Fig 2 from Fogo et al AJKD, © National Kidney Foundation.

The term “focal” is an integral part of the nomenclature of focal segmental glomerulosclerosis (FSGS). Therefore, since not all glomeruli are affected, sampling error is an inherent problem in the pathologic diagnosis of FSGS.  Estimating the probability of a false negative biopsy is a statistical problem that can be expressed as a probability.  For example, one study suggests that >25 glomeruli need to be present in a biopsy sample if one is to confidently detect a lesion that affects 10% of the glomeruli in a kidney.  Of course the number of glomeruli needed would be larger if a smaller proportion of the glomeruli were affected (see Madaio). Another confounding factor is that the segmental lesion is not randomly distributed throughout the kidney.  In early stages of the disease, FSGS tends to selectively affect glomeruli at the corticomedullary junction, which is not present in all biopsies sent for histologic examination.

The effect of sampling error on classification of FSGS subtype is potentially even larger, but has not been specifically addressed in the literature.  The extent of this error would depend on the actual lesions seen.  For example, a single glomerulus with a collapsing lesion would be diagnostic, whereas lesions classified as NOS could have infrequent tip lesions or perihilar sclerosis.  This would result in misclassification of FSGS subtype.

In day-to-day practice, clinical correlation is the best strategy to minimize the effect of biopsy sampling error.  A biopsy from an 8-year-old child with only 8 normal looking glomeruli is best interpreted as minimal change disease.  On the other hand, if a biopsy demonstrates arteriosclerosis and interstitial fibrosis that is not readily explained by age or hypertension, and the patient is not responding to steroids, even a biopsy with 30 normal looking glomeruli is probably FSGS despite not revealing the diagnostic lesion.

Dr. Parmjeet Randhawa
AJKDblog Contributor and AJKD Associate Editor

To view the related installments on FSGS (freely available), please visit the Atlas of Renal Pathology II at AJKD.org.