RESEARCH ARTICLE Open AccessUric acid: association with rate of renal functiondecline and time until start of dialysis in incidentpre-dialysis patientsHakan Nacak 1* , Merel van Diepen 1 , Moniek CM de Goeij 1 , Joris I Rotmans 2 , Friedo W Dekker 1and the PREPARE-2 study groupAbstractBackground: In patients with chronic kidney disease (CKD) hyperuricemia is common. Evidence that hyperuricemiamight 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 timeuntil start of dialysis in pre-dialysis patients.Methods: Data from the PREPARE-2 study were used. The PREPARE-2 study is an observational prospective cohortstudy including incident pre-dialysis patients with CKD stages IV-V in the years between 2004 and 2011. Patients werefollowed for a median of 14.9 months until start of dialysis, kidney transplantation, death, or censoring. Main outcomeswere 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.Results: In this analysis 131 patients were included with a baseline UA level (mean (standard deviation (SD)) of8.0 (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 m 2 /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 m 2 /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 notchange. 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.Conclusion: Although high UA levels are not associated with an accelerated decline in renal function, a high serumUA level in incident pre-dialysis patient is a risk factor for an earlier start of dialysis.Keywords: Uric acid, CKD progression, Pre-dialysis, Prospective cohortBackgroundUric acid (UA) is an emerging risk factor for renal disease,hypertension, and cardiovascular disease. Hyperuricemiais common in patients with chronic kidney disease (CKD)and evidence that hyperuricemia may also play a causalrole in hypertension, vascular disease and progression ofCKD is accumulating [1-9]. In addition, some interventionstudies have shown that treatment of hyperuricemia couldbe beneficial for blood pressure regulation and preserva-tion of kidney function [10,11]. Therefore, screening forhyperuricemia in CKD patients might help to identifypatients that have an accelerated decline in renal functionand thereby an increased risk for progression to ESRD.The association between UA and decline in renal func-tion has been investigated in several studies which includedhealthy individuals [12,13], patients with CKD stages I-II[14,15], patients with diabetes [6], and patients on periton-eal dialysis [16]. However, evidence about this association* Correspondence: h.nacak@lumc.nl1 Department of Clinical Epidemiology, Leiden University Medical Center,Albinusdreef 2, Leiden 2333 ZA, The NetherlandsFull list of author information is available at the end of the article© 2014 Nacak et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly credited. The Creative Commons Public DomainDedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article,unless otherwise stated.Nacak et al. BMC Nephrology 2014, 15:91http://www.biomedcentral.com/1471-2369/15/91
