title: Targeting Uric Acid and the Inhibition of Progression to End-Stage Renal Disease--A Propensity Score Analysis.
abstract: BACKGROUND
  The role of uric acid (UA) in the progression of chronic kidney disease (CKD) remains controversial due to the unavoidable cause and result relationship. This study was aimed to clarify the independent impact of UA on the subsequent risk of end-stage renal disease (ESRD) by a propensity score analysis.
  
  
  METHODS
  A retrospective CKD cohort was used (n = 803). Baseline 23 covariates were subjected to a multivariate binary logistic regression with the targeted time-averaged UA of 6.0, 6.5 or 7.0 mg/dL. The participants trimmed 2.5 percentile from the extreme ends of the cohort underwent propensity score analyses consisting of matching, stratification on quintile and covariate adjustment. Covariate balances after 1:1 matching without replacement were tested for by paired analysis and standardized differences. A stratified Cox regression and a Cox regression adjusted for logit of propensity scores were examined.
  
  
  RESULTS
  After propensity score matching, the higher UA showed elevated hazard ratios (HRs) by Kaplan-Meier analysis (≥ 6.0 mg/dL, HR 4.53, 95%CI 1.79-11.43; ≥ 6.5 mg/dL, HR 3.39, 95%CI 1.55-7.42; ≥ 7.0 mg/dL, HR 2.19, 95%CI 1.28-3.75). The number needed to treat was 8 to 9 over 5 years. A stratified Cox regression likewise showed significant crude HRs (≥ 6.0 mg/dL, HR 3.63, 95%CI 1.25-10.58; ≥ 6.5 mg/dL, HR 3.46, 95%CI 1.56-7.68; ≥ 7.0 mg/dL, HR 2.05, 95%CI 1.21-3.48). Adjusted HR lost its significance at 6.0 mg/dL. The adjustment for the logit of the propensity scores showed the similar results but with worse model fittings than the stratification method. Upon further adjustment for other covariates the significance was attained at 6.5 mg/dL.
  
  
  CONCLUSIONS
  Three different methods of the propensity score analysis showed consistent results that the higher UA accelerates the progression to the subsequent ESRD. A stratified Cox regression outperforms other methods in generalizability and adjusting for residual bias. Serum UA should be targeted less than 6.5 mg/dL.
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Shunya
authors.initials: S
authors.lastname: Uchida
authors.affiliation: Department of Nephrology, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Wen Xiu
authors.initials: WX
authors.lastname: Chang
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Tatsuru
authors.initials: T
authors.lastname: Ota
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Yoshifuru
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.|Support for Community Medicine Endowed Chair, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shiraishi
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.|Support for Community Medicine Endowed Chair, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Kumagai
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Fujigaki
authors.affiliation: Human Physiology and Pathology, Faculty of Pharma Sciences, Teikyo University, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hosoyamada
authors.affiliation: Biomedical and Analytical Sciences, Faculty of Pharma Sciences, Teikyo University, Tokyo, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Kaneko
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Zhong Yang
authors.initials: ZY
authors.lastname: Shen
authors.affiliation: Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Fujimori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D011379:Prognosis; D057216:Propensity Score; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D014527:Uric Acid / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D014527:Uric Acid