Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis

Abstract

Background A comprehensive evaluation of the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality is required for assessment of the impact of kidney function on risk in the general population, with implications for improving the definition and staging of chronic kidney disease (CKD). Methods A collaborative meta-analysis of general population cohorts was undertaken to pool standardized data for all-cause and cardiovascular mortality. The two kidney measures and potential confounders from 14 studies (105,872 participants; 730,577 person-years) with urine albumin-to-creatinine ratio (ACR) measurements and seven studies (1,128,310 participants; 4,732,110 person-years) with urine protein dipstick measurements were modeled. Findings In ACR studies, mortality risk was unrelated to eGFR between 75-105 ml/min/1·73 m2 and increased at lower eGFR. Adjusted hazard ratios (HRs) for all-cause mortality at eGFR 60, 45, and 15 (versus 95) ml/min/1·73 m2 were 1·18 (95% CI: 1·05-1·32), 1·57 (1·39-1·78), and 3·14 (2·39-4·13), respectively. ACR was associated with mortality risk linearly on the log-log scale without threshold effects. Adjusted HRs for all-cause mortality at ACR 10, 30, and 300 (versus 5) mg/g were 1·20 (1·15-1·26), 1·63 (1·50-1·77), and 2·22 (1·97-2·51). eGFR and ACR were multiplicatively associated with mortality without evidence of interaction. Similar findings were observed for cardiovascular mortality and in dipstick studies. Interpretation Lower eGFR (<60 ml/min/1·73 m2) and higher albuminuria (ACR ≥10 mg/g) were independent predictors of mortality risk in the general population. This study provides quantitative data for using both kidney measures for risk evaluation and CKD definition and staging.

Frailty, Kidney Function, and Polypharmacy: The Atherosclerosis Risk in Communities (ARIC) Study

“…These findings highlight the importance of increasing awareness for the frailty phenotype, and perhaps suggest a need for enhanced albuminuria testing in this vulnerable population. Elevated albuminuria has been shown to have a strong association with risk of bone fractures, cardiovascular disease, end-stage renal disease, and mortality in the general population, 30–32 and significant absolute risk increases in the older adult population. 33 …”

Should eGFR and Albuminuria Be Added to the Framingham Risk Score Chronic Kidney Disease and Cardiovascular Disease Risk Prediction

“…The relationship between decreased GFR and CVD has been examined in numerous studies with the majority of studies involving high-risk populations (individuals with hypertension, heart failure, coronary artery disease, acute coronary syndrome, coronary artery bypass surgery, diabetes or age >65 years) [7,16,21,22,23] or low-risk populations [2,3,4,7,8,9,11,12,24] demonstrating increased CVD risk with decreased eGFR. The largest single study to date includes over 1.1 million adults enrolled in the Kaiser Permanente health plan with assessment of traditional CVD risk factors (blood pressure, lipids and smoking), serum creatinine and urinalysis [11].…”

“…The presence of CKD heightens an individual’s risk for cardiovascular disease (CVD), death from cardiovascular disease (CVD) and all-cause mortality [2,3,4,5,6,7,8,9,10,11,12], and this risk increases once eGFR declines below a threshold of 45–60 ml/min/1.73 m 2 [12]. Increased levels of urinary albumin excretion confer increased CVD risk across all ranges of GFR, regardless of how urine albumin excretion is assessed [for example, spot urine albumin/creatinine ratios (ACR), timed urine collections or urine dipstick measurements] [4,10,12,13,14,15,16]. It is important to note that low muscle mass may confound these associations as low urine creatinine excretion is independently associated with increased risk of CVD and mortality [17].…”

Rate of Change in Kidney Function and the Risk of Death: The Case for Incorporating the Rate of Kidney Function Decline into the CKD Staging System

“…The general limitation of creatinine-based estimates of renal function is that they reflect more than just renal function, particularly in the elderly population where muscle-wasting or sarcopenia is an important problem. A low creatinine in an elderly patient may not necessarily reflect improved kidney function, and may actually represent decreased muscle mass that portends an increased risk of death [46,53]. Adopting other markers of renal function, such as cystatin C, in clinical practice, may help address the limitation of creatinine-based equations.…”