Long-term survival and dialysis dependency following acute kidney injury in intensive care: extended follow-up of a randomized controlled trial

Abstract

Background: The incidence of acute kidney injury (AKI) is increasing globally and it is much more common than end-stage kidney disease. AKI is associated with high mortality and cost of hospitalisation. Studies of treatments to reduce this high mortality have used differing renal replacement therapy (RRT) modalities and have not shown improvement in the short term. The reported long-term outcomes of AKI are variable and the effect of differing RRT modalities upon them is not clear. We used the prolonged follow-up of a large clinical trial to prospectively examine the long-term outcomes and effect of RRT dosing in patients with AKI.

Methods and findings: We extended the follow-up of participants in the Randomised Evaluation of Normal vs. Augmented Levels of RRT (RENAL) study from 90 days to 4 years after randomization. Primary and secondary outcomes were mortality and requirement for maintenance dialysis, respectively, assessed in 1,464 (97%) patients at a median of 43.9 months (interquartile range [IQR] 30.0-48.6 months) post randomization. A total of 468/743 (63%) and 444/721 (62%) patients died in the lower and higher intensity groups, respectively (risk ratio [RR] 1.04, 95% CI 0.96-1.12, p = 0.49). Amongst survivors to day 90, 21 of 411 (5.1%) and 23 of 399 (5.8%) in the respective groups were treated with maintenance dialysis (RR 1.12, 95% CI 0.63-2.00, p = 0.69). The prevalence of albuminuria among survivors was 40% and 44%, respectively (p = 0.48). Quality of life was not different between the two treatment groups. The generalizability of these findings to other populations with AKI requires further exploration.

Conclusions: Patients with AKI requiring RRT in intensive care have high long-term mortality but few require maintenance dialysis. Long-term survivors have a heavy burden of proteinuria. Increased intensity of RRT does not reduce mortality or subsequent treatment with dialysis.

Trial registration: www.ClinicalTrials.govNCT00221013.

Conflict of interest statement

RB has received consulting fees from Gambro Pty Ltd. SF has received travel support to present research results at scientific meetings from Eli Lilly, Cardinal Health and CSL Bioplasma. The George Institute for Global Health, an independent not-for-profit institute affiliated with the University of Sydney, has received unrestricted grant support and travel expenses associated with a randomised-controlled trial of fluid resuscitation from Fresenius Kabi. It has also received reimbursement for SF's time as a steering committee member for studies sponsored by Eli Lilly and Eisai. The George Institute has received research funding from Servier, Novartis, Eisai, Merck, Sharp & Dohme, Pfizer Australia, Amgen, Fresenius Kabi Deutschland GmbH, and Sanofi Aventis.

Figures

Figure 1. Study flow diagram.

The primary outcome was mortality, and the secondary outcome was treatment with maintenance dialysis.

Figure 2. Kaplan-Meier survival curve for all study participants from randomization to end of extended follow-up, shown by treatment group.

Figure 3. Kaplan-Meier survival curve censoring deaths before day 90 of follow-up (end point of the RENAL Study follow-up), shown by treatment group.

Figure 4. Cumulative incidence functions, comparing time to the first event of either the requirement for chronic dialysis or death beyond day 90 following randomization (each curve shown by treatment group).

Figure 5. Adjusted Cox model survival curves from randomization, stratified by quartiles of age.