No Evidence of Causal Effects between Renal Impairment and Muscle Wasting: a Two-Sample Mendelian Randomization Study

Abstract

Abstract Background Numerous investigations have explored the potential correlation between renal impairment and muscle loss. However, the establishment of a definitive cause-and-effect relationship between these two remains elusive.Methods We utilized genome-wide association studies summary data from the CKDGen Consortium to identify genetically predicted estimated Glomerular Filtration Rate (eGFR), chronic kidney disease (CKD), and blood urea nitrogen (BUN) involving 567,460, 480,698, and 234,029 participants, respectively. To evaluate site-specific genetically predicted muscle mass, data from the UK Biobank were employed (n ≤ 454,835). The primary analysis relied on the inverse-variance weighted (IVW) method, with additional sensitivity analyses performed to validate the robustness of the MR results.Results No significant evidence could support that genetically predicted CKD was associated with appendicular and trunk muscle wasting [right leg FFM: IVW odds ratio (OR) = 1.010, confidence interval (CI) = 0.989 to 1.032, P-value = 0.355; left leg FFM: IVW OR = 1.009, CI = 0.988 to 1.031, P-value = 0.381; right arm FFM: IVW OR = 1.012, CI = 0.992 to 1.033, P-value = 0.231; left arm FFM: IVW OR = 1.010, CI = 0.990 to 1.030, P-value = 0.320; trunk FFM: IVW OR = 1.012, CI = 0.991 to 1.033, P-value = 0.279]. Similar estimations could also be observed in MR analyses of eGFR and BUN on muscle mass.Conclusions It is unlikely that genetically predicted renal impairment can causally increase the risk of muscle wasting. Clinically observed associations in epidemiologic studies might be attributed to metabolic homeostasis imbalances stemming from renal impairment.