Uric acid: association with rate of renal function decline and time until start of dialysis in incident pre-dialysis patients

Abstract

BackgroundIn patients with chronic kidney disease (CKD) hyperuricemia is common. Evidence that hyperuricemia might also play a causal role in vascular disease, hypertension and progression of CKD is accumulating. Therefore, we studied the association between baseline uric acid (UA) levels and the rate of decline in renal function and time until start of dialysis in pre-dialysis patients.MethodsData from the PREPARE-2 study were used. The PREPARE-2 study is an observational prospective cohort study including incident pre-dialysis patients with CKD stages IV-V in the years between 2004 and 2011. Patients were followed for a median of 14.9 months until start of dialysis, kidney transplantation, death, or censoring. Main outcomes were the change in the rate of decline in renal function (measured as estimated glomerular filtration rate (eGFR)) estimated using linear mixed models, and time until start of dialysis estimated using Cox proportional hazards models.ResultsIn this analysis 131 patients were included with a baseline UA level (mean (standard deviation (SD)) of 8.0 (1.79) mg/dl) and a mean decline in renal function of -1.61 (95% confidence interval (CI), -2.01; -1.22) ml/min/1.73 m2/year. The change in decline in GFR associated with a unit increase in UA at baseline was -0.14 (95% CI -0.61;0.33, p = 0.55) ml/min/1.73 m2/year. Adjusted for demography, comorbidities, diet, body mass index (BMI), blood pressure, lipids, proteinuria, diuretic and/or allopurinol usage the change in decline in eGFR did not change. The hazard ratio (HR) for starting dialysis for each mg/dl increase in UA at baseline was 1.08 (95% CI, 0.94;1.24, p = 0.27). After adjustment for the same confounders the HR became significant at 1.26 (95% CI, 1.06;1.49, p = 0.01), indicating an earlier start of dialysis with higher levels of UA.ConclusionAlthough high UA levels are not associated with an accelerated decline in renal function, a high serum UA level in incident pre-dialysis patient is a risk factor for an earlier start of dialysis.

Serum Uric Acid and Progression of Kidney Disease: A Longitudinal Analysis and Mini-Review

“…For instance, results from a large cohort of the Swedish Renal Registry showed neither the rate of estimated glomerular filtration rate (eGFR) decline nor rapid progression to end stage renal disease (ESRD) was associated with serum UA levels in patients with CKD stage 3 to 5 [10]. This finding is concordant with some recent observational studies of patients with a wide range of renal function at baseline in the U.S. [11], Taiwan [12], and Europe (Germany, Austria, south Tyrol, and Netherlands)[13, 14]. However, large heterogeneity in the definitions of CKD progression and analytic methods among these studies precluded a firm conclusion.…”

“…Although some studies showed no association between hyperuricemia and the progression of CKD [10–14], other studies found hyperuricemia may hasten the failing of renal function measured by eGFR or increase the risk of developing ESRD(Table 4) [31–42]. Among 63,758 subjects with baseline eGFR ≥ 60 ml/min/1.73 m 2 , the subjects with hyperuricemia had an average annual decline of eGFR of 2.5 ± 9.5 mL/min/1.73 m 2 , that was almost twice faster than those of patients with normal uric acid levels [31].…”

Effect of immediate and prolonged GLP‐1 receptor agonist administration on uric acid and kidney clearance: Post‐hoc analyses of four clinical trials

“…Fifth, T2DM patients in Study‐B and Study‐C had relatively low cardiovascular risk, and the duration of follow‐up in Study‐C and Study‐D was relatively short, both of which may limit direct generalization to the recently published GLP‐1RA cardiovascular outcome trials. Interestingly, the association between UA levels and progression of diabetic kidney disease appears to be present only in healthier subjects, that is, those with earlier stages of chronic kidney disease (CKD), and seems to be lost in more advanced CKD . Sixth, the effects of lixisenatide were investigated in the postprandial state and an active comparator was used rather than placebo, which may have led to a more heterogeneous response and thus hampers direct comparison with other reported studies that were performed in the fasting state.…”

“…33 progression of diabetic kidney disease appears to be present only in healthier subjects, that is, those with earlier stages of chronic kidney disease (CKD), 46 and seems to be lost in more advanced CKD. 47,48 Sixth, the effects of lixisenatide were investigated in the postprandial state and an active comparator was used rather than placebo, which may have led to a more heterogeneous response and thus hampers direct comparison with other reported studies that were performed in the fasting state. Seventh, lixisenatide markedly slows the gastric emptying rate, 23 which could affect purine uptake in the postprandial state.…”

Association of renal function with clinical parameters and conditions in a longitudinal population-based epidemiological study

“…Hyperuricemia is common in CKD patients, and the association between uric acid and worsening renal function is well established (35). Animal studies have shown that oxidative stress and endothelial dysfunction due to hyperuricemia cause renal damage (36).…”