Circulating Antinephrin Antibodies in Adult Chinese Patients With IgAN and Nephrotic-Range Proteinuria

Antinephrin autoantibodies are detectable in podocytopathies such as minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS); however, their prevalence and clinical relevance in IgA nephropathy (IgAN) with nephrotic-range proteinuria (NRP) and nephrotic syndrome (NS) are unclear.

This single-center retrospective study enrolled 234 adults with biopsy-proven IgAN and NRP (≥ 3.5 g/d) from 2003 to 2020. Plasma antinephrin IgG and IgM were measured using enzyme-linked immunosorbent assay. Prespecified subgroups included NS (n = 105) and concurrent MCD (n = 17). Clinicopathologic features, treatment, and outcomes were compared by serostatus, with MCD and FSGS cohorts as references.

Overall antinephrin seropositivity was 8% (IgG: 6%, IgM: 2%). The seropositivity rate was 35% in patients with MCD versus 6% in those without. In patients with NS, seropositivity was 14%; rates were 35% with and 10% without MCD. Seropositive patients had heavier proteinuria (median: 8.1 vs. 4.9 g/d), lower serum albumin (21.9 ± 6.5 vs. 31.0 ± 7.2 g/l), fewer urinary red blood cells (RBCs), and similar estimated glomerular filtration rate (eGFR). Their biopsies showed milder chronic lesions (more M0/S0/T0). Seropositive patients more often received glucocorticoids and achieved higher complete remission (CR) rates (67% vs. 30% overall; 80% vs. 43% within NS) and fewer composite renal endpoints (0% vs. 28%). Multivariable analysis showed that antinephrin positivity was associated with a trend toward higher CR rates.

Circulating antinephrin antibodies mark a podocytopathy-like phenotype in IgAN with MCD (MCD-IgAN) and define a distinct NS phenotype in patients with IgAN without overt podocytopathy. Targeted serologic testing could facilitate subgroup identification and guide tailored management.