Mendelian randomization reveals causal effects of kidney function on various biochemical parameters

Abstract

The kidney is a vital organ with diverse biological effects and the burden of kidney function impairment is increasing in modern medicine. As the effects from kidney function on diverse biochemical parameters are yet fully understood, additional investigation to reveal the causal effects is warranted. Here we show the causal estimates from kidney function parameter, estimated glomerular filtration rate (eGFR), on 60 biochemical parameters by performing two-sample Mendelian randomization (MR) study in 337,138 white British UK Biobank participants. A higher genetically predicted eGFR was significantly associated with higher lymphocyte percentage, HDL cholesterol, and alanine aminotransferase. The causal estimates indicated that a higher genetically predicted eGFR was associated with lower urea, urate, insulin growth factor-1, and triglycerides levels. The parameters with significant but non-linear causal estimates were hemoglobin concentration, calcium, vitamin D, and urine creatinine values, identified by non-linear MR. Healthcare providers should understand that changes in eGFR may affect the identified biochemical parameters in diverse patterns. Future study is warranted to expand the knowledge of the mechanisms and clinical implications of the causal effects of eGFR on various biochemical parameters.