Final Diagnosis -- Membranoproliferative Glomerulonephritis Type-III



The biopsy establishes the diagnosis of persistent/recurrent type-3 membranoproliferative glomerulonephritis (Strife variant) as the etiology of the nephrotic syndrome. This type of MPGN most frequently affects young patients. There are secondary associations with Sjögren' s syndrome, cirrhosis, and human immunodeficiency virus infection with pulmonary hypertension. In some patients, this disorder may be a prodrome to systemic lupus erythematosus, and in other patients, the disorder remains idiopathic without secondary associations.

Membranoproliferative glomerulonephritis type III can be subdivided in two variants: MGPN type III of Burkholder and MGPN type III of Strife. They share some features such as thickening of the glomerular capillary walls, double contours, mesangial interposition, and subendothelial deposits. However, in contrast to MPGN type III of Burkholder, subepithelial deposits and spikes are less common in MPGN III of Strife. The type-III MPGN (Strife variant) is also characterized by a distinctive pattern of glomerular basement membrane (GBM) disruption observed by electron microscopy. The deposits have a washed-out or electron lucent appearance with layering of the lamina densa-like material. There is frequently disruption of the GBM lamina densa, often with thickening and expansion of the basement membrane and layering by silver negative basement membrane material. These complex lesions appear to originate from several generations of subepithelial and subendothelial deposits forming in conjunction with multiple interruptions of the lamina densa, such that the deposits are partially confluent. Since each generation of the deposits is covered by new lamina densa-like material, the lesions develop a complex laminated appearance. The nephrotic syndrome, hypertension and impaired renal function are harbingers of a poor prognosis. The patients with Type III MPGN have longer lasting hypocomplementemia, hematuria and proteinuria; experience more disease relapses; and have significantly greater loss of renal function during alternate-day prednisone therapy when compared with MGPN I patients. In addition, survival analyses imply a more guarded prognosis for long-term renal survival for MPGN III.


  1. Anders D, Agricola B, Sippel M et al. Basement membrane changes in membranoproliferative glomerulonephritis. II. Characterization of a third type by silver impregnation of ultrathin sections. Virchow's Archs A Pathol Anat Histopathol, 1977; 376:1.
  2. Strife CF, McEnery PT, McAdams AJ, West CD Membranoproliferative glomerulonephritis with disruption of the glomerular basement membrane Clin Nephrol. 1977 Feb;7(2):65-72.

Contributed by Eumenia Castro, MD and Sheldon Bastacky, MD

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