Background Evaluating urinary uric acid excretion (UUE) has important clinical utilities ; however, 24-h urine collection is usually required and this is both cumbersome and prone to sampling errors. Several simplified methods of evaluating UUE have been proposed, such as the urine uric acid (UA) to creatinine concentration ratio (Uu/Ucr), but correlations between these and the 24-h measured UUE (mUUE) have not been ideal [1-3].
Objectives To develop an equation that can reliably estimate UUE, providing a better tool to identify uric acid overexcretors.
Methods Based on the fact that the ratio of urinary excretion of UA to creatinine equals to the Uu/Ucr ratio, and using the Cockcroft-Gault equation to estimate creatinine clearance , the following equation can be derived to calculate estimated UUE (eUUE):
eUUE (mg/24 hr) = (140-age) x body weight (kg) x [0.85 if female] x Uu/Ucr x 0.2
To validate the equation, we analyzed the data from 6 different phase I studies consisting of 194 healthy volunteers and 38 gout patients. The urine samples were collected in the clinic during the 24-h period prior to the administration of experimental drugs, and the samples were collected in 3 time blocks: 0-6, 6-12, and 12-24 h.
Results The Uu/Ucr ratio and the eUUE using our equation were calculated on urine samples from all 3 time blocks, and they were correlated to the 24-h mUUE. The graph/table show the results for calculations based on the urine samples from the 12- to 24-h period. The Pearson's correlation coefficients for the eUUE vs the 24-h mUUE were all markedly higher compared with those for the Uu/Ucr ratio vs the 24-h mUUE, with associated 95% CI that were either non-overlapping for healthy subjects and the combined sample, or barely overlapping in the sample of gouty subjects where the sample size was small. Similar advantages for the eUUE over the Uu/Ucr ratio were also observed when the calculations of eUUE and the Uu/Ucr ratio were based on the 0-6 and 6-12 h urine samples (data not shown).
Conclusions This novel equation for estimating 24-h UUE includes age, body weight, and gender, which are factors correlated with muscle mass , therefore providing corrections for differences in urinary creatinine excretions among individuals. As a result, the 24-h eUUE correlates better with the 24-h mUUE than the Uu/Ucr ratio does. By using this equation, treating physicians could relatively easily assess whether a patient is an overexcretor of uric acid without the need for a 24-h urine collection. This allows for better management of gout patients and subjects with hyperuricemia. Additional clinical studies are underway to further validate the equation.
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Acknowledgements Research sponsored by Ardea Biosciences/AstraZeneca.
Disclosure of Interest S. Liu Employee of: Ardea Biosciences, Inc, D. Hyndman Employee of: Ardea Biosciences, Inc, M. Cravets Employee of: Ardea Biosciences, Inc, J. Miner Employee of: Ardea Biosciences, Inc
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