Membranoproliferative glomerulonephritis (MPGN) is primarily, though not exclusively, a disease of children . The age range is known to extend into young adulthood with the disease being occasionally diagnosed in older adults. MPGN appears to affect both sexes equally .
The clinical onset of MPGN may be preceded by upper respiratory infections. Up to one-third of affected patients may be hypertensive at the time of diagnosis. Renal dysfunction is known to occur in more than 50% of children. Some patients may suffer from severe anemia, owing to the effects of kidney failure and complement-mediated destruction of red blood cells.
All patients with MPGN have proteinuria and/or hematuria. The degree of proteinuria is varied with a majority of individuals presenting in the nephrotic range (40-70%). Some may also present with acute nephritic syndrome (20-30%), isolated macroscopic hematuria, or microscopic hematuria with subnephrotic range proteinuria.
It is not possible to differentiate the various types of MPGN clinically (there are three types of MPGN). However, type II MPGN is characterized by certain extra-renal manifestations. Notable amongst these are deposits termed drusen in the Bruch’s membrane of the retina. As compared to the drusen seen in age-related macular degeneration, the drusen of MPGN II develops at a much younger age. Partial lipodystrophy is also noted in these patients, years before the onset of clinical disease .
In contrast to adults, children with MPGN have an acute presentation but a slower progression of the disease. Spontaneous remission is rare and the disease varies in severity over its clinical course. MPGN is also known to recur in kidney transplant recipients .
The diagnosis of MPGN is suggested by the presence of hematuria with dysmorphic red blood cells. The degree of proteinuria is variable and the serum creatinine may be normal or raised. The diagnosis is confirmed via a renal biopsy.
Light microscopy may reveal a classic membranoproliferative pattern that includes lobular accentuation of the tuft of glomeruli and duplication of the basement membrane (termed the tram-track appearance).
Immunofluorescence microscopy may reveal the deposition of immune complexes and complement factors. Hypocomplementemia is common in all types of MPGN. In type I disease or immune complex-mediated MPGN, complement activation occurs via the classic pathway, thereby, resulting in low serum C4 concentration and normal/low C3 levels. Type II disease or complement-mediated MPGN show a low serum C3 and normal serum C4 levels due to the activation of the alternative pathway. MPGN type III involves the activation of the alternative and terminal pathways with low levels of C3 and C5-C9 . C3 nephritic factor levels may also be tested.
Electron microscopy may reveal deposits in the mesangium, basement membranes of the glomeruli, and occasionally within Bowman’s capsule  .
Genetic testing for factors involved in the complement regulation may also be performed .