CHRONIC GLOMERULONEPHRITIS

Chronic glomerulonephritis is a heterogeneous group of many glomerular disorders, either primary or secondary, with irreversible impairment of renal functions.

While majority of these conditions are idiopathic, chronic glomerulonephritis may be a consequence of renal damage in: (a) hereditary nephropathies,

(b) toxic injury following drug/chemical exposure, (c) vascular injury, e.g.

glomerulonephritis in older children and adolescents, presenting as steroid-resistant nephrotic syndrome (60-70%) or persistent hematuria (20-30%).

Diagnosis should be suspected in any case with non­resolving acute nephritis or atypical nephrotic syndrome, and rests on renal biopsy with three histological types:

• Type I: Generalized increase in mesangial cells and matrix with immune complex deposits

• Type II: Irregular ribbon-like thickening of capillary walls due to dense deposits and crescent formation

• Type III: Gross thickening, splitting and layering of glomerular basement membrane.

Long-term alternate day steroid therapy is indicated only in those with heavy proteinuria or impaired renal functions.

Prognosis is poor with gradual progression to ESRD, specially in those with nephrotic presentation.

Membranous nephropathy is the commonest cause of nephrotic syndrome in adults, though rare in children. It is usually seen following infections, autoimmune disorders and drugs, e.g. NSAIDs. Some cases may present with recurrent hematuria.

Pathologically, it is characterized by diffuse thickening of glomerular basement membrane due to immune complex deposits on epithelial side, without significant mesangial proliferation.

Most cases resolve spontaneously though some may continue to have mild/moderate proteinuria.

Other important types of glomerulopathies are as follows:

IgA nephropathy (Berger disease): IgA nephropathy is a common cause of recurrent gross hematuria, pathol ogically characterized by segmental mesangial proliferation with predominantly IgA deposits in mesangium.

Clinically more common in males, most cases present with recurrent hematuria, often following a bout of mild respiratory infection. Each episode usually lasts for 3-7 days. Proteinuria may appear over time. Diagnosis is based on renal biopsy with immuno-fluorescence studies. Unlike APSGN, C3 levels are normal.

Disease is usually not progressive and treatment is mainly supportive. Cases with mild proteinuria may be treated with ACE inhibitors while immunosuppressive therapy may be required in cases with nephrotic range proteinuria and deteriorating renal function.

Vasculitic nephropathies: Renal involvement with asymptomatic and/or microscopic hematuria and/ or proteinuria is common in vasculitis syndromes, e.g. systemic lupus erythematosus (SLE) and Henoch- Scholein purpura (HSP).

Glomerulopathy in HSP (also termed as IgA vas­culitis) is usually self-limiting and may be associated with elevated serum IgA levels as well as mesangial proliferation with characteristic IgA deposits in mesan­gium. Frank nephritis or nephrotic syndrome is rare.

Glomerulopathy in SLE is usually progressive with intermittent course. Renal biopsy may be normal on light microscopy but immunofluorescence studies show IgG and C3 deposits in mesangium and capillary walls. Antinuclear antibodies and low serum C3 are present. Frank nephritic and nephrotic syndrome is common and most cases progress to ESRD after variable period. Steroids with cytotoxic agents may arrest progression of disease.

Hereditary glomerulopathies are rare, but should be considered in differential diagnosis of persistent/ recurrent hematuria with similar family history. Three important hereditary nephropathies with predominant glomerular involvement are as follows:

Benign familial hematuria is a rare cause of recurrent gross hematuria with similar family history.

Alport's syndrome is usually an X-linked disorder, characterized by: (a) renal lesions (diffuse thickening of GBM), (b) sensorineural deafness, and (c) ocular defects, e.g. cataracts, anterior lenticonus and macular lesions. Other organs may also be involved. Most cases present in late childhood with recurrent/persistent hematuria and may progress to end stage renal disease in adulthood.

Idiopathic hypercalciuria, is a common cause of recurrent gross or persistent microscopic hematuria, due to an inherited defect in tubular calcium transport defect, leading to hypercalciuria and recurrent calculi (Ch 21.11). Goodpasture disease, is characterized by presence of antibodies against type IV collagen present in alveolar basement membrane of the lungs and glomerular basement membrane of the kidneys. Most cases present beyond childhood with recurrent pulmonary hemorrhage and progressive glomerulonephritis. Similar clinical picture is also seen in many vasculitic syndromes, e.g. SLE, HSP, etc., when termed Goodpasture syndrome.

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