ABSTRACT
Background: Previous results on the association between the estimated glomerular filtration rate (eGFR) and stroke are mixed. Most studies derived the eGFR from serum creatinine, which is affected by non-kidney determinants and thus has possibly biased the association with stroke risk. Methods: In this cohort study, we included 429 566 UK Biobank participants (94.5% white, 54% women, age 56 ± 8 years) free of stroke at enrollment. The eGFRcys and eGFRcr were calculated with serum cystatin C and creatinine, respectively. Outcomes of interest were risk of total stroke and subtypes. We investigated the linear and nonlinear associations using Cox proportional hazards models and restricted cubic splines, corrected for regression dilution bias. Results: During an average follow-up of 10.11 years, 4427 incident strokes occurred, among which 3447 were ischemic and 1163 were hemorrhagic. After adjustment for confounders, the regression dilution-corrected hazard ratios (95% confidence intervals) for every 10 mL/min/1.73 m2 decrement in eGFRcys were 1.10 (1.05-1.14) for total stroke and 1.11 (1.08-1.15) for ischemic stroke. A similar pattern was observed with eGFRcr, although the association was weaker. When either type of eGFR was below 75 mL/min/1.73 m2, the risks of total and ischemic stroke increased exponentially as eGFR decreased. A U-shaped relationship was witnessed if eGFRcr was used instead. There was a null association between eGFR and hemorrhagic stroke. Conclusions: The risks of total stroke and ischemic stroke increased exponentially when the eGFRcys fell below 75 mL/min/1.73 m2.
ABSTRACT
The association between sodium intake and long-term kidney disease endpoints is debated and yet to be proven. We aimed to investigate the associations of estimated 24-h urinary sodium excretion, reflecting daily sodium intake, with the incidence of end-stage kidney disease (ESKD). In this prospective cohort study including 444,375 UK Biobank participant, 865 (0.2%) ESKD events occurred after median follow-up of 12.7 years. For every 1 g increment in estimated 24-h urinary sodium excretion, multivariable-adjusted hazard ratio for incident ESKD was 1.09 (95% confidence interval 0.94-1.26). Nonlinear associations were not detected with restricted cubic splines. The null findings were confirmed by a series of sensitivity analyses, which attenuated potential bias from measurement errors of the exposure, regression dilution, reverse causality, and competing risks. In conclusion, there is insufficient evidence that estimated 24-h urinary sodium excretion is associated with the incidence of ESKD.
