Estimated Glomerular Filtration Rate Decline is Causally Associated with Acute Pulmonary Embolism: A Nested Case-Control and Mendelian Randomization Study

Background Renal dysfunction is highly prevalent among patients with pulmonary embolism (PE). This study combined population-based study and Mendelian randomization (MR) to observe the relationship between renal function and PE. Methods A nested case-control study were performed using data of PE patients and controls were from two nationwide cohorts, the China pUlmonary thromboembolism REgistry Study (CURES) and China Health and Retirement Longitudinal Survey (CHARLS). Baseline characteristics were balanced using propensity score matching and inverse probability of treatment weighting. Restricted cubic spline models were applied for the relationship between estimated glomerular filtration rate (eGFR) decline and the risk of PE. Bidirectional two-sample MR analyses were performed using genome-wide association study summary statistics for eGFR involving 1,201,909 individuals and for PE from the FinnGen consortium. Results The nested case-control study including 17,547 participants (6,322 PE patients) found that eGFR distribution was significantly different between PE patients and controls (p < 0.001), PE patients had a higher proportion of eGFR <60 mL/min/ 1.73 m2. eGFR below 88 mL/min/1.73 m2 was associated with a steep elevation in PE risk. MR analyses indicated a potential causal effect of eGFR decline on PE (odds ratio 1/4 4<middle dot>26, 95% confidence interval: 2<middle dot>07-8<middle dot>79), with no evidence of horizontal pleiotropy and reverse causality. Conclusion Our findings support the hypothesis that renal function decline contributes to an elevated PE risk. Together with the high prevalence of chronic kidney diseases globally, there arises the necessity for monitoring and modulation of renal function in effective PE prevention.