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. 2016 Jan 7;11(1):70-80.
doi: 10.2215/CJN.04230415. Epub 2015 Dec 18.

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

Menno Pruijm  1 , Belen Ponte  1 , Daniel Ackermann  1 , Fred Paccaud  1 , Idris Guessous  1 , Georg Ehret  1 , Antoinette Pechère-Bertschi  1 , Bruno Vogt  1 , Markus G Mohaupt  1 , Pierre-Yves Martin  1 , Sonia C Youhanna  1 , Nadine Nägele  1 , Peter Vollenweider  1 , Gérard Waeber  1 , Michel Burnier  1 , Olivier Devuyst  2 , Murielle Bochud  2
Affiliations

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

Menno Pruijm et al. Clin J Am Soc Nephrol. .

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 age±SD, 45±17 years) who underwent renal ultrasonography and performed a 24-hour urine collection. The Cohorte Lausannoise study included 5706 adults (mean age, 53±11 years) with fresh spot morning urine samples. We calculated eGFRs using the CKD-Epidemiology 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.

Keywords: electrolytes; glomerular filtration rate; humans; hypertension, renal; osmolality; potassium; renal insufficiency, chronic; renal tubular cells; sodium; uromodulin.

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Figures

Figure 1.
Figure 1.
Distribution of uromodulin according to sex. (A) Swiss Kidney Project on Genes in Hypertension (SKIPOGH). (B) Cohorte Lausannoise (CoLaus).
Figure 2.
Figure 2.
Scatterplots showing the association of the eGFR with urinary uromodulin. (A) Swiss Kidney Project on Genes in Hypertension (SKIPOGH): positive association between eGFR and 24-hour urinary uromodulin excretion for eGFR below but not above 90 ml/min per 1.73m2. (B) Cohorte Lausannoise (CoLaus): positive association between eGFR and uromodulin concentration for eGFR below but not above 90 ml/min per 1.73m2. The eGFR was calculated with the CKD-Epidemiology Collaboration (CKD-EPI) equation. The vertical line represents the cut off eGFR 90 ml/min per 1.73m2. When a spline term was used, a significant difference in slope between the two segments for both the SKIPOGH and CoLaus studies was found (P<0.001).
Figure 3.
Figure 3.
Age- and sex-adjusted associations of square rooted 24-hour uromodulin excretion with proxies of functional renal mass. (A) 24-hour creatinine clearance; (B) kidney length; (C) kidney volume; and (D) urinary osmolar excretion.
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Comment in

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