Focal and segmental glomerulosclerosis: clinical and kidney biopsy correlations

Abstract

Background: Primary focal segmental glomerulosclerosis (FSGS) is a common glomerular disease in adults and ranks among the top causes of a primary glomerular disease causing end-stage renal disease (ESRD). Primary FSGS is, however, a diagnosis of exclusion and distinction between primary versus secondary FSGS is not always obvious, resulting in a number of patients with secondary FSGS undergoing unnecessary immunosuppressive therapy.

Methods: We reviewed the Mayo Clinic Renal Pathology Database for patients with a diagnosis of FSGS on native renal biopsy and divided the patients into nephrotic syndrome-associated (NS-associated) and non-nephrotic syndrome-associated (NNS-associated) FSGS as a first approximation followed by dividing the lesion according to the degree of foot process effacement (FPE) on electron microscopy (EM) examination.

Results: A total of 41 patients with FSGS with complete evaluation were identified. Of these, 18 were classified as having NS and 23 were classified as having NNS. Baseline characteristics (age, gender, body mass index, serum creatinine and hematuria) were not different between the groups. All of the patients with NS showed diffuse FPE ranging from 80 to 100% (mean 96%). On the other hand, of the 23 patients in the NNS group, 22 had segmental FPE and showed patchy effacement, with all cases showing 20-60% FPE (mean of 48%).

Conclusion: Adult patients presenting with NS, an FSGS lesion on LM, extensive FPE (≥80%) on EM examination and no risk factors associated with secondary FSGS are likely to have primary FSGS. Conversely, the absence of NS in a patient with segmental FPE on EM strongly suggests a secondary FSGS. Dividing FSGS into the presence or absence of NS together with the degree of FPE on EM examination is more helpful as it provides a more practical way to separate patients into cases of primary versus secondary FSGS.

Keywords: focal and segmental glomerulosclerosis; nephrotic range; nephrotic syndrome; primary; secondary.

Fig. 1.

FSGS: Each panel represents one patient biopsy. The patient shown on the top panel presented with NS, while the patient shown on the bottom panel presented with NNS. Top panel: (A) LM showing FSGS, NOS type (hematoxylin and eosin ×40); (B) EM showing widespread podocyte FPE (×3100). Bottom panel: (C) LM showing FSGS, NOS type (hematoxylin and eosin ×40); (D) EM showing relatively well-preserved podocyte foot processes (×4200). Red arrow points to the FSGS lesion on LM, black arrow points at foot processes.

Fig. 2.

Kaplan–Meier curve showing renal survival (endpoint defined as serum creatinine >5.0 mg/dL or need for dialysis or transplantation) over time in primary and secondary FSGS. Log-rank test (P = 0.8).