Clinicopathological and prognostic study of idiopathic membranous nephropathy with tip or non-tip variant focal segmental glomerulosclerosis: a single-center cohort study

Idiopathic membranous nephropathy (IMN) complicated with focal segmental glomerulosclerosis (FSGS) is not rare, but the impact of variant pathological manifestations of FSGS (tip variant vs non-tip variant) on the clinical and prognosis of IMN patients remains to be further studied. A total of 536 eligible IMN patients were enrolled in the study and divided into three groups based on the variant histopathological presence of FSGS: 387 patients without FSGS (IMN group), 67 patients with tip variant FSGS (tpFSGS group), and 82 patients with non-tip variant FSGS (ntpFSGS group). IMN patients with FSGS had significantly lower serum albumin (IMN vs. tpFSGS vs. ntpFSGS, 21.20 [17.15, 25.25] vs. 18.60 [16.05, 22.10] vs. 17.90 [15.40, 22.03], <i>p</i> < 0.001) and higher 24-hour proteinuria (5.65 [3.60, 7.69] vs. 6.11 [3.97, 8.46] vs. 6.98 [4.77, 8.49], <i>p =</i> 0.003). Additionally, the ntpFSGS group exhibited more advanced histopathological manifestations (pathological stage, <i>p <</i> 0.05). Otherwise, a lower complete remission rate was observed in the ntpFSGS group. Furthermore, multivariate Cox regression analysis demonstrated significantly lower remission in tpFSGS [HR = 0.69, <i>p =</i> 0.029] and ntpFSGS [HR = 0.66, <i>p =</i> 0.014] groups. Adjusted by the immunosuppressive therapy, a worse prognosis was observed in the ntpFSGS group [KM curve, log-rank, <i>p <</i> 0.05], but no significant difference in the IMN group and the tpFSGS group [KM curve, log-rank, <i>p =</i> 0.74]. Our cohort study suggests that idiopathic membranous nephropathy patients with secondary variant FSGS indicated different clinical significance.