Mayo Clinic/Renal Pathology Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of GN

Abstract

Renal pathologists and nephrologists met on February 20, 2015 to establish an etiology/pathogenesis-based system for classification and diagnosis of GN, with a major aim of standardizing the kidney biopsy report of GN. On the basis of etiology/pathogenesis, GN is classified into the following five pathogenic types, each with specific disease entities: immune-complex GN, pauci-immune GN, antiglomerular basement membrane GN, monoclonal Ig GN, and C3 glomerulopathy. The pathogenesis-based classification forms the basis of the kidney biopsy report. To standardize the report, the diagnosis consists of a primary diagnosis and a secondary diagnosis. The primary diagnosis should include the disease entity/pathogenic type (if disease entity is not known) followed in order by pattern of injury (mixed patterns may be present); score/grade/class for disease entities, such as IgA nephropathy, lupus nephritis, and ANCA GN; and additional features as detailed herein. A pattern diagnosis as the sole primary diagnosis is not recommended. Secondary diagnoses should be reported separately and include coexisting lesions that do not form the primary diagnosis. Guidelines for the report format, light microscopy, immunofluorescence microscopy, electron microscopy, and ancillary studies are also provided. In summary, this consensus report emphasizes a pathogenesis-based classification of GN and provides guidelines for the standardized reporting of GN.

The role of the alternative pathway of complement activation in glomerular diseases

“…Increased knowledge of complement and its role in the pathogenesis of kidney diseases has recently led to the reclassification of glomerulonephritis (GN) based on pathophysiology rather than pathomorphology. A new entity, called C3 glomerulopathy (C3G), characterized by the AP dysregulation has been distinguished [7][8][9][10]. The remaining renal pathologies have been categorized as immune-complex GN, pauci-immune GN, anti-glomerular basement membrane (GBM) GN and monoclonal immunoglobulin (Ig) GN.…”

“…The remaining renal pathologies have been categorized as immune-complex GN, pauci-immune GN, anti-glomerular basement membrane (GBM) GN and monoclonal immunoglobulin (Ig) GN. The primary membranous nephropathy (PMN), podocytopathies, and thrombotic microangiopathy (TMA) have not been included in the GN group [7]. In this review, we focus on the pathophysiology of the AP, as a crucial part of the complement system and analyze its role in the pathogenesis of kidney diseases, mainly in various forms of primary and secondary GN, and PMN.…”

“…C3GN, on the other hand, is characterized by subendothelial, mesangial and in some cases subepithelial C3 deposits on EM. On the light microscopy (LM), 71% cases of C3GN show membranoproliferative pattern of injury, though mesangial proliferation, crescent formation, and glomerular sclerosis may also occur [7,8,10,62,67,82,83].…”

“…All affected individuals had an internal duplication of exons 2 and 3 in CFHR5 gene, resulting in an expression of the mutant CFHR5 protein, with reduced affinity for the surface-bound complement. This new entity was called CFHR5 nephropathy, and it was classified as a subtype of C3G [7,75]. Other cases of C3G associated with mutant CFHR proteins have been described.…”

“…In some cases, mixed membranous and proliferative pattern could be observed. According to the new classification, several distinct disease entities, such as primary membranoproliferative glomerulonephritis type I and type III (MPGN I, MPGN III), IgAN, and lupus nephritis (LN) have been included in this category [7,8]. The activation of immune complexes by the CP led to the assumption that other complement pathways are not involved in the disease pathogenesis.…”