Targeting Uric Acid and the Inhibition of Progression to End-Stage Renal Disease—A Propensity Score Analysis

Abstract

BackgroundThe 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.MethodsA 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.ResultsAfter 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.ConclusionsThree 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.

Uric Acid in the Follow-Up Determines 30% Decline in Estimated GFR Over 2 Years: a Propensity Score Analysis

“…To overcome these limitations we recently performed the propensity score analysis to mimic the randomized controlled trial (RCT), examining the causal effect of SUA on the incidence of ESRD [7]. The results revealed that lower levels of SUA may slow the progression to ESRD and that the target threshold appears to be below 6.5 mg/dL.…”

Hematuria is a risk factor towards end-stage renal disease - A propensity score analysis

“…The method also enables one to investigate the causal effect which cannot be otherwise executed due to serious issues such as ethical problems and inability of intervention. Propensity score analysis by use of time-averaged values of test parameters has a great advantage to freely scrutinize the threshold of target values as demonstrated here and previously [9].…”

“…The retrospective CKD cohort already reported (n = 803) was used [9][10][11][12], and in the current study the propensity score analysis was used in such a way as used in the previously published articles [9,12]. Inclusion criteria consisted of CKD stage 3 to 4, age 20 to 84 years and follow-up period ≥ 1 year.…”

“…Creatinine concentration in serum and urine was measured by an enzymatic method and urinary protein concentration measured by a pyrocatechol violet-metal complex assay method. Hematuria measured at every visit was recorded until censoring or reaching estimated GFR 5 mL/min/1.73 m 2 and calculated as TA-MH by trapezoidal rule [9,12]. Estimated GFR was evaluated using the Modification of Diet in Renal Disease (MDRD) study equation for Japanese population [13].…”

“…It is no way questionable that hematuria did not show an independent risk factor by standard Cox regression analysis [9] (supplementary information).…”