Degree of foot process effacement in patients with genetic focal segmental glomerulosclerosis: a single-center analysis and review of the literature

Abstract

Determining the cause of focal segmental glomerulosclerosis (FSGS) has crucial implications for evaluating the risk of posttransplant recurrence. The degree of foot process effacement (FPE) on electron micrographs (EM) of native kidney biopsies can reportedly differentiate primary FSGS from secondary FSGS. However, no systematic evaluation of FPE in genetic FSGS has been performed. In this study, percentage of FPE and foot process width (FPW) in native kidney biopsies were analyzed in eight genetic FSGS patients and nine primary FSGS patients. All genetic FSGS patients showed segmental FPE up to 38% and FPW below 2000 nm, while all primary FSGS patients showed diffuse FPE above 88% and FPW above 3000 nm. We reviewed the literature which described the degree of FPE in genetic FSGS patients and identified 38 patients with a description of the degree of FPE. The degree of FPE in patients with mutations in the genes encoding proteins associated with slit diaphragm and cytoskeletal proteins was varied, while almost all patients with mutations in other FSGS genes showed segmental FPE. In conclusion, the present study suggests that the degree of FPE in native kidney biopsies may be useful for differentiating some genetic FSGS patients from primary FSGS patients.

Figure 1

The degree of FPE (%FPE), shown as the percentage of capillary wall surface that was covered by podocyte foot processes uninterrupted by filtration slits. All patients with genetic FSGS (eight patients) showed segmental FPE ranging from 0 to 38%, while all patients with primary FSGS (nine patients) showed diffuse FPE ranging from 88 to 100%. Percentage of FPE was significantly higher in primary FSGS patients than in genetic FSGS patients (p = 0.0003). Percentage of FPE of maladaptive FSGS (three patients) ranged from 0 to 38%.

Figure 2

Foot process width of patients with primary, genetic and maladaptive FSGS patients. Median FPW was 4504 nm (range, 3534–5722 nm), 1719 nm (range, 647–1960 nm), and 1203 nm (range, 1047–1402 nm) in primary, genetic, and maladaptive FSGS patients, respectively. FPW was significantly larger in primary FSGS patients than in genetic FSGS patients (p = 0.0006).

Figure 3

Representative electron micrographs of a patient with (A) primary FSGS and one with (B) genetic FSGS. (A) The patient (No. 13) with primary FSGS showed 100% FPE. All capillary loops were fully covered by FPE. (B) The patient (No. 1) with genetic FSGS (NUP107 mutation) showed segmental (0%) FPE with no capillary loops fully covered by FPE. The thin white arrows indicate preserved foot processes, and the thick white arrows point to effaced foot processes. Lower panels show images with a higher magnification. Original magnification: 3000× in (A) and (B). The scale bar denotes 10 μm.

Figure 4

Study population in the present study. FSGS, focal segmental glomerulosclerosis; KT, kidney transplantation; EM, electron microscopy.