Associations of Urinary Uromodulin with Clinical Characteristics and Markers of Tubular Function in the General Population

Abstract

Background and objectives Allelic variants in UMOD, the gene coding for uromodulin, are associated with rare tubulointerstitial kidney disorders and risk of CKD and hypertension in the general population. The factors associated with uromodulin excretion in the normal population remain largely unknown, and were therefore explored in this study.Design, setting, participants, & measurements Urinary uromodulin excretion was measured using a validated ELISA in two population-based cohorts that included more than 6500 individuals. The Swiss Kidney Project on Genes in Hypertension study (SKIPOGH) included 817 adults (mean age6SD, 45617 years) who underwent renal ultrasonography and performed a 24-hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age, 53611 years) with fresh spot morning urine samples. We calculated eGFRs using the CKDEpidemiology Collaboration formula and by 24-hour creatinine clearance.Results In both studies, positive associations were found between uromodulin and urinary sodium, chloride, and potassium excretion and osmolality. In SKIPOGH, 24-hour uromodulin excretion (median, 41 [interquartile range, 29-57] mg/24 h) was positively associated with kidney length and volume and with creatinine excretion and urine volume. It was negatively associated with age and diabetes. Both spot uromodulin concentration and 24-hour uromodulin excretion were linearly and positively associated (multivariate analyses) with eGFR,90 ml/min per 1.73 m 2 .Conclusion Age, creatinine excretion, diabetes, and urinary volume are independent clinical correlates of urinary uromodulin excretion. The associations of uromodulin excretion with markers of tubular functions and kidney dimensions suggest that it may reflect tubule activity in the general population.

Management of Tamm–Horsfall Protein for Reliable Urinary Analytics

“…Notably, THP level in urine appears to be a valuable indicator of functional kidney mass and the respective UMOD gene is associated with chronic kidney disease and, especially, diabetic kidney damage by mechanisms to be fully elucidated.…”

Urinary Uromodulin/Creatinine Ratio as a Potential Clinical Biomarker for Chronic Kidney Disease Patients with Gout: A Pilot Study

“…Two recent large-scale observational studies show that the uUMOD is an indicator of tubular health and could be used to identify individuals at higher risk of progressive kidney disease and mortality [26, 27]. Urate crystal nephropathies are common in patients with gout, with frequencies of 79–99% based on autopsy studies [10].…”

Validation of Surrogates of Urine Osmolality in Population Studies

“…Independent of the well-known contribution of antidiuretic hormone to various forms of water disorders, recent epidemiological studies have shown significant associations between indices of the AVP/hydration system and the incidence or progression of diseases including chronic kidney disease (CKD), autosomal dominant polycystic kidney disease, diabetic nephropathy, obesity, metabolic syndrome, and insulin resistance [4,10,11,12,13,14,15,16,17,18,19,20,21]. A number of experimental studies have demonstrated the adverse effects of AVP or a low level of hydration in animal models of these disorders [10,22,23,24,25,26].…”