Urine Uromodulin, Kidney Tubulointerstitial Fibrosis, and Furosemide Response

Abstract

<b><i>Background:</i></b> Interstitial fibrosis and tubular atrophy (IFTA) are common findings on biopsy in chronic kidney disease (CKD) and are strongly predictive of kidney failure. IFTA is poorly correlated with estimated glomerular filtration rate (eGFR) and albuminuria, the most common measures of kidney function. Thus, IFTA is prognostically important, yet its presence and severity are invisible to the clinician except when kidney biopsies are obtained. <b><i>Objectives:</i></b> The objective of this study was to investigate (1) the cross-sectional association between urine uromodulin (uUMOD) and IFTA and (2) to determine whether uUMOD levels were associated with diuretic response after a furosemide stress test. <b><i>Methods:</i></b> We performed logistic regression to evaluate the association between uUMOD and fibrosis. We used linear regression models to assess the association of uUMOD with diuretic response. <b><i>Results:</i></b> Among 52 participants, the mean age was 42 ± 16 years, 48% were women, 23% had diabetes, and the median eGFR was 56 mL/min/1.73 m². The mean uUMOD concentration was 5.1 (8.4) μg/mL. Each halving of uUMOD was associated with 1.74 higher odds (95% CI: 1.10, 2.75) of grade 2 or 3 fibrosis. However, this association was no longer significant after adjusting for baseline eGFR and albuminuria. Each halving of uUMOD was associated with a decreased response to furosemide. This association was also no longer significant after adjusting for baseline eGFR and albuminuria. <b><i>Conclusion:</i></b> In a population of individuals with a wide range of kidney function undergoing clinically indicated kidney biopsies, we did not find an association between uUMOD and interstitial fibrosis or response to loop diuretics after adjusting for eGFR and albuminuria.