Dialysis Treatment Choice Affects Risk of Death in Patients with End-Stage Kidney Disease

Researchers at Johns Hopkins have found that in people with end-stage kidney disease (ESRD), choosing peritoneal dialysis over hemodialysis increases their risk of dying by 50 percent.

The Johns Hopkins findings, published in the journal Annals of Internal Medicine online on August 1, are from one of the first comprehensive, large-scale, follow-up comparison studies in the debate about which kind of dialysis is better.

"Lifelong dialysis is often the only option when a patient's kidneys fail because there are not enough kidneys available for transplantation," says the study's primary author, Bernard G. Jaar, M.D., M.P.H., an assistant professor at the Welch Center for Prevention, Epidemiology and Clinical Research at The Johns Hopkins University School
of Medicine.

"Until now, people with kidney disease have picked the kind of dialysis that best suits their lifestyle, sometimes switching from one method to the other, but we have always wondered if one of the two methods helped people live longer," Jaar adds.

To find out, the study, called the Choices for Healthy Outcomes in Caring for ESRD, or CHOICE for short, followed 1,041 newly diagnosed patients from 81 dialysis clinics across the United States and monitored their health,
mainly through reviews of patient charts and medical records, for eight years while they underwent dialysis treatment.

Initial results showed that during the first year of treatment, patients choosing peritoneal dialysis were doing as well as patients on hemodialysis. However, the Johns Hopkins team noted that patients starting treatment with peritoneal dialysis were healthier overall than those on hemodialysis.

When these differences were taken into account, the researchers discovered that while healthy patients did well on either form of dialysis, hemodialysis was of greater benefit for those patients with coexisting illnesses, such as cardiovascular disease.

After one year of dialysis treatment, the risk of death for patients who started on peritoneal dialysis was greater than the risk of death for patients who started on hemodialysis.

"Our results show that there is clearly a benefit in choosing hemodialysis over peritoneal dialysis, particularly for patients suffering from cardiovascular disease," says the study's principal and senior investigator, Neil R. Powe, M.D., M.P.H., M.B.A., a professor and director of the Welch Center for Prevention, Epidemiology and Clinical Research at
Johns Hopkins. "Patients who initially select peritoneal dialysis should be monitored carefully for a timely switch to hemodialysis, when peritoneal dialysis does not work as well anymore."

Funding for this study was provided by the Agency for Healthcare Research and Quality, and the National Institutes of Health, including the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Heart, Lung
and Blood Institute.


Treating Adults as Adults

The food regimen Michael Boyle puts many of his patients on seems, at first glance, to violate every sound dietary recommendation known to the medical profession. Yet, the Johns Hopkins pulmonologist doesn't blink when telling them to "go to McDonald's for lunch, and stop at Burger King on the way home."

Boyle specializes in cystic fibrosis (CF), a disease that impairs the body's ability to absorb salt and water. Eating high-fat, high-sodium foods - like those served at fast-food restaurants - therefore becomes a must for CF patients.

Starting as a pulmonary fellow at Hopkins, Boyle was used to see adults scattered among the clinic's pediatric patients. Knowing that medical advances were keeping CF patients living longer, he found it incongruous that adults didn't have their own treatment facility and began a change in direction for his medical career.

He focused his fellowship training on cystic fibrosis, and in 1999 started the Johns Hopkins Adult CF Program. Today, the multidisciplinary group he leads includes two pulmonologists, two nurses, a dietitian, a physical therapist and a social worker. It is recognized by clinical care experts as one of the finest adult CF centers in the United States.

"The image of CF used to be a child wearing oxygen, appearing at a telethon," Boyle notes. (In the 1960s, the life expectancy for those with the condition was at best the early teens). Today, the median life expectancy for a CF patient is up to 35, and by 2015, it is expected that there will be more adult patients than pediatric ones.

To read more about cystic fibrosis, click here.


JOHNS HOPKINS MEDICINE INTERNATIONAL SYMPOSIUM

October 26-28, 2005
Innovation & Excellence: A Global Forum
Johns Hopkins Medicine Campus
Baltimore, MD

Cause of Diabetes-Related Erectile Disfunction is Clarified by Johns Hopkins Researchers

A new study from the Brady Urological Institute at Johns Hopkins suggests an over-supply of a simple blood sugar could be a major cause of erectile dysfunction in diabetic men.

Researchers have found that one particular simple sugar, present in increased levels in diabetics, interferes with the chain of events needed to achieve and maintain erection and can lead to permanent penile impairment over time. The results, which have implications for new types of erectile dysfunction treatments targeting this mechanism of erection, are described in the August 16 issue of the Proceedings of the National Academy of Sciences.

Previous research had shown that diabetic erectile dysfunction was partially due to an interruption in an enzyme that starts the chain of vascular events leading to an erection. The Johns Hopkins team suspected O-GlcNAc, a blood sugar present in hyperglycemic (high blood sugar) circumstances, to be that interrupting factor.

"We were interested to determine whether high glucose in diabetes mellitus modifies the endothelial nitric oxide synthase (eNOS) enzyme, which is responsible for the achievement and maintenance of erection," says Biljana Musicki, Ph.D., lead investigator of the study and a research associate in the Brady Urological Institute.

Erectile dysfunction is a common problem for more than half of men with diabetes. Musicki says that an estimated "50 percent to 75 percent of diabetic men have erectile dysfunction to some degree, [a rate] about threefold higher than in non-diabetic men." This is not the same type of erectile dysfunction seen in non-diabetics, and it is less effectively treated with conventional drugs like Viagra.

The study examined rats with type 1 diabetes mellitus as well as the overall mechanism of erection. "Erection begins when a sexual stimulus activates the enzyme neuronal nitric oxide synthase (nNOS) that causes short-term release of nitric oxide (NO) at the nerve endings in the penis," Musicki explains.

This initial release of NO causes rapid and short-term increases in penile blood flow and short-term relaxation of the penile smooth muscle, initiating an erection. The resulting expansion of penile blood vessels and smooth-muscle relaxation allows more blood to flow into the penis. This increased blood flow (shear stress) activates the eNOS in penile blood vessels causing sustained NO release, continued relaxation and full erection.

O-GlcNAc hinders this normal chain of events by inhibiting the activation of eNOS, and consequently reducing the release of NO and preventing the smooth muscle in the penis from relaxing. Without this relaxation, there is no shear stress to stoke the production of more NO and, therefore, no normal, sustained erection.

The team also found that in comparison with the controls, the diabetic rats' erectile response was 30 percent lower, full erections were 40 percent smaller and these erections took 70 percent longer to achieve.

The study emphasizes the reduced blood vessel function present in patients with diabetes. "The mechanism we describe here stresses the critical importance of vascular function in the erectile response. It may suggest new ways of treating erectile dysfunction by targeting specifically this mechanism in penile erection," notes Musicki.

Additionally, speaking to more than just the sexual issues related to erectile dysfunction, the research addresses implications related to the overall understanding of penile health. According to Arthur Burnett, M.D., a professor of urology and head of the research team, "eNOS plays roles in both immediate erectile response and the overall health and function of the penile tissue."

Burnett, whose lab has studied penile erection since the early 1990s, continues, "The insight here is tremendous because it speaks to fundamental biological and vascular" mechanisms of diabetes. "This paper gets back to the physiological relevance of hyperglycemia and how it affects erection.

The article, "Inactivation of phosphorylated endothelial nitric oxide synthase (Ser-1177) by O-GlcNAc in diabetes-associated erectile dysfunction," appears in the Aug. 16 issue of the Proceedings of the National Academy of Sciences and was published online Aug. 5. Melissa F. Kramer and Robyn E. Becker, also of the Brady Urological Institute, collaborated on this study.

This research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Kidney Foundation of Maryland Professional Development Award.

To see an interview with Dr. Arthur Burnett, click here.


Protein Linked to Growth of Organs and Cancer

Johns Hopkins scientists have identified a protein in fruit flies whose counterpart product in humans may help cause cancer. The researchers reported in the August 12 issue of Cell that a protein dubbed Yorkie directly controls the fruit fly's organ size and, when overabundant, causes increased cell growth and decreased cell death, hallmarks of cancer.

Yorkie's relative in mammals, called YAP, appears to do the same thing, the researchers report, which suggests that in humans, a defect in the gene that makes YAP might contribute to cancer.

"Over the past few decades, science has identified a few so-called oncogenes, whose protein products act as accelerators and trigger abnormal cell growth," said Duojia Pan, Ph.D., who carried out most of the study at the University of Texas Southwestern Medical Center at Dallas before coming to the Johns Hopkins Institute for Basic Biomedical Sciences. "YAP seems to be another one and our lab is already investigating the amount of YAP protein in human tumors to see if excessive amounts are there."

The researchers also report Yorkie directly regulates the size of all the fruit fly's organs. "We were surprised to find that by adding Yorkie to levels above normal, the fruit fly's organs grew larger," said Pan. "Likewise, by removing Yorkie to levels below normal, the fruit fly's organs were smaller than usual."

The new findings build on Pan's earlier studies, which showed that fruit flies missing a gene called hippo developed tumors. That study revealed a tumor-suppression pathway involving proteins made by hippo and two other like-minded genes, all three of which function in a chain reaction to chemically add phosphate to other proteins, a process called phosphorylation.

"From those results, we predicted that another protein must be involved in the tumor-suppression pathway that is a target of the phosphorylation cascade," said Pan.

Yorkie turns out to be that "mystery protein," the researchers report. In their experiments, Pan and his colleagues show that the hippo phosphorylation cascade, by adding a phosphate group to the Yorkie protein, turns it off.

When the scientists engineered reduced levels of hippo and other proteins that keep Yorkie in check, Yorkie caused tissues to overgrow by prompting more cells to grow and fewer to die, the hallmarks of cancer.

Further experiments in the fruit fly that replaced Yorkie with YAP showed both proteins play similar roles, suggesting YAP might participate in a tumor-related pathway in mammals.

Pan is now trying to identify the signal that tells genes like hippo to turn on or off once an organ grows to the appropriate size. That signal could be harnessed for therapeutics against cancer.

The study was funded by the National Institutes of Health.

Into the Heart of It

The sobering reality for health care is that cardiovascular disease is the elephant in the room that's only going to get bigger. Already a number-one killer, it could find a feast in the alarming numbers of obese people in the United States (60 million and rising) and the looming horde of baby boomers heading into their senior years. While curbing the disease's appetite through better prevention and therapy is an immediate need, it will require a far different approach from medicine.

Rick Lange knows this better than most. The Hopkins chief of clinical cardiology, along with others, including chief of cardiology Eduardo Marbán and cardiac surgery chief Bill Baumgartner, is shaping the fledgling Johns Hopkins Heart Institute and planning the cardiovascular portion of a new critical care tower with a new direction in mind. The two combined will be twice as big as the current cardiac care space and bring together physicians and researchers from different specialties in a state-of-the-art clinical building to battle this all too common and deadly disease.

The institute's new home, scheduled to open in 2009, will integrate advanced diagnostic and therapeutic services from every cardiac care specialty, including cardiology, cardiac surgery, vascular medicine, radiology and critical care medicine. "We're going to be establishing a new paradigm for cardiac care," says Lange. The new space, he explains, will house both clinical researchers and practicing physicians in an allout effort to advance discoveries "from bench to bedside more efficiently than ever before." In addition, Lange says, the Heart Institute's cardiac wing will enable cardiologists to work shoulder-to-shoulder, for the first time, with an entire team of cardiac care specialists, including interventional radiologists and vascular surgeons, which will lead to better care management. "And that's something managed care companies should know about," he adds.

This integrated cardiology wing, ticketed for completion in 2009, will offer various new services and capabilities, including operating rooms large enough to accommodate CT and MRI scanners and flexible enough to become catheterization labs, if necessary, Lange says. "We're designing the cardiology floor not only for today, but also for the nest 20 to 30 years," he explains.

Foreshadowing things to come, Hopkins today is poised to make its most startling advances ever. Johns Hopkins cardiologists, led by Joshua Hare, have begun the first clinical trial in the United States using adult mesenchymal stem cells to repair muscle damage from a heart attack. Hopkins is developing cutting-edge imaging techniques, such as tissue Doppler, pioneered by Ted Abraham, which takes clearer, more precise views of the heart. Hopkins is also implementing new interventional cardiac catheterization procedures that infuse alcohol into arteries supplying heart muscles to eliminate surgery.

Marbán recruited Lange, a former Hopkin intern and resident who spent more than 20 years at Texas Southwestern Medical Center, to spearhead clinical efforts here. He says that with Lange's experience as director of the Texas Southwestern's catheterization lab and congenital heart disease clinic, "Rick was the logical choice to lead us as we develop new approaches to cardiac care."

Lange is aware of the stakes ahead. "As baby boomers age and we increasingly deal with the cardiac fallout from obesity,", he says, "what we do at the Heart Institute and in the new cardiology wing takes on even a greater meaning."

To visit the Cardiology department website click here.


NEWS FROM JOHNS HOPKINS MEDICINE INTERNATIONAL

Mary Ann Wood was recently recognized for her excellent service and patient care at Johns Hopkins Medicine International. During the annual Staff Recognition party, Steve Thompson, Senior Vice-President of Johns Hopkins Medicine and CEO of Johns Hopkins Medicine International, and Harris Benny, Vice President and COO of Johns Hopkins Medicine International, presented Mary Ann with a plaque and a painting.

"I have a passion to make a difference in the lives of our patients. On hearing Harris, it thrilled me that there was a 'someone' among us who shares this passion... I thought of other colleagues of mine, but when he called my name, it came as a total surprise," says Mary Ann.

"We usually have Employee of the Quarter awards and an Employee of the Year award at Johns Hopkins Medicine International. However, we felt that we need to recognize individuals who embody the values and the spirit of this organization - values such as compassion, integrity and passion. Mary Ann is exactly that individual. She has been with us for many years, during which she has provided nothing but excellent care and true compassion to our patients," says Harris Benny.

All Johns Hopkins Medicine Employees stood up to cheer Mary Ann on the receipt of the award, showing she is not only dear to her patients, but certainly to all her colleagues.


CME COURSES

September 8-9, 2005
Infectious Diseases Update for the Primary Care Practitioner
Johns Hopkins University School of Medicine, Turner Bldg.
Baltimore, MD

September 12-16, 2005
Sixth Annual Johns Hopkins Neuroradiology Review
Johns Hopkins University School of Medicine, Turner Bldg.
Baltimore, MD

September 17, 2005
Female Sexual Dysfunction: Contemporary Innovations in Diagnosis and Treatment
Johns Hopkins University School of Medicine, Turner Bldg.
Baltimore, MD

September 22, 2005
Update on Renal Cell Carcinoma
Harbor Court Hotel
Baltimore, MD

September 24, 2005
Current Concepts in the Multidisciplinary Management of Ovarian Cancer
Johns Hopkins University School of Medicine, Turner Bldg.
Baltimore, MD

September 28-30, 2005
Topics in Gastroenterology and Liver Disease
Johns Hopkins University School of Medicine, Turner Bldg.
Baltimore, MD