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Why do pediatric kidney transplants fail?
Clinical collaboration with Washington University helps to advance research

Written by Karen CarlsonDr. Seifert

Kidney transplants in children are not curative, and although acute rejection rates have improved dramatically in the last 20 years, long-term survival rates have not. One cause for rejection may be chronic allograft injury, a progressive disease characterized by graft fibrosis and variable declines in kidney function, leading to recurrent end-stage kidney disease and a return to dialysis.

Chronic allograft injury is a major health risk, affecting nearly 100 percent of kidney transplant recipients within 10 years. Michael Seifert, M.D., assistant professor of pediatrics at SIU, is working to understand the cause of long-term failure of kidney transplants in children through a collaborative program between SIU and Washington University School of Medicine in St. Louis (WU).

Dr. Seifert will continue his research into allograft injury as part of his appointment as a clinical research scholar, through the Institute of Clinical and Translational Sciences KL2 Career Development Awards Program at Washington University. The appointment began July 1.

Seifert’s cross-sectional study aims to identify a vascular connection to chronic kidney disease-mineral and bone disorder (CKD-MBD) and chronic allograft injury. CKDMBD may be a cause of vascular damage that can lead to chronic allograft injury.

He is investigating the function of endothelial progenitor cells, which are rare cells that line the interior surface of blood vessels. If their function is altered after transplantation because of the CKD-MBD, these same cells may contribute to the destruction of blood vessels (vasculopathy), a component of chronic allograft injury. The results of the study could lead to improved diagnostic methods and treatments.

Seifert specializes in pediatric nephrology and is one of the pediatric specialists recruited for St. John’s Children’s Hospital, a joint endeavor of SIU and St. John’s Hospital in Springfield. He joined SIU in 2010. He also holds an adjunct faculty appointment in pediatrics at WU.

“Dr. Seifert has a unique background in endothelial biology and pediatric transplantation, allowing him to bridge the gap between basic science and clinical application,” said Sandra Puczynski, Ph.D., director of clinical and translational research at SIU School of Medicine.

The collaboration between Washington University and SIU School of Medicine through the KL2 Award will allow Seifert access to additional resources necessary to proceed with this study. Pediatric renal transplant recipients at WU, including some referred from SIU by Seifert, will be able to enroll in the clinical study.

Seifert’s appointment builds on a collaborative effort with Washington University for clinical services with SIU cardiologists and pediatric gastroenterologists. His appointment marks the first expansion of the collaboration to include research, in an effort to help SIU School of Medicine clinical faculty gain formal training in clinical research. The appointment is supported by Washington University’s Clinical Research Training Center.

Ingredients may give new target for diabetes treatment Dr. Premkumar

Louis Premkumar, Ph.D., professor of pharmacology, and his lab have found that an ingredient in raw garlic (allicin) or in yellow mustard and horseradish (allyl isothiocyanate) or in cinnamon bark (cinnamaldehyde) can activate a receptor that will cause the release of insulin. The receptor, TRPA1, is expressed in pancreatic beta cells. “It could be a potential target for developing drugs to enhance insulin release in diabetic patients, particularly for insulin-deficient Type 2 diabetes mellitus,” Dr. Premukar says. The research was published in PLOS ONE, a peer-reviewed, open access journal. (Expression of Transient/Receptor Potential Ankyrin 1 (TRPA1) and Its Role in Insulin Release from Rat Pancreatic Beta Cells; PLOS one, May 2012; 7:5 e38005.)