Impact of Hyperuricemia on Long-term Outcomes of Kidney Transplantation: Analysis of the FAVORIT Study.
Kalil RS, Carpenter MA, et al.American Journal of Kidney Diseases 2017; 09: 09.
Aims
To conduct a post hoc cohort analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT)* study to examine the impact of uric acid concentrations on cardiovascular (CV) events, mortality, and transplant survival.
Interventions
Participants were randomized to receive either a multivitamin including high-dose folic acid, vitamin B6, and vitamin B12, or a low-dose multivitamin with reduced vitamin B6 and vitamin B12 and no folic acid.
Participants
3,512 patients ≥ 6 months posttransplantation, aged 35-75 years with stable kidney function and estimated creatinine clearance ≥30 mL/min for men and ≥25 mL/min for women, and elevated serum homocysteine concentrations ≥12 µmol/L for men and ≥11 µmol/L for women.
Outcomes
The primary outcome measured was a composite of CV events including CV death, acute myocardial infarction, resuscitated sudden death, stroke, or coronary revascularization or other peripheral, carotid, aortic, or renal artery procedures. Secondary outcomes were all-cause mortality and transplant failure.
Follow-up
Every 6 months to a median follow-up of 3.9 years
CET Conclusions
This paper details a post-hoc analysis of results from the FAVORIT study (Folic Acid for Vascular Outcome Reduction in Transplantation), a very large, multicentre study collecting cardiovascular outcomes following renal transplantation. In this analysis of 3,512 patients, the relationship between serum urate levels, cardiovascular events (composite outcome), all cause mortality and transplant survival were assessed. Patients with stable kidney function 6 months after transplantation (live or deceased donors) were eligible. Hyperuricaemia was defined as >7mg/dL for males and >6mg/dL for females. The primary study was a double blind, randomised, controlled trial, however this post-hoc analysis was not. Median follow up was 3.9 years. Linear univariate analysis showed higher baseline serum urate levels to be significantly associated with cardiovascular events (HR=1.06), all-cause mortality (HR=1.09) and transplant failure (HR=1.18). There was however, a significant association between higher serum urate level and lower eGFR, older age, higher BMI and hypertension. The authors therefore conducted multivariate analyses incorporating these risk factors and under these circumstances, high urate levels were not an independent predictor of the 3 primary outcomes. This was a large study and levels of missing data were very low (<1% per variable, except lipid data= 3.4% missing). The report is clear and well written. The association between urate levels, reduced GFR and cardiovascular risk factors has previously been described, and hence it is unsurprising that urate levels themselves are not independent risk factors when these other variables are included in the survival models. Possibly some patients in the group with normal urate levels were already receiving treatment for gout, but this information was not collected.
Data analysis
Per protocol analysis
Quality notes
Previously assessed as *Bostom AG, et al. Homocysteine-lowering and cardiovascular disease outcomes in kidney transplant recipients: primary results from the Folic Acid for Vascular Outcome Reduction in Transplantation trial. Circulation. 2011;123(16):1763-1770.
Trial registration
ClinicalTrials.gov - NCT00064753