The Role of Acute Kidney Injury in Chronic Kidney Disease

Abstract

There is increasing recognition that acute kidney injury (AKI) and chronic kidney disease (CKD) are closely linked and likely promote one another. Underlying CKD now is recognized as a clear risk factor for AKI because both decreased glomerular filtration rate and increased proteinuria have been shown to be associated strongly with AKI. A growing body of literature also provides evidence that AKI accelerates the progression of CKD. Individuals who suffered dialysis-requiring AKI are particularly vulnerable to worse long-term renal outcomes, including end-stage renal disease. The association between AKI and subsequent renal function decline is amplified by pre-existing severity of CKD, higher stage of AKI, and the cumulative number of AKI episodes. However, residual confounding and ascertainment bias may partly explain the epidemiologic association between AKI and CKD in observational studies. As the number of AKI survivors increases, we need to better understand other clinically important outcomes after AKI, identify those at highest risk for the most adverse sequelae, and develop strategies to optimize their care.

Keywords: Acute kidney injury; acute renal failure; chronic kidney disease; epidemiology; outcomes.

FIGURE 1. Pooled adjusted hazard ratios for acute kidney injury according to estimated GFR and albuminuria, reproduced with permission from Gansevoort et al.

Hazard ratios are adjusted for age, sex, and cardiovascular risk factors. Reference category is estimated GFR 95 ml/min/1.73m² plus albumin-to-creatinine ratio 5mg/g or dipstick negative or trace. Left panel shows result for general population cohorts, and right panel for high-risk cohorts. Dots represent statistical significance, triangles represent non-significance, and shaded areas are 95% confidence intervals. Black lines and blue shading represent an albumin-to-creatinine ratio of <30 mg/g or dipstick negative or trace; green lines and green shading represent an albumin-to-creatinine ratio 30–299 mg/g or dipstick 1+; red lines and red shading represent an albumin-to-creatinine ratio ≥300 mg/g or dipstick ≥2+. HR, hazard ratio; AKI, acute kidney injury; GP cohorts, general population cohorts; HR cohorts, high-risk cohorts; eGFR, estimated glomerular filtration rate.

FIGURE 2. Meta-analysis of chronic kidney disease (CKD) and end-stage renal disease (ESRD) associated with acute kidney injury (AKI), reproduced with permission from Coca et al.

(a) Pooled adjusted hazard ratios for CKD after AKI. (b) Pooled adjusted hazard ratios for ESRD after AKI.

FIGURE 3. Rate ratios of the composite outcome of end-stage renal disease or doubling of serum creatinine after acute kidney injury (AKI) by baseline kidney function and proteinuria, reproduced with permission by James, et al.

Blue squares and horizontal bars represent point estimates and 95% CIs respectively for rate ratios of participants who had AKI for various values of eGFR and proteinuria. Red squares and horizontal bars similarly represent the point estimates and 95% CIs for participants who did not have AKI. The referent group for all rate ratios are participants who did not have AKI, and had normal proteinuria and eGFR ≥60 ml/min/1.73m². RR, rate ratio; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease.