/day
49
Other circumstances
Relapse disease
Resume the effective initial therapy, or
High cumulative dosage of cyclophosphamide, change to non-cyclophosphamidebased regimen
In case of antiphospholipid antibody syndrome (APS) involve kidney, treat the patients
with anticoagulants with target INR 2 3
In case of thrombotic thrombocytopenic purpura (TTP), treat the patients with plasma exchange
Pregnancy
In case of possible histologic class of LN has

changed, repeat renal biopsy
Delay pregnancy until achieve complete remission
Evaluation for the precipitating factors: poor

drug compliance, infections, pregnancy, or
drugs (estrogen-containing oral contraceptive pills)
Mode of contraception: condom
Resistant disease
Repeat renal biopsy to distinguish active disease from scarring
In case of active disease, treat the patients
with alternative regimen
In case of failed treatment 2 initial regimens, consider treatment with rituximab, or IV
immunoglobulin (IVIG), or CNIs
SLE with thrombotic microangiopathy (TMA)
Administration of low-dose aspirin during

pregnancy to decrease risk of fetal loss
Do not use cyclophosphamide, MMF, ACEI
and ARB
Switch MMF to azathioprine during the pregnancy
In case of relapse disease during pregnancy,
treat the patients with corticosteroid and/or
azathioprine depend on disease severity
In case of receiving corticosteroid and
azathioprine, continue same dosage for at
least 3 months after delivery
50
Side effect of treatment

Corticosteroid
Hyperglycemia, hypertension, hyperlipidemia, atherosclerosis, adrenal insufficiency
Cushingoid appearance, abnormal hair
growth, weigt gain, growth retardation
Peptic ulcer, pancreatitis
Posterior subcapsular cataract, glaucoma
Psychosis, sleeplessness, pseudotumor
cerebri
Proximal muscle weakness, osteoporosis,
AVN
Infections, panniculitis, spontaneous tendon rupture
Birth defect: 1/1,000 of cleft lip/palate
Increase risk of infertility if cumulative dosage 250 mg/kg (if BW 50 kg = 12.5 g)

Hemorrhagic cystitis
Azathioprine
Bone marrow suppression
Hepatitis
DO NOT concomitantly use with allopurinol, unless severe bone marrow suppression
Increase risk of malignancy if cumulative
dosage > 600 g
MMF
Bone marrow suppression
GI side effect: nausea, vomiting, diarrhea
Pneuonitis
Cyclophosphamide
Bone marrow suppression: nadir at 2
weeks
Increase risk of malignancy if cumulative
dosage 36 g
51
Prognosis
Progress to ESRD 5 - 50%
Class I and II: excellent prognosis
Class IV: least favorable prognosis
Patient survival: 10 years 100%, 20 years 85%
No doubling serum creatinine: 10 years 85%, 20 years 72%
Class V: natural history is less clear
52
References
Appel GB, Radhakrishnan J, and DAgati VD. Secondary glomerular disease. In: Taal MW, et al. editor.
Brenner & Rectors The Kidney. 9th ed. Philadephia: Elsevier Saunders; 2012. p 1192-1277.
Weening JJ, et al. The classification of glomerunephritis in systemic lupus erythematosus revisited. J Am
Soc Neprhol 2004;15:241-250.
Petri M, et al. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012;64:2677-2686.
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of
systemic lupus erythematosus [letter]. Arthritis Rheum 1997;40:1725.
Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical
Practice Guideline for Glomerulonephritis. Kidney Inter., Suppl. 2012;2:139-274.
Ponticell C. Glucocorticoids and immunomodulating agents. In: Ponticelli C, and Glassock RJ. Editor.
Treatment of Primary Glomerulonephritis. 2nd ed. New York: Oxford University Press Inc.; 2009. P 47-126.
53
POST-INFECTIOUS
GLOMERULONEPHRITIS
(PIGN)
54
Definition
An immunologic response of the kidney that
occurs following a non-renal infection
Related terms
Bright disease
Streptococcus-related glomerulonephritis
Post-streptococcal glomerulonephritis
Epidemiology
Incidence and prevalence are lower
in developed countries
Incidence 0.6 39.24 and prevalence 0.02 10.14 cases / 100,000
population
Median age of onset 36 58 years
High prevalence in DM, alcoholism
30 50% associated with gram negative bacilli infection
55
Pathogenesis
Remains unknown, believed to be the deposition of
immune complex within glomerular tuft
Nephritogenic antigens
SpeB (Streptococcal cationic proteinase exotoxin
B) or NSAP (neprhitis-strain-associated protein) or
NPBP (nephritis plasmin-binding protein)
GADPH (Streptococcal gluceraldehyde phosphate
dehydrogenase) or NAPIr (nephritis-associated
plasmin receptor)
The nephritogenic antigens are normally unable to penetrate

through the GBM because of having similar negative charge.
These antigens interact with plasmin and activate procollagenase
and matrix metalloproteinase (MMP) result in degradation and
reducing the negative charge of the GBM. These antigens and immune complexes are now able to pass through the GBM and deposit at subepithelial area to form hump-liked EDD result in foot
processes effacement and proteinuria.
56
Infections associated with PIGN

Infectious syndromes
Skin and throat infections (S. pyogenes, S.
equi, S. constellatus)
Bacterial endocarditis (S. aureus, S. viridans)
Pneumonia (S. pneumoniae, M. pneumoniae)
Visceral abscesses (dental abscess, deepseated abscesses, osteomyelitis)
Shunt nephritis (S. epidermidis, Propionivacterium)
Specific bacterial diseases
Gram positive bacteria: streptococci, staphylococci, pneumococci, enterococci, L. monocytogenes
Fungal infections
C. albicans, H. capsulatum, C. immitis
Viruses
DNA viruses: HBV, VZV, EBV, cytomegalovirus, parvovirus B19, adenovirus
RNA viruses: HIV, coxsackievirus, echovirus,
HAV, dengue virus, HCV, mumps virus, measles virus, hantavirus, rotavirus
Parasitic infections
P. falciparum, P. malariae
S. hematobium, S. mansoni
T. gondii, W. bancrofti, T. spiralis, E. granulosus, E. histolytica
Others
Gram negative cocci: Meningococcus, N.

gonorrhea
oTuberculosis and nontuberculous mycobacterium
Gram negative coccobacilli: Hemophilus
T. pallidum, L. interrogans, C. burnetii, M.

pneumonia, C. pneumoniae
Gram negative bacilli: Salmonella Klebsiella,

Seratia, Yersinia, Proteus, Pseudomonas
Others: Legionellosis, brucellosis, bartonellosis
57
There are 3 major patterns of clinical manifestations
Acute nephritc syndrome
- Prototype of PIGN
- Common after Streptococcal infection
- Some patients had anuria and
nephrotic-range proteinuria
Rapidly progressive glomerulonephritis
- Rare
- Crescent formation in glomeruli
- Associated with aging, S. aureus, gram
negative bacilli, Mycoplasma and M. leprae infection
- Subclinical disease was 4 19 times

more common than classic PIGN
Gross hematuria is possible
Hypertension: 75% of patients
Edema: 90% of patients
Prior infection before onset of disease: pharyngitis 10 days (7 21 days), skin infection
14 21 days
Site of infection: upper respiratory tract 0
67%, skin 6 28%, teeth and oral mucosa 0
23%, heart 0 20%, urinary tract 0 15%, osteomyelitis 0 10%
Some different manifestations between age
group
- In case of crescent formation less than

50%, recovery of renal function are likely
Subclinical glomerulonephritis
- Low-graded proteinuria (< 1 g/day),
pyuria, microscopic hematuria
58
GBM
Fibrocellular
Cresent
Parietal
Epithelial
Cell
Endothelial
Cell
Bowman
Capsule
Podocyte
Mesangial
Cell
Crescent formation
Bowman
Space
Normal glomerulus
59
Investigations
Hematuria: 2/3 had microscopic hematuria, gross hematuria is possible
Proteinuria: 80% had subnephrotic-ranged proteinuria, 20% had nephrotic-ranged proteinuria
Children
Adult
Elderly
Hematuria
97- 100%
86%
100%
Gross hematuria
30%
NA
NA
Proteinuria
47 80%
56 99%
92%
Nephrotic syndrome
4%
20 32%
20%
Renal failure
25 40%
38 51%
72 83%
Hypertension
50 60%
63 89%
81 86%
Heart failure
< 5%
46%
43%
Declined GFR in 60% of patients age of 55 years or more

Throat swab culture: can be found of group A Streptococci infected patients
Transient RTA type 4
Antibodies for detection of recent Streptococcal infection
60
ASO (Anti-streptolysis O): found in 2/3 in patients with URI, and 1/3 in patients with impetigo
Antideoxyribonuclease B (anti-DNaseB), antihyaluronidase (anti-Hase): associated with impetigo
Antistreptokinase, anti-nicotinamide adenine dinucleotidase
Streptozyme test combines several antistreptococcal antibody assays: screening test
Low C3 and CH50, but normal C4 level
61
Renal pathology
Light microscope:
diffuse endocapillary prolifGarland

Starry sky
Mesangial
pattern
pattern
pattern
(Capillary
(diffuse
wall pattern) pattern)
eration, mesangial hypercellularity, PMN infiltration,

some had crescent formation
Immunofluoresence
Positive IgG, C3 staining, occasionally IgM
and rare for IgA
3 patterns of staining which associated with
clinical manifestation patterns
Electron microscope:
Acute
nephritic
syndrome
RPGN
electron dense deposit
(EDD) at subepithelial area (subepithelial hump),

some had EDD at subendothelial and intramembranous area
Subclinical
GN
X
X
62
Treatment
Specific treatment
None for glomerulonephritis
Treatment of underlying infectious diseases
Steroid therapy is controversial
- RPGN and/or high percentage of crescent and severe interstitial lesion: short
course of high-dose intravenous steroid,
follows by 1 - 2 months with prednisolone
- In patients with S. aureus, Brucellosis
and Schistosomiasis infection, glomerulonephritis can progress in spite of eradicate of the organism. Treatment with corticosteroids or cytotoxic agents might
have a role in this circumstance.
Supportive treatment
BP control
Restrict protein intake

Correct electrolytes and acid-base disturbances
RRT if indicated
Prognosis
Resolve of clinical manifestations
Edema and hypertension in 1 2 weeks:
occurs after dieresis
Normal complement level in 8 weeks
No hematuria and proteinuria in months to
year
Complete remission: children almost 100%,
adults about 60%
Hypertesion with urinary abnormalities 5
60%, CKD 0 49%, ESRD 4 34%
Mortality 0 36%
More unfavorable prognosis in aging patients
Volume control: diuretic

Restrict salt intake
63
References
Nasr SH, Radhakrishnan J and DAgati VD. Bacterial infection-related glomerulonephritis in adults. Kidney
Int 2013;83:792-803.
Kanjanabuch T, Kittikowit W and Eiam-ong S. An update on acute postinfectious glomerulonephritis worldwide. Nat Rev Nephrol 2009;5:259-69.
Ponticell C, and Moroni G. Acute post-infectious glomerulonephritis. In: Ponticelli C, and Glassock RJ. Editor. Treatment of Primary Glomerulonephritis. 2nd ed. New York: Oxford University Press Inc.; 2009. P 153178.
Nachman PH, Jennete C, and Falk RJ. Primary glomerular disease. In: Taal MW, et al. editor. Brenner &
Rectors The Kidney. 9th ed. Philadephia: Elsevier Saunders; 2012. p 1100-1191.
64
IgA NEPHROPATHY
(IgAN)
65
Definition
Predominance of IgA deposits, either alone
or with IgG, IgM, or both in the glomerular mesangium
Epidemiology
Most common primary glomerular disease
Hit 3: Formation of pathogenic circulating immune complexes from autoantigen

(galactose-deficient IgA) and O-glycanspecific antibodies
Hit 4: Deposition of pathogenic immune
complexes in the mesangium, activation
of mesangial cells, and induction of glomerular injury
Occurs in all age groups

Most common at age of 10 20 years, 80%
of patients are age of 16 35 years at the
time of biopsy
More common in males than females: male /
female ratio 2:1 to 6:1
Pathogenesis
Multi-hit mechanism
Hit 1: Increased circulating galactosedeficient (at hinge region of heavy chain)
IgA1
Hit 2: Production of anti-glycan antibodies that recognize galactose deficient
IgA1
66
Etiologies
Primary IgAN
Secondary IgAN: associate with
Rheumatologic disorders: HenochSchnlein purpura, seronegative spondyloarthropathy, ankylosing spondylitis, Reiters syndrome, Bergers disease
Classification
Oxford classification: is a pathological classification using 4 scoring system
M: mesangial score; 0.5 (M0) or > 0.5
(M1)
E: Endocapillary hypercellularity; absent
(E0) or present (E1)
Infections: HIV infection, toxoplasmosis,

leprosy
S: segmental glomerulosclerosis; absent

(S0) or present (S1)
GI disorders: liver disease, alcoholic cirrhosis, celiac disease, Crohns disease,

gluten-sensitive enteropathy
T: Tubular atrophy; atrophy/interstitial fibrosis 25% (T0), 26 50% (T1) or

>50% (T2)
Neoplasm: mycosis fungoides, lung cancer, mucin-secreting carcinoma

Hematologic disorders: cyclic neurtopenia,
immunothrombocytopenia (ITP),
Others: scleritis, Sicca syndrome, mastitis,
pulmonary hermosiderosis, dermatitis herpitiformis
Familial IgAN
67
There are 4 patterns of clinical manifestations
Asymptomatic hematuria and/or proteinuria:
50 61%
Nephrotic syndrome : 0 13%, found in 2 patterns of renal pathology

Mesangial IgA deposit with extensive foot
process effacement (coexisting IgAN and
MCD)
Isolated microscopic hematuria 27 36%
- Hematuria: may presence or absence
Microscopic hematuria with proteinuria 16

17%
- Good response to steroid as in MCD,

and excellent prognosis
AKI or RPGN: 25 29%

AKI: ATN
- Occured after gross hematuria, due to
obstruction of RBC casts or Hb degradation product toxicity
- Duration 5 7 days
- Could be spontaneous recovery to need
RRT
RPGN or crescentic IgAN
- Turn to ESRD 50% and 80% at 1 and 5
years, respectively
- In case of there are cellular crescent >
10 20%, immunosuppressive may be
beneficial
Mesangial expansion
- Microscopic hematuria
- Progress to CKD
CKD or ESRD
Hematuria: could be asymptomatic hematuria to
gross hematuria
40 -50% had gross hematuria without dysuria, and tend to occur close to upper respiratory tract infection, so called synpharyngitis or synpharyngitic nephritis
30 40% had microscopic hematuria
Intermittent macroscopic hematuria occurred
in 25% of patients
68
Proteinuria: could be asymptomatic proteinuria to

nephrotic-ranged proteinuria
Most common: subnephrotic-ranged proteinuria
Edema, hypertension
Renal pathology
Light microscope: focal or diffuse mesangial
matrix expansion and hypercellularity, focal
glomerular sclerosis
Azotemia: could be AKI, RPGN, CKD, ESRD
Crescent formation may be found in severe

IgA nephropathy
Systemic symptoms: some had abdominal pain or

flank pain
Some patients had endocapillary proliferation
Investigations
UA: dysmorphic RBC, proteinuria
Normal complement level
Serum galactose-deficient IgA1 level, IgG
specific for galactose-deficient IgA, urine immune complex with galactose-deficient IgA1
Immunofluoresence: positive stain dominant

IgA or codominant for IgA with IgG and IgM,
positive stain for C3, rare for C1q
Electromicrocope: mesangial electron dense
deposit (EDD), minority subendothelial and/or
subepithelial EDD, foot process effacement
IgA / C3 level > 4 4.5
69
Treatment
Specific treatment
Corticosteroid therapy:
Use in patients with GFR > 50 ml/min/1.73
m2 who had persistent proteinuria 1 g/day,
despite 3 6 months of optimized supportive
care
- Prednisolone: 6-month course
1.0 mg/kg/d x 2 months, then
0.8 mg/kg/d x 1 month, then
Similar regimen to the treatment of ANCAassociated GN (see ANCA-associated glomerulonephritis (ANCA-associated GN))
Fish oil therapy
Use in patients with GFR > 50 ml/min/1.73
m2 who had persistent proteinuria 1 g/day,
despite 3 6 months of optimized supportive
care
- Fish-oil supplement 6 g oral bid (1.87 g
of eicosapentaenoic acid and 1.36 g of
docosahexaenoic acid) x 2 years
Mycophenolate mofetil (MMF), antiplatelet therapy, and tosillectomy: not recommend

0.2 mg/kg/d x 1 month, then off
Use in patients with coexisting IgAN and
MCD
- Similar regimen to the treatment of MCD
(see Minimal change disease (MCD))
Cyclophosphamide and azathioprine therapy:
Use in patients with crescentic IgAN (crescent > 50% of glomeruli) and RPGN
70
71
Control BP: target BP depend on degree of
proteinuria
Proteinuria < 1 g/day: < 130/80 mmHg
Proteinuria > 1 g/day: < 125/75 mmHg
ACEI and/or ARB therapy in patients with proteinuria 0.5 g/d, with up-titrating as far as
tolerated to achieve proteinuria < 1 g/day
Avoid dihydropyridine calcium channel blockers if possible
As in general CKD treatment (see Chronic
kidney disease (CKD))
Prognosis
Poor prognostic factors
Clinical factors: severe proteinuria, hypertension, elevated serum creatinine, male,
absence of any history of recurrent macroscopic hematuria, older age at presentation, marked erythrocyturia
Histologic factors: widespread global and/
or segmental glomerulosclerosis, marked
tubulointerstitial fibrosis, marked extracapillary proliferation, marked arteriolar hyalinosis, extension of IgA deposits into the walls
of peripheral capillary loops
Serum creatinine
1.7 mg/dL
- Proteinuria <1 g/day: turn to ESRD
13.4% at 7 years
- Proteinuria 1 g/day: turn to ESRD
78.7% at 7 years
> 3 mg/dL: all patients turn to ESRD, so
called point of no return
72
References
Nachman PH, Jennete C, and Falk RJ. Primary glomerular disease. In: Taal MW, et al.
editor. Brenner & Rectors The Kidney. 9th ed.
Philadephia: Elsevier Saunders; 2012. p
1100-1191.
Wyatt RJ, and Julian BA. IgA nephropathy. N
Engl J Med 2013;368:2402-2414.
Suzuki H, et al. The pathophysiology of IgA
nephropathy. J Am Soc Nephrol
2011;22:1795-1803.
Kang SH, et al. The Oxford classification as a
predictor of prognosis in patients with IgA
nephropathy. Nephrol Dial Transplant
2011;0:1-7.
Ishiguro C, et al. Serum IgA/C3 ratio may predict diagnosis and prognostic grading in patients with IgA nephropathy. Nephron
2002;91:755-758.
erulonephritis. Kidney Inter., Suppl.

2012;2:139-274.
Floege J, and Eitner F. Current therapy for
IgA nephropathy. J Am Soc Nephrol
2011;22:1785-1794.
Manno C, et al. Randomized controlled clinical trial of corticosteroid plus ACE-inhibitors
with long-term follow-up in proteinuric IgA
nephropathy. Nephrol Dial Transplant
2009;24:3694-3701.
Donadio JV, et al. A controlled trial of fish oil
in IgA nephropathy. N Engl J Med
1994;331:1194-1199.
DAmico G. Natural history of idiopathic IgA
nephropathy and factors predictive of disease outcome. Semin Neprhol
2004;24:179-196.
Kidney Disease: Improving Global Outcomes

(KDIGO) Glomerulonephritis Work Group.
KDIGO Clinical Practice Guideline for Glom-
73
ANCA-ASSOCIATED
GLOMERULONEPHRITIS
(ANCA-ASSOCIATED GN)
74
Definition
Necrotizing vasculitis, with few or no immune
deposits, predominantly affecting small vessels (i.e., capillaries, venules, arterioles, and
small arteries), associated with myeloperoxidase (MPO) ANCA (anti-neutrophil cytoplasmic antibodies) or proteinase 3 (PR3) ANCA.
Not all patients have ANCA
Related terms
Epidemiology
Incidence 3.9 cases / 1,000,000 people
Renal-limited ANCA-associated vasculitis 23
25%
ANCA-negative pauci-immune GN 27 38%
75
Pathogenesis
Anti-anti-complementary PR3
The sense strand of PR3 gene encodes
sense PR3, and the anti-sense strand encodes complementary PR3 (cPR3).
Subsequently, the immune system responses against cPR3 by developing anticPR3 antibody.
The immune system, again, responses
against anti-cPR3 antibody and develops
anti-anti-cPR3, which is PR3-ANCA because the epitope of anti-cPR3 was resembled to sense PR3.
ANCAs bind to endothelial cells and
membrane-bound PR3/MPO on neutrophils,
results in inflammation of vascular endothelial
cells, called vasculitis.
Dysregulation of immune system result in further worsening inflammatory response.
76
77
Etiologies
Genetics factors
GPA: HLA-DPB1*0401, SERPINA1, PRTN3
MPA: HLA-DQ
Others: PTPN22, CTLA4
Environment factors
Air pollutants: silica
Infection: S. aureus, E. coli
Medications: propylthiouracil, cocaine
Classification
4 types of ANCA-associated vasculitis (AAV)
Granulomatous with polyangiitis (GPA) or
Wegeners granulomatosis
Eosinophilic granulomatosis with polyangiitis (EGPA) or Churg-Strauss syndrome
Renal limited AAV or idiopathic necrotizing crescentic GN or renal-limited pauciimmune GN
Renal manifestations: RPGN
Extra-renal manifestations: can be found in
others, not renal-limited ANCA-vasculitis
Criteria for diagnosis

At least 2 of the 4 criteria, as followings
Nasal or oral inflammation (oral ulcers
or bloody nasal drainage)
Granulomatous
Abnormal chest radiograph (nodules,
with
fixed infiltrates, cavities)
polyangiitis
Urinary sediment (> 5 RBC/HPF or
(GPA) or
RBC casts)
Wegeners
granulomatosis Granulomatous inflammation on
biopsy (in wall of artery or arteriole,
perivascular, or extravascular)
Eosinophilic
granulomatosis
with
polyangiitis
(EGPA) or
Churg-Strauss
syndrome
At least 4 of the 6 criteria, as followings

Asthma
Eosinophilia >10%
Neuropathy, mono or poly
Pulmonary infiltrates, non-fixed
Paranasal abnormality
Extravascular eosinophils
78
Investigations
Urinalysis: telescopic urine sediments (can
be found in other causes of RPGN) which
composed of
Dysmorphic RBCs or RBC cast
Oval fat bodies
Broad casts
Normal complement level
P-ANCA (anti-MPO antibodies) and C-ANCA
(anti-PR3 antibodies): positive 62 73%
HNE-ANCA (Human neutrophil elastaseANCA): associated with drug-induced AAV
Anti-LAMP-2 antibody (anti-lysosomal membrane protein-2 antibody): controversial
79
Renal pathology
Treatment
Light microscope: crescent formation, fibrinoid necrosis, karryorhectic nuclei
2 phases of treatment
EGPA: presence of eosinophils in interstitium,

tubule
Unable to differentiate between GPA and
MPA
Immunofloresence: no staining, or minimal of IgG
or IgM
Electromicroscope: no EDD, or minimal EDD
Initial treatment
Cyclophosphamide
- Intravenous 15 mg/kg every 2 weeks for
two cycles the every 3 weeks till remission for 3 months, or
- Oral 2 mg/kg/day till remission, then 1.5
mg/kg/day for 3 months
Plus
prednisolone 1 mg/kg/day, and decrease
dosage to 10 mg/day
Rituximab and corticosteroid: alternative
treatment in
- Patients without severe disease
- Contraindicated to cyclophosphamide
Plasmapheresis: additional treatment in patients with
- Dialysis dependent
- Rapidly increasing serum creatinine
80
- Diffuse pulmonary hemorrhage

- Overlap with anti-GBM (glomerular
basement membrane) GN
Discontinue cyclophosphamide therapy who
require dialysis after 3 months of treatment
and do not have extra-renal manifestation of
disease
Maintenance therapy: in patients who achieved
remission, continue treatment for at least 18
months with prednisolone 10 mg/d with
Azathioprine 1 2 mg/kg/day oral
MMF up to 1 g po bid: alternative in patients
who
- Allergic to azathioprine
Etanercept: not use

Relapse disease
In severe case, use similar regimen to initial
treatment
In non-severe case, increasing dose, or reinstituting, or add other immunosuppressive drugs
Resistant disease
Addition of rituximab
Immunoglobulin iv (IVIG) or plasmapheresis: alternative treatment
Transplantation
After complete extra-renal remission for 12
months, not including positive ANCA
- Intolerance to azathioprine
Methotrexate 0.3 mg/kg/week, up to 25 mg/
week: alternative in patients who intolerance
to azathioprine and MMF, and have eGFR
60 ml/min/1.73m2
Trimethoprim-sulfamethoxazole: adjunctive
treatment in patients with upper respiratory
tract disease
81
Prognosis
Histopathological classification of ANCAassociated GN
Class
Renal survival (no development of ESRD) rate according to histopathological classification
Inclusion criteria
Class
Focal
50% normal glomeruli
Crescentic
50% glomeruli with cellular

crescents
Mixed
Sclerotic
< 50% normal, < 50% crescentic,

<50% globally sclerotic glomeruli
50% globally sclerotic glomeruli
1-year renal 5-year renal 7-year renal

survival
survival
survival
Focal
93%
93%
93%
Crescentic
84%
76%
70%
Mixed
69%
61%
50%
Sclerotic
50%
50%
25%
82
References
Jennette JC, et al. 2012 Revised international Chapel Hill consensus conference nomenclature of vasculitides. Arthritis Rheum 2013;65:pp 1-11.
Wilde B, et al. New pathophysiological insights and treatment of ANCA-associated vasculitis. Kidney Int
2011;79:599-612.
Furuta S, and Jayne DRW. Antineutrophil cytoplasm antibody-associated vasculitis: recent developments.
Kidney Int 2013;84:224-249.
Appel GB, Radhakrishnan J, and DAgati VD. Secondary glomerular disease. In: Taal MW, et al. editor.
Brenner & Rectors The Kidney. 9th ed. Philadephia: Elsevier Saunders; 2012. p 1192-1277.
Leavitt RY, et al. The American college of the rheumatology 1990 criteria for the classification of Wegeners granulomatosis. Arthritis Rheum 1990;33:1101-1107.
Masi AT, et al. The American College of Rheumatology 1990 criteria for the classification of Churg-Strauss
syndrome (allergic granulomatosis and angiitis). Arthritis Rheum 1990;33:1094-1100.
Kain R, et al. Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nat Med
2008;14:1088-1096.
Roth AJ, et al. Anti-LAMP-2 antibodies are not prevalent in patients with antineutrophil cytoplasmic autoantibody glomerulonephritis. J Am Soc Nephrol 2012;23:545-555.
Kain R, et al. High prevalence of autoantibodies to hLAMP-2 in anti-neutrophil cytoplasmic antibodyassociated vasculitis. J Am Soc Nephrol 2012;23:556-566.
Slot MC, et al. Occurrence of antineutrophil cytoplasmic antibodies and associated vasculitis in patients
with hyperthyroidism treated with antithyroid drugs: A long-term followup study. Arthritis Rheum
2005;53:108-113.
83
Berden AE, et al. Histopathological classification of ANCA-associated glomerulonephritis. J Am Soc Nephrol 2010;21:1-9.
84
MINIMAL CHANGE
DISEASE
(MCD)
85
Related terms
Lipoid nephrosis
Minimal change glomerulopathy
Epidemiology
Drugs: NSAIDs, gold, lithium, interferon,

ampicillin, rifampin, trimethadione, tiopronin
Tumors: Hodgkins disease, lymphoma, leukemia, solid tumors
10 15% of primary glomerular syndrome in

adults
Allergies: food, dust, bee stings, pollen,

poison ivy, poison oak, dermatitis herpitiformis
70 - 90% of nephrotic syndrome in children

under age of 10 year, and 50% of older children
Others: SLE, following hematopoietic cell

transplantation
Male : female ratio 2:1 3:1
Pathogenesis
Remains unclear
Most likely a consequence of abnormal regulation of T cells
Etiologies and classification

Primary MCD
Abrupt onset of nephrotic syndrome
Hematuria is distinctive unusual
Hypertension is uncommon, but can be
found in aging patient
AKI can be found in adults with MCD, but the
true cause remains uncertain and probably
multifactorial
Secondary MCD
Infections: virus, parasite
86
Investigations
Severe proteinuria
15% of patients have microscopic hematuria
Serum albumin concentration is generally
less than 2 g/dL
Renal function is usually preserved, but can
deteriorate in some adult patients
The diagrams show A) normal glomerular capillary loop and
Renal pathology
Light microscope: normal, or minimal focal segmental mesangial prominence
Immunofloresence: no staining, or low level of mesangial staining of IgM, or C3
Electromicroscope: podocyte foot process effacement, microvillous transformation
B) capillary loop in MCD. The latter shows epithelial (podocyte) foot process effacement (arrow),
and microvillous transformation.
87
Treatment
Frequent relapse and steroid-dependent MCD
Initial episode
Corticosteroid:
Prednisolone
- 1 mg/kg/day (maximum 80 mg/day),
or
- 2 mg/kg every other days (maximum
120 mg/day)
Maintain high-dose of prednisolone for
- Minimum for 4 weeks, if achieve
complete remission
Then, tapered slowly over 6
months
- Maximum for 16 weeks, if not
achieve complete remission
Cyclophosphamide oral: in case of intolerate,
or contraindicate to corticosteroid
Calcineurin inhibitor: in case of intolerate, or
contraindicate to corticosteroid
Infrequent relapse disease: similar regimen to the
treatment of initial episode
Cyclophosphamide 2 2.5 mg/kg/day oral

for 8 weeks
Cyclosporine 3 5 mg/kg/day or tacrolimus
0.05 0.1 mg/kg/day oral for 1 2 years: in
patients who
Relapse during cyclocphosphamide
therpy, or
Wish to preserve their fertility
MMF 500 1,000 mg twice daily for 1 2
years: in patients who intolerant to corticosteroid, cyclophosphamide, and calcineurin inhibitors (cyclosporine, or tacrolimus)
Steroid-resistant MCD
Re-evaluate other causes of nephrotic syndrome, especially FSGS
Statin: not be used in initial episode of MCD
ACEI or ARB: not be used in normotensive patients
Prognosis
Good long-term prognosis
88
References
89
FOCAL SEGMENTAL
GLOMERULOSCLEROSIS
(FSGS)
90
Definition
Histological pattern of glomerular injuries,
segmental obliteration of glomerular capillaries by extracellular matrix
Related terms
Progressive lipoid nephrosis
Focal glomerular scleroses
Epidemiology
Epidemiology Incidence 0.84 21 cases /
1,000,000 people
0 67% of primary glomerular diseases
causing ESRD in US
Pathogenesis
Circulating permeability factors: alters the podocytes structure and increase proteinuria
Serum soluble urokinase receptor (suPAR):
found 2/3 of patients with primary FSGS
Cardiotrophin-like cytokine 1 (CLC-1)
|Integrin-linked kinase (ILK)
Etiologies
Primary FSGS
Secondary FSGS
Familial or genetic: mutation in specific genes
Slit diaphragm protein: nephrin (NPHS1), podocin (NPHS2), CD2-associated protein
(CD2AP)
Cell membrane-associated proteins: transient
receptor potential cation channel 6 (TRPC6),
protein tyrosine phosphatase receptor type O
(PTPRO), laminin-2 (LAMB2), 4-integrin
(ITGB4), tetraspanin CD151 (CD151)
Cytosolic or cytoskeletal proteins: -actinin-4
(ACTN4), phospholipase C1 (PLCE1), my91
osin heavy chain 9 (MYH9), inverted formin 2

(INF2), myosin 1E (MYO1E)
Nuclear proteins: wilms tumor 1 (WT1),
SMARCA-like protein (SMARCAL1)
Mitochondrial components: tRNAleu (mtDNAA3243G), parahydroxybenzoatepolyprenyltransferase (COQ2), coenzyme
Q10 biosynthesis monooxygenase 6 (COQ6)
Lysosomal protein: lysosomal integral membrane protein type 2 (SCARB2)
Unknown cellular location: apolipoprotein L1
(APOL1)
Viral-associated: HIV type 1, parvovirus B19, simian virus 40, cytomegalovirus, EBV
Drug-induced: heroin, IFN-, IFN-, IFN-, lithium,
pamidronate, sirolimus, calcineurin-inhibitor nephrotoxicity, anabolic steroids
vanced renal disease with reduced functioning nephrons

Initially normal renal mass: hypertension,
acute or chronic vaso-occlusive processes
(atheroembolization, thrombotic microangiopathy, renal artery stenosis), elevated bodymass index (obesity, increased lean body
mass [e.g. bodybuilding]), cyanotic heart disease, sickle cell anemia
Classification
Not otherwise specified (NOS)
Perihilar
Cellular
Tip
Collapse
Adaptive
Reduced renal mass: oligomeganephronia,
very low birth weight, unilateral renal agenesis, renal dysplasia, reflux nephropathy, sequel to cortical necrosis, surgical renal ablation, renal allograft, aging kidney, any ad92
Histological variants of FSGS

Subtypes
Defining features
Associations
NOS
1 glomerulus with segmental increases

in matrix obliteraign the capillary lumina
There may be segmental glomerular
capillary wall collapse without overlying
podocyte hyperplasia
Exclude perihilar, cellular, tip, and
collapsing variants
Most common subtype

Primary or secondary
(including genetic forms and
other diverse secondary
causes)
Other variants can evolve
into FSGS (NOS) over time
May present with the

nephrotic syndrome or
subnephrotic-ranged
proteinuria
Common in adaptive FSGS

Predisposition for vascular
1 glomerulus with perihilar hyalinosis, pole is probably due to
with or without sclerosis
normally increased filtration
> 50% of glomeruli with segmental
pressures at the proximal
lesions must have perihilar sclerosis and/ afferent end of glomerular
or hyalinosis
capillary bed, which are
Exclude cellular, tip, and collapsing
heightened under conditions
variants
of compensatory demand
and vasodilatation of the
afferent arteriole
In adaptive FSGS,
patients are more likely
to present with
subnephrotic-ranged
proteinuria and normal
serum albumin level
Perihilar
Clinical features
93
Subtypes
Cellular
Tip
Defining features
Associations
1 glomerulus with segmental

endocapillary hypercellularity occluding Usually primary, but also
lumina, with or without foam cells and
seen in secondary FSGS
karyorrhexis
Least common variant
Exclude tip, and collapsing variants
1 segmental lesion involving the tip

domain (outer 25% of tuft next to origin of
proximal tubule)
The tubular pole must be indentified in
the defining lesion
The lesion must have either and
adhesion or confluence of podocytes
with parietal or tubular cells at the tubular
lumen or neck
The tip lesion may be cellular or sclerosis
Exclude collapsing, and perihilar variants
Clinical features
Usually present with

nephrotic syndrome
Usually presents with

Usually primary
abrupt onset of
Probably mediated by
nephrotic syndrome
physicl stresses on the
More common in white
paratubular segment owing
race
to the convergence of
Best prognosis, high
protein-rich filtrate on the
rate response to
tubular pole, causing shear
gllucocorticoid
stress and possible
Lowest risk of
prolapse
progression
94
Subtypes
Defining features
Associations
Primary or secondary to
Viruses: HIV-1, parvovirus
B19, simian virus 40, EBV,
CMV, hemophagocytic
syndrome
1 glomerulus with segmental or global
Drugs: pamidronate and
Collapsing collapse and overlying podocyte
interferon
hypertrophy and hyperplasia
Vaso-occlusive disease:
atheroemboli, calcineurin
inhibitor nephrotoxicity, and
chronic allograft
nephropathy
Clinical features
Most aggressive variant

Severe nephrotic
syndrome
More common in black
race
Worst prognosis, poor
response to
glucocorticoid
Rapid course tot renal
failure
95
Depend on histopathological variants (see
Histological variants of FSGS)
Renal pathology
Adequate sampling: 25 glomeruli, and include
juxtamedullary glomeruli
Proteinuria: subnephrotic-ranged proteinuria to nephrotic-ranged proteinuria
Light microscope: depend on histopathological

variants (see Histological variants of FSGS)
Normal renal function to rapid declined of

renal function
Immunofloresence: IgM, C3, granular pattern
Investigations
Electromicroscope: tubulorecticular inclusion (TRI)

in HIV-associated nephropathy (HIVAN)
Evaluation of the secondary causes
96
Treatment
Corticosteroid: in primary nephrotic syndrome
Prednisolone 1 mg/kg/day (maximum 80 mg) or 2 mg/kg/day every other days (maximum 120 mg)
Duration of high-dose corticosteroid
- Minimum 4 weeks
- Maximum: up to 16 weeks, or as tolerated, or until complete remission, whichever earlier
After complete remission, slowly tapered off in 6 months
Calcineurin inhibitors (CNI): alternative for patients intolerance to, or contraindicated to high-dose corticosteroid
Relapse disease: treat as relapse MCD
Steroid-resistant FSGS
Cyclosporine 3 -5 mg/mg/day bid for at least 4 6 months
In case of partial or complete remission, continue cyclosporine treatment for at least 12 months, followed by slowly taper off
Combination of MMF with high-dose dexamethasone, in patients who intolerate to cyclosporine
97
Prognosis
Variants
1-year renal survival
3-year renal survival
Tip
88%
76%
Perihilar
89%
75%
NOS
86%
65%
Cellular
83%
NA
Collapsing
74%
33%
Overall
86%
67%
98
References
Wei C, et al. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med
2011;17:952-960.
McCarthy ET, et al. Circulating permeability factors in idiopathic nephrotic syndrome and focal segmental
glomerulosclerosis. Clin J Am Soc Nephrol 2010;5:2115-2121.
Hattori M, et al. Increase of integrin-linked kinase activity in cultured podocytes upon stimulation with
plasma form patients with recurrecnt FSGS. Am J transplant 2008;8:1550-1556.
DAgati, et al. Focal segmental glomerulosclerosis. N Engl J Med 2011;365:2398-2411.
DAgati, et al. Pathological classification of focal segmental glomerulosclerosis: a working proposal. Am J
Kidney Dis 2004;43:368-382.
Thomas DB, et al. Clinical and pathological characteristics of focal segmental glomerulosclerosis pathologic variants. Kidney Int 2006;69:920-926.
99
MEMBRANOUS
NEPHROPATHY (MN)
100
Related terms
Membranous glomerulopathy
Epidemiology
25% of nephrotic syndrome in adults, most
common
Male : female ratio 2:1
Pathogenesis of primary MN
Possible from circulating anti-M-type phospholipase A2 receptor (PLA2R) autoantibodies which most are IgG4 subclass
Sensitivity 75%, and specificity 100%

Primary MN
Secondary MN
Autoimmune disease: SLE, autoimmune
thyroiditis
Infections: HBV, HCV, malaria
Drugs: D-penicillamine, gold
Malignancies: colon cancer, lung cancer,
prostate cancer
Malignancy in MN
25% of patients have negative test on

anti-PLA2R, might be possibly caused
by unknown antigens
In patients older than 60 years, MN associate with malignancy in 20 30% of patients
PLA2R-Ag-Ab immune complexes deposit at subepithelial area, subsequently

complement pathway is activated, results in podocyte injuries and proteinuria
Usually asymptomatic
Median time from diagnosis of MN to diagnosis of cancer is 60 months
Risk factors: older age, and smoking
Remission of malignancy is associated
with reduction in proteinuria
101
Investigations
Proteinuria: most nephrotic-ranged proteinuria, 10 20% subnephrotic-ranged proteinuria
Microscopic hematuria: 1/3 of patients
Hypertension: 2/3 of patients
Renal pathology
Light microscope:
Immunofloresence: positive staining of IgG
and C3 in granular pattern
Electromicroscope: subepitheial immune complex deposits, podocyte foot process effacement, microvillous transformation
102
Pathological staging
Stage I: small EDD at subepithelial area
Stage II: projections of basement membrane material around the subepithelial deposits, appears as a
spike formation
Stage III: new basement membrane material surrounds the EDD, appears as intramembranous EDD
Stage IV: loss of EDD, results in irregular electro-lucent zones within irregularly thickened basement membrane
Stage I
Stage II
Stage III
Stage IV
103
Treatment of primary MN
Evaluation for secondary causes of MN
Immunosuppressive therapy should be started only in patients with NS with one of the followings
Urine protein > 4 g/day, and remains over 50% of the baseline value, and does not progressive decline during antihypertensive and antiproteinuria therapy during an observation period of at least 6
months
Presence of severe, disabling, or life-threatening symptoms related with NS
Rising of serum creatinine 30% within 6 12 months from the time of diagnosis and eGFR > 25 30
ml/min/1.73 m2 and this change is not explained by superimposed complications
Initial therapy
6-month course of alternating monthly cycles of
Corticosteroids IV and oral
Plus
Alkylating agents oral
- Prefer cyclophosphamide rather than chlorambucil
In case of unable to achieve complete remission after completion of this regimen, considered as
a treatment failure if
- Presence of deterioration of kidney function, severe, disabling, or potentially life-threatening
symptoms related to NS
- Unless, after conservative treatment for at least 6 months
104
- Repeat kidney biopsy if the patients have rapid deteriorate of kidney function (double of serum creatinine over 1 2 months) without massive proteinuria (> 15 g/day)
Continuous daily (noncyclical) use of oral alkylating agents may also effective, but my be at a greater
risk of toxicity, particularly when administered for > 6 months
Not use monotherapy regimen with neither corticosteroid nor MMF
Alternative therapy
Cyclosporine or tacrolimus for 6 months, if the patients are contraindicated, or choose to not use cyclical regimen
Monitor drug level during the initial treatment, and whenever unexplained rising in serum creatinine > 20% during the treatment
Gradually decrease the dosage of CNIs every 1 2 months to 50% of initial dosage, and continue for at least 12 months
Discontinue, if unable to achieve complete or partial remission after 6 months of treatment
Resistant to initial therapy
Patients who resistant to cyclical regimen, should switch to CNI-based regimen
Patients who resistant to CNI-based regimen, should switch to cyclical regimen
Relapse disease
Reinstitution of the same therapy that results in initial remission
Cyclical regimen can be repeat only once
105
Prophylactic anticoagulant (warfarin) should be considered in patients with MN and nephrotic syndrome
with serum albumin < 2.5 g/dL and additional risks for thrombosis
Prognosis
Complete spontaneous remission: 25 - 50% at 5 years
Progressive renal impairment: 30% at 8 years, and 62% in patients who had nephrotic-ranged proteinuria
at presentation
Renal survival: 86% at 5 years, 65% at 10 years, and 59% at 15 years
ESRD: 35% at 10 years
106
References
Beck LH, and Salant DJ. Membranous nephropathy: recent travels and new road ahead. Kidney int
2010;77:765-770.
Practice Guideline for Glomerulonephritis. Kidney Inter., Suppl. 2012;2:139-274
107
ACUTE KIDNEY INJURY

(AKI)
DEFINITION
Increase in serum creatinine 0.3 mg/
dL within 48 hours; or
Increase in serum creatinine 1.5
times baseline, which is known or presumed to have occurred within the prior
7 days; or
Urine volume < 0.5 ml/kg/hour for 6
hours
109
STAGING
Stage
Serum creatinine
Urine output
1.5 1.9 times baseline; or

0.3 mg/dL increase
< 0.5 ml/hg/hour for 6-12 hours
2.0 2.9 times baseline
< 0.5 ml/hg/hour for 12 hours
3.0 times baseline; or

Increase in serum creatinine to 4.0 mg/dL; or
Initiation or renal replacement therapy; or
In patients < 1 years, decrease in eGFR to
< 35 ml/min/1.73 m2
< 0.5 ml/hg/hour for 24 hours; or

Anuria for 12 hours
110
ETIOLOGIES
111
Pre-renal AKI
Pre-renal AKI: decreased renal blood flow
Decrease intravascular fluid volume
Renal loss: diuretic, renal salt wasting, primary adrenal insufficiency
Extra-renal loss
- GI loss: vomiting, diarrhea, fistula, GI bleeding, NG suction
- Peritoneal cavity: ascites in cirrhosis, pancreatitis, peritonitis
- Insensible loss: burn, sweating
- Fluid leakage: hypoalbuminemia (serum albumin <2 g/dL), cirrhosis, nephrotic syndrome
- Others: external or occult bleeding, shock
Heart failure
Peripheral vasodilatation: sepsis, adrenal insufficiency, vasodilators, hypoxia, hypercarbia
Obstruction of renal artery
Mechanical obstruction: stenosis, thrombosis, emboli, surgery
Vasculitis: Polyarteritis nodosa, Takayasu arteritis
Vasoconstriction: sepsis, NSAIDs, hepatorenal syndrome
112
Intrinsic renal AKI

Vascular causes: malignant hypertension, TTP,
HUS, DIC, sclerodermal renal crisis
Glomerular causes (acute glomerulonephritis;
AGN): post-infectious glomerulonephritis, IgA
nephropathy
Interstitial causes (acute interstitial nephritis; AIN)
Drugs
- Common causes: penicillin, NSAIDs use
Post-renal AKI
Occurs in
Lower urinary tract obstruction
Upper urinary tract obstruction: bilateral obstruction, unilateral obstruction in solitary
functioning kidney
Nephrolithiasis, retroperitoneal fibrosis, CA bladder, CA cervix, neurogenic bladder, urethral stenosis, urethral stone, obstructed Foley catheter
- Uncommon causes: quinolone, leukemia, lymphoma, sarcoidosis

Infections: various organisms
Tubular causes (acute tubular necrosis; ATN)
Ischemic ATN: prolong pre-renal AKI
Nephrotoxic ATN: aminoglycosides, colistin,
vancomycin, NSAIDs, radiocontrast agents
Intratubular obstruction: tumor lysis syndrome, cast nephropathy, rhabdomyolysis,
crystals (methotrexate, acyclovir, indinavir)
113
APPROACH TO THE
PATIENTS WITH AKI
114
Differentiate between AKI and progression of CKD

Differentiate between AKI and progression of
CKD: onset of renal disease
History of nocturia, history of intermittent
edema, change of urine volume
Investigations: small size kidneys (< 9 cm in
length), anemia of renal disease
Using data from history taking and physical examination to determine the most
possible causes of AKI
Using data from history taking and physical examination to determine the most possible causes of
AKI
Pre-renal AKI: vomiting, diarrhea, bleeding,
diuretic, vasodilator use, underlying diseases
(nephrotic syndrome, cirrhosis), hypotension,
orthostatic hypotension, low JVP
- In patients with heart failure: orthopnea, PND,

chest pain, edema, high JVP
Post-renal AKI: passing stone, underlying diseases (CA bladder, CA prostate, CA cervix, BPH,
neurogenic bladder), positive bimanual palpation
and/or full bladder
Intrinsic AKI; vascular causes: severe hypertension, diarrhea, fever, alteration of consciousness,
underlying disease (scleroderma, atrial fibrillation,
hypercoagulable state)
AGN: hematuria, history of infection (see Postinfectious glomerulonephritis (PIGN) and IgA nephropathy (IgAN), hypertension, edema, high JVP
AIN: penicillin, NSAIDs, quinolone use, leukemia,
lymphoma, sarcoidosis, infection, arthralgia, rash
ATN: prolong pre-renal AKI, red-brown urine (rhabdomyolysis), hematologic malignancy, aminoglycosides, colistin, vancomycin, NSAIDs, radiocontrast agents, methotrexate, acyclovir, indinavir
115
Urine examination
Urinary indices to differentiate
between pre-renal AKI and intrinsic AKI
AIN: presence of WBC in
urine, without bacteriuria,
eosinophiluria by Hansel
stain
ATN: muddy brown cast
AGN: dysmorphic RBCs,
RBC cast, glomerular proteinuria
Ultrasound
Urinary indices
Parameters
Pre-renal Intrinsic renal

AKI
AKI
uNa (mEq/L)
<20
> 40
Urine specific gravity
> 1.020
1.010
Urine osmolality (mOsm/kgHO)
> 500
< 350
sUrea / sCr
> 20
10 - 15
Fractional excretion of Na (FE Na)

[ (uNa/sNa) / (uCr/sCr) ] x 100%
< 1%
>2%
Fractional excretion of urea (FE urea)

[ (uUrea/sUrea) / (uCr/sCr) ] x 100%
< 30%
> 50%
Post-renal AKI: bilateral hydronephrosis, hydroureter
Renal biopsy
sCr: serum creatinine, sNa: serum sodium, sUrea: serum urea or BUN,
uCr: urine creatinine, uNa: urine sodium, uUrea: urine urea
116
Limitation in interpretation of urinary indices

Urine specific gravity: false high in proteinuria, glucosuria, mannitol, colloidal fluid use
sUrea/sCr: false low in rhabdomyolysis, malnutrition
uNa and FE Na: false high in diuretic use, CKD, non-reabsorbable solute excretion (bicarbonate, glucose,
mannitol)
FE Na and FE urea: false low in contrast-induced nephropathy, acute myeloma kidney,
acute urate nephropathy, hepatorenal syndrome, NSAIDs, sclerodermal renal crisis,
TTP, sepsis, acute glomerulonephritis, early obstructive nephropathy, 10-15% of
non-oliguric ATN
117
TREATMENT
118
Treatment
Specific treatment
Correct the causes of AKI
Diet requirement
Fluid requirement (in case of patients in euvolemic status) = urine output + insensible loss
(in general 500 800 ml/d)
Discontinue all nephrotoxic agent when possible
Energy requirement 20 30 kcal/kg/day
Avoid all nephrotoxic agent if possible. In case of

therapeutic alternatives are not available
Protein
Aminoglycoside: prefer single dose daily,

rather than multiple-dose daily treatment and
monitor drug level if possible
Amphotericin B: prefer lipid formulation,
rather than conventional formulation
Ensure volume status and perfusion pressure
Avoid hyperglycemia: keep plasma glucose 110149 mg/dL in critically ill patients
- Noncatabolic AKI without dialysis: 0.8

1.0 g/kg/day
- AKI with dialysis: 1.0 1.5 g/kg/day, and
up to maximum of 1.7 g/kg/day in patients on CRRT (continuous renal replacement therapy) and in hypercatabolic patients
Sodium restriction in case of hypervolemia
Potassium restriction for prevention of hyperkalemia
119
Furosemide may be beneficial in switch the hypervolemic patients with oliguric AKI and to non-oliguric
AKI, but not enhancing kidney function recovery
Indications for initiate renal replacement

therapy
Adjust the drug dosage: eGFR of the patients with

AKI are presumed to be less than 10 ml/min/1.73 m2
Not using dopamine, fenoldopam, atrial natriuretic
peptide (ANP), and recombinant human IGF-1 (rh
IGF-1) to treat AKI
Monitor serum creatinine, urine output
Biochemical
indications
Correct electrolytes and acid-base abnormalities: hyperkalemia, metabolic acidosis, hypocalcemia

If indicated, initiate renal replacement therapy
(RRT)
Modalities of RRT: intermittent hemodialysis
(IHD), SLEDD (sustained low efficacy daily
dialysis), CRRT (continuous renal replacement therapy), PD (peritoneal dialysis)
Adjust the drug dosage according to modalities of RRT
Clinical
indications
Refractory hyperkalemia > 6.5 mEq/L

Refractory metabolic acidosis pH < 7.15
Refractory other electrolyte abnormalities:
hyponatremia, hypernatremia, or
hypercalcemia
BUN > 80 mg/dL
Tumor lysis syndrome with hyperuricemia and
hyperphosphatemia
Refractory volume overload

End organ involvement: pericarditis,
encephalopathy, neuropathy, myopathy,
uremic bleeding
Severe poisoning or drug overdose
Creation of intravascular space for plasma
and other blood product infusions and
nutrition
AKI with multiple organ failure
Severe hypothermia or hyperthermia
Discontinue RRT when it is no longer required

120
Advantages and disadvantages of different RRT modalities in AKI
Modality
Use in
hemodynamically
unstable patients
Solute clearance
Volume control
Anticoagulant
PD
Yes
Moderate
Moderate
No
IHD
No
High
Moderate
Possible without
SLEDD
Possible
High
Good
Possible without
CRRT
Yes
Moderate / High
Good
Possible without
CRRT: continuous renal replacement therapy, IHD: intermittent hemodialysis, PD: peritoneal dialysis, SLEDD: sustained low efficacy daily dialysis
121
The video was taken on the 81-year-old male with AKI due to septic shock. His serum BUN was more
than 100 mg/dL and he became uremic encephalopathy. The physical examination showed positive
frog legs sign. He was resuscitated and underwent hemodialysis.
122
The video was taken on the 81-year-old male with AKI due to septic shock. The video was taken
8 days later when his serum BUN was 94 mg/dL. The physical examination showed positive
flapping tremor sign.
123
CHRONIC KIDNEY DISEASE

(CKD)
DEFINITION
Either of the following present for > 3 months
Markers of kidney damage (one or more)
Albuminuria 30 mg/day, or albumin-tocreatinine ratio 30 g/ g creatinine
Urine sediment abnormalities
Electrolyte and other abnormalities due
to tubular disorders
Abnormalities detected by histology
Structural abnormalities detected by imaging
History of kidney transplantation
Decreased GFR: < 60 ml/min/1.73 m2
125
STAGING
Green: low risk (if no other markers of kidney disease, no CKD);

Yellow: moderately increased risk; Orange: high risk; Red, very high risk.
126
APPROACH TO THE
PATIENT WITH CKD
Determine the duration of kidney disease
If > 3 months, CKD is confirmed
If not > 3 months or unclear, CKD is not confirmed. Patients may have CKD or AKI or AKI
on top CKD, thus the test should be repeated
accordingly.
127
Evaluation of causes: using data from history taking,

physical examination, laboratory measures, imaging and
renal biopsy
Evaluation of GFR
Initial assessment: using serum creatinine and
GFR estimating equation
More accurate ascertainment: using exogenous
filtration marker
Evaluation of albuminuria
Initial assessment: spot urine sample (prefer early
morning urine sample) for reagent strip urinalysis
(UA)
Confirmatory tests for quantitative measurement
Spot urine sample (prefer early morning urine
sample) for albumin-to-creatinine ratio (ACR)
, urine protein-to-creatinine ratio (PCR)
Timed urine sample for albumin excretion
rate (AER) or total protein excretion rate
128
TREATMENT
129
Prevention of CKD progression

Blood pressure control
BP target
Individualize BP targets and agents according to age, underlying diseases, risk of CKD progression,
and tolerance of treatment
In patients with urine AER
- < 30 mg/day (or equivalent): 140/90 mmHg
- 30 mg/day (or equivalent): 130/80 mmHg
ACEI or ARB are recommended in patients with urine AER > 30 mg/day (or equivalent)
Kidney transplant recipients
Target BP 130/80 mmHg
BP-lowering agents depend on timing after transplantation, use of calcineurin inhibitor,degree of albuminuria, and other comorbidities
Insufficient evidence for combining ACEI and ARB therapy for prevent progression of CKD
130
Glycemic control
Glycemic control: target HbA1c about 7.0 %
> 7.0% in individuals with comorbidities or limited life expectancy and risk of hypoglycemia
Avoid <7.0% in patients at risk of hypoglycemia
Lipid control
Lipid control: treatment depend on age of patients and other comorbidities
Cholesterol-lowering Treatment
Non-dialysis-dependent or kidney transplantat recipients
Age 18 49 years: statin if presence one or more of the followings: known coronary disease, DM,
prior ischemic stroke, estimated 10-year incidence of coronary death or non-fatal MI > 10%
Age 50 years
- eGFR 60 ml/min/1.73m2: statin
- eGFR < 60 ml/min/1.73m2: statin or statin with ezetimibe
Dialysis-dependent patients
Not initiate statin or statin with ezetimibe
If patients already receiving statin or statin with ezetimibe at time of initiation RRT: continue these
agents
131
Kidney transplant recipients: statin

Triglyceride lowering treatment: therapeutic
lifestyle changes
Target lipid: LDL-C < 70, HDL-C > 40, nonHDL-C <100, and TG <150 mg/dL
Diet
Protein intake
0.8 g/kg/day in diabetic patients or eGFR <
30 ml/min/1.73 m2
Avoid high protein intake > 1.3 g/kg/day
Sodium intake < 2 g/day (corresponding to 90
mEq/d of sodium or 5 g/d of sodium chloride), unless contraindicated
Potassium restriction: in case of hyperkalemia
Phosphate restriction: in case of hyperphosphatemia
Lifestyle modification
Exercise: 30 minutes 5 times/week
Target BMI 20 25 kg/m2
Stop smoking
Limiting alcohol intake: 2 standard drinks/day
for male, and 1 standard drinks/day for female
132
Management of complications of CKD

Anemia
Evaluation: annually in CKD stage 3, twice a year in CKD stage 4 or 5, and every 3 months in dialysis patients
Definition: Hb < 13.0 g/dL in male and < 12.0 g/dL in female
Evaluation causes of anemia: CBC, absolute recticulocyte count, iron study, B12 and folate level
Treatment
Iron therapy in TSAT (transferring saturation) 30%, and serum ferritin 500 ng/ml
ESA (erythrocyte stimulating agent) therapy
Use with caution in patients with active or history of malignancy and history of stroke
Address all correctable causes of anemia prior to initiation
Initiation of ESA therapy: individualize
In general, patients with Hb < 10.0 g/dL
Target Hb: individualize
In general, 10.0 11.5 g/dL, not intentionally increase > 13.0 g/dL
133
Metabolic bone disease

Evaluation of serum calcium, phosphate, PTH
and alkaline phosphatase in eGFR < 45-60
ml/min/1.73 m2
Target:
Calcium and phosphate level in normal
range
Intact PTH (iPTH)
Non-dialysis patients: no known optimal
level, in case of iPTH level above normal limit: evaluate for hyperphosphatemia, hypocalcemia, and vitamin D
deficiency
Dialysis patients: 2 9 times of upper
normal limit
Treatment
Hyperphosphatemia: phosphate binders
Available agents: calcium carbonate,
calcium acetate, savelamer, lanthanum,
aluminium hydroxide
Calcium-based phosphate binders: restricting dose in patients with hypercalcemia, arterial calcification and/or adynamic bone
Aluminum-containing phosphate
binder: avoid long-term use
High iPTH level
Non-dialysis patients: calcitriol or vitamin D analogue
Dialysis patients: : calcitriol or vitamin D
analogue or combination with calcimimetic drug
Severe hyperparathyroidism with fail to
medical treatment: parathyroidectomy
Metabolic acidosis
Target: normal range of serum bicarbonate level
Treatment: oral sodium bicarbonate in case of
serum bicarbonate level < 22 mEq/L
134
Management of other aspects of CKD

Cardiovascular disease (CVD)
Cardiovascular disease (CVD): considered at increased risk of CVD
Peripheral arterial disease (PAD)

Medications
Adjust drug dosage according to eGFR
Avoid herbal remedies
Imaging studies
Balance risk of contrast-induced AKI against diagnostic value and therapeutic implication of the investigation
Radiocontrast
Avoid high osmolar agents
Use of lowest possible radiocontrast dose
Withdrawal of potentially nephrotoxic drugs before and after the procedure
Adequate hydration with saline before, during and after the procedure
Measurement of eGFR 48 96 hours after the procedure
Gadolinium-based contrast media
135
Not use in patients with CKD stage 5, unless there is no alternative test
In patients with CKD stage 4-5 who require gadolinium-based contrast media, prefer use of macrocyclic
chelate preparation
Bowel preparation
Not use oral phosphate-containing bowel preparation
Vaccination
Hepatitis B vaccine
Influenza vaccine: annually
Pneumococcal vaccine: every 5 years in CKD stage 4-5, nephrotic syndrome, DM, or those receiving immunosuppression
136
Renal replacement therapy (RRT)

Referral to nephrologists for plan of RRT in patients with eGFR < 30 ml/min/1.73 m2
Topics for counselling with the patients:
Indications for RRT
Available modalities of treatment: hemodialysis, peritoneal dialysis, kidney transplantation and conservative treatment
Advantages and disadvantages
Complications
Preparations
Financial issues
Prepare the patients for RRT: vascular access, or Tenckhoff catheter implantation
Indications for RRT
Presence of symptoms and signs attributable to CKD: serositis, acid-base or electrolytes disturbances,
pruritus, inability to control volume status or blood pressure, malnutrition, cognitive impairment, encephalopathy
eGFR < 7 ml/min/1.73 m2
Preemptive kidney transplantation in patients with irreversible CKD over 6-12 months with eGFR <20
ml/min/1.73 m2
137
2-3 / 4-5 .
4-5
/

138
139

150,000-250,000
/
()
(2-3 )
12,000-25,000 ()

15,000-25,000
()
()
~ 20,000 (3-6
)
- 15,000
(6-12 )
-10,000 ( 1 )
140
2,000
1
1,000-1,500 1
20,000
()
1 . 2551
1,500
)
(
)
141
Hemodialysis
142
Peritoneal dialysis
143
Kidney transplantation
144
REFERENCES
Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Inter., Suppl. 2013;3:1-150.
Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney Inter., Suppl. 2012;2:279-335.
Kidney Disease: Improving Global Outcomes (KDIGO) Lipid Work Group. KDIGO Clinical Practice Guideline
for Lipid Management in Chronic Kidney Disease. Kidney Inter., Suppl. 2013;3:259-305.
Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO Clinical Practice
Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Inter., Suppl.
2012;2:337-414.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and the Treatment of Chronic Kidney Disease-Mineral and Bone
disorder (CKD-MBD). Kidney Inter., 2009;76(Suppl 113): S1-S130.
Jellinger PS, et al. American Association of Clinical Endocrinologists Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis. Endocr Pract. 2012;18(Suppl 1):1-78.
. .
, . .91-99. :
, 2555. ISBN 978616723671.
145
COMMON GENETICS
KIDNEY DISEASES
AUTOSOMAL
DOMINANT POLYCYSTIC
KIDNEY DISEASE
147
Epidemiology
Most common form of polycystic kidney diseases
Affected 1 in 800 live births, and 4 6 million worldwide
Autosomal dominant penetrance, but 5% of patients have spontaneous mutation
Classification
Type I: caused by mutation in PKD1 gene
Type II: caused by mutation in PKD2 gene
148
Pathogenesis
Numerous site of PKD1 and PKD2 gene point mutations caused reduction in functional polycystin-1 and
polycystin-2, their encoded proteins.
A two-hit mechanism: germ-line mutation of PKD1 and PKD2 with additional somatic mutation in wild-type
gene to initiate the cysts formation
Chromosomal
Length of
Abberant gene
location
transcript (kb)
Protein
encoded
Molecular
mass
(kD)
Type
Frequency
Type I
85 90%
PKD1
16q13.3
14.5
Polycystin-1
462
Type II
10 15%
PKD2
4q21
5.6
Polycystin-2
110
Polycystin-1 is membrane receptor capable of interacting with extracellular substances as a sensors and signaling through phosphorylation pathways to activate the intracellular response.
Polycystin-2 is a calcium channel.
Polycystin-1 interacts with polycystin-2 and other proteins to form the complexes which can be found at the
cell-matrix interface, cell-cell contacts and luminal cilium. Stimulation on these complexes cause calcium influx, which act as a intracellular second messenger, subsequently effect several signal-transduction cascades
149
and regulate cell proliferation, apoptosis, epithelial cell differentiation, polarity, adhesion, migration, cell shape,
and tubular diameter.
The reduction in functional polycystin causes reduction in intracellular calcium and subsequently over activation of adenylate cyclase, increasing number of cyclic AMP, and lessening intracellular signal-transduction cascades results in
Increase cell proliferation
Increase fluid accumulation
Alter cell polarity
Matrix remodeling
All of these consequences lead to cyst formation in ADPKD patients.
150
Lorem ipsum dolor sit amet, consectetur adipisicing elit, sed do tempor incididunt ut labore et dolore magna aliqua.
151
Defects in the noncanoical Wnt/PCP pathway leading to renal cysts

152
Defects in the noncanoical Wnt/PCP pathway leading to renal cysts

153
Two types of ADPKD have similar pathological and physiological features, but type II disease has a later onset
of symptoms, thus patients with type II disease have
Older mean age of ESRD: 54 years in type I and 74 years in type II
Longer life expectancy: 53 years in type I and 69 years in type II
Progressive enlarge of kidney: mean increase in total kidney volume is 5.3%/year
Renal failure: patients with kidney volume > 1,500 ml have mean decreased in GFR 4.3 ml/min/year
Renal pain: found in 60% of patients, located at flank or abdomen
Causes: renal infection, cyst hemorrhage, renal stone, or ADPKD itself
Hypertension: 50% of patients and increase to nearly 100% of patients with ESRD
Hematuria
Imaging: to identify intraparenchymal or external hemorrhage, bleeding into the collecting system, solid
tumors
Renal colic: in some patients with hematuria
Usually recovery in few days
Urinary tract infection
Renal stones: 20% of patients
154
Usually composed of uric acid and calcium oxalate

Investigation of choice: CT scan of kidneys
Renal cell carcinoma: not frequent than in the normal population
Anemia: less frequent than in other renal diseases because of enhanced production of erythropoietin by
polycystic kidneys
Extra-renal manifestations
Polycystic liver disease:
Most common extrarenal manifestations: 80% of patients
Usually asymptomatic
Associated with estrogen exposure: female, exogenous estrogen use, and repeated pregnancy
Complications: cyst hemorrhage, infections, and rarely torsion or rupture
Cyst in other organs: 5% in pancreas, 8% in arachnoid, and 40% in seminal vesicles
Intracranial aneurysm: found in 16% and 6% of patients with and without family history of aneurysm
Most often asymptomatic
Ruptured: 35 55% risk of combined severe morbidity and mortality
Screening for intracranial aneurysm
Diagnostic tools: MR angiography (MRA) or CT angiography (CTA)
Indications
155
- Family history of aneurysm or stroke

- New onset of headache
- Central nervous system symptoms or signs
Management
- Negative: repeat imaging every 5 10 years
- < 7 mm-aneurysm: repeat imaging every - 1 year
- 7 mm-aneurysm: surgical treatment
Other vascular malformation: dolichoectasias, thoracic aortic and cervicocephalic artery dissections, and
coronary artery aneurysm
Cardiac manifestations: mitral valve prolapsed 25% of patients, aortic insufficiency
Colonic diverticulosis and diverticulitis
Bronchiectasis
156
Diagnosis
Use radiologic imaging to demonstrate the number of cyst in kidney
Criteria for diagnosis ADPKD type 1
Age
Criteria
15 29 years
2 cysts, unilateral or bilateral
30 59 years
2 cysts in each kidney
60 years
Revised criteria for diagnosis ADPKD type 1 and type 2

Age
Criteria
15 29 years
3 cysts, unilateral or
bilateral
30 39 years
3 cysts, unilateral or
bilateral
40 59 years
60 years
Revised criteria for exclusion of ADPKD type 1 and type 2

Age
Criteria
15 29 years
1 cyst
157
CT scan of the patient with ADPKD coronal view
158
Treatment
Specific treatment
No any agents are able to reduce the kidney volume in patients with ADPKD
Summary of the results from landmark randomized control studies in patients with ADPKD
Decrease
kidney volume
Slowed increase in kidney

volume
Slowed decline in
renal function
Sirolimus
No
No
No
Everolimus
No
Yes
No
Somatostain
No
Yes
No
Tolvaptan
No
Yes
Yes
159
BP Control
Target BP 130/80 mmHg
ACEI or ARB: drug of choice
Salt restriction: NaCl < 6 g/day
Diuretics: in case of fail to lower BP with 2
strategies above
Smoking cessation
Hematuria
Bed rest
Analgesics
Hydration: to increase urine flow rate to 2
3 L/day
Avoid sports which at a risk of abdominal
trauma: such as rugby, boxing
Urinary tract infection
Lower tract: treat as in general population
Upper tract
Acute pyelonephritis, or symptomatic

cyst infection
Required hospitalization
Drug of choice: fluoroquinolone
In men: radiologic and urologic evaluation is
indicated
Renal stones: treat as in general population
ESRD:
RRT
Peritoneal dialysis or hemodialysis may
be used
Kidney transplantation
- Similar outcome to non-AKPKD patients
- Identification of ADPKD in related
living donors are requied: MRI
KUB and/or genetic testing
Renal pain: analgesics, transcutaneous stimulation, local injections of anesthetics, laparoscopic
160
or opened surgical unroofing of cysts, or laparoscopic renal denervation

Liver cysts
Avoid exposure to estrogens, or least as possible
Partial hepatectomy: in severe liver enlargement
Pregnancy
Generally uncomplicatied in case of normal
BP and renal function
Increase risk of severe hypertension and
preeclampsia, particularly in patients who
have hypertension and renal impairment before conception
161
References
Torres VE, and Grantham JJ. Cystic diseases of the kidney. In: Taal MW, et al. editor. Brenner & Rectors The Kidney. 9th ed. Philadephia: Elsevier Saunders; 2012. p 1626-1669.
Granthham JJ. Autosomal dominant kidney disease. N Engl J Med 2008;359:1477-85.
Wilson PD. Polycystic kidney disease. N Engl J Med 2004;350:151-164.
Hildebrant F, et al. Ciliopathies. N Engl J Med 2011;364:1533-1543.
Grantham JJ, et al. Volume progression in polycystic kidney disease. N Engl J Med 2006;354:2122-2130.
Ravine D, et al. Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1. Lancet 1994;343:824-27.
Pei Y, et al. Unified criteria for ultrasonographic diagnosis of ADPKD. J Am So Nephrol 2009;20:205-212.
Perico N, et al. Sirolimus therapy to halt the progression of ADPKD. J Am Soc Nephrol 2010;21:1031-1040.
Serra AL, et al. Sirolimus and kidney growth in autosomal dominant polycystic kidney disase. N Engl J Med
2010;363:820-829.
Walz G, et al. Everolimus in patients with autosomal dominant polycystic kidney disease. N Engl J Med
2010;363:830-840.
Hogan MC, et al. Randomized clinical trial of long-acting somatostatin for autosomal dominant polycystic kidney
and liver disease. J Am Soc Nephrol 2010;21:1052-1061.
Torres VE, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med
2012;367:2407-2418.
162
ALPORTS SYNDROME
163
Epidemiology
Accounts for 0.4% of adults with ESRD in United States
Pathogenesis
Type IV collagen composed of 6 genetically distinct chains, 1(IV)- 6(IV) monomer, which are encoded
from COL4A1 - COL4A6, respectively.
Three of chain monomers form into only 3 sets of protomers which are designated as 1.1.2(IV),
3.4.5(IV) and 5.5.6(IV).
Triple helical organization of the type IV collagen family

164
These protomers pair into 3 canonical set of hexamers to from networks, which are 1.1.2(IV)-1.1.2(IV),
3.4.5(IV)-5.5.6(IV) and 1.1.2(IV)-5.5.6(IV).
Assembly and network organization of collagen IV protomers

165
During the embryonic development, component of GBM structure is change from 1.1.2(IV)-1.1.2(IV)
network to 3.4.5(IV)-5.5.6(IV) network to form a mature GBM.
Normal glomerular development and the change of networks component of GBM structure
166
Mutations in the COL4A3, COL4A4, COL4A5 genes which encode 3, 4 and 5 chain collagen type IV, a
component of glomerular basement membrane (GBM), results in arrest of switching of GBM network. The
GBM in the patients with Alports syndrome become persistence of 1.1.2(IV)-1.1.2(IV) network results
in dysconfiguration of GBM.
Glomerular development and the abnormal switching of networks component of GBM structure in the patients
with Alports syndrome
167
Genetics
X-linked inheritance
85% of patients
Mutations in COL4A5 gene encoding 5(IV)
collagen chain
Located on chromosome Xq26-48
COL4A3 and COL4A4 gene encoding 3(IV)

and 4(IV) collagen chain
Located on chromosome 2q35-37
Severity similar to X-linked inheritance
Autosomal dominant
Rare
Male predominate: ESRD at age of 30 40

years, deafness
Missense mutations in COL4A3 and COL4A4

gene encoding 3(IV) and 4(IV) collagen
chain
Female: varying in severity, but less severe

than in male patients
Less severity; benign familial hematuria or

thin basement membrane disease
Concomitant deletion mutations in COL4A6

gene encoding 3(VI) chain are associated
with leiomyomatosis
Autosomal recessive
15% of patients
Homozygous or compound heterozygous nonsense mutations, missense mutations, frame
shifts, small deletions, or splice variants in
168
Hematuria: often the presenting sign
Severity of disease depend on the mutations
High-tone sensorineural hearing loss: 80% of patients
Ocular defects: 40% of patients
Anterior lenticonus: 25% of patients
Perimacular dots and flecks
Posterior polymorphous dystrophy (PPMD)
Microcornea, arcus cornealis, iris atrophy, cataracts,
Family history of deafness and renal failure
169
Diagnosis
Electron microscopic findings in renal biopsy
Immunostaining of 3(IV) and 5(IV) collagen from skin or renal tissue
[ Skin collagen networks composed of 1.1.2(IV)-5.5.6(IV) ]
5(IV)
X-linked
Normal
Male
Female
3(IV)
Autosomal
recessive
X-linked
Autosomal
recessive
Normal
Male
Female
GBM
Mosaic
Mosaic
Skin
basement
membrane
Mosaic
170
Renal pathology
Light microscope: nonspecific, normal or nearly
normal, segmental to diffuse mesangial cell proliferation, matrix increase, and thickening of the
glomerular capillary wall
Treatment
No proven therapy
Control hypertension with ACEI
Light microscope: nonspecific, normal or nearly

normal, segmental to diffuse mesangial cell proliferation, matrix increase, and thickening of the
glomerular capillary wall
Electron microscope: thin GBM thicken over time
into multilamellations and lucent spaces results in
split appearance of the basement membrane;
basket weaving appearance
171
References
Appel GB, Radhakrishnan J, and DAgati VD. Secondary glomerular disease. In: Taal MW, et al. editor. Brenner & Rectors The Kidney. 9th ed. Philadephia: Elsevier Saunders; 2012. p 1192-1277.
Hudson BG, et al. Alports syndrome, Goodpastures syndrome, and type IV collagen. N Engl J Med
2003;348:2543-2556.
172
APPROACH TO COMMON
SYMPTOMS IN NEPHROLOGY
EDEMA
174
Localized edema
Vascular abnormalities
Increased venous pressure
Deep vein thrombosis
Venous insufficiency
Vena cava obstruction
Decreased arteriolar resistance
Calcium channel blocker (CCB)
Lymphatic obstruction
Malignancy
Infection
Hypothyroidism
Congenital anomalies of lymphatic system
ETIOLOGIES
Increased capillary permeability

Inflammation
Angioedema
175
Generalized edema
- Anti-GBM
Liver diseases: cirrhosis
- Immune complex disease
Heart diseases: congestive heart failure
- Pauci-immune glomerulonephritis
Mechanical abnormalities
Other causes of hypoalbuminemia
Pericardial disease
Protein-losing enteropathy
Myocardial disease
Malnutrition
Endocardial disease
Electrical abnormalities
Bradyarrhythmia
Tachyarrhythmia
Kidney diseases
AKI, AKI on top CKD, CKD
Glomerular diseases
Nephrotic syndrome
- Primary causes
- Secondary causes
Nephritic syndrome (NS)
176
APPROACH TO
THE PATIENTS
177
History taking
General appearance
Body weight change, prolong fever
HEENT
Dry eyes, dry mouth, sinusitis
CVS
history of heart disease, cardiovascular risk factors (DM, hypertension, dyslipidemia,

smoking), orthopnea, paroxysmal nocturnal dyspnea (PND), chest pain
RS
History of smoking, hemoptysis
GI
Jaundice, alcohol drinking, family history of liver disease, viral hepatitis (blood transfusion,
unsafe sex, IVDU, tattoo) , constipation, palpable intraabdominal lymph nodes
KUB
Edema (location, duration, onset, intermittent edema), urine (volume, foamy urine,
hematuria, nocturia, passing stone), polyuria
GU
Bleeding per vagina, palpable breast mass, abnormal nipple discharge
NS
Seizure, psychosis, polyneuritis multiplex
Dermatology
Rash, photosensitivity, hair loss, oral ulcer
Rheumatology
Arthritis
Hematology
Palpable lymph nodes, fever, night sweat, anemia, abnormal systemic bleeding, bone pain
Infections
Respiratory tract, skin and soft tissue infection with lag period, synpharyngitis, chronic
infection
Medications
CCB, drug allery, antibiotics (penicillin, quinolone, vancomycin, colistin, aminoglycoside),

contrast exposure, NSAIDs, D-penicillamine, PTU, gold, hydralazine, heroine
Family history
Sensorineural hearing loss, eye disease, chronic kidney disease

178
Physical examination
Vital signs
Body temperature, BP, pulsus paradoxus
General
appearance
Body weight, sign of chronic liver disease
HEENT
Anemia, jaundice, cervical lymphadenopathy, oral ulcer, thyroid examination,

exophthalmos, lid lag/retraction, keratoconjunctivitis sicca, xerostomia, parotid gland
enlargement, Schirmer test, tender on sinus, saddle nose deformity, pinch purpura,
raccoon eye, tongue indentation, anterior lenticonus
CVS
JVP, Kussmaul sign, PMI, heaving, thrill, murmur, pericardial rub, peripheral bruit
(carotid, subclavian, abdominal)
RS
Tracheal deviation, decreased breath sound, consolidation sign, wheezing
Abdomen
Liver and spleen examination, shifting dullness, fluid thrill, bimanual palpation, full
bladder
Extremities
Edema, should pad sign, nail dystrophy, absent of patella
GU
Breast mass, abnormal nipple discharge, PV examination
NS
Polyneuritis multiplex, flapping tremor, visual acuity, Tinel and phalen test, whispering
sound
Skin
Tattoo, malar and discoid rash, photosensitivity, hair loss, peau dorange skin,
vasculitis lesion, dark, pigmented skin and ulcer at medial malleolus area
179
Key to differential diagnosis

Localized edema
Generalized edema
Liver diseases: cirrhosis
Heart diseases: mechanical abnormalities,
electrical abnormalities
Renal diseases: AKI, AKI on top CKD, RPGN,
CKD and NS, nephritic syndrome
Hypoalbuminemia of other
causes
180
COMMON
CAUSES
181
Causes
Symptoms and signs
Investigations
CCBinduced
edema
Dihydropyridine CCB, 1st 6 months of initiation, high dose

Stable BW
Cirrhosis
Jaundice, alcohol drinking, family history of liver disease, viral

hepatitis (blood transfusion, unsafe sex, IVDU, tattoo)
Jaundice, liver and spleen examination, shifting dullness, fluid thrill,
tattoo marks
LFT, USG upper abdomen
Heart
disease
CV risk factors, orthopnea, PND, chest pain, palpitation

Arrthythmia, JVP, Kussmaul sign, PMI, heaving, thrill, murmur,
pericardial rub, peripheral bruit
EKG, cardiac markers, CXR
Foamy urine, edema

UA, UPCI, 24-hr urine protein, Cr,
MN solid tumor
albumin, lipid, HBsAg, Anti-HCV,
FSGS heroine, obesity, HBV/HCV/HIV infection,
Anti-HIV, ANA, Anti-dsDNA, CXR,
Nephrotic
MPGN chronic infection, HCV
EKG, calcium, CBC, SPEP, serum
syndrome LN malar rash, discoid rash, oral ulcer, arthritis, alopecia, vasculitis
free light chain, FBS, CA screening
lesion
(CXR, FOBT, PV, mammogram,
Amyloidosis polyuria, constipation, anemia, bone pain, raccoon
USG abdomen)
eye, pinch purpura, Tinel and Phalen test
182
Causes
Nephritic
syndrome
Symptoms and signs
Investigations
Hematuria, hypertension, edema

IgAN synpharyngitis
UA, UPCI, 24-hr urine protein,
PIGN lag period after URI or skin infection
Cr, complement, Anti-HCV,
MPGN chronic inflammation, HCV, palpable purpura
ANA, Anti-dsDNA, ANCA,
LN malar rash, discoid rash, oral ulcer, arthritis, alopecia, vasculitis
lesion
CXR, EKG, Rheumatoid factor
ANCA-associated disease hemoptysis, sinusitis, saddle nose
deformity, wheezing, mononeuritis multiplex (numbness, weakness)
Protein-losing
enteropathy
Edema
Albumin, cholesterol, stool 1

anti-trypsin
ADPKD
Abdominal distension, bimanual palpation
USG KUB
Alports
syndrome
More common in male, sensorineural hearing loss, anterior

lenticonus
Skin and/or renal biopsy
CCB: calcium channel blocker, CV: cardiovascular, CXR: chest x-ray, FOBT: fecal occult blood test, IVDU: intravenous
drug abuse, USG: ultrasound
183
OLIGURIA AND ANURIA
184
DEFINITION
Oliguria: urine output <400 ml/day
Anuria: urine output <100 ml/day
185
ETIOLOGIES
AKI, AKI on top CKD,
CKD
Nephritic syndrome:
AGN, RPGN, CGN
186
APPROACH TO THE
PATIENTS
Nocturia, history of intermittent
edema: onset of renal disease
Days to week: acute onset, suggests AKI
Weeks to months: subacute onset, suggests RPGN
More than 3 months: late onset,
suggests CKD
Hematuria (see in Hematuria)
187
POLYURIA AND POLYDIPSIA
188
DEFINITION
Urine output >3 L/day
189
ETIOLOGIES
Solute dieresis
Water diuresis
Non-electrolytes diuresis
Primary polydipsia (PP)
Hyperglycemia
Diabetes insipidus (DI)
High protein intake

Osmotic diuretic: mannitol, sorbitol
Electrolytes diuresis
Diuretics
Intravenous fluid
Central DI (CDI)
Pituitary disease: post pituitary surgery, craniopharyngioma,
intracerebral hemorrhage, intracranial tumor (primary, metastasis), Sheehans syndrome, sarcoidosis, histiocytosis X, tuberculosis
Pregnancy: diabetes insipidus of pregnancy (vasopressinase), lymphocytic hypophysitis
Familial CDI
Nephrogenic DI (NDI)
Electrolytes abnormalities: hypercalcemia, hypokalemia
Drug-induced nephrogenic DI: lithium, cisplatin, foscanet, amphotericin B, demeclocycline, methoxyflurane, foscanet
Miscellaneous: obstructive uropathy, interstitial renal disease,
sickle cell disease, amyloidosis
Congenital NDI
190
APPROACH TO
THE PATIENTS
191
History taking
General appearance
Fever, night sweat, weight loss
HEENT
Surgical scar at head, tinnitus
CVS
RS
Chronic cough, hemoptysis
GI
Dysphagia, bowel habit change, anorexia,
KUB
Urine volume, frequency (day:night), nocturia, onset of polyuria
GU
Postpartum hemorrhage, bleeding per vagina, LMP
NS
Blur vision (diabetic retinopathy), bitemporal hemianopia, psychiatric disease
Endocrinology
DM and control, steroid use
Dermatology
Rheumatology
Hematology
Anemia, bone pain, abnormal bleeding
Infections
Contact to tuberculosis patient
Medications
lithium, cisplatin, foscanet, amphotericin B, demeclocycline, methoxyflurane,

foscanet, mannitol, diuretics, TPN, protein intake
Family history
DM
192
Vital signs
BP, PR
General appearance
Body weight
HEENT
Anemia, jaundice, cervical lymphadenopathy
CVS
JVP
RS
Treacheal deviation, sign of consolidation, pleural effusion
Abdomen
Liver and spleen examination, fundal height
Extremities
Skin turgor
GU
NS
Visual field, fundoscopic examination (DR), general neurological examination and

screening for psychiatric disorders
Skin
Shin spot
193
Common causes
Causes
Symptoms and signs
Investigations
Medication mannitol administration, high protein intake

include TPN, diuretic use
Hyperglycemia history or family history of DM, poor
FPG, HbA1c, BUN, Cr, urine Sp.gr., uOsm
Solute diuresis
control DM, steroid use, recurrent infection, diabetic
retinopathy, shin spot
Primary
polydipsia
DI
Psychiatric disease, more polyuria in daytime
Urine Sp.gr., uOsm, water deprivation test,

low to normal serum sodium
Nocturia, weight loss

Central DI head trauma, neurosurgery, postpartum
Urine Sp.gr., uOsm, water deprivation test,
hemorrhage, prefer cool drinks, sudden onset,
normal to high serum sodium, electrolyte,
nocturia, pregnancy, malignancy (weight loss,
anorexia, bowel habit change, dysphagia, bleeding per calcium, albumin, phosphate, CBC, bone
vagina, fever night sweat, tinitus), abnormal palpable
survey, CT brain, MRI pituitary protocol
mass, bitemporal hemianopia, PV
(posterior pituitary bright spot in MRI
Nephrogenic DI medication (lithium, cisplatin, foscanet,
pituitary presence in 95% of patients
amphotericin B, demeclocycline, methoxyflurane,
without CDI, absence in 20% of normal
foscanet), multiple myeloma (bone pain, anemia),
aging)
malignancy (constitutional symptoms, localized
symptoms), tuberculosis, gradual onset
194

Solute dieresis: uOsm >300 mOsm/kgH2O, uOsm / sOsm >
0.9
Electrolyte
Non-electrolyte
Water dieresis: uOsm <250 mOsm/kgH2O, uOsm / sOsm < 0.9
Primary polydipsia
DI
Central
Nephrogenic
195
Water deprivation test

Procedure
NPO: initiation of test depends on the severity of DI
Routine case: after dinner of the day before the test
More severe case: early in the morning of the test
At the start of the test: obtain sOsm, uOsm, serum electrolyte, plasma AVP
Hourly: measure of urine volume, uOsm, body weight, blood pressure
Endpoint: any of the followings
Body weight decreases by 3%
Presence of orthostatic hypotension
uOsm change <10% over 2 consecutive measurements
Serum sodium > 145 mEq/L
At the endpoint
Obtain sOsm, uOsm, serum electrolyte, plasma AVP
Administer of AVP 5 U or DDAVP 1 g subcutaneously
Hourly: measure of uOsm, urine volume for 2 hours
Interpretation
196
After water restriction

uOsm >600 mOsm/kgH2O suggests primary polydipsia
uOsm <600 mOsm/kgH2O suggests DI and minority of primary polydipsia
After AVP/DDAVP administration
Unequivocal uOsm
< 10% increase: NDI, primary polydipsia
> 50% increase: CDI
Equivocal uOsm
10-50% increase
- Non-diagnostic result
- Need correlation between sOsm and plasma AVP level
197
HEMATURIA
198
DEFINITION
Presence of RBCs > 3 cells/HPF
Gross hematuria: presence of RBCs in
urine enough to turn it in red or brown
Microscopic hematuria: detectable
RBCs only in microscopic examination
199
ETIOLOGIES
Negative heme in urine
Porphyrins prophyria, lead poisoning, pellagra

Drugs adriamycin, chloroquine, desferoxamine, levodopa, methyldopa,
metronidazole, nitrofurantoin, phenazopyridine, phebolphthalein,
phenytoin, prochlorperazine, quinine, rifampicin, sulfonamide
Foods artificial food coloring, beets, blackberries, blueberries, fava beans,
paprika, rhubarb
Positive heme in urine
Hemoglobinuria (hemolysis)
Myoglobinuria (rhabdomyolysis)
Nonhematuria
Hematuria
Upper tract pyelonephritis, nephrolithiasis, hypercalciuria, hyperuricosuria,

trauma, papillary necrosis, ureteral stricture, sickle cell disease, renal
infarction, arteriovenous malformation, renal tuberculosis, ADPKD, renal
cell carcinoma, transitional cell carcinoma of renal pelvis or ureter
Non-glomerular in origin
Lower tract cystitis, urethritis, prostatitis, bladder polyp, Schistosoma
haematobium infection
Uncertain Exercise hematuria, benign hematuria, over-anticoagulation,
factitious hematuria
Glomerular in origin
Gross hematuria IgAN, PIGN, pauci-immune GN, LN, MPGN

Microscopic hematuria Immune complex diseases (IgAN, PIGN, LN,
MPGN), pauci-immune GN, anti-GBM (anti-GBM disease, Goodpastures
syndrome), Hereditary nephritis (Alports syndrome, thin basement
membrane disease), other glomerular diseases (FSGS, MN)
200
APPROACH TO
THE PATIENTS
201
History taking
General
appearance
Body weight change, fever
HEENT
sinusitis
CVS
Orthopnea, paroxysmal nocturnal dyspnea (PND)
RS
Wheezing, hemoptysis
GI
Jaundice, alcohol drinking, family history of liver disease, viral hepatitis (blood transfusion,
unsafe sex, IVDU, tattoo) , constipation, palpable intraabdominal lymph nodes
KUB
Urine (volume, foamy urine, hematuria, nocturia, passing stone)
GU
Bleeding per vagina, palpable breast mass, abnormal nipple discharge
NS
Seizure, psychosis, polyneuritis multiplex, subarachnoid hemorrhage
Dermatology
Rash, photosensitivity, hair loss, oral ulcer
Rheumatology
Arthritis
Hematology
Palpable lymph nodes, fever, night sweat, anemia, abnormal systemic bleeding, bone pain
Infections
Respiratory tract, skin and soft tissue infection with lag period, synpharyngitis, chronic infection
Medications
NSAIDs, PTU, hydralazine, anti-TNF, minocycline, methydopa, INH, chlorpromazine,

pyrazinamide, D-penicillamine, heroine
Family history
Sensorineural hearing loss, eye disease, chronic kidney disease

202
Vital signs
Body temperature, BP
General
appearance
Body weight, sign of chronic liver disease
HEENT
Anemia, jaundice, cervical lymphadenopathy, oral ulcer, thyroid examination, exophthalmos, lid lag/
retraction, tender on sinus, saddle nose deformity, anterior lenticonus
CVS
JVP, PMI, murmur
RS
Tracheal deviation, decreased breath sound, consolidation sign, wheezing, creptiation
Abdomen
Liver and spleen examination, shifting dullness, fluid thrill, bimanual palpation
Extremities
Edema, should pad sign, nail dystrophy, absent of patella
GU
NS
Polyneuritis multiplex, flapping tremor, visual acuity, Tinel and phalen test, whispering sound
Skin
Tattoo, malar and discoid rash, photosensitivity, hair loss, vasculitis lesion
203

red-brown urine
Non-hematuria
Negative heme in urine: drugs, food, porphyrins
Positive heme without RBC in urine
Hemoglobinuria (hemolysis): low serum haptoglobin, indirect hemolytic evidences
Myoglobinuria (rhabdomyolysis)
Picture A
The pictures show urine of the patient with rhabdomyolysis from
electrical injury on A) 1st day (comparing with black plastic
board on the right)
204
Hematuria
Hematuria: RBC >3 /HPF in urine
Only in gross hematuria: 3 glass test
Initial hematuria: bleeding from urethra
Terminal hematuria: bleeding from bladder
Total hematuria: bleeding from kidney or ureter
Microscopic hematuria
Non-glomerular hematuria
Urinary tract infection (UTI)
No UTI
Imaging: plain KUB, IVP, ultrasound, CT scan
Cystoscopy: in age >40 years old or high index of suspicious
Cytology: in age <40 years old or low index of suspicious
Glomerular hematuria: blood test and renal biopsy
205
Differentiate glomerular versus non-glomerular hematuria

Non-glomerular hematuria
Urine color
Dark red, brown, cola colored,

smoky
Bright red
Clots
Proteinuria >500 mg/d
RBC morphology
Dysmorphic
Isomorphic
Hypertension
Edema
Urinary voiding symptoms
Back or flank pain
Renal function
Reduced
Normal
Family history
Trauma
Upper respiratory tract infection
Fever, rash
206
Complement levels in acute glomerulonephritis
Low C3 and C4
Lupus nephritis
Cryoglobulinemia
Bacterial endocarditis
Shunt nephritis
MPGN type 1
Low C3 and normal C4
Normal C3 and C4
Post-infectious GN
MPGN type II (dense deposition
disease)
Polyarteritis nodosa
ANCA-associated GN
Hypersensitivity vasculitis
Henoch-Scholein purpura
Anti-GBM disease
IgA nephropathy
207
PROXIMAL MUSCLE
WEAKNESS
208
ETIOLOGIES
Myopathy
Inflammatory myopathy
Dermatomyositis
Polymyositis
Inclusion-body myositis
Infections: HIV, influenza, coxackie virus,
Trichinella spiralis
Non-inflammatory myopathy
Electrolyte imbalances: hypokalemia, hyperkalemia, hypophosphatemia, hypermagnesemia, hypocalcemia, hypercalcemia
Endocrinopathies: hyperthyroidism,
Cushing syndrome, DM
Metabolic causes: glycogen storage diseases, lipid storage myopathy, mitochondrial disease
Muscular dystrophy (MD): Duchene MD,
Becker MD, fascioscapulohumeral MD,
limb-girdle MD, scapuloperoneal syndrome
Congenital myopathies: central core disease, Nemalin myopathy, centronuclear
myopathy
Neuromuscular junction (NMJ) disease
Presynaptic defect: Lambert-Eaton myasthenic syndrome, Botulism, neurotoxin snake
venom
Postsynaptic defect: myasthenia gravis
Polyneuropathy: Guillain-Barre syndrome (GBS),
chronic inflammatory demyelinating polyneuropathy (CIDP), porphyria
Drugs: corticosteroid, statin, colchicines,

chloroquine, alcohol, zidovudine
209
APPROACH TO THE PATIENTS

Differentiate site of lesions of muscle weakness
Upper motor neuron: long tract signs
Lower motor neuron
Distal muscle weakness
Proximal muscle weakness
Anterior horn cell diseases: history of lead exposure, poliomyelitis, familial spinal atrophy
Peripheral neuropathy: loss of sensation
NMJ diseases: fluctuation of symptoms
Myopathies: no loss of sensation, no fasciculation, normoreflexia
Family history of muscle weakness, specific sites of muscle weakness, hepatosplenomegaly
History of infections, muscle pain, malignancy
Skin lesions: V sign, shawl sign, guttron papules
Medications
Check electrolytes, phosphate, magnesium, calcium
Check plasma glucose, morning cortisol, thyroid function
Check CPK
210
HYPERTENSION IN THE
YOUNG
211
DEFINITION
Hypertension at the age of onset <20 years
212
ETIOLOGIES
Renal diseases
Renovascular diseases: renal artery stenosis (fibromuscular dysplasia, atherosclerosis), polyarteritis nodosa
Renal parenchymal diseases: nephritic syndrome, chronic kidney disease
Endocrinopathies: hypothyroidism, hyperthyroidism, acromegaly, pheochromocytoma, Cushing syndrome, hyperaldosteronism, congenital adrenal hyperplasia
Cardiovascular diseases: coarctation of aorta, Takayasus arteritis
Lung diseases: obstructive sleep apnea
Drugs: estrogen, herbs, amphetamine, cocaine, NSAIDs, corticosteroid, decongestants, diet pills, psychiatric
drugs (buspirone, carbamazepine, clozapine, fluoxetine, lithium, tricyclic antidepressant, cyclosporine)
Pregnancy-induced hypertension: preeclampsia, eclampsia
Neurological diseases: dysautonomia, increased intracranial pressure
213
APPROACH TO
THE PATIENTS
214
History taking
Medications, last menopausal period, history of
claudication, snoring, endocrinopathies
Coarctation of aorta: BP 4 extremities, delayed radiofemoral pulses, associated diseases (Turner
syndrome)
Family history of DM, hypertension: suggests essential hypertension
HEENT: lid lag, lid retraction, thyroid examination,
cushingoid appearances, enlarged tongue, cutis
verticis gyrata
CVS: unequal pulses, bruits (abdominal, renal,
subclavian)
Extremities: spade hands
Genitalia: ambiguous genitalia
NS: bilateral hemianopia, fundus examination (silver wire, copper wire appearance, A:V ratio, AV
nicking)
215
Investigations
Serum electrolytes, urine electrolytes, sOsm, uOsm
BUN, creatinine, UA
Doppler renal ultrasound, renal artery MRA, renal angiogram
EKG: LVH
CXR: rib notching, reverse three sign
Aldosterone-renin ratio (ARR) 20 ng/dL per ng/mL/hour: plasma aldosterone concentration (PAC) 15 ng/dL,
plasma renin activity (PRA) <1.0 ng/mL/hour
Urine VMA, urine metanephrine, plasma metanephrine, imaging, MIBG scan
Thyroid function test
1-mg overnight dexamethasone suppression test
Serum IGF-1
216
ANCA-ASSOCIATED GLOMERULONEPHRITIS
(ANCA-ASSOCIATED GN)
Definition
Necrotizing vasculitis, with few or no immune deposits, predominantly affecting small vessels (i.e., capillaries, venules, arterioles,
and small arteries), associated with myeloperoxidase (MPO) ANCA
(anti-neutrophil cytoplasmic antibodies) or proteinase 3 (PR3) ANCA.
Not all patients have ANCA
Related terms
Epidemiology
Incidence 3.9 cases / 1,000,000 people
Renal-limited ANCA-associated vasculitis 23 25%
ANCA-negative pauci-immune GN 27 38%
Related Glossary Terms

Drag related terms here
Index
Find Term
Chapter 1 - Common glomerular diseases
APPROACH TO THE PATIENTS SUSPECTED

GLOMERULAR DISEASES
Clinical presentations of glomerular diseases
Proteinuria: varying in degree of proteinuria, more specific in proteinuria > 2 g/day
Decreased GFR: oliguria, anuria, uremic symptoms
Salt and water retention: edema, hypertension
Differentiate between glomerular syndromes

Nephritic syndrome versus nephrotic syndrome
Nephritic syndrome
Decreased of GFR: edema, oliguria,

hypertension, azotemia
Active urine sediments: dysmorphic RBC, RBC
cast
Subnephrotic-ranged proteinuria
Hyperlipidemia
Nephrotic syndrome Hypoalbuminemia
Edema
Lipiduria: oval fat body, fatty cast
Asymptomatic versus symptomatic
Define onset of disease: history of urine volume and characters
change, nocturia, edema, broad cast in urine (subacute to chronic
onset), ultrasound kidney
Acute onset: days to week
Subacute onset: weeks to month

Index
Find Term
Chapter 1 - Nephritic syndromes
CHRONIC KIDNEY DISEASE (CKD)

Definition
Either of the following present for > 3 months
Markers of kidney damage (one or more)
Albuminuria 30 mg/day, or albumin-to-creatinine ratio 30 g/ g
creatinine
Urine sediment abnormalities
Electrolyte and other abnormalities due to tubular disorders
Abnormalities detected by histology
Structural abnormalities detected by imaging
History of kidney transplantation
Decreased GFR: < 60 ml/min/1.73 m2

Index
Find Term
ETIOLOGIES OF NEPHROTIC SYNDROME

(NS)
Secondary NS
Infections: HBV, HCV, HIV, tuberculosis, infective endocarditis, visceral abscess, shunt nephritis
Autoimmune diseases: SLE, rheumatoid arthritis, Sjgren syndrome
Medications: NSAIDs, gold, D-penicillamine, heroin
Malignancies: hematologic malignancy (Hodgkons and non Hodgkins lymphoma, plasma cell dyscrasia), solid tumors
Metabolic abnormalities: DM, hypertension, obesity
Miscellaneous diseases: reflux nephropathy, analgesic, nephron loss,
amyloidosis

Index
Find Term
Chapter 1 - Asymptomatic proteinuria
GLOMERULAR HEMATURIA
Hematuria
Bed rest
Analgesics
Hydration: to increase urine flow rate to 2 3 L/day
Avoid sports which at a risk of abdominal trauma: such as rugby, boxing

Index
Find Term
Chapter 1 - Approach to the patients with suspected of glomerular diseases
HEMATURIA
Definition
Presence of RBCs > 3 cells/HPF
Gross hematuria: presence of RBCs in urine enough to turn it in red
or brown
Microscopic hematuria: detectable RBCs only in microscopic examination

Index
Find Term
Chapter 5 - Oliguria and anuria
IGA NEPHROPATHY (IGAN)

Definition
Predominance of IgA deposits, either alone or with IgG, IgM, or both
in the glomerular mesangium
Epidemiology
Occurs in all age groups
Most common at age of 10 20 years, 80% of patients are age of 16
35 years at the time of biopsy
More common in males than females: male / female ratio 2:1 to 6:1
Pathogenesis
Multi-hit mechanism
Hit 1: Increased circulating galactose-deficient (at hinge region
of heavy chain) IgA1
Hit 2: Production of anti-glycan antibodies that recognize galactose deficient IgA1
Hit 3: Formation of pathogenic circulating immune complexes
from autoantigen (galactose-deficient IgA) and O-glycanspecific antibodies
Hit 4: Deposition of pathogenic immune complexes in the mesangium, activation of mesangial cells, and induction of glomerular
injury

Index
Find Term
Chapter 2 - Approach to the patients with AKI
MINIMAL CHANGE DISEASE (MCD)

Related terms
Lipoid nephrosis
Minimal change glomerulopathy
Epidemiology
10 15% of primary glomerular syndrome in adults
70 - 90% of nephrotic syndrome in children under age of 10 year,
and 50% of older children
Male : female ratio 2:1 3:1
Pathogenesis
Remains unclear
Most likely a consequence of abnormal regulation of T cells
Primary MCD
Secondary MCD
Infections: virus, parasite
Drugs: NSAIDs, gold, lithium, interferon, ampicillin, rifampin, trimethadione, tiopronin
Tumors: Hodgkins disease, lymphoma, leukemia, solid tumors
Allergies: food, dust, bee stings, pollen, poison ivy, poison oak,
dermatitis herpitiformis
Others: SLE, following hematopoietic cell transplantation

Index
Find Term
NEPHRITIC SYNDROMES ETIOLOGY

Immune complex glomerulonephritis
Lupus nephritis (LN)
Post-infectious glomerulonephritis (PIGN)
IgA nephropathy (IgAN) and Henoch-Schnlein purpura (HSP)
Subacute bacterial endocarditis
Membranoproliferative glomerulonephritis (MPGN)
Cryoglobulinemia
Anti-glomerular basement membrane (GBM)
Anti-GBM disease
ANCA-associated glomerulonephritis
Granulomatosis with polyangitis (GPA) or Wegners granulomatosis
Eosinophilic granulomatosis with polyangitis (EGPA) or ChurgStrauss syndrome
Renal limited pauci-immune glomerulonephritis
Double positive disease

Index
Find Term
Chapter 1 - Nephritic syndromes
POST-INFECTIOUS GLOMERULONEPHRITIS
(PIGN)
Definition
An immunologic response of the kidney that occurs following a nonrenal infection
Related terms
Bright disease
Streptococcus-related glomerulonephritis
Post-streptococcal glomerulonephritis
Epidemiology
Incidence and prevalence are lower in developed countries
Incidence 0.6 39.24 and prevalence 0.02 10.14 cases / 100,000
population
Median age of onset 36 58 years
High prevalence in DM, alcoholism
30 50% associated with gram negative bacilli infection

Index
Find Term
Chapter 2 - Approach to the patients with AKI

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Nephrology

Differentiate between glomerular syndromes

Proteinuria: varying in degree

Decreased of GFR: edema, oliguria,

Isomorphic RBC from light microscope

Classify glomerular syndromes

Evaluation of secondary causes of glomerular disease

Asymptomatic urinary abnormalities

Minimal change disease (MCD)

Membranous nephropathy (MN)

Focal segmental glomerulosclerosis (FSGS)

Acute diffuse proliferative glomerulonephritis

Evaluation of secondary causes according to predicted pathological

Death: due to undiagnosed hematoma

< 150 mg/day

Pathogenesis and etiologies

- Infections: pyeolonephritis, tuberculosis

Urine protein usually < 2 g/day

Benign orthostatic proteinuria

Approach to the patients with asymptomatic proteinuria

Indications for renal biopsy

Indications for renal biopsy

Immune complex glomerulonephritis

Anti-glomerular basement membrane

Hodgkins lymphoma, NSAIDs

HIV, nephron loss, familial, obesity,

HBV, HCV, solid tumors, Dpenicillamine, NSAIDs, gold, SLE,

Chronic infection (infective

Autoimmune diseases: SLE, rheumatoid arthritis,

Clinical manifestation of primary nephrotic syndrome

None, but 1/3 of patients

Minimal mesangial lupus nephritis

Class IV-S (A)

Active lesions: diffuse segmental proliferative lupus nephritis

the proportion of glomeruli with active and with sclerotic lesions.

Abbreviated international society of

Minimal mesangial lupus nephritis

Mesangial proliferative lupus nephritis

Indicate the proportion of glomeruli with active and

Focal lupus nephritisa

the proportion of glomeruli with fibrinoid necrosis and cellular crescents

Diffuse segmental (IV-S) or global (IV-G)

Membranous lupus nephritisc

V may occur in combination with class III or IV

Class VI Advanced sclerosing lupus nephritis

No clinical renal manifestation

Proteinuria: usually < 1 g/day,

Chronic kidney disease, depend of severity of disease

Full house staining: presence of IgG, IgM,

Criteria for diagnosis SLE

4. Nonscarring alopecia (diffuse thinning or hair

5. Synovitis involving 2 or more joints, characterized by

10. Leukopemia (< 4,000/mm3 at least once)

11. Thrombocytopenia (< 100,000/mm3 at least once)

2. Anti-dsDNA antibody level above laboratory

3. Anti-Sm: presence of antibody to Sm nuclear

6. Direct Coombs test in the absence of hemolytic

4. Antiphospholipid antibody positivity as determined

ACR (American college of rheumatology)

Fixed erythema, flat or raised,

Erythematous raised patches with

Skin rash as a result of unusual

Involving 2 or more peripheral

1. Pleuritis convincing history of