Research Updates in Kidney and Urologic Health
Dialysis Meeting Stresses
Need To Promote Fistula Use
Last September, the National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK) sponsored the Critical
Issues in the Care of the Dialysis Patient workshop in Baltimore.
More than 300 health professionals from around the country, including
nephrologists and renal dietitians, participated in the workshop,
which focused on the issues of vascular access and nutrition for dialysis
patients. |
Workshop attendees discussed some disturbing trends in vascular access
choice. Problems in this area can prevent patients from receiving
optimum therapy. When a vascular access fails, a patient must undergo
a repeat procedure, or revision, often requiring hospitalization.
Complications of vascular access account for about 15 percent of all
hospitalizations for hemodialysis patients.1 |
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It is generally accepted that the arteriovenous (AV) fistula is the most
effective, durable way to provide vascular access.2 An artery
in the patient's forearm is connected directly to a vein, a procedure
that causes the vein to become enlarged and provide easy access for needle
insertion. The procedure for the AV fistula must be performed 2 to 6 months
before the vein is to be used in hemodialysis. An alternative way to provide
permanent vascular access is to implant a synthetic or bovine graft. Although
such a graft could be used for dialysis sooner than a fistula could be,
it is more likely to require revision. Catheters and shunts are considered
temporary forms of access.
In 1996, the U.S. Renal Data System (USRDS) found that only 17.9 percent
of patients were using an AV fistula 60 days after the start of hemodialysis
treatment, compared with 50.3 percent using synthetic or bovine grafts.
The remaining 31.8 percent were still using temporary catheters 2 months
after starting hemodialysis.3 Researchers have noted regional
variations in the choice of fistula or graft and a consistent trend away
from fistula use.1
These findings have great significance for the increasing number of patients
who have end-stage renal disease (ESRD) and for the health care system
in general. Estimates for the costs of vascular access operations and
hospitalizations for subsequent complications run as high as $939 million
per year.3 To control these costs and to spare patients the
suffering caused by vascular access failure, patients and their doctors
must learn about the advantages of having an AV fistula rather than a
synthetic graft.
Members of a vascular access workgroup at the Baltimore meeting recommended
developing epidemiological studies to explore barriers to the referral
of patients with chronic renal failure to nephrologists long before dialysis
or transplantation is necessary. Early referral is predicted to increase
the likelihood of appropriate vascular access. The panel urged NIDDK's
Division of Kidney, Urologic, and Hematologic Diseases to sponsor basic
investigations and clinical trials to explore ways to prolong the life
of grafts and fistulas. To learn more about the further development of
this initiative, contact John W. Kusek, Ph.D., director, Clinical Trials
Program, or Lawrence Y. C. Agodoa, M.D., director, End-Stage Renal Disease
Program.
1. Hirth, R. A., Turenne, M. N., Woods, J. D., Young, E. W., Port,
F. K., Pauly, M. V., & Held, P. J. (1996). Predictors of type of vascular
access in hemodialysis patients. JAMA, 276(16):1303–1308.
2. Turenne, M. N., Strawderman, R. L., Woods, J. D., Hirth, R. A., Young,
E., Hornberger, J. C., Agodoa, L. Y. C., & Held, P. J. (1995). Vascular
access survival in hemodialysis patients. Journal of the American Society
of Nephrology, 6(3):504. Abstract.
3. USRDS Coordinating Center. (1997). 1997 Annual Data Report.
Contract No. NO1-DK-3-2202. National Institute of Diabetes and Digestive
and Kidney Diseases, National Institutes of Health, Bethesda, MD.
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NIDDK-Funded Research Made Viagra Possible
When the oral drug sildenafil citrate, better known by its proprietary
name Viagra, received approval from the Food and Drug Administration in
March 1998, the new, noninvasive treatment for erectile dysfunction was
the subject of newspaper headlines, magazine cover stories, radio talk
show discussions, and late-night comedy monologues. The media blitz may
have given some observers the impression that Viagra sprang serendipitously
from a test tube during an overnight experiment in the laboratory.
Many are familiar with the story that sildenafil was being tested as
a treatment for angina when researchers made an unexpected discovery.
Even though the drug showed little promise in relieving chest pain, men
participating in the trials were reluctant to give up their supplies,
reporting that the pills seemed to improve their ability to get and keep
an erection.1
Casual observers got a slightly fuller view of the scientific background
behind the development of Viagra when the Nobel Prize for Medicine was
awarded in October 1998 to three researchers for their work in understanding
the role nitric oxide plays in many body functions, including the relaxation
of smooth muscle in the corpora cavernosa of the penis. Even though the
Nobel laureates had little to do with research into male sexual function,
many media reports identified the development of Viagra as one of the
fruits of nitric oxide research.2
The truth is that, for the past several years, researchers, including
many supported by grants from the National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK), have been studying the chemical and molecular
mechanisms that make penile erection work and the problems that cause
erectile dysfunction.
In 1989, NIDDK-supported researchers compared corpus cavernosum tissue
of men with diabetes with that of men without it and learned that men
with diabetes and erectile dysfunction were more likely to have impaired
neurogenic and endothelium-mediated relaxation of penile smooth muscle.3
In the years that followed, NIDDK continued to support researchers conducting
these and related studies. In 1991, these researchers identified nitric
oxide, released by the nerves, as an agent allowing smooth muscle relaxation.4
A year later, a team that included some of the same NIDDK grantees studied
the role of oxygen tension in supporting nitric oxide synthesis in the
corpora.5
In December 1992, the National Institutes of Health (NIH) held a Consensus
Development Conference featuring many of the researchers studying nitric
oxide and smooth muscle relaxation. One of the recommendations that came
out of that conference was to support "additional basic research
on the physiological and biochemical mechanisms that may underlie the
etiology, pathogenesis, and response to treatment of the various forms
of erectile dysfunction."6
In 1995, NIDDK grantees determined that intracellular cyclic guanosine
monophosphate (cGMP) plays an important role in relaxing smooth muscles.7
When the manufacturer of sildenafil citrate recognized that its failed
heart medicine might have other uses, the company recruited a Sildenafil
Study Group containing many of the NIDDK-funded researchers who had already
uncovered a number of the mechanisms underlying penile erection. Shortly
after Viagra went on the market, the New England Journal of Medicine
published the Sildenafil Study Group's report on clinical trials of the
drug as a treatment for erectile dysfunction. The report's explanation
of sildenafil's biochemical action as a selective inhibitor of cGMP catabolism
owed much to the groundwork laid by earlier NIDDK-funded research.8
1. Kolata, G. Drugs that deliver more than originally promised. (1998,
April 5). New York Times. (3 November 1998).
2. Weiss, R. Body regulator discovery wins Nobel: Three American scientists
found an internal gas oxide with key functions. (1998, October 13). Washington
Post, p. A3.
3. Saenz de Tejeda, I., Goldstein, I., Azadzoi, K., Krane, R. J., &
Cohen, R. (1989). Impaired neurogenic and endothelium-mediated relaxation
of penile smooth muscle from diabetic men with impotence. New England
Journal of Medicine, 320:1025–1030.
4. Kim, N., Azadzoi, K. M., Goldstein, I., & Saenz de Tejeda, I.
(1991). A nitric oxide-like factor mediates nonadrenergic-noncholinergic
neurogenic relaxation of penile corpus cavernosum smooth muscle. Journal
of Clinical Investigation, 88:112–118.
5. Kim, N., Vardi, Y., Padma-Nathan, H., Daley, J., Goldstein, I., &
Saenz de Tejeda, I. (1993). Oxygen tension regulates the nitric oxide
pathway: Physiological role in penile erection. Journal of Clinical
Investigation, 91:437–442.
6. Impotence. NIH
Consensus Statement Online 1992, December 7–9 (cited 1998, October
21);10(4):1–31.
7. Gupta, S., Moreland, R. B., Munarriz, R., Daley, J., Goldstein, I.,
& Saenz de Tejeda, I. (1995). Possible role of Na(+)-K(+)-ATPase in
the regulation of human corpus cavernosum smooth muscle contractility
by nitric oxide. British Journal of Pharmacology, 116(4):2201–2206.
8. Goldstein, I., Lue, T., Padma-Nathan, H., Rosen, R. C., Steers, W.
D. & Wisker, P. A., for the Sildenafil Study Group. (1998). Oral sildenafil
in the treatment of erectile dysfunction. New England Journal of Medicine,
338:1397–1404.
[Top]
NIH To Study Prostatitis
Unexplained Pelvic Pain Is Hallmark
Men who have unexplained discomfort or pain in the pelvic area or chronic
abacterial prostatitis are needed for a 5-year, $5.5 million study funded
by the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK).
The walnut-sized prostate sits forward of the rectum, below the bladder
and surrounding the urethra, the tube through which urine passes out of
the body. Although no one knows how many men have prostatitis, experts
think it is the most common genitourinary ailment in men younger than
50, and the chronic abacterial form—for which there is no known cause
and no diagnostic test or reliable treatment—predominates. Prostatitis
occurs in men of all ages and races and accounts for an estimated 2 million
visits to doctors each year, according to a national survey.
Abacterial prostatitis is a syndrome of pain in the genital area and
lower back, usually accompanied by frequent and urgent urination. It can
effectively chain severely affected men to their bathrooms. Other symptoms
such as burning or pain during voiding or ejaculation vary widely and
may come and go without warning.
"It's amazing to me that we can't reliably treat the majority of
men who have prostatitis. We hope this study will help us do a better
job of diagnosing and treating these men in the future, but we recognize
that the road ahead will probably be quite unpredictable," said Leroy
M. Nyberg Jr., M.D., Ph.D., NIDDK study director.
From November 1998 through October 2001, six medical centers will recruit
more than 600 men for the Chronic Prostatitis Cohort Study. This will
be the first large, multicenter study designed to gather well-defined,
detailed clinical information on the condition and then use that base
to test and evaluate new treatment strategies in the future. The study
will document symptoms, possible risk factors, medical histories, and
treatments; test blood, prostate fluid, semen, and urine; and explore
possible relationships between chronic prostatitis, urethral and bladder
inflammation, and other chronic pelvic pain disorders. Results are anticipated
after September 2002.
Desperate for relief, many men with chronic prostatitis are driven—sometimes
far from home—to expensive, unproven, and often disappointing remedies.
The often-prescribed, powerful antibiotics and drugs to relax the muscles
of the prostate, in fact, often fail.
Earlier studies observed small numbers of patients over short periods
and used varying definitions, so that results were unclear and not comparable
across studies. Besides focusing on hundreds of patients over 3 years,
doctors in this study are also testing a new working definition of chronic
abacterial prostatitis developed via consensus by researchers, physicians,
and patients at an NIDDK workshop in 1995.
Patients may contact the nearest participating center for more information.
Clinics
California
Mark S. Litwin, M.D., M.P.H.
University of California, Los Angeles
Contact: Yining Xie
310–222–3819
Canada
J. Curtis Nickel, M.D.
Queen's University, Kingston, Ontario
Contact: Joe Downey, M.Sc.
613–545–2894
Illinois
Anthony J. Schaeffer, M.D.
Northwestern University, Chicago
Contact: Gwen Haggis, R.N.
312–908–7022
Maryland
Richard B. Alexander, M.D.
University of Maryland, Baltimore
Contact: E. Bronwyn Byron
410–328–5108
Massachusetts
Michael P. O'Leary, M.D., M.P.H.
Brigham and Women's Hospital, Boston
Contact: Judy Spolarich-Kroll or Debra Rhodes, M.D.
617–732–7223
Pennsylvania
Michel A. Pontari, M.D.
Temple University, Philadelphia
Contact: Linda Kish
215–707–3783
The Prostatitis Foundation
Mike Hennenfent
President
309–325–7184 (messages and faxes)
Mcapstone@aol.com
www.prostate.org
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The web site of the National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) provides a wealth of information for physicians
and other health care providers, researchers, patients, or anyone interested
in kidney and urologic diseases. If you are a patient with a chronic or
intractable condition, you may benefit from an experimental medicine or
therapy being tested by NIDDK researchers at NIH. To be considered for
an NIH Clinical Center study, you will need a referral from your physician.
(Studies funded by NIDDK but conducted elsewhere will have various enrollment
criteria.) 
To learn more about participating in the clinical trials funded by NIDDK,
visit the NIDDK Patient Recruitment page. Click on "NIDDK-Funded
Studies" to see which clinical trials are recruiting patients. Click
on "NIH Clinical Center" to learn about procedures for participating
in clinical trials and for a list of trials in all of the Institutes of
the National Institutes of Health, including NIDDK.
Study Seeking Patients
The IgA Nephropathy Study is a trial evaluating alternate-day prednisone
and fish oil supplements in patients with IgA nephropathy. To learn more,
visit the NIDDK Patient Recruitment page or call Ronald Hogg, Southwest
Pediatric Nephrology Study Group, 972–566–5575 or 800–345–4426.
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