This article was posted by the Diabetes Center at UCSF. We repost it here for educational purposes only.
Improving the outlook for simultaneous pancreas-kidney transplants
The body's rejection of transplanted organs and tissues is an unfortunate risk of transplant surgery. Historically, rejection rates in a simultaneous pancreas-kidney (SPK) transplant have been as high as 80% and, in 2001, averaged nearly 20% [1]. What's more, steroid-based immunosuppressive drugs that have been traditionally used to combat rejection are associated with several serious side-effects, including increased risks of osteoporosis and bone and joint problems.
Diabetes Center surgeons Drs. Peter Stock and Chris Freise have been pioneering new methods of immunosuppression for SPK transplants that do not rely upon steroids, with great success.
In a retrospective case review of 40 patients who received a simultaneous pancreas-kidney transplant followed by a steroid-avoiding immunosuppression protocol, the UCSF team reported 95% patient survival 1 year following transplant. Importantly, 87.5% of patients had retained insulin independence for 1 full year after transplantation, indicating their transplanted pancreas was continuing to function, while 92.5% had retained functioning kidney transplants at 1 year.
The study also looked at side effects of this immunosuppression regimen, and found no increased risk of infections or surgical complications. One potential concern with steroid use is abnormal cholesterol levels, and patients on the steroid free regimen required cholesterol lowering drugs only 18% of the time. The use of blood pressure medicines was needed about 50% of the time. Other potential benefits of avoiding steroids include less bone disease, less weight gain, and hopefully fewer cardiovascular problems. These other side effects are being studied by the investigators.
Over the past 15 years, the UCSF Transplant Division has performed nearly 350 pancreas transplants. Most of these have been performed as a simultaneous pancreas and kidney transplant in type 1 diabetic patients who have progressed to end stage kidney failure. Pancreas-kidney transplantation can be a very effective, highly successful treatment for patients with diabetes who are experiencing severe complications including renal failure, severe hypoglycemic unawareness, and debilitating neuropathy. Pancreas-only transplants are now being offered for patients who do not require a kidney transplant, but who have very unpredictable and erratic blood sugar control despite intensive insulin therapy. Success rates for solitary pancreas transplants (as defined by insulin independence) are approximately 90% at 1 year post-transplant.
For more information on the UCSF Kidney and Pancreas Transplantation Program, contact: (415) 353-1551. Or visit Diabetes Center at UCSF
Sunday, February 20, 2005
Progress Seen in Transplants for Diabetes
This article from the New York Times was distributed via e-mail on Feb. 16, 2005 by the JDRF. We post it here for private educational purposes only.
The New York Times
Wednesday, February 16, 2005
By MARY DUENWALD
Doctors may have found a way around a major obstacle in the effort to perfect transplants of islet cells, an experimental treatment for Type 1 diabetes, a severe form that often begins in childhood.
Such transplants usually succeed only if islet cells from the pancreases of two or even three donors are used - a significant drawback, given the scarcity of donor organs. But now, in a trial of eight patients at the University of Minnesota, in Minneapolis, doctors have managed successful transplants of islet cells, which are needed to produce insulin, with the pancreases of single donors.
The use of anti-inflammatory drugs that are normally used to treat arthritis seems to have enabled many more of the transplanted cells to survive, said Dr. Bernhard J. Hering, director of the islet transplant program at the University of Minnesota. Patients were given these drugs before surgery to dampen the inflammation that otherwise destroys as many as half of transplanted islet cells in the first 24 hours, Dr. Hering said.
The doctors also cultured the donated islet cells in the laboratory for two days, rather than transplanting them within hours of isolating them from the donor pancreas. This step appears to give the islet cells greater resilience, Dr. Hering said.
The results of the trial are reported today in The Journal of the American Medical Association.
"This is really a long-awaited development, if it can be reproduced, because it means that the efficiency of islet cells is being increased," said Dr. R. Paul Robertson, scientific director of the Pacific Northwest Research Institute, a diabetes research center in Seattle. Dr. Robertson was not involved in the trial.
Diabetes researchers hope islet-cell transplants, which can be done almost as easily as a blood transfusion, in less than an hour, will one day free many people with Type 1 diabetes from the need to inject themselves with insulin several times a day to control their blood sugar.
But refining the procedure has not been easy. Among the first patients to have successful transplants five years ago, most are using insulin again-though not as much as they needed before their transplants.
Type 1 diabetes, sometimes called juvenile diabetes, occurs when the body's immune system destroys the insulin-producing cells in the pancreas, which are contained in tiny structures called the islets of Langerhans.
An estimated one million people in the United States have Type 1 diabetes.
Although it is possible to transplant the entire pancreas, the risk of death is great enough that the operation is rarely done in people who do not also need a kidney transplant because of diabetes-related kidney failure. Islet-cell transplants are less invasive and less dangerous.
Islet cells, which make up about 2 percent of the pancreas, can be isolated from cadaver pancreases and then transplanted through a catheter into the recipient's liver. They cannot be placed into the pancreas, because that organ is too vulnerable to inflammation.
When islet-cell transplants were first performed in humans, in the 1980's, they were rarely successful. But five years ago, surgeons at the University of Alberta in Edmonton adjusted the combination of immunity-suppressing drugs that are used to prevent rejection of the new cells and achieved successful transplants in eight patients.
Since then, the Edmonton protocol, with some variations, has been used on about 500 patients worldwide, said Dr. James Shapiro, director of the islet-cell transplant program at the University of Alberta, who designed the protocol.
"We've come a long way in a really short time, and I think islet transplantation is here to stay," Dr. Shapiro said. "It's still far from perfect, however."
A total of 73 patients have now received islet-cell transplants in Edmonton, most of whom have had the procedure twice. One year after transplant, 82 percent of patients need no insulin injections. After three years, however, that number falls to about 50 percent, Dr. Shapiro said. But after five years, he said, it appears that only 15 percent will still be independent of insulin.
"It appears that some of the grafts are failing, but it is not a complete failure," Dr. Shapiro said. "Some of the transplanted cells are still producing insulin."
Some of the cells may succumb to the anti-rejection drugs. Or perhaps the autoimmune reaction that caused the patient's diabetes kills them, Dr. Shapiro said.
Last month, working with surgeons in Kyoto, Japan, Dr. Shapiro accomplished the first islet-cell transplant from a living donor. A 27-year-old woman with Type 1 diabetes was given islet cells that had been isolated from half of her mother's pancreas.
Such transplants would expand the supply of donor cells. But some experts are wary of risks to donors.
The New York Times
Wednesday, February 16, 2005
By MARY DUENWALD
Doctors may have found a way around a major obstacle in the effort to perfect transplants of islet cells, an experimental treatment for Type 1 diabetes, a severe form that often begins in childhood.
Such transplants usually succeed only if islet cells from the pancreases of two or even three donors are used - a significant drawback, given the scarcity of donor organs. But now, in a trial of eight patients at the University of Minnesota, in Minneapolis, doctors have managed successful transplants of islet cells, which are needed to produce insulin, with the pancreases of single donors.
The use of anti-inflammatory drugs that are normally used to treat arthritis seems to have enabled many more of the transplanted cells to survive, said Dr. Bernhard J. Hering, director of the islet transplant program at the University of Minnesota. Patients were given these drugs before surgery to dampen the inflammation that otherwise destroys as many as half of transplanted islet cells in the first 24 hours, Dr. Hering said.
The doctors also cultured the donated islet cells in the laboratory for two days, rather than transplanting them within hours of isolating them from the donor pancreas. This step appears to give the islet cells greater resilience, Dr. Hering said.
The results of the trial are reported today in The Journal of the American Medical Association.
"This is really a long-awaited development, if it can be reproduced, because it means that the efficiency of islet cells is being increased," said Dr. R. Paul Robertson, scientific director of the Pacific Northwest Research Institute, a diabetes research center in Seattle. Dr. Robertson was not involved in the trial.
Diabetes researchers hope islet-cell transplants, which can be done almost as easily as a blood transfusion, in less than an hour, will one day free many people with Type 1 diabetes from the need to inject themselves with insulin several times a day to control their blood sugar.
But refining the procedure has not been easy. Among the first patients to have successful transplants five years ago, most are using insulin again-though not as much as they needed before their transplants.
Type 1 diabetes, sometimes called juvenile diabetes, occurs when the body's immune system destroys the insulin-producing cells in the pancreas, which are contained in tiny structures called the islets of Langerhans.
An estimated one million people in the United States have Type 1 diabetes.
Although it is possible to transplant the entire pancreas, the risk of death is great enough that the operation is rarely done in people who do not also need a kidney transplant because of diabetes-related kidney failure. Islet-cell transplants are less invasive and less dangerous.
Islet cells, which make up about 2 percent of the pancreas, can be isolated from cadaver pancreases and then transplanted through a catheter into the recipient's liver. They cannot be placed into the pancreas, because that organ is too vulnerable to inflammation.
When islet-cell transplants were first performed in humans, in the 1980's, they were rarely successful. But five years ago, surgeons at the University of Alberta in Edmonton adjusted the combination of immunity-suppressing drugs that are used to prevent rejection of the new cells and achieved successful transplants in eight patients.
Since then, the Edmonton protocol, with some variations, has been used on about 500 patients worldwide, said Dr. James Shapiro, director of the islet-cell transplant program at the University of Alberta, who designed the protocol.
"We've come a long way in a really short time, and I think islet transplantation is here to stay," Dr. Shapiro said. "It's still far from perfect, however."
A total of 73 patients have now received islet-cell transplants in Edmonton, most of whom have had the procedure twice. One year after transplant, 82 percent of patients need no insulin injections. After three years, however, that number falls to about 50 percent, Dr. Shapiro said. But after five years, he said, it appears that only 15 percent will still be independent of insulin.
"It appears that some of the grafts are failing, but it is not a complete failure," Dr. Shapiro said. "Some of the transplanted cells are still producing insulin."
Some of the cells may succumb to the anti-rejection drugs. Or perhaps the autoimmune reaction that caused the patient's diabetes kills them, Dr. Shapiro said.
Last month, working with surgeons in Kyoto, Japan, Dr. Shapiro accomplished the first islet-cell transplant from a living donor. A 27-year-old woman with Type 1 diabetes was given islet cells that had been isolated from half of her mother's pancreas.
Such transplants would expand the supply of donor cells. But some experts are wary of risks to donors.
Saturday, January 01, 2005
Federal Govt., JDRF Launch Resource for Diabetic Kidney Disease Gene Studies
National Institutes of Health press release -- Dec. 28, 2004
The National Institutes of Health (NIH), Juvenile Diabetes Research Foundation (JDRF), and Centers for Disease Control and Prevention (CDC) announced today the availability of the largest single collection of biosamples and data for research on the genetic causes of kidney disease in type 1 diabetes.
The Genetics of Kidneys in Diabetes (GoKinD) collection has nearly 10,000 DNA, serum, plasma and urine samples, plus genetic and clinical data, from more than 1,700 adults with type 1 diabetes in the United States and Canada. Of those, 818 have had diabetes at least 10 years and have developed kidney disease, a common complication of diabetes. The other 893 have had diabetes at least 15 years but do not have kidney disease. Also in the collection are data and samples from 1,096 parents (548 sets).
“GoKinD is a tremendous resource. We’re thrilled about the promise it represents,” said Rebekah Rasooly, Ph.D., who oversees the project for NIH and directs genetics and genomics programs at NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). “We fund research all the time, but this kind of project reflects a new way of thinking. GoKinD is a gift that will keep on giving, and we are deeply indebted to the individuals and families who made this invaluable resource possible.”
Researchers can apply for DNA, extensive clinical data and some genetic data from GoKinD at www.gokind.org/access; serum, plasma and urine samples will be made available later. Methods of treatment, insulin doses, complications, smoking history and other data have been documented for all GoKinD participants. Also, DNA has been genotyped for genes well-known to predispose to type 1 diabetes. To protect the privacy of patients and families, researchers do not have access to names and other identifying information.
“This study is of exceptional quality and offers a unique opportunity for genetic research,” said Patricia Mueller, Ph.D., chief of CDC’s diabetes and molecular risk assessment laboratory.
Gathering information and samples of the kind, quality and quantity that individual researchers alone would be unable to collect, GoKinD provides a rich means for learning about the genetics of both kidney disease and type 1 diabetes.
“GoKinD will help us tease out genes linked to kidney disease versus those that are primarily important causes of diabetes itself,” said Concepcion R. Nierras, Ph.D., director of research for JDRF.
Both NIH and JDRF will separately consider requests to fund research on GoKinD data and samples. NIH grant applications are at http://grants.nih.gov, and resources for type 1 diabetes research are listed at www.niddk.nih.gov/fund/diabetesspecialfunds/funding.htm. JDRF grant applications are under the research tab at www.jdrf.org.
Once found, genes for susceptibility to kidney disease can be studied to find out what they do, how they do it and how researchers might intervene to prevent the disease or improve treatment. Studies have already linked several genes to susceptibility to type 1 diabetes, but scientists are confident that more genes exist and that other, as yet unknown, genes increase susceptibility to complications such as kidney disease. (Learn more about genetic factors in diabetes at www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=diabetes.chapter.987.)
“These genes alone don’t explain the complete genetic risk for diabetes, and little is known about genes for kidney disease or other complications. Yet, there is clearly a genetic risk for complications, because they run in families and among certain populations,” said Paul L. Kimmel, M.D., F.A.C.P., a nephrologist working part-time with Rasooly and NIDDK on GoKinD. Kimmel also directs the renal disease and hypertension division at George Washington University Medical Center in Washington, D.C.
Diabetes is the leading cause of kidney failure in the United States. In 2002, treatment of kidney failure cost Medicare and private insurers $25 billion for more than 400,000 people, 40 percent of whom had diabetes. Twenty to 40 percent of people with type 1 diabetes will develop kidney failure by the age of 50, but some develop it before the age of 30.
Type 1 diabetes accounts for up to 10 percent of people diagnosed with diabetes in the United States (up to 1 million people). This form of diabetes usually strikes children and young adults, who need several insulin injections a day or an insulin pump to survive. Insulin, though critical for controlling blood glucose, is no cure. Most people with the disease eventually develop one or more complications, including damage to the heart and blood vessels, eyes, nerves, and kidneys.
NIH, JDRF and CDC collaborated on GoKinD. NIH supported the study through a special fund for type 1 diabetes research established by Congress in 1997 and coordinated by NIDDK. In all, the fund will provide $1.14 billion between fiscal years 1998 and 2008, supplementing funds available for type 1 diabetes research through regular NIH appropriations.
Under JDRF, the Joslin Diabetes Center and the George Washington University (GWU) Biostatistics Center (and its associated clinical centers) each recruited about half the patients and their parents. GWU will also distribute GoKinD data. CDC provided genotyping data for the major type 1 diabetes risk factors, HLA DRB1, DQA1, and DQB1 and the -23 insulin gene single nucleotide polymorphism (SNP). In addition, CDC will distribute samples and conduct research on the collection. Biochemical clinical data were provided by the University of Minnesota.
Investigators and centers that recruited participants and provided clinical and genetic data are:
* Stephen A. Brietzke, Univ. of Missouri
* David Brillon, New York Presbyterian Hospital, Cornell Univ.
* George A. Burghen, Univ. of Tennessee
* George W. Burke, Univ. of Miami
* Patricia Cleary, George Washington Univ. Biostatistics Center
* Suzanne Cordovado and Patricia Mueller, CDC
* Debra Counts, Univ. of Maryland Medical System
* James Desemone, Albany Medical Center
* Steven V. Edelman, Univ. of California San Diego
* Carla Greenbaum, Virginia Mason Research Center
* Richard A.Guthrie, Mid-America Diabetes Associates, P.A.
* Irene Hramiak, St. Joseph's Health Care, Univ. of Western Ontario
* Mark Johnson, Univ. of North Carolina at Chapel Hill
* Lois Jovanovic, Sansum Medical Research Center
* John I. Malone, Univ. of South Florida
* Michael Mauer and Mike Steffes, Univ. of Minnesota
* Michael E. May, Vanderbilt Univ. Medical Center
* Larry Melton, Baylor Univ. Medical Center
* Mark E. Molitch, Northwestern Univ.
* Robert E. Ratner, Med-Star Clinical Research Center
* John Rogus, Adam Smiles and James Warram, Joslin Diabetes Center
* William L. Sivitz, Univ. of Iowa
* Maria Szpiech, Medical Univ. of South Carolina
* Neil H. White, Washington Univ. School of Medicine
* Bernard Zinman, Mount Sinai Hospital, Univ. of Toronto
The National Institutes of Health (NIH), Juvenile Diabetes Research Foundation (JDRF), and Centers for Disease Control and Prevention (CDC) announced today the availability of the largest single collection of biosamples and data for research on the genetic causes of kidney disease in type 1 diabetes.
The Genetics of Kidneys in Diabetes (GoKinD) collection has nearly 10,000 DNA, serum, plasma and urine samples, plus genetic and clinical data, from more than 1,700 adults with type 1 diabetes in the United States and Canada. Of those, 818 have had diabetes at least 10 years and have developed kidney disease, a common complication of diabetes. The other 893 have had diabetes at least 15 years but do not have kidney disease. Also in the collection are data and samples from 1,096 parents (548 sets).
“GoKinD is a tremendous resource. We’re thrilled about the promise it represents,” said Rebekah Rasooly, Ph.D., who oversees the project for NIH and directs genetics and genomics programs at NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). “We fund research all the time, but this kind of project reflects a new way of thinking. GoKinD is a gift that will keep on giving, and we are deeply indebted to the individuals and families who made this invaluable resource possible.”
Researchers can apply for DNA, extensive clinical data and some genetic data from GoKinD at www.gokind.org/access; serum, plasma and urine samples will be made available later. Methods of treatment, insulin doses, complications, smoking history and other data have been documented for all GoKinD participants. Also, DNA has been genotyped for genes well-known to predispose to type 1 diabetes. To protect the privacy of patients and families, researchers do not have access to names and other identifying information.
“This study is of exceptional quality and offers a unique opportunity for genetic research,” said Patricia Mueller, Ph.D., chief of CDC’s diabetes and molecular risk assessment laboratory.
Gathering information and samples of the kind, quality and quantity that individual researchers alone would be unable to collect, GoKinD provides a rich means for learning about the genetics of both kidney disease and type 1 diabetes.
“GoKinD will help us tease out genes linked to kidney disease versus those that are primarily important causes of diabetes itself,” said Concepcion R. Nierras, Ph.D., director of research for JDRF.
Both NIH and JDRF will separately consider requests to fund research on GoKinD data and samples. NIH grant applications are at http://grants.nih.gov, and resources for type 1 diabetes research are listed at www.niddk.nih.gov/fund/diabetesspecialfunds/funding.htm. JDRF grant applications are under the research tab at www.jdrf.org.
Once found, genes for susceptibility to kidney disease can be studied to find out what they do, how they do it and how researchers might intervene to prevent the disease or improve treatment. Studies have already linked several genes to susceptibility to type 1 diabetes, but scientists are confident that more genes exist and that other, as yet unknown, genes increase susceptibility to complications such as kidney disease. (Learn more about genetic factors in diabetes at www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=diabetes.chapter.987.)
“These genes alone don’t explain the complete genetic risk for diabetes, and little is known about genes for kidney disease or other complications. Yet, there is clearly a genetic risk for complications, because they run in families and among certain populations,” said Paul L. Kimmel, M.D., F.A.C.P., a nephrologist working part-time with Rasooly and NIDDK on GoKinD. Kimmel also directs the renal disease and hypertension division at George Washington University Medical Center in Washington, D.C.
Diabetes is the leading cause of kidney failure in the United States. In 2002, treatment of kidney failure cost Medicare and private insurers $25 billion for more than 400,000 people, 40 percent of whom had diabetes. Twenty to 40 percent of people with type 1 diabetes will develop kidney failure by the age of 50, but some develop it before the age of 30.
Type 1 diabetes accounts for up to 10 percent of people diagnosed with diabetes in the United States (up to 1 million people). This form of diabetes usually strikes children and young adults, who need several insulin injections a day or an insulin pump to survive. Insulin, though critical for controlling blood glucose, is no cure. Most people with the disease eventually develop one or more complications, including damage to the heart and blood vessels, eyes, nerves, and kidneys.
NIH, JDRF and CDC collaborated on GoKinD. NIH supported the study through a special fund for type 1 diabetes research established by Congress in 1997 and coordinated by NIDDK. In all, the fund will provide $1.14 billion between fiscal years 1998 and 2008, supplementing funds available for type 1 diabetes research through regular NIH appropriations.
Under JDRF, the Joslin Diabetes Center and the George Washington University (GWU) Biostatistics Center (and its associated clinical centers) each recruited about half the patients and their parents. GWU will also distribute GoKinD data. CDC provided genotyping data for the major type 1 diabetes risk factors, HLA DRB1, DQA1, and DQB1 and the -23 insulin gene single nucleotide polymorphism (SNP). In addition, CDC will distribute samples and conduct research on the collection. Biochemical clinical data were provided by the University of Minnesota.
Investigators and centers that recruited participants and provided clinical and genetic data are:
* Stephen A. Brietzke, Univ. of Missouri
* David Brillon, New York Presbyterian Hospital, Cornell Univ.
* George A. Burghen, Univ. of Tennessee
* George W. Burke, Univ. of Miami
* Patricia Cleary, George Washington Univ. Biostatistics Center
* Suzanne Cordovado and Patricia Mueller, CDC
* Debra Counts, Univ. of Maryland Medical System
* James Desemone, Albany Medical Center
* Steven V. Edelman, Univ. of California San Diego
* Carla Greenbaum, Virginia Mason Research Center
* Richard A.Guthrie, Mid-America Diabetes Associates, P.A.
* Irene Hramiak, St. Joseph's Health Care, Univ. of Western Ontario
* Mark Johnson, Univ. of North Carolina at Chapel Hill
* Lois Jovanovic, Sansum Medical Research Center
* John I. Malone, Univ. of South Florida
* Michael Mauer and Mike Steffes, Univ. of Minnesota
* Michael E. May, Vanderbilt Univ. Medical Center
* Larry Melton, Baylor Univ. Medical Center
* Mark E. Molitch, Northwestern Univ.
* Robert E. Ratner, Med-Star Clinical Research Center
* John Rogus, Adam Smiles and James Warram, Joslin Diabetes Center
* William L. Sivitz, Univ. of Iowa
* Maria Szpiech, Medical Univ. of South Carolina
* Neil H. White, Washington Univ. School of Medicine
* Bernard Zinman, Mount Sinai Hospital, Univ. of Toronto
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