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

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.

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The present article examines the final part of the regnal formulas in the Book of Kings, i.e. the epilogue formulary. Most reports of the kings of Israel and Judah end with an epilogue containing formulaic statements about the death of the king and his succession. Typically, the epilogue formula is introduced by the phrase (source reference): 'Now the rest of the acts of PN1, are they not written in the Book of the Chronicles of the Kings of Judah (of the Chronicles of the Kings of Israel)?' and consists of three elements: 1. Dynastic notice ('PN1 slept with his fathers'); 2. Statement of burial; 3. Statement of succession. Sometimes one, two or all three of these elements are altered or lacking. The epilogue formulae of the Judean kings are more consistent than those of the Israelite kings; the latter often lacks a burial notice. Interestingly, the accounts of the deported (arrested) kings (Hoshea: 2 Kgs 17:6, Jehoahaz: 23:34, Zedekiah:25:7 and Jehoiachin: 25:27-30) do not contain an epilogue at all, nor the accounts of the reigns of Ahaziah and Athaliah which mark an episode of disruption in the history of the Davidic kingdom. For all these kings even the phrase 'Now the rest of the acts of PN1, are they not written in the Book of the Chronicles of... ?' is lacking. The absence of an epilogue in these cases is probably due to the fact that the king's succession (cf. element 3) is considered a constitutive and indispensable component of the epilogue. In the first instance, the approach of this study is descriptive and philological; it aims to contribute to the understanding of the notices. Secondly, the study addresses the question how the irregularities and variations within the formulae are to be explained. In particular, the study will pay attention to differences between the epilogue formulae concerning the kings of Israel and those concerning the Judean kings. At the end, questions concerning the epilogues formula's provenance and its formation date and concerning further redactional developments will be considered.