Background: Observational studies evaluating the link between sleep duration and kidney function reported controversial results. In the present study, Mendelian randomization analysis was applied to obtain unconfounded estimates of the casual association of genetically determined sleep duration with estimated glomerular filtration rate and the risk of chronic kidney disease.
Methods: Data from the largest genome-wide association studies on self-reported and accelerometer-derived sleep duration, estimated glomerular filtration rate and chronic kidney disease were analysed in total, as well as separately in diabetic and non-diabetic individuals. Inverse variance weighted (IVW) method, weighted median-based method, MR-Egger and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were applied, as well as the leave-one-out method to rule out the impact of single single-nucleotide polymorphism.
Results: Individuals with genetically longer self-reported sleep duration had a higher chronic kidney disease risk (IVW: β = 0.358, p = 0.047). Furthermore, in non-diabetics, longer self-reported sleep duration was negatively associated with estimated glomerular filtration rate (IVW: β = - 0.024, p = 0.020). Similarly, accelerometer-derived sleep duration was negatively related to estimated glomerular filtration rate in the total population (IVW: β = - 0.019, p = 0.047) and then on-diabetic individuals. No significant association was found between self-reported sleep duration and estimated glomerular filtration rate in the whole population and type-2 diabetes mellitus patients. None of the estimated associations was subjected to a significant level of heterogeneity. MR-PRESSO analysis did not show any chance of outliers for all estimates. The pleiotropy test also indicated low chance of pleiotropy. The leave-one-out method demonstrated that the links were not driven by single-nucleotide polymorphisms.
Conclusions: For the first time, the present study shed a light on the potential harmful effects of longer sleep duration (measured both objectively and subjectively) on kidney function. This finding was observed in the total population and in non-diabetic individuals, but not in those with diabetes. Further research is needed to elucidate the links between sleep duration, estimated glomerular filtration rate and the risk of chronic kidney disease.
Keywords: Chronic kidney disease; Estimated glomerular filtration rate; Mendelian randomization; Sleep duration.