Standardized Classification and Reporting of Glomerulonephritis

Sanjeev Sethi; Fernando C. Fervenza

Disclosures

Nephrol Dial Transplant. 2019;34(2):193-199. 

In This Article

Abstract and Introduction

Abstract

A kidney biopsy is done to determine the etiology of the glomerulonephritis (GN) and the severity of the lesion, to identify whether other lesions, related to or not related to the GN, are present on the kidney biopsy and finally to ascertain the extent of chronicity of the GN. The etiology of GN is based on the classification of GN into five groups: immune complex–mediated GN, antineutrophil cytoplasmic antibody (ANCA)-associated GN, anti-glomerular basement membrane (GBM) GN, monoclonal immunoglobulin-mediated GN and C3 glomerulopathy. Immune complex GN includes multiple specific diseases such as lupus nephritis, IgA nephropathy, infection-related GN and fibrillary GN. ANCA GN, anti-GBM GN and C3 glomerulopathy are specific diseases in themselves, while monoclonal Ig GN includes proliferative GN with monoclonal Ig deposits and monoclonal Ig deposition disease. Thus identification of the class of GN and within it the specific disease determines the etiology of GN. Ancillary studies may be required to confirm the etiology of GN. The severity of the GN is revealed by the pattern of injury, such as crescentic, necrotizing, diffuse proliferative, exudative, membranoproliferative, mesangial proliferative or a sclerosing GN. Secondary diagnosis either related or unrelated to the GN, such as diabetic glomerulosclerosis, acute tubular necrosis or thrombotic microangiopathy, may also be present. The secondary diagnosis may sometimes be the reason for the kidney biopsy. The chronicity of GN is determined by evaluating the extent of glomerulosclerosis, tubular atrophy and interstitial fibrosis and vascular sclerosis present on the biopsy. This review summarizes the approach to standardizing a kidney biopsy report that includes these components in a logical and sequential manner.

Introduction

Having read >1000 kidney biopsies each year for the last 15 years, the five most common questions I get from practicing nephrologists are

  • What is the diagnosis?

  • How active is the lesion?

  • Is there any acute tubular necrosis (ATN)?

  • How much scarring has occurred?

  • Is it treatable or is it too late to treat?

These basic questions are pertinent and very reasonable. Recent advances in understanding the etiology and pathogenesis of glomerulonephritis (GN) have necessitated that we take another look at how we diagnose/classify and report GN to answer these questions. The main reasons for doing so are overreliance on patterns of injury and recognizing and identifying the etiology of GN.

Overreliance on Patterns of Injury

GN, very simply defined, is glomerular injury with ensuing glomerular inflammation that is characterized by increased glomerular cellularity. The increased glomerular cellularity is reflected in a variety of patterns, including mesangial proliferative GN, diffuse endocapillary GN, membranoproliferative GN, crescentic GN and necrotizing GN, all of which can later lead to a pattern of sclerosing GN. For many decades the renal community has focused on these patterns of injury; in many instances, a disease was named after the pattern of injury, such as membranoproliferative GN. It is true that while the patterns of injury often reflect the acuteness and severity (and chronicity) of the injury and might even point to the underlying etiology, dissimilar etiologies may result in similar patterns of injury. For example, GN resulting from accumulation of complement factors due to dysregulation of the alternative pathway of complement (C3 GN), accumulation of immune complexes due to a chronic infection such as hepatitis C or accumulation of monoclonal immunoglobulins (Igs) due to a paraprotein, all with diverse etiologies, can result in a membranoproliferative GN.[1,2] Similarly, an antineutrophil cytoplasmic antibody (ANCA)-associated GN, C3 GN or even a fibrillary GN, again with dissimilar etiologies, can all result in a necrotizing and crescentic GN.

Etiology of GN

Over the last two decades, great strides have been made in understanding the various causes of GN and it has become clear that an etiology can be identified in the majority of cases of GN diagnosed on a kidney biopsy.[3] Thus it was time to (re)focus on the basic classification of GN so that the diagnosis is based on etiology. It was also time to systematically incorporate the etiologic diagnosis into the renal biopsy pathology report.

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