Causal relationship between chronic kidney disease, renal function, and venous thromboembolism: a bidirectional Mendelian randomization study

Chronic kidney disease (CKD) and impaired renal function have been implicated in venous thromboembolism (VTE), but their causal relationships remain uncertain. This study employs Mendelian randomization (MR) to elucidate the potential bidirectional causal effects between CKD, renal function biomarkers, and VTE.
We collated datasets from genome-wide association studies conducted among European individuals to perform MR analyses. The primary method utilized was the random-effect inverse variance-weighted (IVW) approach, with MR-Egger and the weighted median approaches employed as supplemental techniques. Several sensitivity studies were performed to assess the findings’ robustness.
We identified a link between elevated serum creatinine levels and both VTE (OR: 1.14, 95% CI: 1.05–1.24, p = 0.001) and PE (OR: 1.20, 95% CI: 1.08–1.33, p = 0.001). After outlier removal and Bonferroni correction, the Cr-VTE association lost significance (p = 0.005). A suggestive causal relationship was found between eGFR and VTE (OR: 0.38, 95% CI: 0.20–0.73, p = 0.004), DVT (OR: 0.37, 95% CI: 0.16–0.87, p = 0.022), and PE (OR: 0.29, 95% CI: 0.12–0.66, p = 0.004). No causal effects of CKD or BUN on VTE or its subtypes were observed. Reverse causality inferences did not reveal any meaningful results.
This MR analysis provides evidence that elevated serum creatinine is associated with a higher risk of VTE and PE, while reduced eGFR may be a potential risk factor for VTE and its subtypes. These findings highlight the need for proactive monitoring and preventive strategies in individuals with impaired renal function. Further studies are warranted to confirm these associations and explore underlying mechanisms.
CKD and renal impairment have been considered as risk factors for VTE, but previous findings were controversial. We used the bidirectional two-sample MR study to investigate the causal relationships of CKD and renal function indicators with VTE. The result showed that elevated serum creatinine levels increase the risk of VTE and PE, and reduced eGFR is a suggestive risk factor for the development of VTE (DVT and PE), with no evidence of a causal relationship between CKD and BUN and VTE. CKD, chronic kidney disease; VTE, venous thromboembolism; DVT, deep vein thrombosis, PE, pulmonary embolism, eGFR, estimated glomerular filtration rate; BUN, blood urea nitrogen; SNPs, single nucleotide polymorphisms; MR, Mendelian randomization; LD, linkage disequilibrium.