Serum uromodulin concentrations correlate with glomerular filtration rate in patients with chronic kidney disease

Abstract

INTROduCTION Urinary uromodulin excretion has been associated with kidney diseases. However, serum uromodulin concentrations have not been extensively studied in patients with chronic kidney disease (CKD), and the results of published studies are inconsistent.ObjECTIvEs The aims of the study were to evaluate serum uromodulin concentrations in patients with CKD and to assess the utility of serum uromodulin measurements for diagnosing CKD stages.PATIENTs ANd mEThOds This observational study included 170 patients with CKD stages 1 to 5, not treated by renal replacement therapy, and 30 healthy individuals. The serum levels of creatinine, cystatin C, and uromodulin were measured, and estimated glomerular filtration rate (eGFR) was calculated according to the 2012 CKD Epidemiology Collaboration cystatin -creatinine equation.REsuLTs Among patients with CKD, serum uromodulin concentrations were significantly lower than in controls, and were strongly negatively correlated with renal retention markers (ie, serum creatinine and cystatin C) and strongly positively correlated with eGFR. An inverse, hyperbolic relationship between serum creatinine and uromodulin levels was analogous to the well -known association between serum creatinine concentrations and eGFR. A receiver -operating characteristic curve analysis showed a high diagnostic accuracy of the measurement of serum uromodulin concentrations in the assessment of CKD stages.CONCLusIONs Serum uromodulin concentrations are closely correlated with eGFR, which is the recommended measure of renal function. As uromodulin is produced exclusively by renal tubular cells, the assessment of uromodulin levels in patients with CKD may be an alternative method for evaluating the number of functioning nephrons.

Serum uromodulin is a novel predictive marker of renal function in the Japanese population

“…To our knowledge, this is the first study of uromodulin concentrations undertaken in Japanese patients with chronic kidney disease. The results of this study are consistent with previous reports of a strong correlation between the serum uromodulin concentration and kidney function [3][4][5] [18]. Although the authors analyzed serum samples using a custom-made ELISA, those concentrations were extremely low compared with others [3][4][5]17].…”

“…Given that no standard reference protein for uromodulin measurement has been established, we cannot directly compare our data with those in 10 the past reports. Nonetheless, similar results have been reported using other ELISA kits or method [3][4][5]17], and suggest that there is a certain value in the usefulness of uromodulin measurement.…”

“…It is possible that they were not fully evaluated. However, Steubl et al [3] and Fedak et al [4] in 2016 and Scherberich et al [5] in 2018 reported a good correlation between the plasma/serum uromodulin concentration and kidney function using commercially available ELISA kits manufactured by BioVendor (Brno, Czech Republic) and Euroimmun AG (Lübeck, Germany).…”

“…Next, the uromodulin concentration was found to vary between serum and plasma samples. Previous studies have evaluated serum [4,5] and plasma samples [3] and both have shown a good correlation between blood uromodulin and GFR. In this study, we only analyzed serum samples.…”

“…A small amount of uromodulin has recently been detected in blood and its concentration correlates well with estimated glomerular filtration rate (eGFR) values calculated from creatinine and cystatin C [3][4][5]. In the past decade, several genome-wide association studies have identified common variants in the promoter region of the UMOD gene as risk factors for progression to CKD and hypertension [6][7][8][9].…”