Recent genome-wide association studies have identified the uromodulin locus (UMOD), encoding the most common protein in human urine to be associated with hypertension and also with chronic kidney disease (CKD).
Follow-up studies stimulated by findings from genome-wide association studies of kidney disease are already yielding promising results, such as the identification of an association between urinary uromodulin levels and incident CKD.
In order to investigate the potential involvement of uromodulin in chronic kidney disease (CKD), we quantified uromodulin in paired urine and serum from 14 healthy volunteers and 77 CKD patients.
From animal experiments and human studies it is hypothesized that uromodulin entering the renal interstitium either by basolateral secretion or urinary back-leakage in damaged tubuli interacts with and stimulates cells of the immune system and thereby causes inflammation and progression of chronic kidney disease.
We identified significant SNP associations (P < 5 × 10(-8)) with CKD at the UMOD locus, with eGFRcrea at UMOD, SHROOM3 and GATM-SPATA5L1, and with eGFRcys at CST and STC1.