Membranoproliferative Glomerulonephritis — A New Look at an Old Entity

Abstract

M embranoproliferative glomerulonephritis (MPGN), also termed mesangiocapillary glomerulonephritis, is diagnosed on the basis of a glomerular-injury pattern that is common to a heterogeneous group of diseases. MPGN accounts for approximately 7 to 10% of all cases of biopsy-confirmed glomerulonephritis 1-4 and ranks as the third or fourth leading cause of end-stage renal disease among the primary glomerulonephritides. 2,5 Although some diseases associated with MPGN are well known, recent advances have identified additional MPGN-associated conditions. Cl inic a l Pr e sen tat ion MPGN most commonly presents in childhood but can occur at any age. The clinical presentation and course are extremely variable-from benign and slowly progressive to rapidly progressive. Thus, patients can present with asymptomatic hematuria and proteinuria, the acute nephritic syndrome, the nephrotic syndrome, chronic kidney disease, or even a rapidly progressive glomerulonephritis. The varied clinical presentation is caused by differences in the pathogenesis of the disorder and in the timing of the diagnostic biopsy relative to the clinical course. The degree of kidney impairment also varies, and hypertension may or may not be present. Patients who present early in the disease process, when the kidney biopsy shows proliferative lesions, are more likely to have a nephritic phenotype, and those with crescentic MPGN may present with a rapidly progressive glomerulonephritis. In contrast, patients with biopsies showing advanced changes that include both repair and sclerosis are more likely to have a nephrotic phenotype. Patients with classic MPGN often have features of both the acute nephritic syndrome and the nephrotic syndrome-termed the nephritic-nephrotic phenotype. Cl a ssific at ion a nd Pathoph ysiol o gy The typical features of MPGN on light microscopy include mesangial hypercellularity, endocapillary proliferation, and capillary-wall remodeling (with the formation of double contours)-all of which result in lobular accentuation of the glomerular tufts. These changes result from the deposition of immunoglobulins, complement factors, or both in the glomerular mesangium and along the glomerular capillary walls. On the basis of the electron-microscopical findings, MPGN is traditionally classified as primary (idiopathic) MPGN type I (MPGN I), type II (MPGN II), or type III (MPGN III) or secondary MPGN. MPGN I, the most common form, is characterized by subendothelial deposits, and MPGN III has both subepithelial and subendothelial deposits. 6,7 MPGN II is characterized by dense deposits in the glomerular basement membrane

Clinical Findings, Pathology, and Outcomes of C3GN after Kidney Transplantation

“…Light microscopy reveals a proliferative pattern of injury with evidence of mesangial, subendothelial, and, occasionally, subepithelial deposits on electron microscopy. 3,4 Clinically, the disease presents with hematuria, proteinuria, and low serum C3 levels. 2 The renal outcome of patients with C3GN is not as well established.…”

Dense Deposit Disease Mimicking a Renal Small Vessel Vasculitis

“…However, an infectious trigger may overwhelm this compensatory mechanism and lead to deposition of alternate complement components in the glomeruli, inciting various glomerular patterns of injury. 5 Other differential diagnoses of a C3 dominant IF profile include postinfectious GN and juvenile acute nonproliferative GN, discussed below. A small subset of cases of postinfectious GN (C3 dominant immunostaining profile, subepithelial humps on EM) have an atypical clinical course with persistent hypocomplementemia, hematuria, or proteinuria and progression to ESRD.…”

American Society of Nephrology Quiz and Questionnaire 2012

“…Recent studies have shown that dysregulation of the AP also results in C3GN. C3GN is characterized by glomerular C3 deposition and the presence of numerous deposits in the mesangium and capillary walls, including subepithelial deposits (21)(22)(23)(24). Thus, there is considerable overlap in the biopsy findings of patients with atypical postinfectious GN and those with C3GN (25).…”