The effects of ursodeoxycholic acid on albuminuria in people with type 1 diabetes and diabetic kidney disease: a proof-of-concept study.

INTRODUCTION

In animal models of diabetic kidney disease (DKD), ursodeoxycholic acid (UDCA) reduces albuminuria and improves histological changes associated with DKD. The purpose of this study was to investigate the potential renoprotective role of UDCA in people with type 1 diabetes (T1D) and DKD.

METHODS

In this single-centre, double-blind, placebo-controlled crossover trial, participants with T1D and DKD with residual albuminuria (urine albumin to creatinine ratio, > 3 mg/mmol) on a maximum tolerated, stable dose of renin-angiotensin system (RAS) blockade with estimated glomerular filtration rate (eGFR) ≥ 30 ml/min were included. Participants were randomly allocated to UDCA (500 mg BID) or placebo for 24 weeks, with a 4-week washout period in between. The primary endpoint was the change in urine albumin excretion rate (UAER), measured from timed urine collections after 24 weeks of treatment with UDCA compared with placebo.

RESULTS

Thirty-one participants were included, of whom 21 were men; the median age (interquartile range [IQR]) was 54.2 (22.7-75.3) years. The baseline median (IQR) UAER was 26 (12.3-189.0) μg/min for UDCA and 32.1 (19.9-88.2) μg/min for placebo. The median (IQR) posttreatment UAER was 36.2 (14.9-174.0) μg/min for UDCA and 38.5 (17.6-194.0) μg/min for placebo, with no significant difference in UAER between treatments (p-value = 0.4).

CONCLUSION

In this first-ever human study investigating the potential renoprotective effect of UDCA treatment for 24 weeks in people with T1D and DKD, we did not observe a significant reduction in UAER. Further studies are required to evaluate the role of UDCA in DKD.

CLINICAL TRIAL REGISTRATION: https://www.clinicaltrialsregister.eu/ctr-search/trial/2015-003609-41, identifier 2015-003609-41.