Paraneoplastic podocytopathies with nephrotic syndrome in solid cancers with C-Maf Inducing Protein expression

Abstract Background The main features of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) associated with solid cancer (paraneoplastic podocytopathy with nephrotic syndrome, PPNS) remain poorly described. Methods In this French retrospective study, we followed up patients with PPNS and compared them to a control group with idiopathic nephrotic syndrome (INS). Demographic, clinical, laboratory, and pathological data were collected for both groups. Expression of C-Maf Inducing Protein (CMIP) was studied on kidney biopsies and tumor samples from PPNS and controls (patients with INS or cancer without nephrotic syndrome). Results Twenty-one PPNS patients (mean age 68 years, 76% men, 76% MCD) were identified. Baseline biological characteristics in PPNS (median urinary protein to creatinine ratio 0.87 g/mmol, albuminemia 15 g/L, glomerular filtration rate 48 mL/min/1.73m²) and INS (0.90 g/mmol, 15.3 g/L and 60 mL/min/1.73m², respectively) patients were similar. Complete remission of nephrotic syndrome occurred less frequently in PPNS than in INS (25% vs 74%, p=0.008). CMIP was highly detected on podocytes from PPNS and INS, and in tumors from PPNS (13/13 samples, either in tumor cells and/or in lymphocytic infiltrates), but its expression was scarce in tumors not associated with nephrotic syndrome. Immunofluorescence analysis revealed that CMIP overexpression was confined to a CD4⁺ FOXP3⁻PD1⁻ T-cell subpopulation. Conclusions Initial presentation of PPNS is similar to that of INS but complete remission is less frequent. The tight association between nephrotic syndrome and CMIP expression in tumor cells suggests that CMIP might participate in this paraneoplastic syndrome.