More is not better: VA-NIH study yields surprising
finding on treatment for acute kidney injury
June 10, 2008
More intensive treatment—for
example, dialysis six times instead of
three times per week—failed to produce any
added benefit for patients with acute kidney
injury in a large clinical trial sponsored by
VA and the National Institutes of Health.
The results appeared online May 20 in the
New England Journal of Medicine.
In acute kidney injury, the kidneys
suddenly shut down, causing a dangerous
buildup of fluids and waste products in the
body. The condition occurs most often in
hospital patients who have experienced
trauma, toxic side effects from drugs, or
infection following surgery. The risk is
higher in older patients and in those with
chronic kidney disease, high blood pressure,
diabetes, heart disease, or vascular disease.
Despite advances in care in recent
decades, acute kidney injury is costly to
treat and has a high death rate—50 to 80
percent. It affects about 3 percent of VA
patients and anywhere from 1 to 15 percent
of hospitalized patients in general.
Five earlier single-center trials had
yielded mixed findings as to whether more
intensive dialysis might save lives. But the
new VA-NIH trial included more patients
than the previous five studies combined and
is expected to influence how doctors
manage the condition.
"This is an important study that will
change our practice," Harvard Medical
School professor Ajay Singh, MD, told U.S.
News and World Report.
NIH director Elias A. Zerhouni, MD,
said: "We now have definitive evidence that
intensive treatment of acute kidney injury is
no more beneficial in improving treatment
outcomes than the usual level of care. As a
result, the findings of this well-designed
study may help prevent unnecessary
The VA-NIH study, conducted from 2003
to 2007, included 1,124 critically ill patients
at 17 VA hospitals and 10 university
hospitals. Patients were randomly assigned
to either intensive or less-intensive
treatment. The exact type of renal therapy
depended on the patient’s condition.
Patients who did not need drugs to maintain
their blood pressure were given
conventional hemodialysis—three times per
week in the less-intensive arm, six times per
week in the intensive arm. In hemodialysis,
a machine does the job of the kidneys and
filters toxins and extra fluid from the blood.
Patients who needed drugs to increase their
blood pressure were given gentler forms of
renal replacement therapy, in either higher
or lower doses or frequencies. Patients were
able to switch between forms of renal
replacement therapy as their clinical
condition changed, while staying within the
lower-or higher-intensity treatment arm.
About half the patients in both groups
died within the first two months of dialysis.
The difference in death rates was not
statistically significant, according to the authors. There were also
no significant differences between the groups in recovery of kidney
function, the rate of failure of organs other than kidneys, or
patients’ ability to return to prior living situations.
"What we have shown is that the more intensive therapy is not
better than the less intensive strategy," said study chairman Paul
M. Palevsky, MD, chief of the renal section at the VA Pittsburgh
Healthcare System and a professor of medicine at the University of
Pittsburgh School of Medicine. Palevsky added that "unlike earlier
studies that used only a single method of therapy, our use of an
integrated strategy of continuous and intermittent methods of
therapy allows us to apply these study results more readily to
clinical practice. What is important about these results is that they
outline the limits of effective therapy."
The study was cosponsored by VA's Cooperative Studies
Program and NIH’s National Institute of Diabetes and Digestive
and Kidney Diseases.
This article originally appeared in the June 2008 issue of VA Research Currents.