Long-term risks of adverse kidney outcomes after acute kidney injury: a systematic review and meta-analysis

Abstract

Background: Acute kidney injury (AKI) is associated with increased risks of incidence or progression of chronic kidney disease (CKD), kidney failure (KF), or major adverse kidney events (MAKE), however, it remains unclear which individuals have higher risks. Hence, we systematically reviewed the literature to explore differences in kidney dysfunction risks between AKI stages, AKI durations, and clinical settings.

Methods: We performed a systematic search in PubMed and Embase to identify studies that examined at least one outcome of interest in individuals with AKI versus without AKI, with a minimum follow-up of one year. Hazard/odds ratios (HR/OR) were pooled using random effects models. Heterogeneity across patient and disease characteristics was examined using subgroup and meta-regression analyses.

Results: We searched 70 studies, encompassing 1 838 668 individuals, including 165 715 with AKI. All studies were of moderate to high quality. Individuals with AKI had higher risks of CKD incidence [AKI 25.8%/no AKI 8.7%; HR 2.36 [95% confidence interval (CI) 1.77-2.94)]], CKD progression [AKI 43.1%/no AKI 35.6%; HR 1.83 (95%CI 1.26-2.40)], KF [AKI 2.9%/no AKI 0.5%; HR 2.64 (95%CI 2.03-3.25)], and MAKE [AKI 59.0%/no AKI 32.7%; OR 2.77 (95%CI 2.01-3.53)]. The pooled effect estimates for CKD incidence after AKI lasting <3 days remained significant [OR 2.37 (95%CI 1.68-3.07)], even in individuals with AKI stage 1 only [HR 1.49 (95%CI 1.44-1.55)]. Diabetes mellitus, hypertension, requiring acute dialysis, cardiovascular surgery, or coronary artery disease were associated with higher CKD incidence or progression risks.

Conclusions: Risks for kidney dysfunction were higher for all individuals with AKI. Risk estimates were heterogeneous between patient subgroups, based on AKI stage, AKI duration, and clinical setting, yet even individuals with the lowest stage or shortest duration of AKI remained at higher risk for CKD incidence or progression. This highlights the need to develop tailored follow-up strategies to recognize kidney function decline post-AKI and initiate kidney protective measures in a timely fashion.

Keywords: acute kidney injury; chronic kidney disease; kidney failure; long-term outcomes; major adverse kidney event.

Graphical Abstract

Figure 1:

Prisma flow diagram. *Including the reports that were excluded based on clinical settings: pregnancy, solid organ transplantation, stem-cell transplantation, chronic liver disease or heart failure, nephrectomy, and COVID-19 infection.

Figure 2:

CKD incidence or progression in individuals with AKI compared to individuals without AKI. The combined outcome of CKD incidence or CKD progression occurred in 27.4% (14 365/52 380) of individuals with AKI and in 11.5% (142 110/1 234 776) of individuals without AKI. The weighted mean HR for CKD incidence and CKD progression of James et al. 2019 was included. *Outcome is adjusted for baseline kidney function (eGFR). CI, confidence interval; P, prospective; R, retrospective; SCr, serum creatinine; UACR, urinary albumin-to-creatinine ratio.

Figure 3:

Subanalysis on CKD incidence and CKD progression separately in individuals with AKI compared to individuals without AKI. CKD incidence occurred in 25.8% (11 068/42 854) of individuals with AKI and in 8.7% (95 168/1 096 517) of individuals without AKI. CKD progression in individuals with pre-existing CKD occurred in 43.1% (2 844/6 594) of individuals with AKI and in 35.6% (46 214/129 881) of individuals without AKI. UACR, urinary albumin-to-creatinine ratio. *Outcome is adjusted for baseline kidney function (eGFR). CI, confidence interval; P, prospective; R, retrospective; SCr, serum creatinine; UACR, urinary albumin-to-creatinine ratio.

Figure 4:

CKD incidence or CKD progression in individuals with AKI compared to individuals without AKI, stratified for AKI duration. Only ORs included in this meta-analysis. The Assess-AKI studies, See et al. and Xu et al. also reported HRs. Subanalysis only including HRs showed pooled HRs of 2.24 (95%CI 0.87–3.61), 4.54 (95%CI 1.83–7.25), 2.49 (95%CI 1.44–3.54), and 3.91 (95%CI 2.69–5.41) for AKI duration of <3, 3 or more, <7, and 7 or more days, respectively. CI, confidence interval; P, prospective; R, retrospective; SCr, serum creatinine.

Figure 5:

KF in individuals with AKI compared to individuals without AKI. KF occurred in 2.9% (3 666/127 548) of individuals with AKI and in 0.5% (7 560/1 479 866) of individuals without AKI. *Outcome is adjusted for baseline kidney function (eGFR). CI, confidence interval; P, prospective; R, retrospective; SCr, serum creatinine.

Figure 6:

Meta-regression lines to analyze the effect of covariates on the association between AKI and CKD incidence or progression. Every study is represented by a circle. Circle size indicates the study's weight in the random effects model. The line indicates the regression line with 95% confidence intervals. Purple dots represent ORs, orange dots represent HRs. Preferably HRs were included in the meta-regression; however, if HRs were not reported, ORs were used instead. KRT, kidney replacement therapy. *Outcome is adjusted for baseline kidney function (eGFR).