OS 214: Renal Dr.

Agnes Mejia
Glomerulonephritis Exam 1

OUTLINE reversible
I. Introduction If
II. Glomerulonephritis shrunken=ESRD,irrev
III. Pathogenesis of Glomerulonephritis ersible
IV. Approach to Patient with Glomerulonephritis (Normal Filipino
V. Forms of Glomerulonephritis size:9.6 cm in length;
A. IgA Nephropathy Normal Caucasia:11-
B. Poststreptococcal Glomerulonephritis 12 cm)
C. Membranous Glomerulonephritis Urinalysis “window to glomerular -low sp. gravity
VI. Summary disease”  -granular casts
VII. Socioeconomic impact of Glomerulonephritis -early morning urine
VIII. Figures expected to have a
dark, intense color if
Note: The lecturer did not provide the transcribers with a copy kidney is able to
of her ppt so the contents of this trans are based on the concentrate urine
transcribers (and Gerard’s ) notes. Please read chapter 277 - concentrated (Sp.
of Harrison’s on Glomerular Disease, especially the general gravity 1.020-1.030)
information on Glomerular disease, Glomerulonephritis, and -Acute GN – red cell
the topics IgA nephrotpathy, PSGN, MGN. Other specific casts; RBCs
topics not discussed (e.g minimal change disease, etc) are degenerate to
not included in the exam DAW. Questions in the exam will fine/coarse granular
mainly come from Harrison’s. casts

I. INTRODUCTION *if creatinine is high, BUN is expected to be abnormal; if BUN

A. Case of ER, presented with: is high, creatinine is not necessarily high
 high BP (140/90), high HR, RR 30/min
 pale, sallow (in between pallor and jaundice) D. Final Diagnosis:
 “peculiar fetor” – fruity smell Uremia secondary to ESRD (CKD Stage V)
 evidence of cardiac damage (Grade II Av block) but secondary to Chronic Glomerulonephritis (CGN)
not yet in CHF due to absence of s3
 no evidence of liver involvement Basis for diagnosis:
CGN
B. Primary Impression: UREMIA - young adult, hypertension at age 19
Symptoms seen in ER Full-blown uremia: - hematuria, pyuria
(not seen in ER) - small kidneys
vomiting somnolence ESRD
tremors seizures - shrunken kidneys
anorexia disorientation
weakness coma **thus, ER was erroneously treated as UTI for 3 years in a
SOB male with no symptoms and an abnormal urinalysis
Pruritus
Easy fatigability II. Glomerulonephritis
restlessness -inflammation of the glomerular capillaries

C. Labs Requested a. Normal Kidneys:

- smooth surface
Lab Purpose Finding in ER - pinkish cortex
CBC Check for anemia due Low Hg - reddish medulla
to pallor - yellow calyces, pelvis
BUN To asses kidney elevated -In GN: kidneys are pale
function, but creatinine
is more important
b. Glomerulus
Creatinine Single most important increased
- 600 thousand – 2 million
test for uremia (uremic
if azotemic); *prematures have less glomeruli  higher tendency for
Electrolytes To check for acidosis Decreased hypertension  higher tendency for renal disease at age 50
Ca - ball of capillaries (“berries”) with afferent and efferent
arterioles (histology: stalk – where efferent and afferent
P Elevated arterioles run)
- glomerular capillaries filter 120-180 L/d of plasma water
K Needed if urgent Elevated -filtration occurs through a physicochemical barrier governed
by pore size and negative electrostatic charge
action is required
-glomerulus is an imperfect barrier
e.g. albumin-despite its negativity, readily passes
ABG Needed if urgent Uncompensated
through due to its small radius (3.6nm vs. 4nm radius
action is required Metabolic acidosis
of glomerular basement mebrane (GBM) slit-pores);
(low pH, low HCO3;
albumin is reabsorbed in the proximal tubules (urine
causes tachypnea)
normally contains only 8-10 mg)
CXR To rule out pneumonia Heart not enlarged *Glomerulonephritis can affect any part of the glomerulus
but with congestion (mesangium, parietal epithelium, basement membrane,
EKG Check for Peaked T waves podocytes) and will manifest differently.
hyperkalemia (hyperkalemia) -In GN: glomeruli are full of scars
UTZ Visualize the kidney: Small shrunken
If enlarged (e.g. 12 kidney
cm)=acute GN,
November2 2008/Tues Page 1 of 6
noems, choosey, jow, kitts
 OS 214: Renal Dr. Agnes Mejia
Glomerulonephritis Exam 1

Pathogenesis: V. Forms of Glomerulonephritis

(1) (2)
Circulating immune complexes In-situ immune complexes Form Prototype Disease
Acute Nephritic IgA Nephropathy
T-cells (CD 4/8) Infectious Disease PostStreptococcal GN
Associated; Nephritic (PSGN)
Glomerular injury Nephrotic Membranous GN

Mononuclears
A. IgA Nephropathy
Cytokine release -immune complex mediated GN defined by the presence
of diffuse mesangial IgA deposits often associated with
Attract more inflammatory cells mesangial hypercellularity
-circulating immune complexes get deposited in the
Glomerular damage mesangium or podocytes (not the BM)
-IgM, IgG, C3, or immunoglobulin light chains can be
*In summary, GN may be caused by circulating or in situ codistributed with IgA
immune complexes, but whichever the cause is, they both - Mild – do not undergo dialysis
follow the path of inflammation via T-cell activation RPGN (rapidly progessive)- end up in dialysis after 6
*Immunofluorescence can be used to determine whether mos
immune complexes are in-situ or circulating
*Overlapping etiologies may display common patterns of
injury (syndrome); this is evident in microscopy: • Epidemiology
- -most common form of GN worldwide
IgA Nephropathy - -30% in Asia and Pacific RimEast > West
- 20% in southern Europe
- low prevalence in N. Europe & N. America
- -Male > Female
Poststrep GN (PSGN) – same pattern of injury can be seen in - -peak incidence: 2nd-3rd decade of life
lupus, immune-complex GN - -rare familial clustering
• Presentation
-most common presentations are:
a. recurrent episodic macroscopic hematuria
Membranous GN (MGN) –same pattern can be seen in following a respiratory infection in children
idiopathic, Hepatitis, drug-induced b. asymptomatic microscopic hematuria seen in
adults
IV. Approach to Patient with Glomerulonephritis -between episodes, urinalysis is normal
A. History and PE -in persistent hematuria, increasing proteinuria is found
- confined to the kidneys or systemic? acute or chronic?
- signs and symptoms
• Differentials
dysuria – pain during urination? -Henoch-Schonlein Purpura- can be distinguished for IgA
nocturia – urination at night? Nephropathy by prominent systemic sx, younger onset
hematuria – blood in the urine? (<20yrs old), preceding infection and abdominal
retention/incontinence – incomplete voiding? complaints
frequency – urinating more often? -Crohn’s disease, chronic lover disease, GI
sediments adenocarcinoma, etc –also present with IgA deposition in
frothy urine – like beer mesangium; can be differentiated due to absence of
edema significant glomerular inflammation.
- last known urinalysis/creatinine • Progression
- pregnancy status (preeclampsia); birth control pills
-generally a benign disease, but 25-30% progress to
- Blood pressure
renal failure over 20-25 yrs.
– must give exact value, not just saying normal or
-5-30% go into complete remission
high, because what is high for one person may be
-sometimes recur post transplant
normal for another
-risk factors for renal failure: HPN, proteinuria, absence of
-Urinalysis
episodic macroscopic hematuria, male, older age of
– window to glomerular disease
onset, sever renal biopsy changes
-Quality of urine: clear, cloudy or bloody (gross
- “Point of no return” – stage where treatment is
hemturia)
insufficient usually when creatinine is at least 2
*painless gross hemturia suggests malignancy; if it is
-the clinical prognostic index (CPI) of GN–made in
painful, then it suggests urethritis
Verona, Italy; a scoring system that predicts the prgnosis
of GN
Table 277-1. Urine assays for albumin/proteinuria (HPIM)
2pts for Serum Creatinine> 1.4mg/dl
24Hr Albumin/ Dipstick 24Hh
1pt for Proteinuria> 1g/24 hrs
Albumin creatinine proteinuri Urine
1pt for presence of HPN
(mg/24h) ratio a Protein
1pt patient > 30 years old
(mg/G) (mg/24h)
-Score of 0-2*: higher 10-year renal survival
Normal 8-10 <30 - <150 3-5: lower 10-year renal survival; most likely to
Microalbu 30-300 30-300 -/trace/1+ - end up in dialysis
minuria *hence, creatinine is the single most impt
Proteinuria >300 >300 Trace-3+ >150 predictors of survival since it automatically
gives you 2pts if abnormal

November2 2008/Tues Page 2 of 6

noems, choosey, jow, kitts
 OS 214: Renal
Glomerulonephritis
• Treatment
Evidence-based: ACEI-ARB, Steroids, fish oil
Non-evidence Based: tonsillectomy
2. PostStreptococcal Glomerulonephritis (PSGN)
• also known as Postinfectious GN
• prototype for acute endocapillary proliferative GN
• Epidemiology
typically sporadic
children between 2-14 yrs (10% in px>40yrs)
Males > Females
familial/cohabitant incidence is high-40%
M types of Streptococci (nephritogenic strains)
impetigo- M types 2, 47, 49, 55, 57, 60
-PSGN develops 2-6 wks after a skin infection
pharyngitis- M types 1,2, 3, 4, 12, 25, 49
-PSGN develops 1-3 wks after pharyngitis
• Presentation
-classic presentation of acute nephritic px: HPN,
hematuria, RBC casts, pyuria, mild to moderate
proteinuria
-oliguric renal failure
-systemic symptoms include headache, malaise,
anorexia, flank pain (swollen renal capsule) in 50% of
cases
-in the 1st week of symptoms: 90% have depressed
CH50, decreased C3 (because they are circulating and
get deposited in the GBM)
-positive strep cultures are inconsistent
Renal Biopsy
-diffurse proliferative: little bowma’s space seen
-hypercellularity of mesangial and endothelial cells
-glomerular infiltrates of PMN leukocytes
-granular subendothelial immune deposits of IgG, IgM,
C3, C4, C5-9
-subepthelial deposits-“humps”
-RPGN – with crescents
• Diagnosis
-renal biopsy is not necessary
-subliclinical cases are reported to be more common than
clinical nephritis and characterized by asymptomatic
microscopic hematuria and low serum complement levels
• Treatment
- supportive
HTN
Edema
Dialysis if indicated (oliguric)
-antibiotic tx for strep infection for px and cohabitants
-no role for immunosuppressive tx even if crescents are
present
-good prognosis, rare recurrence, permanent renal failure
is very uncommon (1-3%)
-complete resolution of heamturia and proteinuria in
children occur in 3- 6 weeks of onset of nephritis
3. Membranous Glomerulonephritis
-also called Mebranous Nephropathy (MGN)
-in situ formation of immune complexes with megalin-receptor
associated protein as the putative agent
• Epidemiology
-30% of nephrotic syndrome (NS) in adults
-rare in children but most common NS in the elderly
-peak incidence between 30-50 years
- Males > Females (2:1)
November2 2008/Tues
Dr. Agnes Mejia
Exam 1
-25-30% secondary to malignancy (tumors of lung,
breast, colon), infection (Hep B, malaria,
schistosomiasis), rheumatologic disorders like lupus
-other etiologies are Drug-induced MGN
-Unknown/Idiopathic is still the most common MGN
• Presentation
-80% with nephrotic syndrome (NS)* and nonselective
proteinuria
-50% with microscopic hematuria
Nephrotic Syndrome
-heavy proteinuria (24h urine total protein > 3g), minimal
hematuria, hypoalbuminemia, hypercholesterolemia, HPN
-if untreated leads to progressive glomerular injury,
decline in GFR and renal failure
Edema
-There are 2 theories for the cause of edema due to NS:
underfill and overfill
1. Underfill  protein spillage  low albumin (albumin
acts as the magnet that attracts fluid)  low oncotic
pressure  low intravascular volume  secondary
sodium retention  EDEMA
2. Overfill  low GFR  primary Na retention 
Expanded ECF volume  EDEMA
Renal Biopsy
-LM: uniform thickening of the BM along the peripheral
capillary loops
-Immunolorescence: diffuse granular deposits of IgG and
C3
-EM: electron dense subepithelial deposits
• Progression
-some reports suggest that degree of tubular atrophy or
interstitial fibrosis are better predictors than the stage of
glomerular disease
-high recurrence rates
-spontaneous remission occur in 20-30% of patients and
occur late in the course after year of NS
-1/3 have relapsing NS but maintain normal renal fcns
-1/3 develop Renal failure of die of complications of NS
-risk factors for worse prognosis: male, older age, HPN,
persistent proteinuria
-MGN has highest reported incidence of renal vein
thrombosis, pulmonary embolism and DVT complications
among NS
• Treatment
-symptomatic treatment: edema (oral loop diuretics, low
Na diet, target is loss of 1-2lbs or fluid per day), HPN,
dyslipidemia, hypercholesterolinemia (lipid lowering
agents to decrease risk for CVS disease), proteinuria
(inhibition of RAS)
-immunosuppresive drugs (steroids and
cyclophosphamide, chlorambucil, cyclosporine) for
primary MGN and persistent protyeinuria (>3.0g/24hrs)
-experience with mycophenolate mofetil or anti-CD20
antibody is limited
-prophylactic anticoagulation (controversial but
recommended) in px with sever proteinuria
VI. SUMMARY
Be aware
- Family History: HTN, DM, CVD, Gout, Dialysis
Be suspicious
- BP > 140/90
- Frothy/cloudy urine
- Crea > 1.5 mg/dL or 132 umol/L
- GFR < 60
Page 3 of 6
noems, choosey, jow, kitts
 OS 214: Renal Dr. Agnes Mejia
Glomerulonephritis Exam 1

- Nocturia
- Dysuria

Set the Alarm

- Urinalysis

3 Syndromes and their signs

Form Prototype Disease Proteinuria Albuminuria
Acute IgA Nephropathy +/++ +++
Nephritic
Infectious PSGN +/++ +++
Disease
Associated;
Nephritic
Nephrotic MGN ++++ +

G
F
R

Creatinine,

*the GFR should be greatly decreased before creatinine

manifests with an abnormality. hence, be suspicious agad!

Therapeutic Intervention Postinfectious   (poststreptococcal)   glomerulone­

AntiInflammatory: Prednisone, tacrolimus, MMF, ritazimab
Reduce Proteinuria: ACEI, ARB phritis.The glomerular tuft shows proliferative changes with 
e.g. FSGS-progression, remission, relapse if numerous PMNs, with a crescentic reaction in severe cases 
mainatained on prednisone, but if given combination
therapy of prednisone and mycophenolate, disease (Top). These deposits localize in the mesangium and along 
is kept in remission the   capillary   wall   in   a   subepithelial   pattern   and   stain 
VII. Socioeconomic impact of Glomerulonephritis
Dialysis: Php40,000 per month dominantly for C3 and to a lesser extent for IgG (Middle). 
Kidney transplant: Php1.2 M Subepithelial   hump­shaped   deposits   are   seen  by   electron 
Maintenance medications: Php60,000 per month
microscopy (Bottom). 
*hence: set the alarm! because GN is a TREATABLE disease;
if treated early, there’s no need for these expensive
interventions

VIII. Figures

November2 2008/Tues Page 4 of 6

noems, choosey, jow, kitts
 OS 214: Renal Dr. Agnes Mejia
Glomerulonephritis Exam 1

IgA nephropathy
There is variable mesangial expansion due to mesangial 
de  posits,   with   some   cases   also   showing   endocapillary 
proliferation   or   segmental   sclerosis   (Top).By 
immunofluorescence, deposits are evident ( Middle).

Membranous glomerulopathy. Membranous glomeru­ 
lopathy   is   due   to   subepithelial   deposits,   with   resulting 
basement membrane reaction, resulting in the appearance of 
spike­like projections on  silver stain (Top). The deposits are 
Hyaline Cast
directly   visualized   by   fluorescent   anti   IgG,   revealing   diffuse 
granular capillary loop staining (Middle). By elec­ 
tron microscopy, the subepithelial location of the deposits and 
early   surrounding   basement   membrane   reaction   is   evident, 
with overlying foot process effacement (Bottom)

Preformed  immune  deposits  can  preciptate  from   the  circulation 

and collect along the glomerular basement membrane (GBM) in 
the   subendothelial   space   or   can   form   in   situ   along   the 
subepithelial space.

November2 2008/Tues Page 5 of 6

noems, choosey, jow, kitts
 OS 214: Renal Dr. Agnes Mejia
Glomerulonephritis Exam 1

Amplification   mediators   such   as   locally   derived   oxidants   and 

proteases   expand   this   inflammation,   and   depending   on   the 
location of the target antigen and the genetic polymorphisms of 
the   host,   basement   membranes   are   damaged   with   either 
endocapillary or extracaillary proliferation. 

Immunofluorescent   staining   of   glomeruli   with   labeled   anti­IgG 

demonstrating linear staining (mid) from a patient with anti­GBM disease 
or immune deposits from a patient with membranous glomerulonephritis 
compared to IgG lumpy­bumpy staining (bottom). 

The   mechanisms   of   glomerular   injury   have   a   complicated 

pathogenesis.   Immune     deposits   and   complement   deposition 
classically   draw   macrophages   and   neutrophils   into   the 
glomerulus. T lymphocytes may follow to participate in the injury 
pattern as well.

November2 2008/Tues Page 6 of 6

noems, choosey, jow, kitts