ASSOCIATION OF URINARY LEVELS OF UROMODULIN AND UMOD RS1333226 WITH SERUM URIC ACID

Abstract

Objective: It was reported that low uromodulin is associated with increased uric acid reabsorption in proximal tubule but also tubular uric acid affect uromodulin excretion. On the other hand, UMOD mutations have been identified in patients with familial juvenile hyperuricemia nephropathy and similar diseases characterized by increased levels of serum uric acid (SUA). Our objective was to find out whether urine uromodulin levels depending on UMOD polymorphism rs1333226 are associated with differences in SUA concentrations. Design and method: A group of 350 untreated subjects (men 45,9 %, mean age 40 years), subgroup of larger cohort from the ENAH study (random sample of rural population) were enrolled into the study. Subjects were divided into 3 groups based on the 33th and 77th percentiles of SUA (Median SUA levels were 210, 299, and 410 mmol/L, respectively). Urinary uromodulin levels were measured by Enzyme Linked Immunosorbent Assay (ELISA) and genotyping for UMOD rs1333226 by RT-PCR with the fluorescence-based TaqMan system. Only samples with urine creatinine in normal ranges were included in analyses. Uromodulin was indexed to urine creatinine. Results: Negative correlation between urine uromodulin and serum uric acid levels was observed (44, 36, and 30 mmol/g in the 1st, 2nd, and 3rd SUA groups (p = 0.01). There were no significant differences among GFR CKD-EPI values among groups. There was a positive correlation between BMI and SUA as well as between waist circumference and SUA. We found no difference in rs1333226 allele frequencies across 3 groups; allele A 82% and allele G 18%. Conclusions: Our findings showed a negative correlation between urinary uromodulin and SUA therefore being in agreement with previous studies reporting that uromodulin affects uric acid kidney excretion. On the other hand we did not find difference in rs1333226 allele frequencies across SUA groups which could mean that this UMOD SNP is not associated with UA reabsorption. However, this should be proven on larger number of patients.