INTRODUCTION AND AIMS: High nephron endowment decreases the risk of developing chronic kidney disease (CKD). Actual methods to assess nephron mass are indirect or invasive. The level of uromodulin in urine is a candidate to estimate nephron mass, since the protein is exclusively synthesized by the thick ascending limb of the loop of Henle and essentially released into the urine. We hypothesized that if urinary uromodulin is a proxy of nephron mass, it should be associated with all known predictors of biopsy-assessed nephron-mass in the general population, and as proof of principle, its excretion should halve after kidney donation.
METHODS: We studied two different populations to verify our hypothesis. Firstly, 24h uromodulin urinary excretion (24h UEE) was measured in 1032 participants from a multi-center family-based population study (Swiss Kidney Project in Genes on Hypertension: SKIPOGH). The associations between all known predictors of nephron mass (birth weight, age, female sex, uric acid and body height) and 24h UUE were compared using multiple linear regression analysis. Secondly, we compared pre and post-donation urine uromodulin-to-creatinine ratio in 35 living kidney donors (LKD).
RESULTS: In SKIPOGH, data were available for 498 men and 540 women with a mean age of 47.4±17.5 yr and mean eGFR 96±18 mL/min/1.73m2. Mean 24h UUE levels were 43.1±22.5mg. In fully adjusted mixed regression analysis, age, female sex and uric acid were negatively associated with 24h UUE (all: P<0.01), while birth weight correlated positively (p=0.02). In the LKD group, there were 25 women, mean age 52.8±9.8 years and eGFR 93±18 ml/min /1.73 m2. Urine uromodulin-to-creatinine ratio decreased form 32±23 one day before to 14.6±9.4 mg/g three days after kidney donation (*paired t-test, P <0.001). At one year urine uromodulin-to-creatinine ratio was 21.6±2.9 mg/g (**P =0.03 vs baseline, Figure 1).
CONCLUSIONS: Urinary excretion of uromodulin correlates with all known predictors of nephron mass, including birth weight, in the healthy population and living kidney donors, suggesting that measuring uromodulin levels is a useful surrogate marker for the risk of CKD.
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