Systematic Review of IgA Nephropathy Coexisting With Alport Syndrome

In recent years, IgA nephropathy (IgAN) coexisting with Alport syndrome (AS) has been increasingly reported. However, the clinicopathological and molecular features, treatment, and prognosis of this entity have not been fully elucidated.

We first retrospectively analyzed pediatric patients with IgAN coexisting with AS (IgAN-AS) admitted to our center, and performed galactose-deficient IgA1 (Gd-IgA1) immunostaining on renal biopsy specimens. We then systematically searched PubMed, Scopus, Web of Science, Wanfang Data, and the China National Knowledge Infrastructure for publications reporting on patients with IgAN-AS.

A total of 81 patients from 72 families were included. Microscopic hematuria was a universal finding. Nephrotic-range proteinuria was significantly more frequent in children than in adults (73.7% vs. 8.8%). Pathological findings confirmed the dual diagnosis, with mesangial IgA-dominant deposits and significant glomerular basement membrane abnormalities, including thinning (69.5%, 41/59) and typical AS-related changes (28.8%, 17/59). Genetic analysis identified 66 distinct pathogenic variants across COL4A3/A4/A5 genes in 77 patients. Immunologic findings were heterogeneous, with inconsistent Gd-IgA1 deposition or circulating levels. Among patients evaluated for treatment response, complete remission (CR) and partial remission (PR) were observed in 7.1% (1/14) and 64.3% (9/14), respectively, during immunosuppressive treatment. In 27 patients with follow-up data, the median age at last visit was 16.0 (10.0-24.0) years, and 11 (40.7%) reached the kidney end point.

IgAN-AS appears to be a heterogeneous condition with potentially unfavorable kidney outcomes. Some patients exhibited both immune and structural injury, suggesting that biomarkers with high sensitivity and specificity for IgAN may aid in disease stratification.