Change in albuminuria as surrogate endpoint for progression of chronic kidney disease strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies lacking.
A study was done to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies. Knowing that if we can use the change in microalbumin as the first sign of kidney failure, then we would have an early start in the prevention of kidney failure.
In this meta-analysis, they collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were age 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. They extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. The primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. They defined an end-stage kidney disease event as initiation of kidney replacement therapy. They quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. They further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. They also did multiple subgroup analyses, and also repeated analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC.
Data from 675,904 individuals and 7,461 end-stage kidney disease events were included in the primary outcome analysis. The analysis showed that change in the urine albumin-to-creatinine ratio (ACR) was associated with the risk of end-stage kidney disease; the hazard ratio for end-stage kidney disease was 0.78 following a 30% decrease in ACR, after adjusting for regression dilution. These findings were consistent across the included cohorts; however, change in ACR was more strongly predictive of end-stage kidney disease among those patients who had a higher baseline ACR. Similar results were obtained for the urine protein-to-creatinine ratio.
From the results, it was determined that the change in albuminuria was consistently associated with subsequent risk of end-stage kidney disease across a range of cohorts, lending support to the use of change in albuminuria as a surrogate endpoint for end-stage kidney disease in clinical trials of progression of chronic kidney disease in the setting of increased albuminuria.
This is not the first study showing the importance of monitoring microalbuminurea. In a study published in Diabetes Care in 2018, the association between 2-year changes in urine albumin–to–creatinine ratio (UACR) and the risk of clinical outcomes in type 2 diabetes was assessed. They analyzed data from 8,766 participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Post-Trial Observational Study (ADVANCE-ON). Change in UACR was calculated from UACR measurements 2 years apart, classified into three groups: decrease in UACR of ≥30%, minor change, and increase in UACR of ≥30%. By analyzing changes from baseline UACR groups, categorized into thirds. The primary outcome was the composite of major macrovascular events, renal events, and all-cause mortality; secondary outcomes were these components.
The results showed that over a median follow-up of 7.7 years, 2,191 primary outcomes were observed. Increases in UACR over 2 years independently predicted a greater risk of the primary outcome, whereas a decrease in UACR was not significantly associated with lower risk (HR 0.93; 95% CI 0.83–1.04). So it was concluded that changes in UACR predicted changes in the risk of major clinical outcomes and mortality in type 2 diabetes, supporting the prognostic utility of monitoring albuminuria change over time.
- UACR predicted changes in the risk of major clinical outcomes and mortality in type 2 diabetes.
- The results indicate that change in albuminuria may be a useful surrogate endpoint for end-stage kidney disease.
- Checking microalbuminuria is a cost effective test to do in the physician’s office.
Lancet, Jan. 08, 2019 https://doi.org/101016/S2213-8587(18)30314-0
Diabetes Care 2018 Jan; 41(1): 163-170.https://doi.org/10.2337/dc17-1467