Primary Glomerulopathies (Nephritic Syndrome)

PRIMARY GLOMERULOPATHIES (NEPHRITIC SYNDROME)

Acute poststreptococcal glomerulonephritis (APSGN) (or acute proliferative glomer-ulonephritis or postinfectious glomerulonephritis) is an immune complex disease that typically occurs 2–4 weeks after a streptococcal infection of the throat or skin. There is a decreasing incidence in the United States; children are affected more often than adults.

The infecting organism is most commonly β -hemolytic group A streptococci, but APSGN can also be caused by other bacteria, viruses, parasites, and even systemic diseases (SLE and polyarteritis nodosa). Clinically, it presents with nephritic syn-drome with elevated antistreptolysin O (ASO) titers (when related to streptococcal infection) and low C3.

Renal biopsy. Light microscopy shows an infiltrate of neutrophils in the glomeruli; the process is diffuse, that is, it involves all the glomeruli. Immunofluorescence shows granular deposits of IgG and C3 throughout the glomerulus within the cap-illary walls and some mesangial areas. Electron microscopy shows subepithelial immune complex deposits (humps).

Treatment is conservative fluid management. Most children (>95%) have a good prognosis, with complete recovery, but severe disease can also occur (RPGN 1% and chronic glomerulonephritis 2%). In adults, 15-50% develop end-stage disease.

Rapidly progressive glomerulonephritis (RPGN) (crescentic glomerulonephritis) is group of diseases characterized by glomerular crescents and a rapid deterioration of renal function.

Anti-glomerular basement membrane antibody-mediated crescentic glomer­ ulonephritis has a peak incidence at age 20-40, and males are affected more frequently than females.

Pulmonary involvement is called Goodpasture syndrome. These patients have pul-monary hemorrhage and hemoptysis.

Renal biopsy findings include hypercellularity, crescents, and fibrin deposition in glomeruli. Immunofluorescence shows a smooth and linear pattern of IgG and C3 in the glomerular basement membrane (GBM). By electron microscopy, there are no deposits, but there is glomerular basement membrane disruption.

Even with treatment (plasma exchange, steroids, and cytotoxic drugs), the prognosis is poor because of risks of severe and life-threatening pulmonary hemorrhage and renal failure. Early aggressive treatment may prevent end-stage renal failure.

Immune-complex mediated crescentic glomerulonephritis

•         Any of the immune complex nephritides can cause crescent formation.

•         IF shows a granular pattern and EM shows discrete deposits.

Pauci-immune crescentic glomerulonephritis

•         Antineutrophilic cytoplasmic antibodies (ANCA) are present in serum.

•         IF and EM are negative for immunoglobulins and complement components.

IgA nephropathy (Berger disease) is the most common cause of glomerulonephritis in the world, being particularly common in France, Japan, Italy, and Austria. It affects children and young adults (mostly males).

IgA nephropathy is characterized by recurrent gross hematuria (a predominately nephritic presentation), whose onset may follow a respiratory infection. IgA nephropathy can be associated with celiac sprue and Henoch-Schönlein purpura or can be secondary to celiac sprue or liver disease.

The pathogenesis is unknown, but may be related to a possible entrapment of cir-culating immune complexes with activation of the alternate complement pathway; it may also be related to a genetic predisposition.

Renal biopsy. Light microscopy may show normal glomeruli or mesangial prolif-eration. Immunofluorescence shows mesangial deposits of IgA and C3. Electron microscopy shows mesangial immune complex deposits.

Many cases slowly progress to renal failure over 25 years.

Membranoproliferative glomerulonephritis (MPGN) is a form of glomerular disease that affects both the glomerular mesangium and the basement membranes; it occurs in 2 types, Type I and Type II (dense deposit disease).

The clinical presentation is variable, and may be nephritic, nephrotic, or mixed. MPGN may be secondary to many systemic disorders (systemic lupus erythemato-sus, endocarditis), chronic infections (HBV, HCV, HIV), and malignancies (chronic lymphocytic leukemia).

Laboratory studies show decreased serum C3 and the presence of C3 nephritic fac-tor (MPGN type II).

Light microscopy demonstrates a lobulated appearance of the glomeruli due to mesangial and endothelial cell proliferation and/or deposition of subendothelial immune complex deposits. Splitting of the basement membrane (“tram-tracking”) may be seen with a silver or periodic acid-Schiff (PAS) stain.

Immunofluorescence in type I MPGN shows a granular pattern of C3 often with IgG, C1q, and C4; in type II, immunofluorescence shows a granular and linear pat-tern of C3 deposition.

Electron microscopy in type I shows subendothelial and mesangial immune com-plex deposits, and in type II shows dense deposits within the glomerular basement membrane.

MPGN typically has a slowly progressive course, resulting in chronic renal failure over the course of 10 years. There is a high incidence of recurrence in transplants.

Alport syndrome is a rare X-linked disorder caused by a defect in type IV collagen. It is characterized by hereditary nephritis, hearing loss, and ocular abnormalities. The most common mutation causing Alport is in the COL4A5 gene coding for the alpha-3, -4, and -5 chain of type IV collagen.

Gross or microscopic hematuria begins in childhood. Hearing loss (leading to sen-sorineural deafness) and various ocular abnormalities of the lens and cornea can occur. Alport is a progressive disease that ultimately results in renal failure.

Electron microscopy shows alternating thickening and thinning of basement mem-brane with splitting of the lamina densa, causing a “basketweave” appearance.