Diuretics, Mortality, and Nonrecovery of Renal Function in Acute Renal
Failure


Author Information <http://jama.ama-assn.org/issues/v288n20/rfull/#aainfo>
Ravindra L. Mehta, MD; Maria T. Pascual, RN, MPH; Sharon Soroko, MS; Glenn
M. Chertow, MD, MPH; for the PICARD Study Group
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.
JAMA. 2002;288:2547-2553
JOC21128
Acute renal failure (ARF) in hospitalized patients may be associated with
low, normal, or excess extracellular volume, depending on the cause of the
ARF, accompanying conditions (eg, heart failure, liver disease), and
patterns of administration of crystalloids and colloids. Diuretic agents are
frequently given to augment renal salt and water excretion in the setting of
extracellular volume overload.
Diuretics are also frequently given during ARF in an effort to "convert"
oliguric to nonoliguric ARF, since oliguria has been recognized as a proxy
for the severity of ARF and the likelihood of requiring dialysis. 1-4
<http://jama.ama-assn.org/issues/v288n20/rfull/#r1>  Despite the ubiquity of
this practice, there is scant evidence that diuretics provide any material
benefit to patients with ARF. Indeed, the "conversion" of oliguric to
nonoliguric ARF may reflect the severity of disease (diuretic-responsive
ARF) rather than a valid (and favorable) response to therapy. 5-7
<http://jama.ama-assn.org/issues/v288n20/rfull/#r5>  Moreover, the use of
diuretics may increase the risk of ARF when given before radiocontrast
exposure 8-10 <http://jama.ama-assn.org/issues/v288n20/rfull/#r8>  and in
other clinical settings, 11-13
<http://jama.ama-assn.org/issues/v288n20/rfull/#r11>  raising the
possibility that diuretics may be harmful in patients with established ARF.
Several randomized clinical trials have explored the use of diuretics in
established ARF and have not shown benefit in survival or recovery of renal
function, although all studies were hampered by low statistical power. 14-17
<http://jama.ama-assn.org/issues/v288n20/rfull/#r14>
We hypothesized that the use of diuretics during ARF would be associated
with an increase in mortality, hospital length of stay, and nonrecovery of
renal function in critically ill patients with ARF due to either direct
effects or indirect effects of delaying dialytic support. To explore these
questions, we examined data from a cohort of critically ill patients with
ARF. Recognizing the limitations of comparing therapies that have not been
randomly assigned, we attempted to adjust for confounding and practice
variation with regression methods complemented by propensity scores.



METHODS



Study Cohort

Data were collected on all intensive care unit (ICU) patients with ARF who
received nephrology consultation at 4 teaching hospitals (University of
California San Diego Medical Center, San Diego Veterans Affairs Medical
Center, San Diego Naval Hospital, and University of California, Irvine,
Medical Center) from October 1989 to September 1995. Acute renal failure was
defined using standard laboratory parameters. For patients with no history
of kidney disease or known laboratory values, ARF was defined either by a
blood urea nitrogen (BUN) level of 40 mg/dL or higher (14.3 mmol/L) or a
serum creatinine level of 2.0 mg/dL or higher (177 µmol/L). For others, ARF
was defined by a sustained rise in serum creatinine levels of 1 mg/dL or
more (88.4 µmol/L) compared with baseline. Exclusion criteria included
previous dialysis, kidney transplantation, urinary tract obstruction, and
hypovolemia. Informed consent was obtained from all study participants or
their next-of-kin.
Patients were followed up prospectively from the time of initial nephrology
service consultation through hospital discharge. A total of 851 ARF cases
were initially evaluated. No information on vital status was available in 31
patients (4%). Of the 820 remaining, data sufficient to calculate generic
and disease-specific severity of illness scores for risk adjustment were
available in 605 patients (74%). Information on the use of diuretics from
the initial ICU consultation day onward was available in 552 patients (91%),
who comprised the analytic sample.
The primary outcome measure was all-cause hospital mortality. We also
considered the combined end point of either mortality or nonrecovery of
renal function and lengths of ICU and hospital stay. Recovery of renal
function was defined as being dialysis independent with a serum creatinine
level of 2.0 mg/dL or less (177 µmol/L) or no more than 20% higher than
baseline at the time of hospital discharge. The origin of ARF was classified
as follows: ischemic acute tubular necrosis, nephrotoxic acute tubular
necrosis, multisystem disorder, or uncertain.
Baseline vital signs, hemodynamic data (where available), and laboratory
data were recorded for the first ICU day and each day from the time of
nephrology consultation. Renal function was assessed daily from records of
urine output, BUN level, and serum creatinine level. Generic and
disease-specific severity-of-illness scores were computed on each successive
ICU day. We determined the number of organ systems in failure based on a
modification of the criteria of Chang et al. 18
<http://jama.ama-assn.org/issues/v288n20/rfull/#r18>  We used published
criteria for each organ system failure. 19
<http://jama.ama-assn.org/issues/v288n20/rfull/#r19>  We categorized
patients as taking or not taking diuretics on each of the first 7 days
following consultation and "ever" or "never" using diuretics during this
week. Additionally, we categorized patients treated with 1 vs 2 or more
diuretic agents and identified specific medications and daily doses for
secondary analyses. Oliguria was defined as urine output of less than 400
mL/d. To estimate the response to diuretics, we calculated the total daily
dose of loop diuretic (in furosemide equivalents) divided by the total urine
output in milliliters. For this calculation, 1 mg of bumetanide was
considered to be equivalent to 40 mg of furosemide.
Statistical Analysis

Continuous variables were expressed as mean (SD) (or 10% and 90% confidence
limits) or median and compared with the t test or the Wilcoxon rank sum test
where appropriate. Categorical variables were expressed as proportions and
compared with the Mantel-Haenszel chi2 test. Variables with significant
associations on univariate screening were considered candidates for
multivariable analysis, along with age, sex, and race. Multivariable
logistic regression was performed using backward variable selection, with
variable exit criteria set at P<.05. Variables not selected by the automated
procedure were added back into models individually to evaluate for residual
confounding. The area under the receiver operating characteristic curve was
used to assess model discrimination. 20
<http://jama.ama-assn.org/issues/v288n20/rfull/#r20>  Calibration was
estimated using the Hosmer-Lemeshow goodness-of-fit test. 21
<http://jama.ama-assn.org/issues/v288n20/rfull/#r21>
In addition to adjusting for significant covariates in multivariable
regression, residual confounding and selection effects were addressed using
propensity scores. 22 <http://jama.ama-assn.org/issues/v288n20/rfull/#r22>
To develop the propensity score, we included in a separate multivariable
logistic regression analysis all factors that differed among the diuretic
and no diuretic groups, using a more liberal significance criterion of
P<.25. With diuretic use as the dependent variable, we fit a model
predicting the likelihood or "propensity" of diuretic use. We then
incorporated the propensity score as a covariate in a logistic regression
model using mortality as the dependent variable. Inclusion of the propensity
score as a covariate in a multivariable regression theoretically normalizes
the likelihood of treatment (in this case, diuretics) and may effectively
adjust for unobserved confounding and selection bias, thereby refining
regression estimates. We performed these analyses again using the combined
end point of mortality or nonrecovery of renal function. Although the
primary analysis incorporated data from the day of consultation, we
conducted companion analyses for other time points. Finally, we used the
Kaplan-Meier product limit method 23
<http://jama.ama-assn.org/issues/v288n20/rfull/#r23>  to calculate the time
to death or the provision of dialysis for ARF (censored at day 60) and
compared survival curves with the log-rank test. P.05 (2-tailed) was
considered statistically significant. All analyses were conducted using SAS
statistical software, version 8 (SAS Institute Inc, Cary, NC).



RESULTS



Factors Associated With Diuretic Use

Characteristics for the diuretic and no diuretic groups on the day of
nephrology consultation are shown in Table 1
<http://jama.ama-assn.org/issues/v288n20/fig_tab/joc21128_t1.html> . Few
data were missing, except for the invasive physiologic variables, which were
individually available in 40% to 76% of patients. The mean age was
significantly higher and BUN and creatinine levels significantly lower among
diuretic-treated patients on day 1 of ICU consultation. There were no
significant differences in APACHE II (Acute Physiology and Chronic Health
Evaluation II) or APACHE III scores. Among patients who underwent invasive
hemodynamic monitoring, those with higher pulmonary capillary wedge pressure
and lower cardiac index were more likely to be given diuretics. The
proportion of patients given diuretics overall declined from 59% to 44% to
40% during the first 3 days following consultation, although an increasing
fraction of those taking diuretics were nonoliguric (59% to 80% to 86%).
Although there were initially no differences in severity-of-illness scores,
mean APACHE III scores were lower in diuretic-treated patients on day 2
(91.9 vs 87.3, P = .08) and day 3 (92.8 vs 82.7, P<.001). Sixty-six (29%) of
the 226 patients not taking diuretics at the time of consultation were given
diuretics during the following week.
Calculation of the Propensity Scores

The following equations were used to derive the propensity score for
diuretic use on the first day of consultation:
(1) X = (Age 0.113) - (Nephrotoxic Etiology of ARF 0.5645) - (BUN 0.00727) +
(Acute Respiratory Failure 0.5837) + (History of Congestive Heart Failure
0.8803) - 0.4394
(2) Propensity Score = (e or 2.7182818X)/[1 + (e or 2.7182818X)]
The propensity score itself can be interpreted as the likelihood of being
given diuretics based on the observed array of covariates included in the
model. The mean propensity score was 0.59 (ie, the fraction of patients
given diuretics on day 1); the range was 0.225 10-6to 0.910.
Mortality and Nonrecovery of Renal Function and Diuretic Use

Two hundred ninety-four (53%) of 552 patients died in-hospital. Fifty-six
(19%) of 294 patients who died recovered renal function before death. Among
the 258 patients who survived (47%), 17 (7%) were dialysis dependent after
discharge. We therefore fit distinct logistic regression models for
in-hospital mortality, nonrecovery of renal function, and the combined
outcome of mortality or nonrecovery of renal function ( Table 2
<http://jama.ama-assn.org/issues/v288n20/fig_tab/joc21128_t2.html> ). In the
covariate-adjusted models, we included age, sex, and the first consultation
day values for heart rate, BUN, creatinine, log urine output, and
respiratory, hematologic, and liver failure based on previous analyses. 24
<http://jama.ama-assn.org/issues/v288n20/rfull/#r24>  Diuretic use was
associated with a 68% (95% confidence interval [CI], 6%-164%) increase in
in-hospital mortality and a 77% (95% CI, 14%-176%) increase in the odds of
death or nonrecovery of renal function. In these models, there were no
significant interactions between diuretic use and urine output. Neither a
history of congestive heart failure nor the presence of cardiac organ system
failure explained the increased risks observed.
There was no difference in hospital length of stay by use of diuretics on
the first day of consultation (median, 21.5 vs 22.5 days; P = .95). However,
subsequent diuretic use was associated with significantly longer lengths of
stay (median difference, 4-10 days; all comparisons were at least P<.01 for
each of consultation days 2-7). The median time from consultation to first
dialysis was also significantly prolonged among patients given diuretics
(median difference, 1-2 days; P<.01 for each of consultation days 1-7).
Since many patients crossover as users and nonusers of diuretics, we also
compared results of patients classified as "ever" vs "never" users of
diuretics, excluding individuals who died within the first week following
consultation. In these analyses (n = 416), the odds ratio (OR) of death or
nonrecovery of renal function in "ever" users of diuretics was 2.01 (95% CI,
1.26-3.20). These results remained statistically significant after covariate
(OR, 3.15; 95% CI, 1.74-5.70) and covariate and day 1 propensity score
adjustment (OR, 3.12; 95% CI, 1.73-5.62). As with the primary analyses,
these models exhibited good discrimination and were well calibrated.
Single vs Combination Diuretic Use, Specific Diuretic Use, and Dosage

Several diuretic agents and diuretic combinations were used. Of the 326
patients given diuretics on ICU consultation day 1, 203 (62%) were given
furosemide, 189 (58%) were given bumetanide, 106 (33%) were given
metolazone, and 13 (4%) were given hydrodiuril. Loop and thiazide diuretics
in combination were given to 105 patients (32%). The median (with 10%-90%
range) doses of furosemide, bumetanide, and metolazone were 80 (20-320), 10
(2-29), and 10 (5-20) mg/d, respectively. Although diuretic use was
associated with mortality, nonrecovery of renal function, and prolonged time
to initiation of dialysis, there were no significant differences among
patients taking single vs combination diuretics for any of these parameters.
Index of Diuretic Responsiveness

Since higher doses of diuretics are often used in patients who are oliguric
or have declining urine output, we calculated the furosemide dose equivalent
per milliliter per day of urine output as an index of the degree of diuretic
responsiveness and, potentially, the severity of renal injury. The median
dose equivalent per milliliter ratio was 0.34 mg/mL (10%-90% range,
0.02-4.22). Expressed in clinical terms, the 10% to 90% ratio ranged from
very responsive (1000 mL associated with a single 20-mg dose of furosemide)
to very unresponsive (114 mL associated with 240 mg of furosemide given
twice daily). We a priori selected a ratio of 1.0 to stratify analyses by
diuretic responsiveness. Patients with a dose equivalent per milliliter
ratio of 1.0 or higher on the day of consultation had a higher odds of death
or nonrecovery compared with nonusers of diuretics (OR, 2.94; 95% CI,
1.61-5.36). In contrast, patients with a dose equivalent per milliliter
ratio of less than 1.0 experienced no significant increase in risk (OR,
1.15; 95% CI, 0.79-1.68). Results were similar when analyses were stratified
by a dose equivalent per milliliter ratio of 0.5 (OR, 2.75; 95% CI,
1.66-4.54; and OR, 0.97; 95% CI, 0.65-1.45; for dose equivalent per
milliliter ratios of 0.5 and <0.5, respectively). In other words, the
increase in risk was borne largely by patients who were relatively
unresponsive to diuretics. Moreover, the risk associated with a high dose
equivalent per milliliter ratio was magnified over time (day 2 following
consultation: OR, 3.61; 95% CI, 1.58-8.21; day 3 following consultation: OR,
7.12; 95% CI, 1.67-30.27).
Figure 1 <http://jama.ama-assn.org/issues/v288n20/fig_tab/joc21128_f1.html>
shows the relative differences in mean creatinine levels, mean BUN levels,
and median urine output for patients stratified by diuretic use and the dose
equivalent per milliliter ratio, with values censored at the initiation of
dialysis. Figure 2
<http://jama.ama-assn.org/issues/v288n20/fig_tab/joc21128_f2.html>  shows
the association between the dose equivalent per milliliter ratio and the
time to death or dialysis for ARF during hospitalization, comparing patients
not taking diuretics and those with high and low dose equivalent per
milliliter ratios (log-rank chi2, P<.001).



COMMENT



Diuretics have been widely used in ARF despite little evidence of benefit.
25 <http://jama.ama-assn.org/issues/v288n20/rfull/#r25> , 26
<http://jama.ama-assn.org/issues/v288n20/rfull/#r26>  Indeed, several
prospective clinical trials have evaluated the effect of loop diuretic
agents, usually at high doses, in prevention and/or treatment of ARF. 14
<http://jama.ama-assn.org/issues/v288n20/rfull/#r14> , 17
<http://jama.ama-assn.org/issues/v288n20/rfull/#r17> , 27
<http://jama.ama-assn.org/issues/v288n20/rfull/#r27>  Most studies 15-17
<http://jama.ama-assn.org/issues/v288n20/rfull/#r15>  were relatively small
and confounded by cointerventions such as low-dose dopamine hydrochloride or
mannitol. Aside from augmenting urine output, few studies have demonstrated
any material benefit of diuretics in ARF, whereas other studies have
suggested potential deleterious effects. 12
<http://jama.ama-assn.org/issues/v288n20/rfull/#r12> , 26-28
<http://jama.ama-assn.org/issues/v288n20/rfull/#r26>  For example, Lassnigg
et al 12 <http://jama.ama-assn.org/issues/v288n20/rfull/#r12>  showed that
postoperative ARF (defined as an increase in serum creatinine level of 0.5
mg/dL [44 µmol/L]) was more frequent in patients given furosemide (15%)
compared with dopamine (2%) or isotonic sodium chloride (0%).
In this study, 59% of patients were taking diuretics at the time of
nephrology consultation and 12% started taking diuretics after consultation.
Diuretic use at the time of consultation was significantly associated with
older age, presumed nephrotoxic (rather than ischemic or multifactorial) ARF
origin, a lower BUN level, acute respiratory failure, and a history of
congestive heart failure. After adjusting for covariates associated with the
risk of death, 24 <http://jama.ama-assn.org/issues/v288n20/rfull/#r24>
diuretic use was significantly associated with in-hospital mortality and
nonrecovery of renal function, even after adjustment for nonrandom treatment
assignment using propensity scores.
Possible explanations for the associations observed include a direct toxic
effect of diuretics or indirect effects either related or unrelated to renal
function. Providers of care in ICUs may underestimate the severity of renal
injury when urine output is sustained. Although we and others have shown
oliguria to be associated with adverse outcomes in ARF, 19
<http://jama.ama-assn.org/issues/v288n20/rfull/#r19> , 24
<http://jama.ama-assn.org/issues/v288n20/rfull/#r24> , 29-33
<http://jama.ama-assn.org/issues/v288n20/rfull/#r29>  it is unclear whether
diuretic use modifies the effect of oliguria on mortality or nonrecovery of
renal function. We have previously shown that oliguria and a low serum
creatinine level (associated either with low creatinine generation or
dilution with extracellular volume overload) are the 2 factors most closely
related to delay in nephrology consultation among patients who have ARF on
ICU admission. 34 <http://jama.ama-assn.org/issues/v288n20/rfull/#r34>  If
nonoliguria delays recognition of ARF or recognition of the severity of ARF,
then the use of diuretics might influence ICU management, including the
timing of dialysis. The relative 1- to 2-day delay in time from consultation
to initiation of dialysis in patients taking diuretics suggests that
practice patterns differ among patients taking and not taking diuretics. If
persons die from rather than with ARF, as others and we have suggested,
35-37 <http://jama.ama-assn.org/issues/v288n20/rfull/#r35>  delay in
initiation of dialysis (waiting for a response to diuretics) may have
untoward effects. These effects could include the worsening of respiratory,
cardiovascular, central nervous system, and immune function due to volume
overload and the effects of uremia.
In addition to the major findings linking diuretic use to mortality and
nonrecovery, we highlighted the potential importance of severity of renal
injury in determining ARF outcomes. Biopsies are rarely performed in
patients with ARF, and no reliable, valid index of ARF severity has yet been
developed. In this study, we showed that the increased risk associated with
diuretic use was largely borne by those individuals who were relatively
resistant to the agents, confirming and extending the findings previously
reported by Cantarovich and Verho 38
<http://jama.ama-assn.org/issues/v288n20/rfull/#r38>  in a multicenter
French study. In addition, we found that the degree of diuretic resistance
on consultation day 1 predicted subsequent changes in BUN and creatinine
concentrations, with the former paradoxically rising faster in more
diuretic-responsive patients. If this index (total daily furosemide dose
equivalent per milliliter per day of urine output) were validated in other
settings, it might serve as a means to risk stratify patients early in ARF.
In other words, if a patient with early ARF has low or declining urine
output despite high doses of loop diuretics, then further delay in
instituting corrective therapy may not be warranted, since the likelihood of
death or the need for dialysis in the short term is extremely high. In this
way, the practice of a "diuretic challenge" need not be abandoned but rather
modified. Ultimately, identifying the optimal timing of initiation of
dialysis (or hemodiafiltration) in ARF will have to be determined in a
prospective randomized trial.
There are several important limitations to this study. Even with propensity
score adjustment, we cannot truly evaluate the effect of diuretics, as we
could in a prospective randomized trial. Although the propensity score can
adjust for confounding by indication and selection bias, we cannot eliminate
residual confounding due to unobserved factors. We had no kidney biopsy data
and no method by which direct toxic injury induced by diuretics could be
proved or refuted. Therefore, we were unable to derive any mechanistic
explanation for the findings described herein. Although this was a
multicenter study, the hospitals were all within a single region, and the
results described may not be generalizable to other regions or practice
settings (eg, settings where the availability of dialysis services may
differ). These patients were critically ill. Therefore, we cannot
extrapolate the results to individuals with less severe forms of ARF or with
ARF in the absence of critical nonrenal disease. Moreover, since all
patients included in this study had a significant increase in serum
creatinine levels, we cannot infer that diuretics would be harmful in
patients very early in ARF, although there is no evidence that they would be
of benefit based on studies in ARF prevention. 27
<http://jama.ama-assn.org/issues/v288n20/rfull/#r27>
Although the data were collected mainly in the 1990s, ARF practice patterns
have not changed significantly since that time. In randomized clinical
trials (1995-1999) that tested the efficacy of other agents known to augment
urine output (eg, atrial natriuretic peptide, low-dose dopamine), 43% to 55%
of patients with ARF in the ICU were treated with diuretics, even with
sustained oliguria. 28 <http://jama.ama-assn.org/issues/v288n20/rfull/#r28>
, 39 <http://jama.ama-assn.org/issues/v288n20/rfull/#r39>  In a recent
survey of the European Workgroup of Cardiothoracic Intensivists, 12
<http://jama.ama-assn.org/issues/v288n20/rfull/#r12>  11 of 38 used
continuous infusions of furosemide for "renoprotection" and 34 of 38 used
furosemide bolus injections when urine output decreased to less than 0.5
mL/kg per hour. Although some nonrenal ICU therapies (eg, methods of
mechanical ventilation, frequency of pulmonary artery catheter use, choice
of antibiotics) have changed during the past several years, it is unlikely
that these changes have modified the relations among diuretic use and
outcomes in critically ill patients with ARF.
In summary, we determined that diuretic use was associated with adverse
outcomes in ARF. The increase in mortality and nonrecovery of renal function
observed may be due to a direct deleterious effect of diuretic agents, a
delay in the institution of renal support (in effect, forestalling dialysis
with volume overload or with anticipated reversal of azotemia), or other or
unknown factors. Although we cannot securely determine that diuretics are
harmful, it is highly unlikely that diuretics afford ARF patients any
material benefit. In the absence of compelling contradictory data from a
randomized, blinded clinical trial, we should discourage the widespread use
of high-dose diuretics in critically ill patients with ARF.



Author/Article Information


Author Affiliations: Division of Nephrology, University of California, San
Diego, Medical Center (Dr Mehta and Mss Pascual and Soroko); and Divisions
of Nephrology, Moffitt-Long Hospitals and UCSF–Mt Zion Medical Center,
University of California, San Francisco (Dr Chertow).

Corresponding Author and Reprints: Glenn M. Chertow, MD, MPH, Department of
Medicine Research, University of California San Francisco, UCSF Laurel
Heights, Suite 430, 3333 California St, San Francisco, CA 94118-1211
(e-mail: [log in to unmask] <mailto:[log in to unmask]> ).
Author Contributions: Study concept and design: Mehta, Chertow.
Acquisition of data: Mehta, Pascual.
Analysis and interpretation of data: Mehta, Pascual, Soroko, Chertow.
Drafting of the manuscript: Mehta, Pascual, Chertow.
Critical revision of the manuscript for important intellectual content:
Mehta, Soroko, Chertow.
Statistical expertise: Soroko, Chertow.
Obtained funding: Mehta, Chertow.
Administrative, technical, or material support: Mehta.
Study supervision: Mehta, Pascual, Chertow.
Funding/Support: This study was supported by grant RO1-DK53412-0 from the
National Institutes of Health, National Institute of Diabetes and Digestive
and Kidney Diseases, Bethesda, Md.
Previous Presentation: This study was presented in abstract form at the
ASN/ISN World Congress of Nephrology, San Francisco, Calif, October 15,
2001.
Members of The Project to Improve Care in Acute Renal Disease (PICARD) Study
Group include Ravindra L. Mehta, MD, University of California, San Diego;
Glenn M. Chertow, MD, MPH, University of California, San Francisco; Emil
Paganini, MD, Cleveland Clinic Foundation, Cleveland, Ohio; T. Alp Ikizler,
MD, Vanderbilt University, Nashville, Tenn; and Jonathan Himmelfarb, MD,
Maine Medical Center, Portland.




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Edward E. Rylander, M.D.
Diplomat American Board of Family Practice.
Diplomat American Board of Palliative Medicine.