Higher death rate and non-recovery of kidney function seen in ICU patients given diuretics

November 26, 2002

A substantially higher death rate and inability to recover from kidney failure was documented in a study of 552 critically ill, hospitalized patients who were given diuretics, the most commonly used therapy for kidney failure.

Published in the November 27, 2002 issue of the Journal of the American Medical Association (JAMA), the study suggests that physicians treating patients in acute kidney failure should reassess the use of diuretics, particularly when there is a limited response in terms of increased urine output.

A large percentage of patients who don't respond to diuretics may require dialysis, the use of a medical device to support kidney function by removing impurities that are usually eliminated by normal kidneys, said first author Ravindra Mehta, M.D., University of California, San Diego professor of medicine. He also noted that a delay in treatment, while physicians wait for diuretics to have an effect, can lead to numerous adverse medical outcomes.

The study was conducted over six years at four California hospitals by researchers at the UCSD School of Medicine and the University of California, San Francisco (UCSF).

Comparing kidney-failure patients who were prescribed diuretics to those who were not, researchers found that diuretic use was associated with a 68 percent increase in mortality and a 77 percent increase in the non-recovery of kidney function.

Diuretics are commonly prescribed to increase urine output in patients whose kidneys fail to produce enough urine, an indicator that harmful waste products are being retained, rather than filtered out by the kidneys. Previous studies have shown that 300,000-500,000 hospitalized patients in the U.S. develop kidney failure after admittance, making it a fairly common occurrence. Approximately 50-75 percent of these patients are traditionally given diuretics.

Noting that the JAMA paper describes an observational study, Mehta added that further investigations are needed to determine the direct causal link between diuretics and adverse outcomes.

The 552 patients studied had been admitted for a variety of medical conditions, and were then diagnosed with acute renal (kidney) failure in intensive care units at UCSD Medical Center, the San Diego Veterans Affairs Medical Center, San Diego Naval Hospital, and UC Irvine Medical Center from October 1989 to September 1995. Patients were followed from the time of initial consultation by a kidney specialist through hospital discharge or death. To compensate for variables, such as age, sex, race and additional disease or organ malfunction, the researchers used sophisticated statistical analysis to compare patients given diuretics to those who were not.

In addition to the increased mortality and non-recovery of kidney function, the investigators also found a variation in the time between consultation with a kidney specialist and the start of dialysis treatment, as physicians waited for a response to the diuretic therapy. "Delay in initiation of dialysis (waiting for a response to diuretics) may have untoward effects," the researchers said in the study. "These effects could include the worsening of respiratory, cardiovascular, central nervous system, and immune function due to volume overload and the effects of uremia."

An accompanying editorial in JAMA said the study is timely and clinically important because administration of diuretics to ICU patients in kidney failure is still a relatively common practice. "Until data from a sufficiently powered clinical trial can properly answer the question of whether critically ill patients are harmed by loop diuretics, the practice of routine administration of these agents to such patients should be discouraged," the editorial stated.

"This study illustrates that kidney failure is prevalent and too frequently under-diagnosed by ICU providers," Mehta said. "Kidney failure is dangerous and the longer it goes on, the likelihood of an adverse outcome increases. Physicians need to be aware that even small changes in kidney function can have deleterious effects. They need to recognize kidney failure early on and consider immediate dialysis as their first treatment of choice."
Additional authors were Glenn M. Chertow, M.D., MPH, UCSF, and Maria T. Pascual, R.N. and MPH, Sharon Soroko, M.S., UCSD Department of Medicine. The study was funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases.

Note: An additional study published by Mehta and others October 15, 2002 (Vol. 113) in the American Journal of Medicine used the same group of ICU patients to compare the relationship between the time a kidney specialist is consulted and the outcomes experienced by patients. The researchers found that delayed consultation was associated with increased mortality and worsening condition, whether or not dialysis was ultimately required. Mehta noted that this is another argument for immediate attention to kidney function in critically ill patients. This paper can be seen at the following website: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12427493&dopt=Abstract.

University of California - San Diego

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