Impaired fasting glucose and development of chronic kidney disease in non-diabetic population: a Mendelian randomization study.

ABSTRACT: INTRODUCTION:Diabetes mellitus is a risk factor of chronic kidney disease (CKD); however, the relationship between fasting glucose and CKD remains controversial in non-diabetic population. This study aimed to assess causal relationship between genetically predicted fasting glucose and incident CKD. RESEARCH DESIGN AND METHODS:This study included 5909 participants without diabetes and CKD from the Korean Genome Epidemiology Study. The genetic risk score (GRS9) was calculated using nine genetic variants associated with fasting glucose in previous genome-wide association studies. Incident CKD was defined as estimated glomerular filtration rate (eGFR) <60?mL/min/1.73?m2 and/or proteinuria (?1+). The causal relationship between fasting glucose and CKD was evaluated using the Mendelian randomization (MR) approach. RESULTS:The GRS9 was strongly associated with fasting glucose (?, 1.01; p<0.001). During a median follow-up of 11.6 years, 490 (8.3%) CKD events occurred. However, GRS9 was not significantly different between participants with CKD events and those without. After adjusting for confounding factors, fasting glucose was not associated with incident CKD (OR 0.990; 95% CI 0.977 to 1.002; p=0.098). In the MR analysis, GRS9 was not associated with CKD development (OR per 1 SD increase, 1.179; 95%?CI 0.819 to 1.696; p=0.376). Further evaluation using various other MR methods and strict CKD criteria (decrease in the eGFR of ?30%?to a value of <60?mL/min/1.73?m2) found no significant relationship between GRS9 and incident CKD. CONCLUSIONS:Fasting glucose was not causally associated with CKD development in non-diabetic population.

SUBMITTER: Kim H 

PROVIDER: S-EPMC7252970 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature