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Clinical presentation, classification, and causes of membranoproliferative glomerulonephritis

Fernando C Fervenza, MD, PhD
Sanjeev Sethi, MD, PhD
Section Editor
Richard J Glassock, MD, MACP
Deputy Editor
Albert Q Lam, MD


Membranoproliferative glomerulonephritis (MPGN) is a pattern of glomerular injury on renal biopsy with characteristic light microscopic changes. The clinical presentation is similar to that in other types of glomerulonephritis. In patients with active disease, the urine sediment reveals hematuria, typically with dysmorphic red cells (picture 1 and picture 2) and occasionally with red cell casts (picture 3); there is a variable degree of proteinuria; and the serum creatinine may be normal or elevated. Occasional patients with indolent disease present late in the course at a time when active inflammation has subsided. Such patients may have a bland urine sediment with a variable degree of proteinuria and elevation in serum creatinine. The diagnosis is made by renal biopsy [1]. (See "Glomerular disease: Evaluation and differential diagnosis in adults" and "Etiology and evaluation of hematuria in adults", section on 'Glomerular versus nonglomerular bleeding'.)

As will be described below, there are two major types of MPGN, which are based upon immunofluorescence microscopy: immune complex-mediated and complement-mediated. Hypocomplementemia is common in all types of MPGN [2-6]. In immune complex-mediated MPGN, complement activation occurs via the classic pathway and is typically manifested by a normal or mildly decreased serum C3 concentration and a low serum C4 concentration. In complement-mediated MPGN, there are usually low serum C3 and normal C4 levels due to activation of the alternate pathway [3]. However, complement-mediated MPGN is not excluded by a normal serum C3 concentration, and it is not unusual to find a normal C3 concentration in adults with dense deposit disease (DDD) [6] or C3 glomerulonephritis (C3GN). (See 'Complement-mediated MPGN' below.)

Among patients who have the different forms of MPGN described below, there are generally no differences in clinical presentation with the possible exception of patients with DDD, which is a form of complement-mediated MPGN that is associated with drusen formation that may be seen on fundoscopic examination and with partial lipodystrophy. (See "C3 glomerulopathies: Dense deposit disease and C3 glomerulonephritis", section on 'Extrarenal abnormalities'.)

This topic will review the pathology and pathogenesis of MPGN, a proposed classification based upon immunofluorescence microscopy, the original classification of MPGN based upon electron microscopy (EM), and the limitations of this approach. The treatments of the different types of MPGN, including recurrent MPGN following renal transplantation, are discussed elsewhere. (See "Evaluation and treatment of membranoproliferative glomerulonephritis" and "C3 glomerulopathies: Dense deposit disease and C3 glomerulonephritis" and "Recurrence of idiopathic immune complex-mediated membranoproliferative glomerulonephritis (MPGN) after transplantation".)


Membranoproliferative glomerulonephritis (MPGN), also known as mesangiocapillary glomerulonephritis, is a pattern of glomerular injury on light microscopy that is characterized by mesangial hypercellularity, endocapillary proliferation, and double-contour formation along the glomerular capillary walls (picture 4A-B). The term "MPGN" is derived from the two characteristic histologic changes:

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Literature review current through: Nov 2017. | This topic last updated: Jan 13, 2016.
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