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Erythropoietin and iron supplements have been used for 30 years to treat anemia in patients with chronic kidney disease, but erythropoiesis-stimulating agents can only be safely used to increase hemoglobin levels to 11 g per deciliter. Roxadustat, a member of a new class of drugs called hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors, stimulates erythropoiesis and regulates iron metabolism. As reported in The New England Journal of Medicine, results from two Phase 3 randomized, clinical trials in China suggest that roxadustat may be beneficial for patients with chronic kidney disease. During the 26-week trials, 154 patients with chronic kidney disease not receiving dialysis and 305 patients undergoing long-term dialysis were randomized to receive either roxadustat or epoetin alfa (or a placebo for patients not receiving dialysis). Hemoglobin levels increased and hepcidin levels decreased in both groups of patients receiving roxadustat. Furthermore, roxadustat increased transferrin levels while maintaining serum iron levels and attenuated decreases in transferrin saturation levels. However, patients taking roxadustat were more likely to have hyperkalemia and upper respiratory infections. Allowing hemoglobin levels to be normalized, roxadustat may transform the treatment of chronic kidney disease. Ongoing clinical trials are monitoring roxadustat’s use over longer periods and in other populations. References: Chen N, Hao C, Peng X, Lin H, et al. Roxadustat for anemia in patients with kidney disease not receiving dialysis. The New England Journal of Medicine 2019 Chen N, Hao C, Liu BC, Lin H, et al. Roxadustat treatment for anemia in patients undergoing long-term dialysis. The New England Journal of Medicine 2019 Kaplan J. Roxadustat and anemia of chronic kidney disease. The New England Journal of Medicine 2019

(CNN)Taking one of the most-prescribed medications in the world -- proton pump inhibitors -- might dramatically increase a person's risk for kidney failure and kidney disease, new research suggests. The study was released Thursday in the Journal of the American Society of Nephrology. Doctors prescribe proton pump inhibitors, also known as PPIs, to help people who suffer from regular heart burn, ulcers, gastroesophageal reflux disease or acid reflux. They are sold under the names Prevacid, Prilosec, Nexium, Protonix, Aciphex and others. About 15 million Americans have prescriptions for them, although people can get them without a prescription -- so the number who use them is likely much higher. The medications are popular because they relieve symptoms pretty quickly. It was also thought that they had a low toxicity. Looking at data from the U.S. Department of Veterans Affairs, the study's authors found 173,321 people who used PPIs and 20,270 took a PPI alternative known as histamine H2 receptor blockers. The authors, who work at Washington University in St. Louis and at the Clinical Epidemiology Center at the VA St. Louis Health Care System, analyzed data from these patients five years later. They found that a large percentage of those patients who were taking PPIs were now having more kidney problems than those patients who took the alternative histamine H2 receptor blockers. Patients who took PPIs had a 96% increased risk of developing kidney failure and a 28% increased risk of chronic kidney disease compared to the patients who took the histamine H2 receptor blockers. Earlier studies have shown that taking PPIs have been linked to acute interstitial nephritis, also a problem that may be likely to end in kidney failure. A study that ran online in JAMA in January also found a link between PPIs and a higher risk of chronic kidney disease, also known as CKD. Like this study, it also was observational and doesn't provide evidence of causality, but as the earlier study said, "even a casual relationship between PPI use and CKD could have a considerable public health effect given the widespread extent of use." Other side effects from taking PPIs include an increased risk of pneumonia, double the risk ofinfection from C. difficile and a small risk of osteoporosis, earlier studies have shown. The authors of this research suggest that PPIs are overprescribed. Previous research, including a2008 study and others have shown the same. The authors of the new study conclude if a person has a prescription for a PPI, it should be used sparingly and only taken for a short period of time. Source: http://edition.cnn.com/2016/04/14/health/proton-pump-inhibitors-kidney-failure/

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Dana Edson was talking with a friend from her church in Kerrville, TX. Her friend’s son was in need of a kidney transplant. Edson offered to be tested to see if she was a match for Mark Ridgaway, whom she’d never met. Ridgaway had been given a kidney transplant from his mother 16 years ago, but he was in need of another transplant and had been on a wait list for over a year. It turned out that Edson was match, but instead of donating a kidney to Ridgaway, Dr. Osama Gaber – director of the J.C. Walter Jr. Transplant Center at Houston Methodist – asked her to enter a swap program. She agreed on one condition: “I wouldn’t want to give my kidney if Mark had to wait three years for his, and that’s when (Dr. Gaber) gave me the guarantee that Mark would get his the same day as I gave mine,” says Edson. When it was all said and done, Edson’s willingness to enter the program resulted in a six-way kidney swap. 71-year old Rudyne Walker was the last of the six to receive a kidney. She was in stage five renal failure when she received, Edson’s. “I got from Dana a kidney that is young and vigorous and excited about life. I haven’t had a kidney like that in 40-years. It moves me when I’m not ready to go,” said Walker. In order for a recipient to receive a kidney, they must have a donor willing to enter the swap program. Kellie Canaday worked with Walker at Exxon. Canaday had offered to donate a kidney for Walker but they weren’t a match. Maria Coronado ended up receiving Kellie’s kidney. Juan Coronado shed 30 pounds to help his wife. Maria had been dealing with dialysis for two years. Juan’s kidney went to Steve Miller, whom Coronado had never met. Miller had been battling with diabetes for 43 years and like Ridgaway, was in need of a second transplant. Olivia Miller wanted to help her husband, but she was not a match. So instead she helped Esmerelda Guerrero. Guerrero and her husband Cesar are Jehovah’s Witnesses from New Mexico. They had been turned down in their effort to receive a kidney transplant for Esmerelda because they refuse to have blood transfusions. Fortunately for them, Houston Methodist is one of a select few hospitals that perform bloodless transfusions. “We have a program for Jehovah’s Witness transplants. We do actual lung transplants with Jehovah’s Witnesses. So, we give them hormones to raise their blood count, we prepare them differently for the transplant,” says Dr. Gaber. While Cesar didn’t provide a kidney for his wife, he was still able to help. Felix Rodriguez received Cesar’s kidney. Sandra Izquierdo wanted to help her brother, Felix, but couldn’t because she wasn’t a match. Instead her kidney went to Mark Ridgaway. Six donors and six recipients, all thanks to the kindness of strangers, though they all consider themselves family now. Dr. Gaber says months of preparation went into performing the “six-way” organ swap. “You actually need 12 operating rooms and it is hard on the hospital because of the complexity, you don’t want to make mistakes. The kidney needs to go to the right place,” said Dr. Gaber. With more than 1,400 people on the Methodist kidney transplant wait list, the hospital hopes more people will participate in the program. http://www.houstonpublicmedia.org/articles/news/2016/08/01/162583/houston-methodist-performs-six-way-kidney-swap/

Clint Smith, at home in New Orleans, had a procedure that altered his immune system to allow his body to accept a kidney from an incompatible donor. It “changed my life,” he said. Credit William Widmer for The New York Times In the anguishing wait for a new kidney, tens of thousands of patients on waiting lists may never find a match because their immune systems will reject almost any transplanted organ. Now, in a large national study thatexperts are calling revolutionary, researchers have found a way to get them the desperately needed procedure. In the new study, published Wednesday in The New England Journal of Medicine, doctors successfully altered patients’ immune systems to allow them to accept kidneys from incompatible donors. Significantly more of those patients were still alive after eight years than patients who had remained on waiting lists or received a kidney transplanted from a deceased donor. The method, known as desensitization, “has the potential to save many lives,” said Dr. Jeffery Berns, a kidney specialist at the University of Pennsylvania’s Perelman School of Medicine and the president of the National Kidney Foundation. It could slash the wait times for thousands of people and for some, like Clint Smith, a 56-year-old lawyer in New Orleans, mean the difference between receiving a transplant and spending the rest of their lives ondialysis. The procedure, Mr. Smith said, “changed my life.” Researchers estimate about half of the 100,000 people in the United States on waiting lists for a kidney transplant have antibodies that will attack a transplanted organ, and about 20 percent are so sensitive that finding a compatible organ is all but impossible. In addition, said Dr. Dorry Segev, the lead author of the new study and a transplant surgeon at the Johns Hopkins University School of Medicine, an unknown number of people with kidney failure simply give up on the waiting lists after learning that their bodies would reject just about any organ. Instead, they resign themselves to dialysis, a difficult and draining procedure that can pretty much take over a person’s life. Desensitization involves first filtering the antibodies out of a patient’s blood. The patient is then given an infusion of other antibodies to provide some protection while the immune system regenerates its own antibodies. For some reason — exactly why is not known — the person’s regenerated antibodies are less likely to attack the new organ, Dr. Segev said. But if the person’s regenerated natural antibodies are still a concern, the patient is treated with drugs that destroy any white blood cells that might make antibodies that would attack the new kidney. The process is expensive, costing $30,000, and uses drugs not approved for this purpose. The transplant costs about $100,000. But kidney specialists argue that desensitization is cheaper in the long run than dialysis, which costs $70,000 a year for life. Although by far the biggest use of desensitization would be for kidney transplants, the process might be suitable for living-donor transplants of livers and lungs, researchers said. The liver is less sensitive to antibodies so there is less need for desensitization, “but it’s certainly possible if there are known incompatibilities,” Dr. Segev said. With lungs, he said, desensitization “is theoretically possible,” although he said he was not aware of anyone doing it yet. In the new study, 1,025 patients at 22 medical centers who had an incompatible donor were compared to an equal number of patients who remained on waiting lists for an organ or who had an organ from a deceased but compatible donor. After eight years, 76.5 percent of those who received an incompatible kidney were still alive, compared with 62.9 percent who remained on the waiting list or received a deceased donor kidney and 43.9 percent who remained on the waiting list but never got a transplant. The desensitization procedure takes time — for some patients as long as two weeks — and is performed before the transplant operation, so patients must have a living donor. It is not known how many have someone willing to donate a kidney, but doctors say they often see situations in which a relative or even a friend is willing to donate but is incompatible. “Often patients are told that their living donor is incompatible, so they are stuck on waiting lists,” for a deceased donor, Dr. Segev said. In recent years, an option called a kidney exchange has helped some in this situation. Patients who have incompatible living donors can swap donors with someone whose donor may be compatible with them. Often, there are chains of patient-donor pairs leading to a compatible organ swap. That process can be successful, said Dr. Krista L. Lentine, the medical director of the living donation program at the Saint Louis Center for Transplantation, but patients often still cannot find a compatible organ because they have antibodies that would reject almost every kidney. In those cases, “desensitization may be the only realistic option for receiving a transplant,” said Dr. Lentine, who was not involved with the study. Dr. Jeffrey Campsen, a transplant surgeon at the University of Utah Health Sciences Center who also was not a study investigator, said his group focused on exchanges and had been fairly successful. But he also comes across patients whose donors do not want to participate. “There is a hurdle if the donor and patient have an emotional bond,” he said. The new data showing the success of desensitization “lets people get behind it,” Dr. Campsen said, adding, “I do think it is something we would consider.” Mr. Smith, the New Orleans patient who went through desensitization, had progressive kidney disease that slowly scarred his kidneys until, in 2004, they stopped functioning. His sister-in-law, Allison Sutton, donated a kidney to him, and he had a transplant, but after six and a half years, it failed. He went on dialysis, spending four days a week hooked up to dialysis machines for hours. It was keeping him alive, he told his friends, but it was not a life. Then a nurse suggested that he ask Johns Hopkins about its desensitization study. “I was like, whatever I could do,” he said. He discovered that he qualified for the study. But he needed a donor. One day, his wife, Sheryl Smith, was talking on the phone to a college friend, Angela Watkins, who lives in Augusta, Ga., and mentioned that Mr. Smith was praying for a donor. Mrs. Watkins’s husband, David Watkins, a judge in state court, had been friends with Mr. Smith in college and the two wives, also college friends, had kept in touch over the years. Mrs. Watkins told her husband about the conversation, and they asked themselves if they should offer to donate. “We talked and researched and prayed,” Judge Watkins said. Finally, he said, they came to a conclusion. “We have a moral obligation to at least see if we would qualify.” And he thought that he should be the one to go first. If he did not qualify, his wife could be tested. Mr. Smith warned his old friend that donating was an enormous undertaking. “He said, ‘You can’t grasp what you are doing.’ I heard him but it didn’t register,” Judge Watkins said. “I told him, ‘I have something you need, so what’s the big deal?’ ” Of course, it was a big deal. Although Judge Watkins had prepared by getting himself in top physical shape, it still took about six months to recover from the operation. That was four years ago, and Mr. Smith’s new kidney is still functioning and he is back to his active life, forever grateful to his friend. “Every night,” he says, “during my nightly prayers with my wife, I thank God for bringing David and Allison to me and for giving me the gift of life. “But for David giving me this gift, I would still be in that dialysis chair.” Correction: March 9, 2016 Because of an editing error, an earlier version of this article misstated the role of Dr. Krista L. Lentine, the medical director of the living donation program at the Saint Louis Center for Transplantation, in the study of kidney transplants. She was not involved. Source:http://www.nytimes.com/2016/03/10/health/kidney-transplant-desensitization-immune-system.html?ref=health