Patients with CKD with Wide Fluctuations in Plasma Uric Acid Levels Are Prone to Have Faster Decline in eGFR and High Chance of Orthopedic Admissions

Background: Plasma uric acid level is known to be associated not only with gouty attacks and urolithiasis but also with CKD progression and higher cardiovascular mortality. In some CKD patients, plasma uric acid levels are occasionally found to be widely fluctuated; the clinical significance of those fluctuations has not been extensively studied. In the era of growing numbers of elderly population, this fluctuation might be associated with unfavorable patient prognosis such as orthopedic admissions. Methods: A hospital-wide study with all the laboratory data for a period of 4 years and 2 months was conducted. Non-dialysis patients with an age 18 or more in whom the eGFR slope was calculated over 731 days or more, with a median eGFR < 60 mL/min/1.73m2, and with at least 3 uric acid measurements, were included in the study. Uric acid level fluctuations were analyzed by 3 parameters: standard deviation (SD), coefficient of variation (CV) and interquartile range (IQR). Hospital admission records were retrieved over 52 months following the above survey period of uric acid fluctuations. Results: A total of 1,103 patients met the inclusion criteria. Those with wide fluctuations in plasma uric acid (i.e., those who had the widest quartile in CV) had faster eGFR decline than patients in the narrower 3 quartiles (-2.67 +- 5.74 vs -1.01 +- 2.55 mL/min/1.73m2/yr, P<0.0001; Because a virtually identical trend was confirmed also in analyses with SD and IQR, CV will be used thereafter). Hyperuricemic patients (i.e., patients with higher-than-median plasma uric acid level) had faster eGFR decline compared with normouricemic patients (-2.61+- 6.30 vs -1.02 +- 3.31 mL/min/1.73m2/yr, P=0.0015). The eGFR decline was even faster in widely-fluctuated hyperuricemic patients compared with the rest (eGFR decline: -3.65 +- 6.30 vs -1.66 +- 4.99 mL/min/1.73m2/yr, P<0.0001). Interestingly those who had wide fluctuations in uric acid level were found to have significantly higher risk of orthopedic admissions in the following 52 months compared with those with narrow fluctuation (14.9% vs 9.1%; chi-squared test, P=0.020). Conclusion: Wide fluctuation in plasma uric acid level is associated with faster eGFR decline and risk of orthopedic admissions.