LAB 2: Glomerular Diseases (nephritic syndrome)
Case 1: (Answer: Post-infectious glomerulonephritis)
A 12-year-old Costa Rican boy is brought into clinic by his parents because of dark brownish-red urine over the
last 24 hours. The family has been visiting friends in Indianapolis for two-weeks. While touring the Children’s
Museum two days ago they noticed their son had puffiness around his eyes. The week prior to leaving home,
the child had a febrile illness associated with a sore throat but he improved within five days while taking
children’s Tylenol. On exam the boy has a blood pressure of 132/92 mmHg as well as periorbital and ankle
edema bilaterally. A Monospot test was negative. No family history of kidney disease.
Questions:
A. What would you expect the urinalysis to show? Blood & protein in urine by dipstick; dysmorphic RBCs
or red cell casts by urine micro.
B. What blood tests would you order and what would you expect them to show? Do any of these tests help
you to determine if a renal biopsy is necessary?
1. serum creatinine, electrolytes, albumin
2. in post-infectious (poststreptococcal) glomerulonephritis, the serum complement C3 is usually
low and C4 is usually normal, indicating alternative pathway of complement activation (same for
MPGN-2). In 10-20% of kids with post-infectious GN the C3 is normal. In classical pathway of
complement activation, C4 is usually low and C3 is normal to low (e.g., MPGN-1). C3 and C4 are
usually low in lupus nephritis.
3. Anti-streptolysin O antibody (ASO) titer & Streptozyme (detects a wider spectrum of antiStreptococcal antibodies) are the 2 commonly used tests to evaluate for previous Strep
infection. Strep skin infections often do not generate an elevated anti-ASO titer (cholesterol
esters in skin may interfere with antibody recognition of antigen). ASO & Streptozyme are each
positive in approx. 16% to 18% of healthy children. Therefore, in a child with
hypocomplementemic glomerulonephritis, a positive Streptozyme suggests but does not
confirm the nephritis as truly streptococcal. A negative Streptozyme suggests an alternative
diagnosis (and suggests the need for a renal biopsy). The bug is often group A beta hemolytic
strep.
4. Other serology? ANA and dsDNA (rule out lupus nephritis), ANCA (vasculitis), hepatitis B & C
antigens and antibodies (usually drawn as a “hepatitis panel”) and anti-GBM antibody
(Goodpasture’s, although uncommon in kids).
C. Is this an example of nephrotic or nephritic syndrome? Why? Hematuria, hypertension, renal failure
(elevated BUN and creatinine)
D. Which portion of the nephron would you expect to be abnormal? Glomerulus (source of blood in urine)
E. What is the expected characteristic pathology associated with this patient? Pathologist shows biopsy:
1. Light Microscopy: Glomerulonephritis means too many cells in glomerulus
A. Resident cells are proliferating: mesangial and/or endothelial
B. Non-resident leukocytes are infiltrating: monocytes/macrophages, lymphocytes, and
neutrophils (acute/exudative).
The glomerulonephritis of postinfectious is usually endocapillary [meaning hypercellularity
of mesangium and within capillary loops (intracapillary hypercellularity)]. May see crescents.
2. Immunofluorescence: coarse granular (lumpy bumpy) IgG and C3 along capillary loops
3. Electron Microscopy: electron dense subepithelial immune deposits (humps)
Case 2: (Answer: Lupus glomerulonephritis)
A 29-year-old Country-Western singer (67 kg Caucasian female) presents with complaints of facial rash,
generalized malaise, pleuritic chest pain, and diffuse joint pain that has gradually worsened over the last week.
On exam she has a blood pressure of 160/98 mmHg, a palpable malar rash in a butterfly distribution over her
face, and a pleural rub. Negative family history. She smokes unfiltered cigarettes, drinks two 6-packs of Lone
Star Pilsner each week, recently lost her boyfriend and her Bluetick Coon dog ran away.
Questions:
A. What is the reason for the edema and hypertension? The patient has nephritic syndrome. The GFR
may decrease due to glomerulonephritis (glomerular hypercellularity may decrease renal blood
flow and/or alter vascular permeability). This decreases one’s ability to handle fluid and salt loads,
predisposing to edema and hypertension. In addition, the juxtaglomerular apparatus (JGA) detects
the decrease in filtration (low filtrate flow), and this activates renin-angiotensin-aldosterone system
(angiotensin II is a potent vasoconstrictor).
B. What is the clinical syndrome? nephritic syndrome Why? Hypertension, hematuria
C. What simple “bedside” (point-of-care) test could you do to support your clinical diagnosis? urine dipstick
(confirmed by urine microscopy)
D. What blood tests would provide further support for your diagnosis? +anti-dsDNA, +ANA, low serum
complements
E. What would you expect a renal biopsy on this patient to show? Pathologist shows biopsy:
1. Light Microscopy: there may be a variety of findings with SLE but this biopsy shows: diffuse
proliferative glomerulonephritis (polys, karyorrhexis, wire loops, +/- crescents and fibrin) +/interstitial nephritis
2. Immunofluorescence: intense granular immune deposition in glomeruli (capillary loop &
mesangial) and perhaps TBM, of many immune reactants: “fullhouse” (IgG, IgA, IgM, C3,
C1q)
3. Electron Microscopy: many electron dense deposits throughout the glomeruli including large
subendothelial, mesangial, subepithelial deposits.
F. Is this an example of: (1) in situ immune complex deposition or (2) circulating immune complexes with
antigen of endogenous origin (DNA) or (3) circulating immune complex deposition with antigen of
exogenous origin?
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Case 3: (Answer: Anti-GBM glomerulonephritis)
A 55-year-old pharmaceutical representative (102 kg African American man) presents with complaints of
increasing shortness of breath over the last week. Yesterday he coughed up blood but reports no fever or
chills. He usually smokes a pack of cigarettes a day and one cigar per week but he quit 3 weeks ago. No
alcohol. His territory includes Indiana, Michigan, Kentucky and Ohio so he spends many hours sitting in his car.
On exam he has a blood pressure of 178/100 mmHg, bilateral crackles on auscultation of the chest and 1+
edema of the lower extremities. The patient has no rashes. CXR reveals bilateral infiltrates and serum
creatinine is 8.9 mg/dl. His creatinine was 0.9 mg/dl six months ago when he had a work-related physical
exam. PPD at that time was negative. No family history of renal disease.
Questions:
A. What clinical syndrome does this man have? What are the potential causes for this syndrome? (1) rapidly
progressive glomerulonephritis (2) pulmonary-renal syndrome (pulmonary hemorrhage + decline in
renal fct) R/O Goodpasture syndrome. (Why is this not nephrotic syndrome?) hypertension, acute
renal failure with rapid progression (elevated creatinine)
B. What simple test could you do in the office to provide support for your clinical diagnosis? Urine dipstick
and micro (UA) - look for blood and protein in urine
C. What other clinical and laboratory tests would be helpful in sorting out this problem? What would you
expect them to show? CXR, lung function tests, renal function tests, ANCA (vasculitis), anti-GBM
antibody titers (anti-GBM ds. Or Goodpasture’s), ANA (lupus), ASO/streptozyme (poststreptococcal
glomerulonephritis).
D. What is the significance of the previous serum creatinine and urinalysis? Establishes baseline for
previously normal renal function
E. Would you do a tissue biopsy on this patient? If so, would you biopsy the lung or the kidney: A renal
biopsy might not be indicated if the patient’s presentation (positive anti-GBM titers) is consistent
with anti-GBM disease. However, in some hospitals it may take 1-2 weeks to receive results of antiGBM labs. However, a renal biopsy interpretation may be obtained within hours (<24 hours). If
pulmonary symptoms are more severe, a lung biopsy may be indicated (although the complication
of bleeding is potentially more life threatening in lung than kidney).
F. If you decide to do a renal biopsy what would you expect it to show? Pathologist shows biopsy:
1. Light Microscopy crescentic glomerulonephritis
2. Immunofluorescence linear IgG (anti-GBM)
3. Electron Microscopy no distinctive immune-type deposits. +/- fibrin and crescents.
H. Is this an example of: (1) in situ immune complex deposition or (2) circulating immune complexes with
antigen of endogenous origin or (3) circulating immune complex deposition with antigen of exogenous origin?
*
RPGN is a clinical syndrome in which glomerular damage is accompanied by rapid and
progressive decline in renal function. Can be irreversible in weeks or months. Pathology
characterized by crescents in glomeruli, often diffuse. Examples include postinfectious,
idiopathic, or systemic diseases: Goodpasture's syndrome, SLE, vasculitis, Wegener's, HSP,
essential cryoglobulinemia. RPGN associated with Goodpasture's syndrome is a classic example
of anti-GBM ds.