IMPORTANCE Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US.OBJECTIVE To evaluate associations of lower eGFR... Show moreIMPORTANCE Chronic kidney disease (low estimated glomerular filtration rate [eGFR] or albuminuria) affects approximately 14% of adults in the US.OBJECTIVE To evaluate associations of lower eGFR based on creatinine alone, lower eGFR based on creatinine combined with cystatin C, and more severe albuminuria with adverse kidney outcomes, cardiovascular outcomes, and other health outcomes.DESIGN, SETTING, AND PARTICIPANTS Individual-participant data meta-analysis of 27 503 140 individuals from 114 global cohorts (eGFR based on creatinine alone) and 720 736 individuals from 20 cohorts (eGFR based on creatinine and cystatin C) and 9 067 753 individuals from 114 cohorts (albuminuria) from 1980 to 2021.EXPOSURES The Chronic Kidney Disease Epidemiology Collaboration 2021 equations for eGFR based on creatinine alone and eGFR based on creatinine and cystatin C; and albuminuria estimated as urine albumin to creatinine ratio (UACR).MAIN OUTCOMES AND MEASURES The risk of kidney failure requiring replacement therapy, all-cause mortality, cardiovascular mortality, acute kidney injury, any hospitalization, coronary heart disease, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The analyses were performed within each cohort and summarized with random-effects meta-analyses.RESULTS Within the population using eGFR based on creatinine alone (mean age, 54 years [SD, 17 years]; 51% were women; mean follow-up time, 4.8 years [SD, 3.3 years]), the mean eGFR was 90 mL/min/1.73m(2) (SD, 22 mL/min/1.73m(2)) and the median UACR was 11mg/g (IQR, 8-16mg/g). Within the population using eGFR based on creatinine and cystatin C (mean age, 59 years [SD, 12 years]; 53% were women; mean follow-up time, 10.8 years [SD, 4.1 years]), the mean eGFR was 88 mL/min/1.73m(2) (SD, 22 mL/min/1.73m(2)) and the median UACR was 9mg/g (IQR, 6-18mg/g). Lower eGFR (whether based on creatinine alone or based on creatinine and cystatin C) and higher UACR were each significantly associated with higher risk for each of the 10 adverse outcomes, including those in the mildest categories of chronic kidney disease. For example, among people with a UACR less than 10mg/g, an eGFR of 45 to 59 mL/min/1.73m(2) based on creatinine alone was associated with significantly higher hospitalization rates compared with an eGFR of 90 to 104 mL/min/1.73m(2) (adjusted hazard ratio, 1.3 [95% CI, 1.2-1.3]; 161 vs 79 events per 1000 person-years; excess absolute risk, 22 events per 1000 person-years [95% CI, 19-25 events per 1000 person-years]).CONCLUSIONS AND RELEVANCE In this retrospective analysis of 114 cohorts, lower eGFR based on creatinine alone, lower eGFR based on creatinine and cystatin C, and more severe UACR were each associated with increased rates of 10 adverse outcomes, including adverse kidney outcomes, cardiovascular diseases, and hospitalizations. Show less
Background The safety of restarting angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) after acute kidney injury (AKI) is unclear. There is concern that... Show moreBackground The safety of restarting angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) after acute kidney injury (AKI) is unclear. There is concern that previous users do not restart ACEI/ARB despite ongoing indications. We sought to determine the risk of adverse events after an episode of AKI, comparing prior ACEI/ARB users who stop treatment to those who continue. Methods We conducted two parallel cohort studies in English and Swedish primary and secondary care, 2006-2016. We used multivariable Cox regression to estimate hazard ratios (HR) for hospital admission with heart failure (primary analysis), AKI, stroke, or death within 2 years after hospital discharge following a first AKI episode. We compared risks of admission between people who stopped ACEI/ARB treatment to those who were prescribed ACEI/ARB within 30 days of AKI discharge. We undertook sensitivity analyses, including propensity score-matched samples, to explore the robustness of our results. Results In England, we included 7303 people with AKI hospitalisation following recent ACEI/ARB therapy for the primary analysis. Four thousand three (55%) were classified as stopping ACEI/ARB based on no prescription within 30 days of discharge. In Sweden, we included 1790 people, of whom 1235 (69%) stopped treatment. In England, no differences were seen in subsequent risk of heart failure (HR 1.10; 95% confidence intervals (CI) 0.93-1.30), AKI (HR 0.90; 95% CI 0.77-1.05), or stroke (HR 0.99; 95% CI 0.71-1.38), but there was an increased risk of death (HR 1.27; 95% CI 1.15-1.41) in those who stopped ACEI/ARB compared to those who continued. Results were similar in Sweden: no differences were seen in risk of heart failure (HR 0.91; 95% CI 0.73-1.13) or AKI (HR 0.81; 95% CI 0.54-1.21). However, no increased risk of death was seen (HR 0.94; 95% CI 0.78-1.13) and stroke was less common in people who stopped ACEI/ARB (HR 0.56; 95% CI 0.34-0.93). Results were similar across all sensitivity analyses. Conclusions Previous ACEI/ARB users who continued treatment after an episode of AKI did not have an increased risk of heart failure or subsequent AKI compared to those who stopped the drugs. Show less
