Early Versus Late Renal Replacement Therapy After Cardiac Surgery

Study Overview
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Brief Summary
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The question of timing of initiation of renal replacement therapy (RRT), early versus late, has seldom been the focus of high-quality or rigorous evaluation. As a consequence, initiatives aimed at identifying the optimal timing of initiation of RRT in acute kidney injury (AKI) have been given the highest priority for investigation by the Acute Kidney Injury Network (AKIN). Accordingly, the investigators conducted a prospective, controlled, interventional trial, comparing two treatment groups in which the only variable was the RRT initiation strategy, to determine whether early versus late initiation in patients with AKI after cardiac surgery is associated with a survival benefit or more favorable outcomes.

Detailed Description
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Acute kidney injury after cardiac surgery is strongly associated with in-hospital mortality and morbidity. This is an area where effective treatments are lacking and trial are difficult to perform. To date no randomized controlled trial (RCT) has sufficiently estimated the impact of RRT timing of initiation on patient outcome, and the present prospective, controlled, interventional, single-center trial attempts to compare patient outcome with early versus late initiation of RRT. Previous studies in cardiac surgery setting have been retrospective ones and have been hampered by lead-time bias, and drop out patients. To overcome these biases all patients who underwent cardiac surgery were prospectively enrolled in the trial and were divided in two treatment groups: the early approach was used during the first 10-months, and the late approach during the next 10-months. To improve the information gained from this non-classical randomized study and to minimize bias, the investigators enrolled almost all patients with few exclusion criteria during two following short periods, used intention-to-treat analysis and treated all patients according to local protocols and international guidelines, except for RRT initiation strategy. Outcome parameters were hospital mortality, and ICU and hospital length of stay. Early therapy was started after 6 hours of urine output of less than<0,5ml/Kg/h, whereas in the late group RRT therapy was started on the basis of persistent (lasting more than 12 hours) oliguria. Data obtained from the database were analyzed using Statistical Package for Social Science (SPSS Inc, Chicago, IL). Continuous variables are presented as mean±SD, categorical variables were summarized as frequencies and percentages. The Student t test or Pearson X square test were performed to evaluate differences between groups and to analyze subgroups. For statistics, a p<0.05 was considered significant. Power calculation was based on previous reports13 on cumulative mortality following cardiac surgery. 50% reduction of mortality was hypothesized when the more conservative approach to cardiac surgery-AKI was applied. The suggested number of patients was about 900 patients per group. The main limitation of the present study include the non-classical randomization, nevertheless we conducted an interventional trial comparing two treatment strategies in two different groups of patients, prospectively followed and suitable for both treatments.

Official Title
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Early and Late Timing Indication for Starting Renal Replacement Therapy in Acute Renal Failure After Cardiac Surgery: a Prospective, Controlled, Interventional, Single-center Trial

Conditions
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Acute Kidney Injury

Intervention / Treatment
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* Procedure: Early RRT
* Procedure: Late RRT


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients submitted to cardiac surgery at Ospedali Riuniti of Ancona during the study period Planned use of extracorporeal circulation Exclusion criteria: Preoperative dialysis Planned off-pump cardiac surgery Pts (or proxy) did not sign informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Early RRT<br>In the early arm renal replacement therapy was started on the basis of refractory oliguria: urine output <0,5ml/Kg/h for > 6 hours | Procedure: Early RRT<br>* In the early arm renal replacement therapy was started on the basis of refractory oliguria: urine output <0,5ml/Kg/h for > 6 hours<br>|
| Active Comparator: Late RRT<br>In the late arm at least one the following criteria must be fulfilled prior to initiation of renal replacement therapy: persistent and refractory oliguria (<0,5 ml/Kg/h >12h), despite therapy refractory extravascular fluid overload azotemia > 40mmol/L or 240 mg/dL metabolic acidosis (pH<7,2) hyperkaliemia (k+>6 mmol/L) | Procedure: Late RRT<br>* In the late arm at least one the following criteria must be fulfilled prior to initiation of renal replacement therapy: persistent and refractory oliguria (<0,5ml/Kg/h >12h), despite therapy refractory extravascular fluid overload azotemia >40mmol/L or 240mg/dL metabolic acidosis (pH<7,2) hyperkaliemia (k+>6mmol/L)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| operative mortality | death during the same hospitalization as surgery, or after discharge, but within 30 days of surgery | death during the same hospitalization as surgery, or after discharge, but within 30 days of surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital length of stay | Hospital length of stay (days): from operative day to discharge or death | during the same hospitalization for surgery, but within 30 days from surgery | 
| ICU length of stay | from entrance to ICU after the end of surgery to discharge to ward facilities | during the same hospitalization for surgery, but within 30 days from surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute kidney injury, Cardiac surgery, Renal replacement therapy