Albuminuria changes are associated with subsequent risk of end-stage renal disease and mortality

Abstract

Current guidelines for chronic kidney disease (CKD) recommend using albuminuria as well as estimated glomerular filtration rate (eGFR) to stage CKD. However, CKD progression is solely defined by change in eGFR with little regard to the risk implications of change in albuminuria. This is an observational study from the Stockholm CREAtinine Measurements (SCREAM) project, a health care utilization cohort from Stockholm, Sweden, with laboratory measures from 2006-2011 and follow-up through December 2012. Included were 31,732 individuals with two or more ambulatory urine albumin to creatinine ratio (ACR) tests. We assessed the association between change in ACR during a baseline period of 1, 2, or 3 years and end-stage renal disease (ESRD) or death. Using a 2-year baseline period, there were 378 ESRD events and 1712 deaths during a median of 3 years of follow-up. Compared to stable ACR, a 4-fold increase in ACR was associated with a 3.08-times (95% confidence interval 2.59 to 3.67) higher risk of ESRD while a 4-fold decrease in ACR was associated with a 0.34-times (0.26 to 0.45) lower risk of ESRD. Similar associations were found in people with and without diabetes mellitus, with and without hypertension, and also when adjusted for the change in eGFR during the same period. The association between change in ACR and mortality was weaker: ACR increase was associated with mortality, but the relationship was largely flat for ACR decline. Results were consistent for 1-, 2-, and 3-year ACR changes. Thus, changes in albuminuria are strongly and consistently associated with the risk of ESRD and death.

Keywords: albuminuria; changes in albuminuria; death; end-stage renal disease; estimated glomerular filtration rate.

Figure 1

Distribution of 2-year ACR fold changes (Panel A) and adjusted hazard ratio of end-stage renal disease (ESRD, Panel B) and mortality (Panel C) associated with a 2-year fold change in ACR. Adjusted for baseline (log) ACR, baseline eGFR (knot at 60 ml/min/1.73 m²), age, gender, total cholesterol, diabetes mellitus, hypertension and history of cardiovascular disease. Filled circles denote statistical significance (P<.05) compared with the reference (diamond) at stable ACR (1-fold change). Grey area represents 95% confidence intervals.

Figure 2

Distribution of 2-year ACR fold changes (Panels A and B) and adjusted hazard ratio of end-stage renal disease (ESRD, Panels C and D) and mortality (Panels E and F) associated with a 2-year fold change in ACR stratified by the presence of diabetes mellitus. Adjusted for baseline (log) ACR, baseline eGFR (knot at 60 ml/min/1.73 m²), age, gender, total cholesterol, hypertension and history of cardiovascular disease. Median ACR (IQR) was 19 (7, 106) mg/g in non-diabetics and 16 (7, 60) mg/g in diabetics. Filled circles denote statistical significance (P<.05) compared with the reference (diamond) at stable ACR (1-fold change). Grey area represents 95% confidence intervals. P value for the product diabetes x ACR fold change >0.1.

Figure 3

Forest plots of 4-fold decrease (A) and 4-fold increase (B) in ACR during a 2-year period and ESRD risk, overall and in subgroups. NA indicates that there were no ESRD events in persons with ACR <30 mg/g and a ≥4-fold decrease in ACR during the 2-year period. “Not using RAAS-I” indicates participants were not taking a RAAS-I at the start or end of the 2-year baseline period. “Using RAAS-I” indicates participants were taking a RAAS-I at the start and end of the 2-year baseline period. “Starting or stopping RAAS-I” indicates that participants had a change in RAAS-I use from the start to the end of the 2-year baseline period.