Depression increases the risk of kidney stone: Results from the National Health and Nutrition Examination Survey 2007–2018 and Mendelian randomization analysis

To investigate whether depression increases the kidney stone risk.First, we performed an observational study in the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Depression severity was evaluated using the Patient Health Questionnaire-9 (PHQ-9) and classified into no, mild, moderate, and severe depression groups. Multivariable-adjusted logistic regression was used to assess the correlation between depression severity and kidney stone risk. Second, Mendelian randomization (MR) was applied to decrease the bias and avoid the reverse causality in the observational study. Genetic instruments were obtained from a large genome-wide association study (GWAS) meta-analysis of depression involved 246,363 cases and 561,190 controls. We obtained summary data for kidney stone from another large GWAS, which integrates data from 6536 stone formers and 388,508 controls. Inverse variance weighted (IVW) was the primary analytical method.In the observational study, a total of 24,892 individuals were enrolled. Individuals with moderate (OR 1.38, 95 % CI 1.05-1.83, P = 0.022) and severe (OR 1.56, 95 % CI 1.02-2.40, P = 0.040) depression had a higher risk of kidney stone (P for trend = 0.006) compared with the control. For the MR, results also showed that genetically predicted depression was causally associated with a higher risk of kidney stone disease (OR 1.26, 95 % CI 1.04-1.53, P = 0.017) in IVW.Depression might be associated with kidney stone risk. This finding is needed to be verified in further prospective cohort studies with a large sample size and enough follow-up time.