Clinical

Resource: Ghosh, Mayo Clinic Internal Medicine Board Review 2008, 8th
Edition, Lippincott, Williams & Wilkins. Part I Nephrology (pages 614-625)
Glomerular Disease Clinical Presentation
1.
Contrast microalbuminuria and overt proteinuria.
Microalbuminuria - Urinary albumin excretion of 30-300

mg/1.73 m2 per 24 hrs

Over proteinuria - Urinary albumin > 300 mg/1.73 m2 per

24 hrs
Even minimal proteinuria is associated w/

cardiovascular risk; no such thing as normoalbuminuria

1.

1.

1.

Define the nephrotic syndrome.

Urinary protein > 3.5 g/1.73 m2 per 24 hours,
hypoalbuminemia (<3.0 g/dL), peripheral edema,
hypercholesteremia, and lipiduria

Describe the laboratory and physical findings associated with

the nephrotic syndrome.
Edema can be prominent

Urinalysis: waxy casts, free fat, oval fat bodies, lipiduria

(Maltese crosses)
Complications:

hypogammaglobulinemia (inc risk of infections, e.g.

cellulitis, spontaneous peritonitis)

Vit D deficiency (d/t loss of Vit D-binding protein)

iron deficiency anemia (d/t hypotransferrinemia)

Name the thrombotic complication of nephrotic syndrome.
Thrombotic complications d/t increased levels of
prothrombotic factors and decreased antithrombin III and
antiplasmin
renal vein thrombosis

1.

Describe the urinary findings in nephritic syndrome.

Urinary protein < 3.5 g/1.73 m2 per 24 hours,
hypoalbuminemia (<3.0 g/dL), peripheral edema,
hypercholesteremia, and lipiduria
Oliguria, edema, HTN, proteinuria ( usually < 3.5 g/1.73

2
m per 24 hours), and an active urinary sediment

Glomerular Disease that Presents with Nephritic Syndrome

Discuss the causes, glomerular changes, microscopic findings and lab findings,
of post streptococcal glomerulonephritis.
o
Cause- acute glomerulonephritis nephritis that develops 1-4 weeks
after pharyngitis or skin infection w/ (nephritogenic) strains of group A hemolytic streptococci
o
Presentation is the abrupt onset of nephritic syndrome
Active urinary sediment (dysmorphic RBCs or RBC casts or both)

is present in all cases.

Urine has a cola or smokey appearance; due to

methemoglobin formation
Oliguria, HTN, edema, and proteinuria (<3 g/1.73 m 2 per 24 hrs)

o
Lab findings: cultures are negative, but titers for antistreptolysin (ASO),
antistreptokinase, antihyaluronidase, and antideoxyribonuclease (antiDNAse B) may provide evidence of recent streptococcal infection
Total hemolytic complement (CH50) and C3 levels are usually

decreased; but C4 levels are normal

Immunofluoresence: granular deposition of IgG and C3 in a

starry-sky, meseangial, or garland pattern

o
Microscopic findings: diffuse hypercellularity of the glomerular tufts, w/
mesangial and endothelial cell proliferation, infiltration of PMNs
(exudative), and subepithelial humps w/ silver stain
o
Pathologic characteristic: presence of large humps, which are domeshaped subepithelial deposits in the glomerular basement membrane
(GBM)

1 Discuss the clinical presentation of IgA nephropathy.

o
Mesangial proliferative glomerulonephritis; diffuse deposition of IgA in
the mesangium
o
Typical presentation: episodic macroscopic hematuria (usually
accompanying an intercurrent upper respiratory tract infection
[synpharyngitic]), often w/ RBC casts, but most commonly w/
asymptomatic microscopic hematuria and proteinuria
o
Pathogenesis is linked to abnormal integrity of the intestinal mucosa
resulting in overexposure to ubiquitous environmental antigens
exaggerated production of galactose-deficient (GD)-IgA1 by B cells
1 Discuss the light microscopy findings and the immunofluorescence findings of
IgA nephropathy.
o
Microscope- glomeruli may look normal or may show mesangial
expansion
o
Immunoflourescence is diagnostic and demonstrates strong IgA
staining w/in the mesangium
1 Describe the presentation of Henock-Schonlein purpura.
o
Systemic form of IgAN; microscopic or gross hematuria (or both) along
with RBC casts, purpura, and abdominal pain

1 Discuss the presentation, lab findings, and causes of membranoproliferative

glomerulonephritis.
o
Diffuse proliferation of the mesangium and thickening of glomerular
capillary walls, as seen w/ light microscopy
MPGN Type I- affects mainly kids (8-16 y/o); main cause is

cryoglobulinemia in a pt w/ hep C virus infection.

MPGN Type II- rare disease found in adults; associated w/ partial

lipodystrophy and drusen bodies in the retina (macular degeneration)

o
Presentation
1/3 of pts present w/ asymptomatic hematuria and proteinuria

Another 1/3rd have nephrotic syndrome and preserved renal

function
10-20% of pts present w/ nephritic syndrome

HTN is very common

o
Lab Findings
MPGN type I and cryoglobulinemic MPGN the levels of C3 & 4,

and CH50 are persistently low, due to activation of both complement

pathways
MPGN type II the alternative pathway is active therefore they

have persistently low C3 levels but normal C4.

A C3 nephritic factor is typically present; autoantibody to

alternating pathway C3 convertase persistent C3 breakdown

Renal biopsy: diffuse global thickening of capillary walls and

endocapillary hypercellularity lobular appearance

Silver staining: tram-track or double contour appearance due

to the interposition of mesangium btwn the GBM and endothelium

resulting in a neomembrane deposition and development of
glomerular capillaries
Immunofluorescence shows granular deposition of IgG and C3 in

the mesangium and outlines the lobular contours

1 Discuss the treatment of membranoproliferative glomerulonephritis.
o
MPGN type I
Long-term: corticosteroids

Temporary relief (slows progression): dipyridamole and aspirin

o
MPGN type II - Tx in adults is unknown

Rapidly Progressive Glomerulonephritis Crescentic

Glomerulonephritis
Define RPGN.
o
Acute, rapidly progressive (days to weeks to months) deterioration of
renal function associated with active urinary sediment and a focal
necrotizing crescenteric glomerulonephritis seen on light microscopic
examination of renal biopsy specimens
Describe Wegeners Granulomatosis.

Granulomatous inflammation involving the respiratory tract and

necrotizing vasculitis affecting small and medium-size vessels; a
necrotizing glomerulonephritis is common

Describe Polyarteritis Nodosa vasculitis.

o
Presentation: necrotizing inflammation of medium-size or small arteries
w/o glomerulonephritis or vasculitis in capillaries, or venules.
o
ANCA-negative; in some pts the disease is associated w/ hepatitis B
virus infection; normal glomeruli

Describe the other major organ system involved with Goodpasture Disease and
describe the mechanism of renal impairment.
o
Pulmonary-renal syndrome caused by circulating anti-GBM Abs and
linear staining seen along the GBM and alveolar basement membrane on
immunofluorescence
Ab is directed against the 3 chain of type IV collagen

Glomerular Disease That Usually Presents as Nephrotic Syndrome

Discuss the usual presentation of minimal change nephropathy.
o
Absence of structural glomerular abnormalities, except for the
widespread fusion of epithelial cell foot process seen on electron
microscopy, in a pt w/ nephrotic syndrome
Most common cause of nephrotic syndrome in kids (<10 y/o)

o
Kids present with an abrupt onset of nephrotic syndrome
The presence of nephrotic syndrome in a pt w/ normal urinalysis

results indicates MCN

o
In Adults, HTN and renal insufficiency may be present

1 Discuss the causes, of minimal change nephropathy.

o
Pathogenesis is unknown
o
Association w/ Hodgkin lymphoma suggests that MCN may be of Tlymphocyte abnormalities, w/ t cell producing a lymphokine that is toxic to
glomerular epithelial cells
Results in fusion of foot processes and detachment of podocytes,

loss of heparin sulfate negative-charge barrier of the basement

membrane and increased glomerular permeability to protein.
o
Clear association w/ drugs, allergy, and malignancy (lymphoma and
thymoma)
o
Secondary causes
Viral- MONO and HIV

Drugs- NSAIDs

Tumors- Hodgkin lymphoma, mycosis fungoides, and thymoma

Allergies- food, immunization, bee sting, and poison ivy

1 Discuss the treatment of minimal change nephropathy.

o
Responds to corticosteroid tx (cornerstone therapy)

Given for 4-8 wks after remission

Alt tx:cyclophosphamide, chlorambucil, and cyclosporine

1 Discuss the clinical features of membranous nephropathy.

o
Leading cause of nephrotic syndrome in white adults; rare in kids
o
Pathogenic cause is not known
Causes immune complex localization and the subsequent

development of proteinuria and nephrotic syndrome

Presence of autoantibodies to the M-type phospholipase A 2

receptor
o
Present w/ Proteinuria > 2.0 g/1.73 m2 per 24 hrs
o
Initially, renal function is preserved in the majority of patients and
glomeruli may appear normal under the light microscope
Advanced disease- capillary walls are thickened and there are

subepithelial projections (spikes) along the capillary walls

o
Spontaneous complete remission occurs in 25% of pts and partial
remission in 50%
Spontaneous remission is rare in pts w/ proteinuria >10 g/1.73

2
m per 24 hours
1 Discuss the causes of membranous nephropathy (primary vs. secondary).
o
Primary- in the majority of cases, the etiologic agent is unknown and
the disorder is termed idiopathic nephrotic syndrome
o
Secondary- associated w/ autoimmune diseases (ex: SLE), infections
(ex: Hep B and C), medications (ex: NSAIDs, penicillamine, gold), and
neoplasia (ex: colon and lung cancer)
o
Both types have similar presentation
1 Briefly list major medication classes that can cause membranous nephropathy.
o
NSAIDs and Penicillamine
1 Discuss treatment of membranous nephropathy.
o
Initial therapy is directed to control of edema, HTN, hyperlipidemia,
and reduction of proteinuria via ACEs and ARBs
o
Immunosuppressive therapy for pts who remain nephrotic after a trial
of maximal Angiotensin II Blockade (6 months)
Combo use of corticosteroids and cytotoxic agents, cyclosporine,

or tacrolimus
o
Pathoma: Poor response to steroids; progresses to renal failure

Other Glomerular Disorders

Name the most common cause of End Stage Renal Disease (ESRD) in
the United States.
diabetic nephropathy.

Name the early manifestation of renal disease associated with diabetic

nephropathy.
The first manifestation of diabetic nephropathy is microalbuminuria (20200mcg/min or 30-300mg/1.73m^2 per 24 hours). This is important because it
is a good primary predictor of renal disease. Over time, microalbuminuria can
evolve to proteinuria (>300mg/1.73m^2 per 24 hours) and then full-blown
nephrotic syndrome.
Name the lesion on renal biopsy pathognomonic for diabetic
nephropathy.
Renal biopsies will show different things depending on the stage of the
disease (You only need to know what is in red, everything else is background
info):
Earliest stage: Glomerular hypertrophy and thickening of the glomerular base
membrane.
As it progresses: Arteriolar hyalinosis and arteriosclerosis.
Then: Progressive mesangial expansion (diffuse diabetic glomerulosclerosis)
and nodular formation (Kimmelstiel-Wilson nodules, which are pathognomic for
diabetic nephropathy). Capsular drop lesions and fibrin cap lesions are also
pathognomic findings.
Late: Tubular atrophy and interstitial fibrosis.

Name two factors/interventions that can slow the rate of progression

of diabetic nephropathy.

The progression of diabetic nephropathy can be slowed down with tight

glycemic control (glycated hemoglobin <7.0%) and the use of ACEI or ARBs (to
keep systolic BP <125mmHg).

Discuss the role of ACE inhibitors and/or Angiotensin Receptor

Blockers in the diabetic patient.

They keep systolic BP under 125mmHg. If the patient with diabetes develops
microalbuminuria, they should start ACEIs or ARBs even if they have normal BP
(remember, microalbuminuria is an indicator of renal disease).

In what circumstances is renal biopsy necessary regarding the patient

with diabetic nephropathy?

Renal biopsy is indicated for patients with an atypical course of the disease
(eg. Nephrotic-range proteinuria within the first 10 years in type 1 diabetes or if
loss of renal function is rapidly progressive.

Renal biopsies are not necessary for patients with long-term diabetes,
especially if retinopathy is present.

Describe the immune deposit location in SLE nephritis.

Immune deposits (in the case of SLE nephritis, its IgG, IgM, IgA, C1q, and C4)
are localized to the glomerular capillary subendothelium (wire-loop).

*Not part of this objective but also seen under electron microscopy are
tubuloreticular inclusions which are characteristic but not diagnostic of SLE
nephritis.