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Kidney Function Measures and Mortality: A Mendelian Randomization Study
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DOI：10.1053/j.ajkd.2023.10.014.png)
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Rationale & Objective: Individuals with a low estimated glomerular fi ltration rate (eGFR) are at a high risk of death. However, the causes underpinning this association are largely uncertain. This study aimed to assess the causal relationship of low eGFR with all-cause and cause- specific fi c mortality. Study Design: Retrospective cohort study incorporating Mendelian randomization (MR). Setting & Participants: Individual-level data from 436,214 White participants (54.3% female; aged 56.8 +/- 8.0 years) included in the UK Biobank. Exposures: eGFR estimated using cystatin C (eG FRcyst). cyst ). Outcomes: The outcomes of interest included all-cause mortality, cardiovascular mortality, cancer mortality, infection mortality, and other- cause mortality. Analytical Approach: Cox proportional hazards analysis for the conventional observational analyses; linear and nonlinear MR analyses implemented using genetic allele scores as instrumental variables representing kidney function to estimate the effect of kidney function on the survival outcomes. Results: During a median follow-up of 12.1 years, there were 30,489 deaths, 6,098 of which were attributed to cardiovascular events, 15,538 to cancer, 1,516 to infection, and 7,227 to other events. In the conventional observational analysis, eGFRcyst cyst exhibited a nonlinear association with all the outcomes. MR analysis suggested that a genetically predicted lower eGFRcyst cyst was linearly associated with a higher rate of cardiovascular mortality (HR, 1.43; 95% CI, 1.18-1.75) across the entire measurement range (every 10-mL/min/1.73 m2 2 decrement). Nonetheless, no causal associations between eGFRcyst cyst and all-cause mortality (HR, 1.07; 95% CI, 0.98-1.17) or any types of noncardiovascular mortality were detected. Limitations: Potential misclassification fi cation of the actual cause of death, a nonrepresentative sample, and potential error in the interpretation of the magnitude of associations generated in MR analyses. Conclusions: These fi ndings suggest a potential causal association between low eGFR and cardiovascular mortality in the general population, but no causal relationship with all-cause mortality or noncardiovascular mortality was observed. Further studies in other populations are warranted to confirm fi rm these fi ndings.
Keyword:
GLOMERULAR-FILTRATION-RATE
CARDIOVASCULAR MORTALITY
ATRIAL-FIBRILLATION
ALL-CAUSE
POPULATION
EPIDEMIOLOGY
RISK
ALBUMINURIA
ASSOCIATION
期刊
IF:
8.2
论文数:
1.0W
被引数:
2.6W
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