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 >300 mg/g and eGFR <60 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.

Figure 1.

Association of albuminuria level or eGFR at baseline with the risk for adverse outcomes. The centers of the square are placed at the point estimates, and vertical lines represent the corresponding 95% CIs. The area of each square is proportional to the inverse variance of each estimate. The estimates are adjusted for baseline covariates, including age, gender, duration of diabetes, log-transformed eGFR (or log-transformed UACR), SBP, history of currently treated hypertension, history of macrovascular disease, HbA_1c, LDL cholesterol, HDL cholesterol, log-transformed triglycerides, body mass index (BMI), electrocardiogram abnormalities, current smoking, and current drinking. The hazard ratios (HRs) and 95% CIs for the regression lines were corrected with the regression dilution attenuation coefficient of log-transformed UACR (1.98) and log-transformed eGFR (1.96).

Figure 2.

Combined effects of albuminuria and eGFR levels at baseline on the risk for adverse outcomes. The estimates are adjusted for baseline covariates, including age, gender, duration of diabetes, SBP, history of currently treated hypertension, history of macrovascular disease, HbA_1c, LDL cholesterol, HDL cholesterol, log-transformed triglycerides, BMI, electrocardiogram abnormalities, current smoking, and current drinking.

Figure 3.

Comparison of the impact of baseline factors on the risk for adverse outcomes. HRs and 95% CIs were estimated using a multivariable-adjusted model, including age, gender, baseline logUACR, baseline logGFR, baseline SBP, baseline HbA_1c, baseline LDL cholesterol, baseline HDL cholesterol, and the following baseline covariates: Duration of diabetes, history of currently treated hypertension, history of macrovascular disease, triglycerides, BMI, electrocardiogram abnormalities, current smoker, and current drinker, and corrected with the attenuation coefficient of 1.98, 1.96, 2.37, 2.98, 2.29, and 1.74 for logUACR, log GFR, SBP, HbA_1c, LDL cholesterol, and HDL cholesterol, respectively. The values are shown as the estimates per 1-SD increment (logUACR, SBP, HbA_1c, and LDL cholesterol) or decrement (logGFR and HDL cholesterol) in each variable.

Figure 4.

Association of albuminuria and eGFR levels during follow-up with the risk for cardiovascular events. Closed and open squares represent HR in subgroups for eGFR of ≥60 and <60 ml/min per 1.73 m², UACR of <30 and ≥30 mg/g, or SBP of <140 and ≥140 mmHg. The estimates are adjusted for age; gender; follow-up log-transformed eGFR (or follow-up log-transformed UACR); follow-up SBP; follow-up HbA_1c; follow-up LDL cholesterol; follow-up HDL cholesterol; follow-up log-transformed triglycerides; follow-up BMI; randomized study treatment; and baseline covariates, including duration of diabetes, history of currently treated hypertension, history of macrovascular disease, electrocardiogram abnormalities, current smoking, and current drinking. In the subgroup analysis, the risk factor relevant to the subgroup was excluded from the multivariable model. The HRs and 95% CI for the regression lines were corrected with the regression dilution attenuation coefficient of log-transformed UACR (1.98) and log-transformed eGFR (1.96).