Patients with gout differ from healthy subjects in renal response to changes in serum uric acid.
OBJECTIVE
Our objectives were to determine whether a change in serum uric acid (sUA) resulted in a corresponding change in the fractional excretion of uric acid (FEUA) and whether the renal response was different in patients with gout versus healthy subjects.


METHODS
FEUA was calculated from previously published studies and four new phase I studies in healthy subjects and/or patients with gout before and after treatment to lower or raise sUA. Treatments included xanthine oxidase inhibitors to lower sUA as well as infusion of uric acid and provision of a high-purine diet to raise sUA. Plots were created of FEUA versus sUA before and after treatment. For the phase I studies, percent change in FEUA per mg/dL change in sUA was calculated separately for healthy subjects and patients with gout, and compared using Student's t test.


RESULTS
Analysis of previously published data and the new phase I clinical data indicates that changing sUA by a non-renal mechanism leads to a change in FEUA. The magnitude of change is greater in subjects with higher baseline FEUA versus patients with gout. Healthy subjects excrete more urate than do patients with gout at physiological urate-filtered load; this difference disappears when the urate-filtered load is decreased to ∼5000mg/24hours.


CONCLUSIONS
These observations are consistent with a less saturated urate reabsorption system in patients with gout versus healthy subjects, resulting in elevated retention of uric acid. Further investigation could lead to the discovery of mechanisms responsible for the etiology of hyperuricemia/gout.
Biology Department, Ardea Biosciences Inc., 92121 San Diego, CA, USA. Electronic address: liusha168@gmail.com.
Sha
S
Liu
Hospital Universitario Cruces, Biocruces Health Research Institute, and Basque Country University, Vizcaya, Spain.
Fernando
F
Perez-Ruiz
Biology Department, Ardea Biosciences Inc., 92121 San Diego, CA, USA.
Jeffrey N
JN
Miner
D000328:Adult; D000368:Aged; D005260:Female; D006073:Gout / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006074:Gout Suppressants / Q000627:therapeutic use; D064368:Healthy Volunteers; D006801:Humans; D033461:Hyperuricemia / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D014527:Uric Acid / Q000097:blood* / Q000378:metabolism / Q000652:urine; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors; D055815:Young Adult
D006074:Gout Suppressants; D014527:Uric Acid; D014969:Xanthine Oxidase
Fractional excretion of uric acid; Gout; Serum uric acid