Highlight
– Study evaluates cost-utility of accelerated vs. standard KRT initiation in critically ill patients with severe AKI.
– Standard initiation increases quality-adjusted life years (QALYs) but at higher costs.
– Incremental cost-effectiveness ratio (ICER) for standard initiation is $23,208 per QALY gained, under commonly accepted thresholds.
– Economic findings are sensitive to postdischarge costs and regional variations in KRT dependence.
Study Background and Disease Burden
Acute kidney injury (AKI) is a prevalent and severe condition in critically ill patients, often necessitating kidney replacement therapy (KRT) as a life-saving intervention. The optimal timing for initiating KRT remains controversial, with conflicting evidence regarding the potential benefits of accelerated versus standard initiation strategies. In addition to clinical uncertainty, the economic ramifications related to timing strategies remain poorly understood. This is particularly important given the high healthcare costs and resource utilization associated with KRT and its complications. Understanding the long-term cost-effectiveness of KRT initiation timing could inform clinical decision-making, health policy, and resource allocation in critical care nephrology.
Study Design
This economic evaluation leveraged outcomes from the Standard vs Accelerated Initiation of Renal Replacement Therapy in AKI (STARRT-AKI) randomized clinical trial, conducted from October 2015 to September 2019 across multiple international centers. The trial enrolled 146 critically ill patients with severe AKI, randomly assigning 73 patients to accelerated KRT initiation and 73 patients to standard initiation.
A state-transition Markov model was developed integrating clinical trial data and administrative health databases from Alberta, Canada, to simulate long-term costs and patient-centered outcomes beyond the original trial period. The model incorporated four health states: no chronic kidney disease (CKD), severe CKD, KRT dependence, and death. Cost inputs were expressed in 2024 Canadian dollars. The primary economic measure was the cost per quality-adjusted life-year (QALY) gained, combining survival and quality-of-life metrics.
Monte Carlo simulations (n=5000) were used to derive expected costs, QALYs, incremental cost-effectiveness ratios (ICERs), and incremental net monetary benefits (INMBs), assuming a willingness-to-pay threshold of $50,000 CAD per QALY.
Key Findings
Baseline demographics showed comparable groups: accelerated initiation mean age 59.67 years (SD 14.5), 71.3% male; standard initiation mean age 61.88 years (SD 12.9), 65.8% male.
Economically, standard initiation was more expensive, averaging $251,370 (SD $155,801) per patient compared to $231,518 (SD $183,302) for accelerated initiation. However, it delivered superior clinical effectiveness with 7.49 QALYs (SD 2.03) versus 6.64 QALYs (SD 1.76) in the accelerated group.
The computed ICER for standard versus accelerated initiation was $23,208 per QALY gained, well below typical Canadian willingness-to-pay thresholds, suggesting cost-effectiveness. The incremental net monetary benefit (INMB) was $22,648 (95% credible interval $15,980 to $29,316), favoring standard initiation.
Sensitivity analyses highlighted that results were particularly influenced by postdischarge healthcare costs and regional heterogeneity in rates of long-term KRT dependence. Variability in statistical assumptions and health state transition probabilities introduced uncertainty, but the main cost-effectiveness conclusion remained robust within plausible parameter ranges.
Expert Commentary
The STARRT-AKI economic evaluation provides important insights into the complex trade-offs between clinical outcomes and healthcare expenditures associated with KRT initiation timing. Its linkage of randomized trial data to real-world administrative costs is a notable strength, enabling long-term perspective on patient-centered outcomes and burden on the healthcare system.
Nevertheless, the study’s generalizability beyond the Canadian healthcare system requires cautious interpretation due to differences in regional care delivery, reimbursement frameworks, and population characteristics. Additionally, the model assumptions regarding quality of life adjustments and chronic kidney disease progression could impact the findings. It is critical for clinicians and policymakers to balance these economic findings alongside clinical risks and benefits individual to patient contexts.
Current nephrology and critical care guidelines do not unanimously endorse accelerated versus standard KRT initiation; thus, this data adds valuable economic considerations to support clinical decision-making in severe AKI management.
Conclusion
This comprehensive health economic analysis suggests that, within a Canadian context, standard initiation of renal replacement therapy in critically ill patients with severe acute kidney injury is likely cost-effective compared to accelerated initiation. While associated with higher immediate costs, standard initiation confers improved quality-adjusted survival that justifies expenditures under typical willingness-to-pay thresholds.
These findings underscore the importance of considering long-term health economics alongside clinical outcomes in guiding KRT initiation timing. Further research is warranted to validate these results in diverse health systems and to explore strategies minimizing postdischarge resource use and chronic KRT dependency.
References
Round J, Akpinar I, Yan C, Patel N, van Katwyk S, Montgomery C, Wald R, Bagshaw SM; STARRT-AKI Investigators. Cost-Utility Analysis of Accelerated and Standard Strategies for Renal Replacement Therapy Initiation. JAMA Netw Open. 2025 Oct 1;8(10):e2535343. doi:10.1001/jamanetworkopen.2025.35343. PMID:41042508.
Wang HE, et al. Timing of initiation of renal replacement therapy in patients with acute kidney injury: A systematic review and meta-analysis. Crit Care. 2020;24(1):604.
Kidney Disease: Improving Global Outcomes (KDIGO) AKI Guideline Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl. 2012;2(1):1-138.
Srisawat N, Kellum JA. Acute kidney injury: epidemiology and diagnostic approaches. Adv Chronic Kidney Dis. 2020;27(1):1-9.
