Spectrum of acute renal failure in the intensive care unit: the PICARD experience.

BACKGROUND: Acute renal failure (ARF) in the critically ill is associated with extremely high mortality rates. Understanding the changing spectrum of ARF will be necessary to facilitate quality improvement efforts and to design successful interventional trials. METHODS: We conducted an observational cohort study of 618 patients with ARF in intensive care units at five academic medical centers in the United States. Participants were required to sign (or have a proxy sign) informed consent for data collection. A comprehensive data collection instrument captured more than 800 variables, most on a daily basis, throughout the course of ARF. Patient characteristics, dialysis status, and major outcomes were determined and stratified by clinical site. RESULTS: The mean age was 59.5 years, 41% were women, and 20% were of minority race or ethnicity. There was extensive comorbidity; 30% had chronic kidney disease, 37% had coronary artery disease, 29% had diabetes mellitus, and 21% had chronic liver disease. Acute renal failure was accompanied by extrarenal organ system failure in most patients, even those who did not require dialysis. Three hundred and ninety-eight (64%) patients required dialysis. The in-hospital mortality rate was 37%, and the rate of mortality or nonrecovery of renal function was 50%. The median hospital length of stay was 25 days (26 days, excluding patients who died). CONCLUSION: There is a changing spectrum of ARF in the critically ill, characterized by a large burden of comorbid disease and extensive extrarenal complications, obligating the need for dialysis in the majority of patients. There is wide variation across institutions in patient characteristics and practice patterns. These differences highlight the need for additional multicenter observational and interventional studies in ARF.

Reasons for non-enrollment in a cohort study of ARF: the Program to Improve Care in Acute Renal Disease (PICARD) experience and implications for a clinical trials network.

BACKGROUND: Acute renal failure (ARF) is associated strongly with in-hospital mortality and morbidity. Previous clinical trials of ARF have been hampered by the heterogeneous population affected, difficulty defining ARF, delays in identification of ARF, and significant comorbid conditions, among other factors. METHODS: The Program to Improve Care in Acute Renal Disease (PICARD) phase I was a multicenter cohort study aimed to identify clinical characteristics and practice patterns associated with adverse and favorable outcomes in patients with ARF in intensive care units. Although PICARD used no interventions, signed informed consent was required of all study subjects or their proxies. RESULTS: Signed informed consent was obtained in 645 of 1,243 ARF episodes (52%). The fraction of patients not enrolled and reasons for non-enrollment varied widely across the 5 PICARD centers. Refusal by potential study subjects was infrequent, although the absence of family or proxy (15%) and refusal by family or proxy (18%) accounted for large fractions of non-enrolled subjects. Death (23%) and discharge (11%) before study personnel could evaluate patients were additional important reasons for non-enrollment. CONCLUSION: Understanding reasons for non-enrollment may help rationalize mortality and other outcome differences seen in clinical trials and cohort studies that require informed consent compared with historic reports of "all comers" with ARF.

Diuretics, mortality, and nonrecovery of renal function in acute renal failure.

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.

Nephrology consultation in acute renal failure: does timing matter?

PURPOSE: Patients who develop acute renal failure in the intensive care unit (ICU) have extremely high rates of mortality and morbidity. The goals of this study were to identify correlates of the timing of nephrology consultation in acute renal failure, and to explore the relation between timing of consultation and outcomes. METHODS: We explored associations among timing of nephrology consultation and in-hospital mortality, lengths of hospital and ICU stay, and recovery of renal function in 215 ICU patients with acute renal failure at four U.S. teaching hospitals. We used multivariable logistic regression and propensity scores to adjust for confounding and selection effects. RESULTS: Nephrology consultation was delayed (>or=48 hours) in 61 patients (28%) (median time to consultation, 4 days). Lower serum creatinine levels (P <0.0001) and higher urine output (P = 0.002) were associated with delayed consultation. Delayed consultation was associated with increased mortality among dialyzed (31/42 [74%] vs. 50/103 [49%], P = 0.006) and nondialyzed patients (10/19 [53%] vs. 11/51 [22%], P = 0.01), and increases in lengths of hospital (median, 19 days vs. 16 days, P = 0.01) and ICU stay (17 days vs. 6 days, P <0.0001). The association between delayed consultation and mortality was attenuated by covariate adjustment, and was no longer statistically significant after adjustment for propensity score (odds ratio = 2.0; 95% confidence interval: 0.8 to 5.1). CONCLUSION: In acute renal failure, delayed nephrology consultation was associated with increased mortality and morbidity, whether or not dialysis was ultimately required. Using observational data, we cannot determine whether these findings reflect residual confounding, selection bias, adverse effects of delayed recognition of acute renal failure, or the benefits of nephrology consultation.

Refining predictive models in critically ill patients with acute renal failure.

Mortality rates in acute renal failure remain extremely high, and risk-adjustment tools are needed for quality improvement initiatives and design (stratification) and analysis of clinical trials. A total of 605 patients with acute renal failure in the intensive care unit during 1989-1995 were evaluated, and demographic, historical, laboratory, and physiologic variables were linked with in-hospital death rates using multivariable logistic regression. Three hundred and fourteen (51.9%) patients died in-hospital. The following variables were significantly associated with in-hospital death: age (odds ratio [OR], 1.02 per yr), male gender (OR, 2.36), respiratory (OR, 2.62), liver (OR, 3.06), and hematologic failure (OR, 3.40), creatinine (OR, 0.71 per mg/dl), blood urea nitrogen (OR, 1.02 per mg/dl), log urine output (OR, 0.64 per log ml/d), and heart rate (OR, 1.01 per beat/min). The area under the receiver operating characteristic curve was 0.83, indicating good model discrimination. The model was superior in all performance metrics to six generic and four acute renal failure-specific predictive models. A disease-specific severity of illness equation was developed using routinely available and specific clinical variables. Cross-validation of the model and additional bedside experience will be needed before it can be effectively applied across centers, particularly in the context of clinical trials.