Even when their blood pressure is kept strictly under
control with the best available medicine,
African-American patients with chronic kidney disease
continue to lose their kidney function over
time, research led by a Johns Hopkins team shows. The
finding suggests that treating chronic kidney
disease, or CKD, in this population may be vastly more
complex than researchers had previously
thought, with blood pressure control being only one piece
of the therapeutic puzzle.
The study, called AASK (for African-American Study of
Kidney Disease and Hypertension), is
the longest to date focusing on blood pressure in patients
with CKD. AASK followed 1,094 African-
American patients with this condition for up to 11 years.
Through a combination of medications, most
of these patients kept their blood pressure in the
recommended range for CKD, which is lower than
130/80. However, the vast majority still went on to develop
steadily worsening kidney function, often
leading to dialysis, kidney transplantation or death.
"Kidney disease still progressed at an alarming rate,
even when our participants received
outstanding medical care for their high blood pressure,"
said study leader Lawrence Appel, professor
of medicine at the Johns Hopkins School of Medicine. "Blood
pressure is important, but it's not the
whole picture. We still have a long way to go in figuring
out the best way to treat patients with CKD."
Appel and his colleagues at 21 clinical centers across
the country chose to focus their study on
African-Americans, who suffer disproportionately from
kidney disease associated with high blood
pressure. In whites, high blood pressure causes about 19
percent of all end-stage renal disease cases,
in which kidneys have essentially lost their function. In
African-Americans, the corresponding figure
is about 37 percent.
Researchers aren't sure why high blood pressure often
leads to CKD. The prevailing theory is
that high pressure strains delicate tufts of capillaries
known as glomeruli, which filter blood and
create urine in kidneys.
To investigate whether keeping blood pressure low
would slow or possibly stop CKD progression,
the researchers designed their study in two phases; the
first would take place between February
1995 and September 2001, and the second between October
2001 and June 2007.
In the first phase, the researchers randomly assigned
all 1,094 patients to one of three drugs
commonly used to lower blood pressure--an ACE inhibitor, a
beta-blocker or a calcium channel blocker.
Each patient also was assigned to one of two blood pressure
goals--a standard goal (about 140/90 or
lower) and a more aggressive goal (130/80 or lower). The
researchers tracked each patient's blood
pressure and kidney function, determined through blood and
urine tests, as well as his or her overall
At the end of the first phase, the researchers found
that about a third of the patients had
lost at least half their kidney function, developed
end-stage renal disease or died, even though almost
all the patients were well within their blood pressure
goals. Of the remaining patients, the scientists
recruited 759 to continue on to the study's next phase, in
which they capitalized on what they'd
learned so far. Early findings from the first phase showed
that the ACE inhibitor worked better than
the other treatments, so the remaining patients began
taking that drug. They were also given the
more aggressive blood pressure goal of 130/80.
Over the next five years, the researchers again
tracked patients' blood pressure, kidney
function and overall health. However, regardless of their
new and improved treatment, a third of
these patients still lost at least half their kidney
function, developed end-stage renal disease or died.
These results, published in the April 28 Archives of
Internal Medicine, shouldn't discourage
patients with CKD from continuing their blood pressure
therapy, Appel said. "Outcomes would certainly
be worse if they didn't control their blood pressure," he
said. However, he adds that the findings
suggest that other factors beyond just blood pressure may
be at play in worsening CKD. Blood
pressure spikes at night, high salt intake or exposure to
heavy metals like lead or mercury may
influence kidney disease progression. "Lots of different
factors need examining," he said.
Appel and his colleagues plan to investigate these
additional factors in future studies. This
study was supported by the National Institute of Diabetes
and Digestive and Kidney Diseases,
National Center for Minority Health and Health Disparities,
and King Pharmaceuticals Co.
Another Johns Hopkins author was Jeanne Charleston.