Diffuse foot process effacement in IgA nephropathy: MCD-Like versus non-MCD-like phenotypes and response to...

Diffuse foot process effacement (FPE) is an ultrastructural associated with severe proteinuria and adverse renal outcomes in IgA nephropathy (IgAN). Among IgAN patients with diffuse FPE, light-microscopic patterns delineate two distinct clinicopathologic entities-MCD-like (MCD-IgAN) and non-MCD-like IgAN (DFPE-IgAN), yet their clinical features, histologic characteristics and prognosis remain incompletely characterized.

In this multicenter retrospective cohort study, 1 528 biopsy-proven primary IgAN cases (2021-2024 2023) were screened, and 358 patients with diffuse FPE (≥ 80% of glomerular capillary loops) were identified and classified as MCD-IgAN (n = 112) or DFPE-IgAN (n = 246) using predefined histologic criteria. Two-stage propensity score matching balanced baseline characteristics between phenotypes and, within each phenotype, between initial strategies: corticosteroid monotherapy (CS) versus corticosteroids plus additional immunosuppressants (CS + IS). Primary outcomes were time from treatment initiation to first complete remission (CR) and overall remission (OR) of proteinuria within 12 months, adverse events were recorded.

After matching, patients with MCD-IgAN exhibited more nephrotic features but better preserved eGFR, whereas those with DFPE-IgAN had heavier IgA/C3 deposition and higher Oxford activity and chronicity scores. Over 12 months of follow-up, complete and overall remission were achieved more frequently in MCD-IgAN than in DFPE-IgAN (72% vs 28% and 96% vs 87%, respectively), with parallel advantages in eGFR, serum albumin and residual proteinuria. In DFPE-IgAN, CS + IS was associated with approximately two-fold higher cumulative probability of CR and OR compared with CS alone, whereas in MCD-IgAN, adding other immunosuppressants to CS conferred no clear additional benefit. Adverse events were infrequent and similar across groups-treatment strata, and subgroup analyses suggested a greater benefit of CS + IS in DFPE-IgAN with subnephrotic proteinuria or tubulitis.

MCD-IgAN behaves as a steroid-sensitive podocytopathy in which CS monotherapy is generally sufficient, whereas DFPE-IgAN, embedded in a heavier immune complex and chronic lesion burden, appears to benefit from early combination immunosuppression.