Albuminuria and Kidney Function Independently Predict Cardiovascular and Renal Outcomes in Diabetes

Abstract

There are limited data regarding whether albuminuria and reduced estimated GFR (eGFR) are separate and independent risk factors for cardiovascular and renal events among individuals with type 2 diabetes. The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study examined the effects of routine BP lowering on adverse outcomes in type 2 diabetes. We investigated the effects of urinary albumin-to-creatinine ratio (UACR) and eGFR on the risk for cardiovascular and renal events in 10,640 patients with available data. During an average 4.3-yr follow-up, 938 (8.8%) patients experienced a cardiovascular event and 107 (1.0%) experienced a renal event. The multivariable-adjusted hazard ratio for cardiovascular events was 2.48 (95% confidence interval 1.74 to 3.52) for every 10-fold increase in baseline UACR and 2.20 (95% confidence interval 1.09 to 4.43) for every halving of baseline eGFR, after adjustment for regression dilution. There was no evidence of interaction between the effects of higher UACR and lower eGFR. Patients with both UACR Ͼ300 mg/g and eGFR Ͻ60 ml/min per 1.73 m 2 at baseline had a 3.2-fold higher risk for cardiovascular events and a 22.2-fold higher risk for renal events, compared with patients with neither of these risk factors. In conclusion, high albuminuria and low eGFR are independent risk factors for cardiovascular and renal events among patients with type 2 diabetes.

Clinical impact of albuminuria and glomerular filtration rate on renal and cardiovascular events, and all-cause mortality in Japanese patients with type 2 diabetes

“…Recently, KDIGO reported the definition, classification and prognosis of CKD based both on estimated GFR and urinary levels of albumin excretion, emphasizing that a decrease in GFR as well as macroalbuminuria is important for renal outcomes of CKD [8]. In addition, the Action in Diabetes and Vascular disease: preterAx and diamicro-N-MR Controlled Evaluation (ADVANCE) study reported that reduced eGFR with macroalbuminuria was associated with a higher risk for renal events [6]. Interestingly, the Casale Monferrato study revealed that macroalbuminuira was the main predictor of mortality, independently of both eGFR and cardiovascular risk factors [12].…”

“…The FIELD study also revealed that normoalbuminuric patients with eGFR 30-59 ml/min per 1.73 m 2 had a higher risk of cardiovascular events, cardiovascular death, non-coronary heart disease deaths, death from any cause than normoalbuminuric patients with eGFR C60 ml/min per 1.73 m 2 [7]. Interestingly, in the ADVANCE study, patients with normoalbuminuria and eGFR \60 ml/min/1.73 m 2 had a 3.95-fold higher risk for renal events, a 1.33-fold higher risk for cardiovascular events and a 1.85-fold higher risk for cardiovascular death [6]. In contrast, Vlek et al [20] reported that eGFR \60 ml/min per 1.73 m 2 without UACR mainly influenced the risk of vascular events (hazard ratio 1.50; 1.05-2.15), but did not affect all-cause mortality.…”

“…To date, UACR levels and reduced eGFR have independently been reported to predict cardiovascular and real outcomes in diabetes [6]. Previously, diabetic patients with microalbuminuria/macroalbuminuira had a risk for adverse outcomes, including cardiovascular events, cardiovascular death, and renal events as reported by the ADVANCE study [6].…”

“…Previously, diabetic patients with microalbuminuria/macroalbuminuira had a risk for adverse outcomes, including cardiovascular events, cardiovascular death, and renal events as reported by the ADVANCE study [6]. Importantly, the present study, consisting of 4328 Japanese patients with type 2 diabetes, was critically different from the ADVANCE study in terms of (1) being a historical cohort study consisting of 10 centers, (2) longer observation period (median 7.0 years), (3) including the assessment of all-cause mortality, (4) including assessment of each event based on the new classification CKD stages, and (5) providing a diabetic nephropathy score to predict the prognoses of renal events, cardiovascular events, and all-cause mortality.…”

“…A high urinary albumin-to-creatinine ratio (UACR) and low estimated glomerular filtration rate (eGFR) have been believed to be predictors for diabetic ESKD and death [5][6][7]. Kidney Disease Improving Global Outcomes (KDIGO) provided a new classification for chronic kidney disease (CKD) by adding stages that stratified urinary albumin excretion as well as eGFR and emphasizing clinical diagnosis [8].…”