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

Abstract

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.

Toward Noninvasive Diagnosis of IgA Nephropathy: A Pilot Urinary Metabolomic and Proteomic Study

“…Uromodulin, also known as Tamm-Horsfall glycoprotein, is the most abundant protein in normal urine [ 17 ]. It is produced by the thick ascending limb of the loop of Henle [ 17 ] and may serve as a unique renal regulatory glycoprotein, specifically binding several cytokines, including IL-1 and TNF.…”

“…Uromodulin, also known as Tamm-Horsfall glycoprotein, is the most abundant protein in normal urine [ 17 ]. It is produced by the thick ascending limb of the loop of Henle [ 17 ] and may serve as a unique renal regulatory glycoprotein, specifically binding several cytokines, including IL-1 and TNF. Other studies found elevated levels of a fragment of uromodulin in the urine of patients with IgAN compared to that of healthy controls and patients with other glomerulonephritides [ 19 ].…”

“…Other studies found elevated levels of a fragment of uromodulin in the urine of patients with IgAN compared to that of healthy controls and patients with other glomerulonephritides [ 19 ]. A complex of uromodulin and IgA may be a diagnostic marker of IgAN; its value may be in the diagnosis of patients with an early phase of the disease with an ongoing inflammatory activity [ 17 ]. Other investigators have found increased urinary levels of complexes composed of IgA and IgG in patients with IgAN [ 18 ] or uromodulin fragments [ 19 ].…”

Glomerular Diseases

“…Wu et al, using a form of mass spectrometry, identified a uromodulin fragment that in receiver-operating characteristic analysis showed areas under the curve of 0.998 for distinguishing patients with IgAN from healthy controls and 0.815 for distinguishing patients with IgAN from those with other glomerular diseases (40). Obara et al developed an ELISA for a urinary complex of IgA with uromodulin and found a sensitivity of 82% and specificity of 73% in differentiating IgAN from other kidney diseases (41).…”

Association of Urinary Laminin G-Like 3 and Free K Light Chains with Disease Activity and Histological Injury in IgA Nephropathy

“…In the last decade, a few noninvasive diagnostic tests for detecting IgAN and a series of prognostic biomarkers have been suggested (4)(5)(6)(7)(8)(9)(10)(11)(12). However, the ability to accurately predict individual patient-level risk at the time of diagnosis or during early followup remains limited and mainly relies on clinical and histologic features (13).…”