Research Updates in Kidney and Urologic Health
DKUHD Program Initiatives for 1999
The National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) provides leadership for a national research program in kidney
and urologic diseases through its Division of Kidney, Urologic, and Hematologic
Diseases (DKUHD). Each year, DKUHD works with NIDDK's Advisory Council—representing
a broad range of non-Federal scientific, educational, and medical institutions—to
plan and develop a set of program initiatives designed to yield fundamental,
innovative, and valuable contributions to human health. The following
list of DKUHD program initiatives for 1999 demonstrates the division's
commitment to maintaining the phenomenal progress of recent years in understanding
the biological processes that result in kidney and urologic diseases.
Polycystic Kidney Disease (PKD). In the past few years, much progress
has been made in understanding the genetic mechanisms that underlie the
development of kidney cysts. In addition to supporting ongoing genetic
studies, DKUHD is initiating a program to develop and test accurate, reproducible
techniques to monitor PKD progression so that potential interventions
can be evaluated. This program will apply the latest advances in imaging
technology so that clinicians can use information about kidney size and
the portion of the renal parenchyma occupied by cysts to determine how
far the disease has progressed. Other potential markers of progression,
such as cells found in the urine, will also be tested as potential diagnostic
tools. DKUHD has issued a request for applications for a consortium of
participating clinical centers to cooperate in this program with a data
coordinating and imaging analysis center. Applications must be received
by March 10, 1999. Contact: Gladys H. Hirschman, M.D., director, Chronic
Renal Diseases and Pediatric Nephrology Programs.
Nephropathy Susceptibility Genes. DKUHD supports some 40 grants
investigating the molecular mechanisms behind renal disease and the progression
to end-stage renal failure. Recent insights into abnormal deposits of
collagen IV and other large molecules in renal disease have supplied clues
to the genetic factors contributing to disease progression. A new initiative
designed to provide resources for study will develop a repository of genetic
samples from families with established histories of renal disease. This
resource will make it possible for researchers to learn why some people
with risk factors for kidney disease, such as diabetes or the PKD gene,
progress rapidly to end-stage renal failure while others with the same
risk factors appear to be protected. Researchers are also encouraged to
investigate the genetic factors behind the disproportionate number of
minorities who progress rapidly to end-stage renal failure, especially
African Americans and Native Americans. Contact: Gladys H. Hirschman,
M.D., director, Chronic Renal Diseases and Pediatric Nephrology Programs.
Urinary Incontinence. DKUHD and the National Kidney and Urologic
Diseases Information Clearinghouse have conducted two workshops and a
national awareness campaign to draw attention to, and seek solutions for,
the growing problem of urinary incontinence. At the January 1998 workshop
on Research Issues and Opportunities, participants noted a lack
of evaluative studies comparing the long-term outcomes of existing treatment
options for urinary incontinence. In 1999, DKUHD will collaborate with
other agencies within the National Institutes of Health in issuing a request
for applications to fund research to address this need for information
about the long-term outcomes of various treatment strategies, including
behavioral therapies, drugs, and surgery. Contact: Leroy M. Nyberg, M.D.,
Ph.D., director, Urology Program.
Cardiovascular Disease in Patients with Renal Disease. People
with end-stage renal disease (ESRD) may be up to 50 times more likely
to have cardiovascular problems than people in the general population.
These problems are the most important cause of morbidity and mortality
in patients with ESRD. Even before patients with renal disease reach the
end stage, they are at increased risk for cardiovascular disease. DKUHD
is supporting ongoing research into the relationship between renal insufficiency
and abnormal lipid metabolism. Patients with renal disease are also likely
to have elevated levels of serum homocysteine, a known risk factor for
cardiovascular disease. One arm of this initiative will search existing
databases (such as the Framingham study and the Baltimore Longitudinal
Study on Aging) to gather more information about the problem. DKUHD is
also planning collaborative efforts with other divisions and agencies
to evaluate the feasibility of clinical trials testing homocysteine-lowering
interventions in kidney transplant patients and in patients with proteinuria
or mild to moderate renal insufficiency. Potential institutional partners
are NIDDK's Division of Diabetes, Endocrinology, and Metabolic Diseases;
the National Heart, Lung, and Blood Institute; and the National Institute
on Aging. Contact: Camille A. Jones, M.D., M.P.H., director, Epidemiology
Program; or John W. Kusek, Ph.D., director, Clinical Trials Program.
Hemolytic Uremic Syndrome (HUS). Hemolytic uremic syndrome is
the most common cause of acute renal failure in infants and children.
The first stages of the illness involve gastrointestinal symptoms such
as abdominal pain, vomiting, and bloody diarrhea, which are brought on
by an infection in the digestive system. The infecting agent is usually
a strain of the Escherichia coli bacterium that produces a toxin,
which destroys red blood cells and the platelets that normally contribute
to clotting. The toxin also damages the glomerular membrane, thus reducing
or shutting down kidney function. Blood and kidney problems appear about
1 week after the gastrointestinal symptoms subside. In recent years, DKUHD-supported
research has made great progress in identifying and understanding the
biochemical events that lead to HUS, but no treatment has been found to
prevent or reduce the effects of the toxin. The division will continue
to support studies to provide insights into the pathogenesis of HUS and
new research to develop strategies to prevent it during the critical interval
between a bout of gastroenteritis and the actual development of HUS. Contact:
Gladys H. Hirschman, M.D., director, Chronic Renal Diseases and Pediatric
Nephrology Programs.
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Research on Racial Disparities in Kidney Disease:
Gene Study Initiative Added to AASK Trial
Nearly 100,000 African Americans are being treated for end-stage renal
disease (ESRD). This number represents almost one-third of all ESRD patients,
a far greater percentage of African Americans than there are in the general
population. The risk of developing ESRD is four times greater for African
Americans than for Americans of European descent. While diabetes is the
leading cause of ESRD in the general population, it is second to hypertension
among African Americans, who are six times more likely than Caucasians
to develop ESRD from high blood pressure. Between 1993 and 1995, the incidence
of hypertensive ESRD was 283.6 per million in African Americans, compared
with 46.7 in Caucasians, 87.8 in Asian/Pacific Islanders, and 95.1 in
Native Americans/Alaska Natives.
Since 1992, the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) has supported the African-American Study of Kidney Disease
and Hypertension (AASK) to assess how controlling blood pressure affects
renal function. This study, which is being conducted at 21 sites throughout
the United States, is now in the third year of the full-scale portion
of a clinical trial scheduled to conclude in 2001. The study has two focal
points. The first is to determine the blood pressure level that best protects
the kidneys. The second is to compare different classes of antihypertensive
drugs to see which are most effective in lowering blood pressure in African
Americans and which are most protective of the kidneys. The AASK trial
should provide extensive evidence on which to base a recommendation for
the African-American population.
A new initiative will also explore reasons for the enhanced vulnerability
of African Americans to kidney diseases. The Nephropathy Susceptibility
Genes Initiative will evaluate the genetic determinants responsible for
renal failure in patients with diabetes and in African Americans. Program
staff are evaluating the feasibility of collecting DNA samples from patients
participating in the AASK trial and their family members as part of this
new initiative. To learn more about AASK, contact Lawrence Y. C. Agodoa,
M.D., director, End-Stage Renal Disease Program. To learn more about the
Nephropathy Susceptibility Genes Initiative, contact Paul L. Kimmel, M.D.,
director, Diabetic Nephropathy Program.
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Manpower Initiative Strengthens Training
for Clinical Researchers
In 1999, the Division of Kidney, Urologic, and Hematologic Diseases (DKUHD)
of the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK) at the National Institutes of Health (NIH) will provide new opportunities
for recently graduated doctors to receive the training they need to become
experienced clinical researchers. Funding will encourage grantees to study
clinical trial methodology and epidemiology. These opportunities are part
of an NIH-wide program designed to promote the development of a new generation
of physician-scientists.
DKUHD currently supports two Institutional Training Grants in clinical
research training, and program directors administering other Institutional
Training Grants have also devoted slots to clinical research training.
The new NIH Manpower Program initiative will provide additional funding
to encourage clinical departments to collaborate with others providing
coursework in public health, biostatistics, and epidemiology.
The funding will be made available through the National Research Service
Award Institutional Training Grant mechanism. The Manpower Program staff,
directed by Charles H. Rodgers, Ph.D., anticipates that three or four
new training programs will be established with these funds. Also, existing
programs can receive funds to supply coursework that meets the criteria
for this initiative.
"This effort provides a sound foundation for graduates of these
programs to move on to the new Mentored Patient-Oriented Research Career
Development Award," said Rodgers. "The two experiences would
provide between 7 and 8 years of training encompassing coursework, research
practicums, and patient-oriented research providing a well-trained cadre
of clinical investigators."
For more information about the Manpower Program, go to the NIH web site
at www.nih.gov/training/
or address questions to
Charles H. Rodgers, Ph.D.
Director, Manpower Program
DKUHD/NIDDK/NIH
Natcher Building, Room 6AS-19A
45 Center Drive MSC 6600
Bethesda, MD 20892–6600
Tel: 301–594–7717
Fax: 301–480–3510
E-mail: rodgersc@ep.niddk.nih.gov
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