The complex of immunoglobulin A and uromodulin as a diagnostic marker for immunoglobulin A nephropathy

BACKGROUND: The only tool to diagnose immunoglobulinn A nephropathy (IgAN) is renal biopsy which requires hospitalization; moreover, renal biopsy has a risk of critical bleeding. Therefore, a non-invasive method for accurate diagnosis of IgAN is desirable and a must-to-have tool for the clinics. For this purpose, we evaluated the diagnostic value of the IgA–uromodulin complex in the urine of patients with IgAN for its feasibility and adequacy. METHOD: We determined the IgA–uromodulin complex as a candidate for a diagnostic marker of IgAN by immunoprecipitation, liquid chromatography−mass spectrometry (LC–MS) and Western blot analysis. The enzyme-linked immunosorbent assay (ELISA) for the IgA–uromodulin complex was developed and applied to urine samples obtained from various kidney disease patients. RESULT: One hundred and three of 126 urine samples (81.7%) from IgAN patients were positive for the IgA–uromodulin complex, while only 25 out of 94 urine samples (26.6%) in other kidney disease patients were positive. Sensitivity was 81.7%, specificity was 73.4%, and diagnosis efficiency was 78.2%. The complex was negative in eight urine samples obtained from patients with Alport syndrome which is almost impossible to discriminate from IgAN by routine urinalysis. CONCLUSION: Detection of the urinary IgA–uromodulin complex by ELISA is a useful non-invasive method to diagnose IgAN.