Diuretics, Mortality, and Nonrecovery of Renal Function in Acute Renal Failure
This review may be edited
Posted By: A. Delaney
E-Mail: apdelane@doh.health.nsw.gov.au
Posted Date: 6/12/02
Title: Diuretics, Mortality, and Nonrecovery of Renal Function in Acute Renal Failure
Authors: Ravindra L. Mehta, MD; Maria T. Pascual, RN, MPH; Sharon Soroko, MS; Glenn M. Chertow, MD, MPH; for the PICARD Study Group
Reference: JAMA. 2002;288:2547-2553
Link: Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract: Context Acute renal failure is associated with high mortality and morbidity. Diuretic agents continue to be used in this setting despite a lack of evidence supporting their benefit.
Objective To determine whether the use of diuretics is associated with adverse or favorable outcomes in critically ill patients with acute renal failure.
Design Cohort study conducted from October 1989 to September 1995.
Patients and Setting A total of 552 patients with acute renal failure in intensive care units at 4 academic medical centers affiliated with the University of California. Patients were categorized by the use of diuretics on the day of nephrology consultation and, in companion analyses, by diuretic use at any time during the first week following consultation.
Main Outcome Measures All-cause hospital mortality, nonrecovery of renal function, and the combined outcome of death or nonrecovery.
Results Diuretics were used in 326 patients (59%) at the time of nephrology consultation. Patients treated with diuretics on or before the day of consultation were older and more likely to have a history of congestive heart failure, nephrotoxic (rather than ischemic or multifactorial) origin of acute renal failure, acute respiratory failure, and lower serum urea nitrogen concentrations. With adjustment for relevant covariates and propensity scores, diuretic use was associated with a significant increase in the risk of death or nonrecovery of renal function (odds ratio, 1.77; 95% confidence interval, 1.14-2.76). The risk was magnified (odds ratio, 3.12; 95% confidence interval, 1.73-5.62) when patients who died within the first week following consultation were excluded. The increased risk was borne largely by patients who were relatively unresponsive to diuretics.
Conclusions The use of diuretics in critically ill patients with acute renal failure was associated with an increased risk of death and nonrecovery of renal function. Although observational data prohibit causal inference, it is unlikely that diuretics afford any material benefit in this clinical setting. In the absence of compelling contradictory data from a randomized, blinded clinical trial, the widespread use of diuretics in critically ill patients with acute renal failure should be discouraged.
Are the Results Valid?
1. Were there clearly identified comparison groups that were similar with respect to important determinants of outcome, other than the one of interest?
The two groups on whom the primary analysis was conducted were those taking or not taking diuretics on the day of consultation with the nephrologist. When the two groups (taking or not taking diuretics on the day of nephrology consultation) were compared there were a number of significant differences between them. These were adjusted for in later analyses by co-variate analysis and by calculation of a propensity score.
2. Were the outcomes and exposures measured in the same way in the groups being compared?
Exposure to diuretic therapy was measured the same way in both groups. Outcomes were clearly defined, (death, no need for dialysis, and non recovery of renal function by pre-defined criteria), reasonably objective and measured the same way in both groups.
3. Was follow-up sufficiently long and complete?
Follow-up was complete for the patients analysed. It should be noted that of the 851 patients that were identified with acute renal failure 299 (35%) had insufficient data completed to be followed up adequately, which is a little unusual in a prospective study. No outcome data for these patients is presented. If outcomes were similar between patients with complete data and those that could not be included due to missing data, we could conclude that missing data was a 'random' event and thus less likely to introduce bias. If the outcome of the patients with missing data was significantly different from the outcome of patients with complete data, it is possible that the exclusion of patients with missing data introduced bias.
4. Is the temporal relationship correct?
There is not a definite temporal relationship between diuretic use and poor outcome demonstrated. The use of diuretic therapy may be indicative of worse underlying cardiac and renal impairment, which could be the cause for the measured difference in outcome.
5. Is there a dose response gradient?
The authors report that patients who recieved higher doses of diuretic and had a poor response as measured by urine output had a worse prognosis. Again, this may indicate a dose response gradient or indicate that the underlying renal insult was more severe in those people who didn't respond to a diuretic challenge.
What are the Results?
1. How strong is the association between exposure and outcome?
The raw data needed to calculate relative risk are not presented in the paper. The results are presented as odds ratios (OR's).
For the primary outcome measure of all-cause in-hospital mortality the unadjusted OR (95%confidence intervals)was 1.37 (0.97-1.92), which does not quite reach statistical significance.
The OR when adjusted for covariates was 1.65 (1.05-2.58) and adjusting for both covariates and the propensity score was 1.68 (1.06-2.64), indicating a small increase in the risk of death associated with the use of diuretics.
There were also similar OR's indicating a small increased risk for nonrecovery of renal function and for the composite end-point of death or nonrecovery of renal function associated with the use of diuretics.
2. How precise is the estimate of risk?
The 95% confidence intervals are presented above.
Will the Results Help Me In Caring For My Patients?
1. Are the results applicable to my practice?
Acute renal failure is a common problem in critical care medicine. The characteristics of the patients, their underlying medical conditions and the causes of the renal failure in these patients is not dissimilar to the sort of patients that are in many ICU's. It may not apply to patients whose sole problem is acute renal failure who are not sick enough to be admitted to an ICU.
2. What is the magnitude of the risk?
The magnitude of the risk demonstrated in this study is small. The lower end of the confidence intervals for all groups is close to 1. When the nature of the study is taken into consideration, it makes drawing substantial conclusions regarding the effect difficult.
3. Should I attempt to stop the exposure?
At the moment, this study should not be sufficient to cause a change in clinical practice. The magnitude of the effect demonstrated is small and the limitations of the cohort design make drawing definitve conclusions difficult. It does however raise doubts about the use diuretics in intensive care patients with acute renal failure. Further prospective randomised studies are needed to definitively answer this question and to sort out the role of diuretics in the management of acute renal failure.

What other people had to say about:
Diuretics, Mortality, and Nonrecovery of Renal Function in Acute Renal Failure

Add Your Comment
[ Back ]

Any questions or comments please contact Gordon S. Doig
Implemented and designed by John Soer and Gordon Doig
Page last modified on Friday August 10, 2001