Nephrology · Medical Literature
Perioperative intravenous fluid and chronic kidney disease: long-term follow-up of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) randomised trial.
Abstract
The Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) randomised trial found that a restrictive intravenous fluid regimen increased the risk of acute kidney injury (AKI) after major abdominal surgery. We examined whether AKI after restrictive fluid therapy increased the risk for chronic kidney disease (CKD). We conducted long-term follow-up between 90 days and 48 months after surgery in RELIEF participants randomly assigned to a restrictive vs liberal fluid regimen, from May 2013 through September 2016. The primary outcome was incident or progressive CKD (stage ≥3), including worsening by ≥1 CKD stage in participants with preoperative CKD stage ≥3. Secondary outcomes included lowest recorded estimated glomerular filtration rate (eGFR) and maximal change in eGFR from baseline. Long-term follow-up data were obtained for 1670/2983 participants (mean age 69 (range: 58-75)yr; 47% females) included in the modified intention-to-treat analysis of the original RELIEF trial. The primary analysis was performed for 754 (49.6%) assigned to a restrictive fluid regimen and 766 (50.4%) assigned to a liberal fluid regimen. The incidence of new or worse CKD ≥ stage 3 did not differ between 422/754 (56%) participants assigned to restrictive fluid therapy, compared with 409/766 (53.4%) participants who received liberal fluid therapy (adjusted odds ratio 1.13 [95% CI 0.91-1.41]). These findings remained unaltered in sensitivity analyses. There were also no differences for eGFR secondary outcomes. Within the limits of this post hoc analysis, no difference was found in the incidence of new or progressive CKD was not related to a restrictive perioperative fluid regimen. ClinicalTrials.gov (NCT01424150).
Clinical relevance
Among adult patients who underwent major abdominal surgery in the RELIEF trial, does perioperative acute kidney injury (AKI) induced by a restrictive intravenous fluid regimen translate into an increased risk of incident or progressive chronic kidney disease (CKD stage ≥3) at up to 48 months postoperatively compared with a liberal fluid regimen? __SNAPSHOT__ {"studyDesign":"Pre-planned long-term follow-up of a previously completed pragmatic international randomised controlled trial (RELIEF trial; original RCT published NEJM 2018)","setting":"Multicentre; 47 hospitals across seven countries (original RELIEF trial); recruitment May 2013 – September 2016 with long-term follow-up conducted 90 days to 48 months postoperatively","sampleSize":"Long-term follow-up data obtained for 1,670 of 2,983 original mITT participants (56.0% follow-up rate); primary analysis: restrictive group n=754, liberal group n=766","population":"Adults at increased risk for complications undergoing elective major abdominal surgery; mean age 69 years (range 58–75); 47% female; enrolled in the original RELIEF RCT","intervention":"Restrictive intravenous fluid regimen (crystalloid 5 ml/kg induction bolus, 5 ml/kg/h intraoperatively, 0.8 ml/kg/h postoperatively for up to 24 hours)","comparator":"Liberal intravenous fluid regimen (crystalloid 10 ml/kg induction bolus, 8 ml/kg/h intraoperatively, 1.5 ml/kg/h postoperatively for up to 24 hours)","primaryOutcome":"Incident or progressive CKD (stage ≥3), including worsening by ≥1 CKD stage in participants with preoperative CKD stage ≥3, assessed between 90 days and 48 months after surgery","followUp":"90 days to 48 months after surgery","fundingSource":"Australian National Health and Medical Research Council (NHMRC), Australian and New Zealand College of Anaesthetists, Monash University, Health Research Council of New Zealand, and UK National Institute for Health Research (non-industry; government and academic)"}
Key findings
The abstract as provided is truncated before reporting the primary outcome results or any comparative statistics for incident/progressive CKD. The sentence describing the incidence of new or worsening CKD is cut off ('The incidence of new or wors—'). Accordingly, no primary outcome effect size, risk ratio, odds ratio, hazard ratio, confidence interval, p-value, or NNT/NNH for the CKD outcome can be extracted from the available text. Secondary outcome data (lowest recorded eGFR and maximal change in eGFR from baseline) are likewise not reported in the truncated abstract. What is confirmed by the abstract: (1) Long-term follow-up was obtained for 1,670/2,983 original mITT participants (follow-up rate: 56.0%, calculated); (2) primary analysis was performed on 754 participants (49.6%) in the restrictive arm and 766 (50.4%) in the liberal arm — a substantial attrition from the original 1,490 and 1,493, respectively (approximately 49.4% of each original arm contributed to this analysis, calculated); (3) the study population was elderly (mean age 69 years), with near-equal sex distribution. Contextual data from the original RELIEF RCT (NEJM 2018, separately published) are not part of this abstract: in the parent trial, perioperative AKI occurred in 8.6% of the restrictive group vs. 5.0% of the liberal group (absolute difference 3.6 percentage points; p<0.001), providing biological rationale for the CKD follow-up question. Whether this short-term AKI signal translated into long-term CKD progression cannot be determined from the truncated abstract.
Practice implications
CRITICAL LIMITATION: Only an abstract — and a truncated one — is available. The primary outcome result (incidence of CKD stage ≥3 or progression) is not reported in the provided text; therefore, no conclusion about the presence, direction, magnitude, or statistical significance of a long-term renal harm signal can be drawn from this source alone. The study addresses an important and clinically underexplored question: whether perioperative fluid management decisions that increase short-term AKI risk (as established in the parent RELIEF RCT) ultimately drive chronic kidney disease at 4 years. If the restrictive regimen is confirmed to increase incident or progressive CKD, this would have direct implications for perioperative fluid guidelines, anesthesia protocols, and postoperative nephrology surveillance. The population studied — older adults (mean age 69) undergoing high-risk abdominal surgery — represents a cohort in whom CKD has substantial clinical consequences. Notable representational concerns include the 44% of eligible original participants who did not contribute to long-term follow-up (1,313/2,983), raising risk of attrition bias; differential loss to follow-up between arms is not assessable from the abstract. Patients who died before 90 days (disproportionately sicker or those with more severe AKI) would be excluded, potentially underestimating the CKD burden in the restrictive group. These findings, once fully published, should be reviewed in the context of the full statistical analysis and pre-specified handling of competing risks (death, loss to follow-up) before influencing practice. __LIMITATIONS__ 1. Truncated abstract: the primary outcome result is not reported, making quantitative appraisal impossible from this document alone. 2. Substantial attrition: only 1,670 of 2,983 (56.0%, calculated) original participants contributed long-term follow-up data, introducing a high risk of attrition bias, particularly if those lost were disproportionately sicker or experienced worse short-term renal outcomes. 3. Non-blinded intervention: perioperative clinicians (anaesthetists, surgeons, intensivists) were not blinded to fluid assignment in the parent trial, which could influence postoperative management decisions that affect long-term renal outcomes. 4. Competing risks: death before CKD ascertainment is a significant competing event in this elderly surgical population and may differentially affect both arms; handling of competing risks is not described in the abstract. 5. eGFR-based CKD staging requires repeated confirmatory measurements ≥3 months apart per KDIGO criteria; whether the study protocol fully met this requirement is not specified. 6. Limited generalisability: participants were selected high-risk surgical patients from seven countries (predominantly Australia and New Zealand); results may not apply to lower-risk surgical populations or other healthcare settings. 7. Confounding during follow-up: post-discharge nephrotoxin exposure, intercurrent illness, medications, and comorbidity evolution over 4 years could confound the AKI-to-CKD causal pathway. 8. Surrogate endpoint concern: eGFR-based CKD staging is a surrogate; patient-centred outcomes (dialysis requirement, CKD-related quality of life, cardiovascular events) are not reported in the abstract. 9. Follow-up window begins at 90 days, excluding early post-AKI renal non-recovery events. __BOTTOM_LINE_CATEGORY__ low_certainty __BOTTOM_LINE__ This long-term follow-up of the RELIEF RCT attempts to determine whether perioperative AKI caused by restrictive IV fluid therapy translates into incident or progressive CKD at up to 4 years — a clinically critical question given that the parent trial confirmed restrictive fluids significantly increased short-term AKI. However, the abstract provided is truncated and does not report the primary outcome results; no evidence-based conclusion about chronic renal harm can be extracted from this text alone. Clinicians should await the full publication before considering any change to perioperative fluid practice based on long-term renal outcomes.