Year 2021
September 2021


Abstract Title
Increased plasma uric acid level and risk of developing kidney disease in type 2 diabetes: Observational studies and Mendelian randomization analysis



Khoo Teck Puat Hospital1

Background & Hypothesis

Plasma uric acid (pUA) is associated with chronic kidney disease (CKD), but observational studies are inconsistent and open to biases, especially confounding. We evaluated the association and causal relationships of pUA with incident CKD and rapid decline in estimated glomerular filtration rate (eGFR), respectively, in type 2 diabetes (T2D).


Baseline pUA was measured in 1,297 patients with normoalbuminuria followed for a mean of 6 years. Association between pUA and incident CKD was tested using cox regression in two T2D cohorts (SMART2D,case=81, control=815;DN,case=46,control=355). We adopted Mendelian randomisation (MR) to facilitate causal inference using a genetic risk score calculated from 4 single nucleotide polymorphism as an instrumental variable for pUA, applied to 1,146 non-CKD patients at baseline in the T2D cohorts. Rapid eGFR decline was defined as > 5ml/min/1.73m2 per year, derived from longitudinal eGFR data (case=160,control=986).


In multivariate model, 1 mg/dL increment in pUA was independently associated with 18% risk of incident CKD (DN, adjusted hazard ratio [HR] 1.18, 95% CI [1.02 – 1.37], P=0.026; SMART2D, HR 1.18, 95%CI [1.03-1.36], P=0.017). In MR analysis, genetically predicted pUA was associated with 27% higher odds of rapid eGFR decline (odds ratio 1.27,95%CI [1.08-1.50], P=0.003). No horizontal pleiotropy was observed.

Discussion & Conclusion

T2D patients with elevated pUA are at increased risk of developing CKD. Distinct from reported cross-sectional MR studies, we provided genetic evidence to suggest a likely causal link between pUA and early rapid eGFR decline. Overall, early intervention for elevated pUA may provide benefit in delaying the onset of CKD in T2D patients.