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Epidemiology, classification, and pathogenesis of focal segmental glomerulosclerosis

Authors
Jochen Reiser, MD, PhD
Fernando C Fervenza, MD, PhD
Sanjeev Sethi, MD, PhD
Section Editors
Richard J Glassock, MD, MACP
Brad H Rovin, MD
Deputy Editor
Albert Q Lam, MD

INTRODUCTION

Focal segmental glomerulosclerosis (FSGS) is a histologic lesion, rather than a specific disease entity, that is commonly found to underlie the nephrotic syndrome in adults and children, particularly in the United States, Brazil, and many other countries [1-6]. FSGS is characterized by the presence of sclerosis in parts (segmental) of some (focal) glomeruli on light microscopic examination of a kidney biopsy specimen. (See "Etiology, clinical features, and diagnosis of minimal change disease in adults", section on 'Primary MCD versus primary FSGS'.)

The term "FSGS" is somewhat misleading, however, since the lesions of FSGS are not as focal or segmental in distribution as the name suggests. In experimental models of FSGS, for example, nearly all glomeruli have sclerotic lesions on three-dimensional morphometric analysis, but light microscopic examination reveals only a limited number of glomeruli with segmental sclerotic lesions. Since the average volume of a sclerotic lesion in FSGS is approximately 12.5 percent of the total glomerular volume, evaluation of kidney biopsies by conventional single sections largely underestimates the number of sclerotic glomeruli [7]. Thus, precise quantification of sclerotic glomeruli requires three-dimensional morphometric analysis of entire glomeruli and the examination of sufficient glomeruli to ensure that the biopsy specimen is representative of glomeruli in the whole kidney. Kidney biopsies with few glomeruli (ie, fewer than 15) cannot confidently exclude the diagnosis of FSGS, and, due to sampling error, some cases will be misclassified as minimal change disease.

The lesion of FSGS can be classified into primary, secondary, and genetic forms. Primary FSGS, like minimal change disease, arises as a consequence of multiple pathways causing injury to the podocyte. Secondary FSGS generally occurs as an adaptive phenomenon that results from a reduction in nephron mass, a scar from a healing inflammatory lesion, or direct toxicity from drugs or viral infections. FSGS can also be caused by a number of genetic mutations in genes that code for proteins expressed in podocytes and at the slit diaphragm. The presence of an FSGS lesion in a renal biopsy does not itself establish a diagnosis but should initiate an evaluation to identify a specific etiology, since distinguishing between the different forms of FSGS has important implications for treatment and prognosis.

The lesion of FSGS must also be distinguished from the lesion of focal global glomerulosclerosis (FGGS), which is frequently a manifestation of normal aging and can be superimposed on a lesion of FSGS, particularly in older patients [8].

The epidemiology, classification, and pathogenesis of FSGS will be reviewed in this topic. The treatment of both primary FSGS and recurrent disease in the renal transplant are discussed separately. (See "Treatment of primary focal segmental glomerulosclerosis" and "Focal segmental glomerulosclerosis in the transplanted kidney".)

                                          

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Literature review current through: May 2017. | This topic last updated: Jun 16, 2017.
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