Update on membranoproliferative GN

Abstract

Membranoproliferative GN represents a pattern of injury seen on light microscopy. Historically, findings on electron microscopy have been used to further subclassify this pathologic entity. Recent advances in understanding of the underlying pathobiology have led to a proposed classification scheme based on immunofluorescence findings. Dysregulation of the complement system has been shown to be a major risk factor for the development of a membranoproliferative GN pattern of injury on kidney biopsy. Evaluation and treatment of this complex disorder rest on defining the underlying mechanisms.

Figure 1.

Membranoproliferative GN (MPGN). Light microscopy hematoxylin & eosin stain. Reprinted from Glen Markowitz, with permission.

Figure 2.

Simplistic breakdown of the new MPGN classification using immunofluorescence as the basis and an approach to evaluation when the kidney biopsy indicated MPGN. DDD, dense deposit disease; IF, immunofluorescence; SPEP, serum protein electrophoresis; TMA, thrombotic microangiopathy; UPEP, urine protein electrophoresis.

Figure 3.

Dense deposit disease electron microscopy. Reprinted from Glen Markowitz, with permission.

Figure 4.

Alternate pathway (AP) schematic. Activation of the AP begins with C3 interacting with C3 convertase. C3 convertase is activated or inhibited by a variety of factors and proteins. C3b and C3 convertase promote formation of C5 convertase. C5 convertase, acting on C5, results in formation of C5a and C5b. C3a and C5a attract neutrophils. C5b interacts with C6–C9 to form membrane attack complex.