Located at one of the world’s leading research institutions, the Pediatric Kidney Transplant Program is pursuing investigations along a number of avenues that promise to substantially improve kidney transplantation outcomes. Clinical Research on Kidney Transplantation in ChildrenUnder the direction of Associate Professor of Pediatrics Minnie Sarwal, MD, MRCP, DCH, PhD, clinical researchers are studying transplant survival trends, infant transplantation, and the reasons why some transplant recipients fail to follow posttransplant medication regimens, one of the leading causes of lost kidney function. The work on nonadherence has been done with Dr. Richard Shaw, associate professor of child psychiatry at Stanford University. Dr. Sarwal and Shaw have devised a novel approach to monitor for, and possibly reduce, nonadherence in these patients.Dr. Sarwal is also currently directing an effort to develop a new histological (tissue-based) method for assessing drug nephrotoxicity (kidney poisoning), another common cause of progressive kidney damage and decline in transplant function over time. The aim of this work is to develop a scoring strategy for biopsy diagnosis that can be used to safely reduce drug doses following transplantation and reduce the risk of toxicity. Dr. Sarwal and Dr. Oscar Salvatierra have developed a novel steroid-free immunosuppression protocol that is now part of a large nationwide multicenter trial, comparing a steroid-free approach to pediatric kidney transplantation with a steroid-minimizing approach. This study, funded by the National Institutes of Health and industry, began in March 2004. Back to top Rejection and Transplant Acceptance at the Molecular LevelBasic science researchers working under the direction of Dr. Minnie Sarwal are exploring thousands of genes of the mouse and human genome to determine which ones play a role in rejecting and accepting transplanted kidneys. This work led to a recent publication in the New England Journal of Medicine, which identified distinct therapeutic and prognostic categories of acute rejection for the first time. The results form the basis for improved diagnosis, and thus treatment, of rejection episodes in different patients. Dr. Sarwal is also studying the signature of acute rejection in kidney and blood. Understanding this molecular level of rejection may make it possible to diagnose impending or ongoing rejection with a simple blood or urine test.Another exciting area of research in Dr. Sarwal's laboratory is the study of the molecular mechanisms of transplantation tolerance — that is, stable graft function in the absence of all immunosuppression. New pathways have been discovered in patients who have developed spontaneous tolerance for their kidney transplants. This information will be used to develop improved monitoring tools to possibly allow the safe reduction, or even withdrawal, of immunosuppression in patients with stable graft function. Dr. Sarwal's research is also adding to our understanding of the role genes play in patients who are on steroids after transplantation, compared to those on steroid-free immunosuppression, and of the effects of transplanted adult-sized kidneys on the immune systems of the infants who receive them. Back to top Mechanisms of Glomerular InjuryAt the heart of the kidney are hundreds of thousands of tiny filters known as the glomeruli (singular, glomerulus). In many types of kidney disease, the glomeruli become more and more scarred and damaged over time, until finally the kidney no longer functions.The Pediatric Nephrology Division’s Kevin V. Lemley, MD, PhD, in conjunction with the laboratory of Bryan Myers, MD, of Stanford's Division of Nephrology (Adult), is studying the mechanisms underlying progressive damage to the glomerulus. This research is investigating a number of serious kidney diseases, including transplant rejection, steroid-resistant nephrotic syndrome, lupus nephritis, IgA nephropathy and diabetic kidney disease. Dr. Lemley’s research is funded by the National Institutes of Health. This research has important implications for understanding the basic mechanisms of kidney disease. It also may lead to methods for detecting and diagnosing glomerular injury early in the process, perhaps before it is irreversible, and for predicting the likely course of kidney disease. Back to top PublicationsThe Kidney Transplant Program’s physicians have published the results of their work in a wide variety of professional journals and scholarly books. This list includes research published since 1997.Articles Hammer GB, Chuljian P, Al-Uzri A, Conley S, Orlandi P, Salvatierra O. Intraoperative management of small children undergoing kidney transplantation. Am J Anesthesiology. 1997;24:37–39. Alfrey EJ, Conley SB, Tanney DC, Mak R, Scandling J, Dafoe DC, Hammer GB, Orlandi PO, Page L, Salvatierra O. Use of an augmented urinary bladder can be catastrophic in renal transplantation. Transpl Proc. 1997;29:154–155. Salvatierra O, Tanney D, Mak R, Alfrey E, Lemley K, Mackie F, So S, Hammer GB, Krane EJ, Conley SB. Pediatric renal transplantation and its challenges. Transpl Rev. 1997;11:51–69. Salvatierra O, Alfrey EJ, Tanney DC, Mak R, Hammer GB, Krane EJ, So S, Lemley KV, Dafoe DC, Orlandi PD, Page JL, Conley SB. Superior outcomes in pediatric renal transplantation. Arch Surg. 1997;132:842–849. Alfrey EJ, Salvatierra O, Tanney DC, Mak R, Scandling JD, Dafoe DC, Hammer GB, Orlandi PD, Page L, Conley SB. Bladder augmentation can be problematic with renal failure and transplantation. Pediatr Nephrol. 1997;11:672-675. Salvatierra O, Singh T, Shifrin R, Conley S, Alexander S, Tanney D, Lemley K, Sarwal M, Mackie F, Alfrey E, Orlandi P, Zarins C, Herfkens F. Successful transplantation of adult-sized kidneys into infants requires maintenance of high aortic blood flow [rapid communication]. Transplantation. 1998;66:819–823. Salvatierra O, Alexander SR, Krensky AM. Pediatric kidney transplantation at Stanford. Pediatr Transplantation. 1998;2:165–176. Salvatierra O, Singh T, Shifrin R, Conley S, Alexander S, Tanney D, Lemley K, Sarwal M, Mackie F, Alfrey E, Orlandi P, Zarins C, Herfkens R. Transplantation of adult-sized kidneys into infants induces major blood flow changes. Transpl Proc. 1997;31:236–237. Salvatierra O: Management of vesicoureteral reflux in renal allografts transplanted into pediatric recipients. Pediatr Transplantation. 1999;3:171–175. Salvatierra O, Sarwal M, Alexander S, Lemley K, Yorgin P, Al-Uzri A, Lu A, Millan M, Alfrey E. A new, unique and simple method for ureteral implantation in kidney recipients with small, defunctionalized bladders [rapid communication]. Transplantation. 1999;68:731–738. Mackie FE, Umetsu D, Salvatierra O, Sarwal M. Pulmonary capillary leak syndrome with intravenous cyclosporine A in pediatric renal transplantation. Pediatr Transplantation. 2000;4:35–38. Millan M, Sarwal M, Lemley KV, Yorgin P, Orlandi P, So S, Alexander S, Salvatierra O. 100% 2-year graft survival can be attained in high-risk, < 15 kg infant recipients of kidney allografts. Arch Surg. 2000;135:1063–1069. Sarwal MM, Cecka JM, Millan MT, Salvatierra O. Adult-sized kidneys without ATN provide exceedingly superior long-term graft outcomes for infants and small children: a single center and UNOS analysis. Transplantation. 2000;70:1728–1736. Sarwal M, Bartsch L, Salvatierra O. Posterior urethral valves with renal insufficiency in infancy, the choice of management is critical. Nephrology Rounds. 2000;3(10):1–6. Sarwal M, Jani A, Chang S, Huie P, Wang Z, Salvatierra O, Clayberger C, Sibley R, Krensky AM , Pavlakas M. Granulysin expression is a marker for acute rejection and steroid resistance in human renal transplantation. Human Immunology. 2001;62:21–31. Sarwal M, Chang S, Barry C, Chen X, Alizadeh A, Salvatierra O, Brown P. Genomic analysis of renal allograft dysfunction using cDNA microarrays. Transpl Proc. 2001;33:297–298. Salvatierra O: Presidential address (XVIII International Congress of the Transplantation Society). Transpl Proc. 2001;33:33–48. Sarwal MM, Yorgin P, Alexander S, Millan MT, Belson A, Granucci L, Major C, Costaglio C, Sanchez J, Orlandi P, Salvatierra O. Promising early outcomes with a novel, complete steroid avoidance immunosuppression protocol in pediatric renal transplantation [rapid communication]. Transplantation. 2001;72:13–21. Millan MT, Shizuru J, Hoffmann P, Dejbakhsh-Jones S, Scandling JD, Grumet FC, Tan J, Salvatierra O, Strober S. Mixed chimerism and immunosuppressive drug withdrawal after HLA-mismatched kidney and progenitor transplantation [rapid communication]. Transplantation. 2002;73:1386–1391. Falco DA, Nepomuceno RR, Krams SM, Lee PP, Davis MM, Salvatierra O, Alexander SR, Esquivel C, Cox KL, Frankel LR and Martinez O. Identification of Epstein Barr virus specific CD8+T lymphocytes in the circulation of pediatric transplant recipients. Transplantation. 2002;74:501–510. Salvatierra O. Felix Rapaport Memorial Lecture: Moving towards a perfect transplant for pediatric kidney recipients. Transpl Proc. 2002;34:2763–2765. Bartsch L, Sarwal M, Orlandi P, Yorgin P, Salvatierra O. Limited surgical interventions in children with posterior urethral valves can lead to better outcomes following renal transplantation. Pediatr Transplantation. 2002;6:400–405. Chua M-S, Barry C, Chen X, Salvatierra O, Sarwal MM. Molecular profiling of anemia in acute renal allograft rejection using DNA microarrays. Am J Transplantation. 2003;3:17–22. Satterwhite T, Chua M-S, Hsieh S-C, Chang S, Scandling J, Salvatierra O, Sarwal MM. Increased expression of cytotoxic effector molecules: Different interpretations for steroid-based and steroid-free immunosuppression. Pediatr Transplantation. 2003;7:53–758. Sarwal M, Chua M-S, Kambham N, Hsieh S-C, Satterwhite T, Masek M, Salvatierra O. Molecular heterogeneity in acute renal allograft rejection identified by DNA microarray profiling. N Engl J Med. 2003;349:123–136. Vidhun J, Masciandro J, Varich L, Salvatierra O, Sarwal M. Safety and risk stratification of percutaneous biopsies of adult-sized renal allografts in infant and older pediatric recipients. Transplantation. 2003;76:552–557. Sarwal MM, Vidhun JR, Alexander SR, Satterwhite T, Millan M, Salvatierra O. Continued superior outcomes with modification and lengthened follow-up of a steroid avoidance pilot with extended daclizumab induction in pediatric renal transplantation. Transplantation. 2003;76:1331–1339. Millan M, Berquist WE, So SK, Sarwal MM, Wayman KI, Cox K, Filler G, Salvatierra O, Esquivel CO. 100% kidney allograft survival with simultaneous liver and kidney transplantation in infants with primary hyperoxaluria — a single center experience. Transplantation. 2003;76;1458–1463. Editorials Salvatierra O. A wake-up call for new strategies to improve living donor graft outcomes in pediatric kidney recipients. Transplantation. 2000;70:262–263. Salvatierra O, Sarwal M. Renal perfusion in infant recipients of adult-sized kidneys is a critical risk factor. Transplantation. 2000;70:412–413. Salvatierra O. Pre-transplantation voiding cystography is not necessary for all potential pediatric kidney recipients. Pediatr Transplantation. 2001;5:73–74. Salvatierra O: Transplant physicians bear full responsibility for the consequences of kidney donation by a minor. Am of Transplantation. 2002;2:297–298. Invited Articles Millan MT, Salvatierra O. Kidney transplantation in infants. Neo Reviews. 2000;1(9):E180–E188. Salvatierra O. Renal transplantation in infants and small children: Outcomes, techniques and management. Transplantation and Immunology Letter. 2000;16(4):4–12. 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