Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data

Abstract

BackgroundThe utility of estimated glomerular filtration rate (eGFR) and albuminuria for cardiovascular prediction is controversial.MethodsWe meta-analyzed individual-level data from 24 cohorts (with a median follow-up time longer than 4 years, varying from 4.2 to 19.0 years) in the Chronic Kidney Disease Prognosis Consortium (637,315 participants without a history of cardiovascular disease) and assessed C-statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in 5-year timeframe, contrasting prediction models consisting of traditional risk factors with and without creatinine-based eGFR and/or albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria).FindingsThe addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR and more evident for cardiovascular mortality (c-statistic difference 0.0139 [95%CI 0.0105–0.0174] and 0.0065 [0.0042–0.0088], respectively) and heart failure (0.0196 [0.0108–0.0284] and 0.0109 [0.0059–0.0159]) than for coronary disease (0.0048 [0.0029–0.0067] and 0.0036 [0.0019–0.0054]) and stroke (0.0105 [0.0058–0.0151] and 0.0036 [0.0004–0.0069]). Dipstick proteinuria demonstrated smaller improvement than ACR. The discrimination improvement with kidney measures was especially evident in individuals with diabetes or hypertension but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these conditions. In participants with chronic kidney disease (CKD), the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the c-statistic for cardiovascular mortality declined by 0.023 [0.016–0.030] vs. <0.007 when omitting eGFR and ACR vs. any single modifiable traditional predictors, respectively.InterpretationCreatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when they are already assessed for clinical purpose and/or cardiovascular mortality and heart failure are the outcomes of interest (e.g., the European guidelines on cardiovascular prevention). ACR may have particularly broad implications for cardiovascular prediction. In CKD populations, the simultaneous assessment of eGFR and ACR will facilitate improved cardiovascular risk classification, supporting current CKD guidelines.FundingUS National Kidney Foundation and NIDDK

Diabetes, Kidney Disease, and Cardiovascular Outcomes in the Jackson Heart Study

“…This finding has direct clinical implications for CV risk stratification and intensive therapeutic targeting of the subpopulations at the highest risk for future CV events and mortality. For example, as pointed out in previous studies (34), full assessment of kidney function, including not only eGFR but also, urine albumin excretion, is likely to be beneficial for complete CV risk assessment.…”

“…Previous work in largely white populations has shown that CKD contributes significantly to CV risk stratification (34) and that the combination of diabetes and CKD is associated with comparable rates of incident myocardial infarction to preexisting CHD (35). Given our focus on incident outcomes (stroke and CHD), prevalent stroke (or CHD) could not be included in our assessment of risk factor for incident stroke (or CHD).…”

Baseline Renal Dysfunction in Acute Ischemic Stroke Patients: Prevalence and Impact on Early Mortality.

“…[16][17] . Renal function can be roughly assessed by serum creatinine level but more accurately evaluated from estimated glomerular filtration rate (eGFR), which is usually automatically calculated in a clinical setting, based on serum creatinine and basic demographic findings.…”

Hemoglobin, Albuminuria, and Kidney Function in Cardiovascular Risk: The ARIC (Atherosclerosis Risk in Communities) Study

“…Underlying mechanisms are multifactorial, but cardiac overload, vascular calcification, and arterial stiffness in reduced glomerular filtration rate (GFR) can cause ventricular‐arterial coupling mismatch 1, 2. In addition, albuminuria, the other important marker for defining and staging CKD,3 reflects endothelial function4 and low‐grade inflammation5 and is strongly associated with CVD risk 6…”