The outcomes of primary membranous nephropathy treated with cyclophosphamide are superior to calcineurin inhibitors in patients with renal vascular lesions: A multi-center retrospective cohort study.

BACKGROUND

The difference of the outcomes of primary membranous nephropathy (PMN) with renal vascular lesions treated with cyclophosphamide (CTX) compared to calcineurin inhibitors (CNIs) remains undetermined.

METHODS

872 patients with PMN finished CNIs or CTX-based therapy between 2003 and 2018 from three centers in China were followed up at most to 120 months. A propensity-score matched (PSM) method was used to analyze the difference of outcomes between those receiving CTX- and CNIs-based therapy. Primary endpoints were defined as a composite of a 50 % decline in eGFR, progression to end-stage renal disease, or all-cause mortality. Dual immunohistochemical staining of CD31 and α-smooth muscle action were applied to detect pathological vascular lesions.

RESULTS

A total of 761 patients were included in the study. After PSM, no significant difference of proteinuria complete remission rate was found between 126 paired patients (HR, 1.32; 95 % CI, 0.95 to 1.83; p = 0.10). However, CTX-based therapy was associated with significantly better renal survival compared to CNI-based therapy. (median, 156 months vs. 108 months; hazard ratio [HR], 0.31; 95 % confidence interval [CI]0.16 to 0.61; p = 0.001). Subgroup analyses showed that CTX-based therapy was superior to CNIs-based therapy among patients with hyalinosis damage (HR, 0.16; 95 % CI 0.05 to 0.50; p = 0.002;), arteriosclerosis (HR, 0.31; 95 % CI 0.15 to 0.62; p = 0.001), or hypertension (HR, 0.21; 95 % CI 0.08 to 0.53; p = 0.001).

CONCLUSIONS

CTX-based therapy exhibited a significantly improved composite endpoint of PMN patients with vascular lesions compared to CNIs-based regime.