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Pitt Analysis Questions Use of Acute Hemodialysis Treatment

PITTSBURGH, Aug. 20, 2014 – A common approach to treating kidney failure by removing waste products from the blood did not improve survival chances for people who suddenly developed the condition, in an analysis led by experts at the University of Pittsburgh School of Medicine.

Their findings, published online in the journal PLOS One, suggest acute hemodialysis, an aggressive method that is standardly used for people with sudden kidney failure, may not provide a definitive benefit to the patient.

“Our findings question the accepted notion that acute hemodialysis decreases mortality,” said Amber Barnato, M.D., senior author of the study and associate professor of clinical and translational science at the Pitt School of Medicine. Dr. Barnato acknowledges that the study is far from conclusive because it lacks detailed clinical data. “It is impossible to draw conclusions based on an observational study, but I do wonder whether it is time to do a clinical trial on the timing and delivery of acute hemodialysis in the context of acute renal failure and critical illness.”

Dr. Barnato and her team examined records for 2,131,248 patients admitted to Pennsylvania hospitals between October 2005 and December 2007. Some of the patients had varying degrees of kidney failure without end-stage renal disease; 6,657 of those patients had received acute hemodialysis. At one year, patients who received acute hemodialysis had nearly twice the risk of death as similarly ill patients who did not receive acute hemodialysis.

“The most striking finding is the increased mortality risk for patients who received acute hemodialysis, even after risk adjustment which limited the sample to the sickest patients,” said lead author Sarah Ramer, M.D., now of Rutgers New Jersey Medical School, who performed much of the research while a Clinical Scientist Training Program medical student at Pitt. “We know that there is variation in how doctors decide if and when to dialyze a hopspitalized patient. If patients given acute hemodialysis are not carefully chosen, some patients might end up not being helped by the treatment.”

Additional authors on the study are Elan D. Cohen, M.S., and Chung-Chou H. Chang, Ph.D., both of the University of Pittsburgh; and Mark L. Unruh, M.D., now of the University of New Mexico School of Medicine.

Funding for this research was provided by a Doris Duke Clinical Research Fellowship and National Institutes of Health grant R01AG035112.

Naturally Occurring Antibodies May be Treatment for BK Nephropathy in Kidney Transplant Patients

SAN FRANCISCO, July 30, 2014 – A viral infection known as BK that commonly causes kidney transplant dysfunction in patients taking high doses of immunosuppressants may be treated with naturally occurring antibodies that already are widely available, according to UPMC-led research that was presented this week at the World Transplant Congress in San Francisco.

The BK virus infects most healthy children in the U.S., but the infection is usually asymptomatic and readily cleared by the immune system. However, following natural infection, latent virus persists in the kidneys for an indefinite time because antibodies in the plasma and circulating T-cells remain at levels that are high enough to prevent virus reactivation.

“However, if the immune system is suppressed — for example by kidney transplant medications designed to prevent rejection of the organ — viral infection flares up and damages the kidney. This causes a condition called BK virus nephropathy,” said Parmjeet Randhawa, M.D., a UPMC pathologist and professor of transplant pathology at the University of Pittsburgh, who led the research. “Currently, there are no anti-viral drugs or vaccines specifically designed for BK nephropathy, and none is likely to be licensed for at least the next 10 years.”

Dr. Randhawa and his team found that anti-BK antibodies are present at very high levels in immunoglobulin preparations currently being used to treat other viral infections, as well as immunologic disorders such as antibody mediated rejection of transplanted organs. These antibodies interact with a BK virus surface protein called VP-1 and effectively neutralize the virus. Such neutralized viruses can no longer infect human cells.

“By artificially constructing viruses varying in the composition of the proteins on their surface, we have shown that this neutralizing action is effective against all six common BK virus strains circulating in human populations,” Dr. Randhawa said. “These findings open the way to conduct clinical trials for preventing and treating BK nephropathy in kidney transplant patients.”

As the proposed immunoglobulin preparations are natural products derived from healthy human subjects, associated side effects are expected to be minimal, Dr. Randhawa said.

Collaborators on the study were Diana Pastrana, Ph.D., and Christopher Buck, Ph.D., both of the National Cancer Institute; Gang Zeng, M.D., of the University of Pittsburgh Department of Pathology; Mel Berger, Ph.D., of CSL Behring, in King of Prussia, Pa.; and Sundaram Hariharan, M.D., and Ron Shapiro, M.D., both of UPMC.

NIH Awards $5.8 Million to Pitt Center for Kidney Research

PITTSBURGH, Oct. 8, 2013 – The Pittsburgh Center for Kidney Research has been awarded a five-year grant totaling $5.8 million from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health (NIH). The grant will support research facilities, educational programs and pilot projects to enhance kidney-focused research at the University of Pittsburgh and related institutions.

The Pittsburgh Center for Kidney Research is one of seven George M. O’Brien Kidney Research Core Centers in the U.S., and also is supported by the University of Pittsburgh School of Medicine and the Department of Medicine. Established in 1987 by the NIDDK, the O’Brien centers bring together scientists from multiple institutions to collaborate on basic, clinical and applied aspects of biomedical research in renal physiology and pathophysiology.

The Pittsburgh Center for Kidney Research supports four research facilities encompassing cellular physiology, single nephron and metabolomics, kidney imaging and model organisms at the University of Pittsburgh; the center also supports a research facility at the Icahn School of Medicine at Mount Sinai in New York.

“Our Center for Kidney Research is designed to facilitate research that advances our understanding of how the kidney works, with a goal of improving how we diagnose and treat kidney diseases,” said Thomas Kleyman, M.D., chief, UPMC Renal-Electrolyte Division, Sheldon Adler Professor of Medicine at Pitt’s School of Medicine, and center director.

Of the 98 investigators who participate in the Pittsburgh Center for Kidney Research, 58 are faculty members at the University of Pittsburgh, 35 are at other U.S. institutions and five are at foreign institutions.

UPMC is ranked No. 16 in the country for nephrology, according to the 2013 U.S. News and World Report hospital rankings.

 

Dendritic Cell Therapy Improves Kidney Transplant Survival in Preclinical Model, Pitt Experts Say

PITTSBURGH, June 28, 2013 – A single systemic dose of special immune cells prevented rejection for almost four months in a preclinical animal model of kidney transplantation, according to experts at the University of Pittsburgh School of Medicine. Their findings, now available in the online version of the American Journal of Transplantation, could lay the foundation for eventual human trials of the technique.
Organ transplantation has saved many lives, but at the cost of sometimes lifelong requirements for powerful immunosuppressive medication that can have serious side effects, said senior investigator Angus Thomson, Ph.D., D.Sc., distinguished professor of surgery and of immunology, Pitt School of Medicine. Scientists have long sought ways to encourage the organ recipient’s immune system to accept or tolerate the donor organ to reduce the need for drugs to stave off rejection.
“This study shows it is possible to prepare the patient’s immune system for a donor kidney by administering specially treated immune cells from the donor in advance of the transplant surgery,” Dr. Thomson said. “This could be very helpful in the context of planned kidney donations from living relatives, and could one day be adapted to transplantation from deceased donors.”
For the project, the research team generated immune cells called dendritic cells (DCs) from the blood of rhesus macaques that would later provide a kidney to recipient monkeys. Dendritic cells are known to be key regulators of the immune system by showing antigens to T-cells to either activate them against the foreign protein or to suppress the T-cell response. The researchers treated the donor DCs in the lab to prevent them from fully maturing and having the capacity to trigger an immune reaction against foreign proteins.
One week before having a kidney transplant, recipient monkeys received a single infusion of treated DCs obtained from their respective donor animals. Another group of monkeys was transplanted without receiving the cells, but both groups were given the same regimen of immunosuppression drugs, a modified protocol for experimental purposes that eventually results in donor organ rejection. The researchers found that the donor kidney was rejected in about 40 days among animals that got only the drugs, but survived for about 113 days in the group that had a prior infusion of treated DCs.
The modified donor DCs sent signals to the recipient immune system to stay quiet and not launch an attack against the donor organ, explained lead author Mohamed Ezzelerab, M.D., research assistant professor, Department of Surgery, Pitt School of Medicine.
“The results indicate that we achieved immune system regulation without side effects of the DCs, but better yet, the monkeys were healthier from a clinical perspective,” he said. “They maintained a better weight, had less protein in the urine and fewer signs of kidney damage than the other group. Ultimately, all these factors played a role in prolonging organ survival in the group that received DC therapy.”
Co-authors of the paper include other researchers from the Thomas E. Starzl Transplantation Institute, and the departments of Surgery, Immunology, Medicine and Pathology, Pitt School of Medicine. The project was funded by National Institutes of Health grant AI051698.

Biomarkers May Predict Acute Kidney Injury in Critically Ill Patients

PITTSBURGH, Feb. 6, 2013 – An international, multi-center study led by UPMC researchers found biomarkers that can tell a physician if a patient is at risk for acute kidney injury (AKI), a condition that often affects those in intensive care and can occur after serious infections, surgery, or taking certain medications. The results, now available online and published in the current edition of the journal Critical Care, provide insight into the potentially deadly condition that affects up to 7 percent of all hospitalized patients.

Existing methods of determining kidney function, such as measuring serum creatinine and urine output, may not indicate changes for several days, allowing time for significant kidney damage to occur. Biomarkers, which are naturally occurring proteins or other molecules in the blood, urine, or other body fluids or tissues, may help physicians more accurately determine the risk of AKI in critically ill patients so that early treatment can minimize progression and save lives. 

“If unchecked, AKI can lead to loss of kidney function, often resulting in lower quality of life or even death. Our data show that these biomarkers provide more information than traditional tests for kidney function and give us a better understanding of what physically happens when a kidney is damaged,” said senior investigator John Kellum, M.D., a critical care physician at UPMC and professor of critical care at the University of Pittsburgh.

AKI risk is difficult to determine because the condition is typically caused by something outside of the kidney, including sepsis, nephrotoxins and oxygen deprivation. The study aimed to identify early markers in order to detect AKI when interventions could provide benefit. Researchers collected blood and urine samples of more than 1,000 critically ill patients in North America and Europe. The biomarkers, known as TIMP-2 and IGFB7, signal that the kidneys are stressed and not functioning properly but may still recover. They are indicators of cell damage, a key component in the onset of AKI.

“These biomarkers send an early ‘alarm’ from the site of the injury and offer a better chance at treatment that can prevent further damage,” Dr. Kellum said.

Co-authors of the study include researchers from 35 medical centers worldwide.

The study was sponsored by Astute Medical Inc. Dr. Kellum has received consulting fees from Astute Medical.

‘Kidney Attack’ As Serious as Heart Attack, Warns UPMC Critical Care Expert

PITTSBURGH, May 9, 2012 – Kidney complications during hospitalization are as frequent and as dangerous to patients as heart attacks, and the medical community must implement recently developed guidelines to better detect and respond to the problem, said a critical care expert at UPMC and the University of Pittsburgh School of Medicine today in the online version of the Journal of the American Medical Association.

Acute kidney injury (AKI) is not well understood by doctors, and is even more unfamiliar to the public, wrote John A. Kellum, M.D., professor and vice chair for research, Department of Critical Care Medicine, Pitt School of Medicine; Rinaldo Bellomo, M.D., of Austin Hospital and Melbourne University, Australia; and Claudio Ronco, M.D., Ospedale San Bortolo, Vicenza, ltaly.

“Research shows that as many as 60 percent of patients in the intensive care unit will develop kidney problems, which can lead to long-term, life-threatening complications,” Dr. Kellum said. “Doctors, patients and families should perhaps view the dangers of and the need to avoid a ‘kidney attack’ with the same sense of urgency that heart attack provokes.”

Until recently, there were no recommendations about when to start treatments, such as a medication change, correcting fluid overload, or dialysis, in response to abnormal kidney function, he said. But in March, an international panel of experts co-chaired by Dr. Kellum established clinical practice guidelines to end the confusion.

At UPMC, an effort will launch this month in which an alert will appear in the electronic medical record when certain lab tests of kidney function are abnormal. It will cue the medical staff to seek advice about appropriate therapeutic strategies from nephrologists or, in the case of severe illness, critical care specialists.

“That’s a simple way of making sure that the patient gets assessed early by clinicians who have the most experience in managing AKI,” Dr. Kellum said. “UPMC already includes a sign of kidney attack – very low urine   output – as a trigger for its rapid-response team. The idea is to address kidney attacks just as we do with cardiac arrest and other scenarios in which a patient becomes dangerously ill very quickly.”

And, as detection and public awareness of AKI improves, there could be more support for research into the problem, said the authors, who noted also that estimates indicate that in 2012, 3 million people worldwide could die of AKI, which currently has no definitive treatment.

Surgical Pathology of Organ Transplantation Conference

On May 4 and 5, 2012, join the lively discussion at the Surgical Pathology of Organ Transplantation Conference in Pittsburgh, Pa.

Organ procurement and the care of the transplanted patient occurs all over the world, in facilities large and small, academic and rural. The body of knowledge is growing exponentially. This event is designed for:

  •  pathologists
  • transplant surgeons
  • hepatologists
  • gastroenterologists
  • nephrologists
  • pulmonologists
  • cardiologists
  • oncologists
  • immunologists
  • infectious disease specialists
  •  residents, fellows and other health care professionals

You can view the conference brochure and agenda here.

The University of Pittsburgh School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The University of Pittsburgh designates this live activity for a maximum of 11.25 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Other health care professionals are awarded 1.1 continuing education units (CEU’s) which are equal to 11.25 contact hours.

UPMC is Only Health System Named ‘Most Wired’ for 13 Consecutive Years

PITTSBURGH, July 11, 2011 – For the 13th consecutive year, UPMC has been named one of the 100 “Most Wired” health systems in the country, the only organization to earn that distinction, according to Hospitals & Health Networks, the journal of the American Hospital Association (AHA).

UPMC also is one of the winners of the 2011 Most Wired Innovator Awards for its development of eVisits, a Web-based system for providing secure “electronic housecalls” to patients. This pioneering approach to health care is available to patients of most UPMC primary care physicians and provides a safe, convenient and cost-effective alternative to in-person visits or phone calls for more than 20 conditions. eVisits, using physician-created, structured questionnaires, are integrated into UPMC’s extensive electronic medical records (EMRs) to ensure continuity of patient care.

The awards will be presented at the 2011 Health Forum and AHA Leadership Summit in San Diego, July 17 to 19.

“UPMC is a long-time leader in adopting, developing and commercializing smart technology that improves care for patients. We are honored to be consistently recognized for these achievements by Hospitals & Health Networks and proud of the dedicated team of clinicians and technologists at UPMC who have made this possible,” said Daniel Drawbaugh, chief information officer of UPMC.

The 13th annual Most Wired Survey and Benchmarking Study included more than 1,300 hospitals and health systems across the country and measured the use of technology in clinical quality and safety, business and administrative functions, and ambulatory and community services.

Over the past five years, UPMC has invested more than $1.3 billion in technology to support clinical excellence and administrative efficiency as it creates new models of accountable care. UPMC is one of the nation’s earliest and most sophisticated users of EMRs. Children’s Hospital of Pittsburgh of UPMC in 2009 was the first pediatric facility in the nation to achieve HIMSS Stage 7 status for its virtually paperless environment and the most comprehensive use of EMRs, while seven other UPMC hospitals are Stage 6, as measured by HIMSS Analytics, a subsidiary of the Healthcare Information and Management Systems Society.

Last year, UPMC ranked fifth in the InformationWeek500, a list of the nation’s top technology innovators across all industries, and also was honored with the Healthcare Innovation Award for creating a system that allows radiologists and physicians to access imaging studies from across UPMC to better care for patients.

UPMC Presbyterian Shadyside President and UPMC Kidney Specialist to be Honored by National Kidney Foundation

PITTSBURGH, March 9, 2011 - UPMC Presbyterian Shadyside President John Innocenti has been named this year’s Corporate Gift of Life Awardee and Thomas Kleyman, M.D., chief of the University of Pittsburgh Renal-Electrolyte Division, has been named Medical Gift of Life Awardee by the National Kidney Foundation (NKF) Serving the Alleghenies.

Innocenti and Dr. Kleyman will receive their awards at the foundation’s annual Kidney Gift of Life Gala on Saturday, March 19 at the Circuit Center & Ballroom on the South Side.  “With World Kidney Day on March 10, we are honored to have outstanding individuals as our Gift of Life Awardees,” said Kevin Ho, M.D., a nephrologist at UPMC and the event chair.

“In addition to Mr. Innocenti’s leadership within the UPMC hospital system, he served as our NKF Corporate Walk Chairman in 2009 and 2010, making public appearances and attracting both sponsorship and contributions,” Dr. Ho said.

Dr. Kleyman is being honored for his contributions to kidney research. Dr. Kleyman is the director of the Pittsburgh Center for Kidney Research.

“Dr. Kleyman has contributed to our general understanding of how the kidneys process sodium and continues to advance nephrology research on multiple fronts,” Dr. Ho said.