TAG: "Kidney"

UC Davis Transplant Center opens Fresno location

Clinic will expand access to kidney, pancreas transplant care in Central California.

Luke Preczewski, UC Davis

Luke Preczewski, UC Davis

The UC Davis Transplant Center — one of the nation’s premier transplant programs — has opened a new clinic in Fresno to expand access to kidney and pancreas transplant care in Central California.

The clinic provides pre- and post-transplant medical evaluations for recipients and kidney donors. Transplant surgery will still be provided at the center’s main location at UC Davis Medical Center in Sacramento.

The Fresno clinic is located at 1189 E. Herndon Ave. and will be open one day per month. The number of clinic days will increase based on patient need. To arrange for a referral or schedule an evaluation, call toll free (800) 821-9912.

Fresno is the largest city in California without a transplant center within 25 miles, yet about 17 percent of California’s kidney transplant patients are in the Fresno region. One of the closest centers is at UC Davis Medical Center, which is about 170 miles away.

“We wanted to reduce that travel time as much as possible for patients and their families,” said Luke Preczewski, executive director of the transplant program.

UC Davis performed 339 kidney transplants in 2013, making it by volume the second-largest program in the nation. According to 2012 data from the Scientific Registry of Transplant Recipients, UC Davis offers the shortest average adult kidney transplant wait time (37.2 months) of any California hospital.

For information about the UC Davis Transplant Center, visit www.ucdmc.ucdavis.edu/transplant.

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New link found between obesity, early decline in kidney function

Body mass index “in and of itself” increases risk of developing chronic kidney disease.

Vanessa Grubbs, UC San Francisco

Vanessa Grubbs, UC San Francisco

A new UC San Francisco-led study of nearly 3,000 individuals links obesity to the development of kidney disease. The work also shows that, when properly measured, declines in kidney function are detectable long before the emergence of other obesity-related diseases such as diabetes and high blood pressure.

Healthy kidneys are vital to the proper functioning of the heart and brain, as well as the skeletal and immune systems, and the research adds additional urgency to the call for doctors to intervene early in life with obese patients, the researchers said.

“We’re getting larger and larger at younger and younger ages, so the problems we will see that are directly related to obesity are going to become more common and they’re going to start earlier in life,” said Vanessa Grubbs, M.D., UCSF assistant adjunct professor of medicine and first author of the new study. “Even before the level at which we can diagnose illnesses, decline in kidney function is happening. Is it reversible? We’re not sure. Preventable? It stands to reason that it would be.”

In the new study, published online in The American Journal of Kidney Diseases on Dec. 2, Grubbs and senior author Kirsten Bibbins-Domingo, Ph.D., M.D., professor of medicine, led a team that analyzed 10 years’ worth of health data from CARDIA (Coronary Artery Risk Development in Young Adults), a national multicenter research project that has tracked the health of thousands of black and white young adults since its beginnings in 1985.

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A miracle baby

Dialysis couldn’t stop one woman’s dream of motherhood.

Growing up, Elizabeth Hill had her entire life planned. She would be her family’s first college graduate, a successful professional and, above all, a mother. “I always knew I was born to be a mom,” she says.

At 17, however, she was diagnosed with lupus, a disease that can attack almost any part of the body. “At first I fell into a deep depression,” the Yorba Linda resident explains. “But then I decided I was going to live a normal life.”

She did just that, earning her degree and later working as a human resources manager — a job she loved.

Hill was still living with lupus, though. By 2008, her kidneys were irreparably damaged by the disease. She received a kidney transplant, but it failed after just two years.

Seriously ill, Hill began dialysis treatments to cleanse her blood of the impurities normally eliminated by the kidneys. The treatments were lifesaving, but being on dialysis meant she would probably never have children.

“Dialysis patients rarely become pregnant,” says Dr. Carol Major, a UC Irvine Health maternal-fetal medicine specialist. And if they do, they usually miscarry.

This is because “a developing fetus is extremely vulnerable to metabolic changes that take place during dialysis,” explains Dr. Kamyar Kalantar-Zadeh, chief of the UC Irvine School of Medicine’s Division of Nephrology & Hypertension.

Then — against the odds — Hill learned she was pregnant. “I had a million emotions,” she says. “I’d been told this would never happen, but now it had.”

The 34-year-old Hill was immediately referred to UC Irvine Health, one of the nation’s leading centers for treating kidney disease and managing high-risk pregnancies. UC Irvine Health kidney and obstetric-gynecologic specialty services both have been ranked among the best in the country by U.S. News & World Report.

Hill’s treatment team included nephrologists as well as obstetricians with expertise in managing complex, high-risk pregnancies. “We coordinated her treatment across all specialties on a daily basis,” says Major, who cared for Elizabeth throughout her pregnancy.

“To better maintain the delicate balance so critical for mother and baby,” says Kalantar, “Elizabeth underwent dialysis six times a week instead of the usual three.”

During dialysis, the fluid removed had to be carefully measured and analyzed to ensure that the developing fetus was still receiving enough fluid volume. And after each dialysis session, Hill underwent fetal heart rate monitoring for more than an hour to make sure the baby was doing well. On Sundays — the one day Hill didn’t make the trek to UC Irvine Medical Center — she and Major texted each other.

“Dr. Major and I have this amazing bond,” Hill explains. “She’s so incredibly wonderful and caring. I’ve never met a doctor like her.”

Even with the unprecedented care she received, Hill’s pregnancy was extremely difficult — jeopardized by anemia and a liver condition that caused intolerable itching.

“When Elizabeth developed liver problems, we called in our liver disease experts,” Kalantar says. “We tailored treatment to her unique needs, using all our expertise and resources to deal with each setback.”

Hill braved all the complications, risks and discomfort, having faith that her baby would be healthy. Her determination paid off.

Baby Audrey was born in November 2012, just four weeks short of full-term. “It was the most unbelievable feeling in the world,” recalls Hill. “Dr. Major kept telling me, ‘We did it. She’s perfect.’”

Hill is back on dialysis three days a week, and mom and baby are thriving, thanks to Hill’s extraordinary strength and determination, her faith, her husband, Sean, and her UC Irvine Health doctors.

“Elizabeth is an amazing woman and mother,” says Major. “She was told she would never get pregnant, yet she got the proper care and had a completely successful pregnancy. Her story is a source of hope for other women who are facing the same challenges.”

To learn more about kidney disease and dialysis services, visit ucirvinehealth.org/dialysis. For more information about high-risk pregnancy care, visit ucirvinehealth.org/high-risk or call (714) 456-2911.

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Scientists halt deadly organ tissue scarring in its tracks

UCSF-led study uses drug to target fibrosis of lungs, liver and kidney.

Dean Sheppard, UC San Francisco

Dean Sheppard, UC San Francisco

UC San Francisco scientists report that they were able to arrest, and even reverse, tissue scarring of the liver, kidneys and lungs in mice.

The scarring, also known as fibrosis, is a major factor in nearly half of all deaths in developed countries.

“Scarring is a critical component of organ dysfunction in most chronic diseases – kidney failure, liver failure, lung failure, heart failure,” said Dean Sheppard, M.D., UCSF professor of medicine and senior author of the new study. “But there’s no effective therapy for tissue scarring that’s approved by the FDA [Food and Drug Administration]. Although scarring contributes to the progression of all these diseases, we currently have no way to treat it.”

The scientists accomplished the work by targeting a family of proteins on the surface of certain cells.

In the study, first author Neil C. Henderson, M.D., Ph.D., a former postdoctoral associate in Sheppard’s laboratory and now at the University of Edinburgh, and an international team of scientists first devised a genetic technique to selectively knock out a five-member family of receptors known as alpha V integrins (“INT-uh-grins”) in the collagen-producing fibroblast cells of mice. These cells drive the excessive scarring seen in fibrosis.

The genetic deletion had a strong protective effect: Methods that reliably induce liver scarring in normal mice had little effect on mice lacking alpha V integrins. Knocking out alpha V integrins also protected the mice from fibrosis of the lungs and kidney.

On the other hand, the scientists did not observe any protective effect when they knocked out individual members of the alpha V integrin family, suggesting that fibrosis may be best treated by targeting the family as a whole.

The study was reported online on Nov. 10 Nature Medicine.

Based on these findings, members of the team based at St. Louis University in Missouri designed a drug that specifically blocks the action of all five alpha V integrins, and the compound prevented fibrosis as effectively as the genetic deletion of these integrins. Moreover, the drug, known as CWHM 12, was able to prevent the progression of established fibrosis in the liver and lungs, and even to reverse some of the damage caused to those organs by fibrotic disease.

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Enzyme restores function with diabetic kidney disease

Mouse findings reverse prevailing theory, point to potential treatment options.

Transmission electron micrograph of a cell mitochondrion. (Image courtesy of Thomas Deerinck, National Center for Microscopy and Imaging Research, UC San Diego)

Transmission electron micrograph of a cell mitochondrion.

Researchers at the UC San Diego School of Medicine say that while a prevailing theory suggests elevated cellular levels of glucose ultimately result in diabetic kidney disease, the truth may, in fact, be quite the opposite. The findings could fundamentally change understanding of how diabetes-related diseases develop – and how they might be better treated.

Writing in today’s (Oct. 25) issue of Journal of Clinical Investigation, Kumar Sharma, M.D., professor of medicine and director of the Center for Renal Translational Medicine (CRTM) at UC San Diego; Laura Dugan, M.D., professor of medicine and Larry L. Hillblom Chair in geriatric medicine; Young You, Ph.D., CRTM; Robert Naviaux, M.D., Ph.D., professor of medicine; and colleagues describe first-ever studies of real-time superoxide production in the kidneys of live mice with type 1 diabetes.

Current theory posits that impaired diabetic kidney function in humans as well as in mice is the result of chronically high glucose (sugar) levels which prompt energy-generating mitochondria in cells to produce an overabundance of superoxide anion – a highly reactive, toxic molecule that ultimately leads to downstream cellular damage, organ dysfunction and disease.

But Sharma, who also works for the Veterans Administration San Diego Healthcare System, and colleagues upend this theory. Rather than detecting higher-than-normal levels of superoxide in the damaged kidneys of the diabetic mice, the researchers discovered reduced superoxide production and suppressed mitochondrial activity. When they stimulated the mitochondria by activating a key energy-sensing enzyme called AMPK, superoxide production increased but evidence of diabetic kidney disease markedly declined.

“Mitochondrial superoxide does not seem to be a causative factor of diabetic kidney disease,” said Sharma. “Indeed, when mitochondrial superoxide is increased with AMPK activation, there is reduced kidney disease, suggesting that improving mitochondrial function and superoxide production is actually beneficial for diabetic complications. This idea is a sea change in the field of diabetic complications.”

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Vitamin D does not contribute to kidney stones, study asserts

Results may lessen concerns about taking vitamin D supplements.

Cedric Garland, UC San Diego

Cedric Garland, UC San Diego

Increased vitamin D levels may prevent a wide range of diseases, according to recent studies.  However, some previous studies led to a concern that vitamin D supplementation could increase an individual’s risk of developing kidney stones.

However, a study of 2,012 participants – published in the American Journal of Public Health – found no statistically relevant association between 25-hydroxyvitamin D (25 (OH)D) serum level in the range of 20 to 100 ng/mL and the incidence of kidney stones.

This study – led by Cedric F. Garland, Dr.P.H., adjunct professor in the Division of Epidemiology, Department of Family and Preventive Medicine at the UC San Diego School of Medicine – used data from the nonprofit public health promotion organization GrassrootsHealth to follow more than 2,000 men and women of all ages for 19 months.

Only 13 individuals self-reported a kidney stone diagnosis during the study.

“Mounting evidence indicates that a vitamin D serum level in the therapeutic range of 40 to 50 ng/mL is needed for substantial reduction in risk of many diseases, including breast and colorectal cancer,” said Garland, adding that this serum level is generally only achieved by taking vitamin supplements. “Our results may lessen concerns by individuals about taking vitamin D supplements, as no link was shown between such supplementation and an increased risk for kidney stones.”

The study did show that older age, male gender and higher body mass index (BMI) were all risk factors for developing kidney stones.  According to the researchers, individuals with high BMI need higher vitamin D intake than their leaner counterparts to achieve the same 25 (OH)D serum level.

Additional contributors to the study include Stacie Nguyen, Leo Baggerly and Christine French of GrassrootsHealth, San Diego; Robert P. Heaney, M.D., of GrassrootsHealth and the Department of Medicine at Creighton University in Omaha, Nebraska; and Edward D. Gorham, Ph.D., M.P.H., UC San Diego Department of Family and Preventive Medicine.

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Urine biomarkers reveal mitochondrial dysfunction in diabetic kidney disease

Study suggests suppression of mitochondria is a key characteristic of diabetic kidney disease.

X-ray of human kidneys

X-ray of human kidneys

Researchers at the UC San Diego School of Medicine have identified 13 metabolites – small molecules produced by cellular metabolism – that are significantly different in patients with diabetes and chronic kidney disease compared to healthy controls.

Twelve of the 13 metabolites are linked to mitochondrial function, suggesting that suppression of mitochondria – the powerhouses of cells – is a fundamental characteristic of diabetic kidney disease. The findings are published in the November edition of the Journal of the American Society of Nephology.

“This work provides strong evidence that reduced mitochondrial function is a dominant feature of human diabetic kidney disease,” said first author Kumar Sharma, M.D., professor of medicine and director of the Center for Renal Translational Medicine at UC San Diego. “We found that a specific cellular pathway, AMPK-PGC1a, likely plays a key role to reduce mitochondrial function and content, which means that new therapeutic approaches that restore and increase mitochondrial function and content could ameliorate or perhaps even arrest chronic kidney disease.”

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$5.6M grant renewal expands research in acute kidney failure

Funding will expand study into deadly disease.

Ravindra Mehta, UC San Diego

Ravindra Mehta, UC San Diego

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDKD) – part of the National Institutes of Health – has renewed a grant shared by the UC San Diego and the University of Alabama at Birmingham schools of medicine. The five-year, $5.64 million renewal will extend and expand research into acute kidney failure, or acute kidney injury, which kills 70 to 80 percent of patients in intensive care units who develop the disease.

The rate of acute kidney injury has increased in recent years as more patients are older, diabetic, obese and hypertensive, and mortality rates from the disease have not improved in the past 40 years.

Since 2008, researchers at the two universities have joined forces as part of the O’Brien Center for Acute Kidney Injury Research, one of seven federally funded centers in the country aimed at making state-of-the art technologies and resources readily accessible to researchers pursuing studies in relevant areas related to kidney disease.

The center serves as a national core resource to identify and fund promising research and to provide important scientific services to the funded investigators, including work to find genetic determinants for early detection and expand an international registry.

“The O’Brien Center has provided an unprecedented opportunity for UC San Diego School of Medicine to partner with UAB over the past five years to create a unique resource for acute kidney injury research,” said Ravindra L. Mehta, M.D., professor of clinical medicine at UC San Diego Health System and associate director of the center.  “Combining the resources at both centers has enabled us to develop an international collaborative network of investigators who are addressing several important questions in acute kidney injury.”

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Portable device invented for common kidney tests

UCLA researchers develop device that attaches to smartphones and provides instant results.

Albumin tester

Albumin tester

A lightweight and field-portable device invented at UCLA that conducts kidney tests and transmits data through a smartphone attachment may significantly reduce the need for frequent office visits by people with diabetes and others with chronic kidney ailments.

The smartphone-based device was developed in the research lab of Aydogan Ozcan, a professor of electrical engineering and bioengineering at the UCLA Henry Samueli School of Engineering and Applied Science, and associate director of the California NanoSystems Institute. Weighing about one-third of a pound, the gadget can determine levels of albumin in the patient’s urine and transmit the results within seconds. Albumin is a protein in blood that is a sign of danger when found in urine.

Ozcan’s lab also developed the opto-mechanical phone attachment, disposable test tubes, Android app and software to transmit the data. The research was published this month by the peer-reviewed journal Lab on a Chip.

“Albumin testing is frequently done to assess kidney damage, especially for diabetes patients,” Ozcan said. “This device provides an extremely convenient platform for chronic patients at home or in remote locations where cell phones work.”

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Dialysis patients fare better when doctors have fewer patients

UC Irvine study finds 2 percent increased risk of death for every 50 additional patients.

Kamyar Kalantar-Zadeh, UC Irvine

Kamyar Kalantar-Zadeh, UC Irvine

A study led by UC Irvine Health nephrologist Dr. Kamyar Kalantar-Zadeh shows that dialysis patients treated by kidney specialists with a higher patient caseload have a greater risk of dying prematurely than do those who receive care from specialists with a lower caseload.

The study, to appear in the upcoming issue of the Journal of the American Society of Nephrology, is the first of its kind to examine the association between nephrologists’ caseloads and mortality risk in a large urban U.S. setting.

“Our data suggest that patients receiving care from nephrologists with lower caseloads may have greater survival [rates],” Kalantar-Zadeh, chief of the division of nephrology and hypertension at the UC Irvine Health School of Medicine, said in a report from the American Society of Nephrology.

“Such data may help direct health policies and guidelines more effectively,” added Kalantar-Zadeh, M.D., Ph.D., M.P.H.

With more than 1.5 million people on dialysis worldwide, many kidney specialists oversee the care of large numbers of patients. For the study, Kalantar-Zadeh and his colleagues examined whether hemodialysis patients being treated by nephrologists with higher patient caseloads had a greater risk of dying prematurely than those who received care from nephrologists with fewer cases.

A total of 41 nephrologists, whose caseloads ranged from 50 to 200 dialysis patients in urban areas of California, were retrospectively ranked according to their dialysis patients’ mortality rate between 2001 and 2007.

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Comprehensive care benefits transplant patient, her family

Teen’s life renewed with new kidney.

The most recent statistics from the National Kidney Foundation indicate that there are more than 118,000 people waiting for lifesaving organ transplants around the country. A vast majority of those individuals are in need of new kidneys. In an 11-county region surrounding UC Davis Medical Center and covered by the organ donor network Sierra Donor Services, more than a thousand people now await lifesaving transplants for heart, liver, lung, kidney, intestine and pancreas. Locally and nationally the need for organs far exceeds the number of donations.

Working hard to address such daunting needs, the UC Davis Transplant Center has become one of the nation’s top sites for kidney transplantation. Its program, which received an excellence award in 2012 from the independent firm HealthGrades for superior clinical outcomes, is now the fourth-largest program of its kind in the nation.

The center offered the type of comprehensive expertise that young Berenice Jasso needed several years ago when a challenging illness became life-threatening and, ultimately, could only be cured with a new kidney. For nearly two years, the then-13 year old and her family lived in fear that at any moment Berenice could lapse into convulsions, wake up blind, fall into a coma or lose her memory because of the illness.

Lavjay Butani, a UC Davis specialist in pediatric kidney disease, helped identify Berenice’s condition and determined that she needed a transplant. Fortunately, in Berenice’s case, a donor was easily found. Her mother, Maria, turned out to be a perfect match and able to donate one of her kidneys.

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Investigating a link between oral health and kidney function

Study receives major boost from UCSF’s K Scholars program.

Medical research has already documented a link between cardiovascular disease and periodontal disease, or serious gum infection. Now researchers say preliminary studies suggest a connection between gum infections and kidney disease as well.

“This is a very new and emerging area, and there have only been a few studies,” said Vanessa Grubbs, M.D., an assistant professor and pulmonary specialist in the UC San Francisco’s School of Medicine who is determined to advance this research as part of her commitment to preventing the chronic health problems associated with kidney disease.

Vanessa Grubbs, UC San Francisco

“If we at least start to show that treating periodontal disease can slow the progression of kidney disease, the long-term ramifications for dental policy and how we manage patients with chronic kidney disease are huge,” said Grubbs, who is also a nephrologist, or kidney expert, based at San Francisco General Hospital and Trauma Center.

Funding routine dental care for people at all income levels could potentially become a priority as a way to prevent kidney disease, and the cost savings would be significant, she said. “It’s certainly cheaper to pay for preventative dental care than dialysis.”

She also noted that both kidney disease and periodontal disease disproportionately impact poorer populations.

Periodontal disease is an inflammatory response to persistent infection, caused by bacteria getting trapped in the gum’s porous tissues. Just as research indicates this inflamed state can affect major organs such as the heart, possibly through bacteria in the blood stream, studies show kidneys are similarly at risk, Grubbs said. Her goal is to prove this link in longitudinal research.

Teaming up with professors George Taylor, D.M.D., and Mark Ryder, D.M.D., from the UCSF School of Dentistry, Grubbs is launching a first-of-its-kind randomized, controlled study to track the progression of kidney disease in patients receiving treatment for periodontal disease.

All patients will have both conditions. Two-thirds will receive immediate and follow-up periodontal care, and the remaining control group will receive the dental care if it’s medically necessary. Kidney function will be measured in several ways, such as analyzing unique biomarkers in blood and urine associated with kidney damage.

Grubbs received research funding from the National Institutes of Health (NIH), and plans to follow the patients for one year as a pilot study, which could be expanded based on results.

After years in the preliminary stages, the study received a major boost from the K Scholars program managed by UCSF’s Clinical and Translational Science Institute (CTSI), said Grubbs, who was a K Scholar in 2011.

The K Scholars program is designed to support the career development of junior faculty from all UCSF schools who are committed to building careers in clinical and translational research. The program provides support for scholars to conduct high quality research, foster and nurture multidisciplinary collaborations and explore novel research directions, and develop the range of skills necessary to achieve a successful independent academic research career. Types of support include partial salary funding, expert advice, mentoring and regular project review sessions with a multidisciplinary group of K Scholar peers.

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