To watch a videotaped interview with this patient, visit clevelandclinic.org/transplant. clevelandclinic.org/transplant

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1 SHARI MOSLEY KIDNEY TRANSPL ANT RECIPIENT Now that I have the transplant, I ve been given back my freedom. Shari Mosley, 23, Woodmere, Ohio. Seven years and one day after starting dialysis three times every week due to kidney failure, Shari underwent a kidney transplant. Freed from a life scheduled around dialysis treatments as well as complications from fistulae, Shari just graduated with a bachelor s degree in fashion merchandising and looks forward to completing a master s degree in business administration. To watch a videotaped interview with this patient, visit.

2 RENAL TRANSPLANTATION Leadership 2009 Highlights Clinical activity in renal transplantation remained strong at Cleveland Clinic s Glickman Urological & Kidney Institute in We performed 161 transplants in Transplantation, more than other clinical endeavors, is carried out with significant regulatory oversight. All Cleveland Clinic programs were among the first to be re-certified by CMS. In February, Cleveland Clinic collaborated with St. Vincent Hospital in Indianapolis to establish a Renal Transplant Program. The Renal Transplant Program was led by Bashir Sankari, MD, surgical director; Alvin Wee, MD, attending surgeon; and Mahendra Govani, MD, medical director. Drs. Sankari and Wee are both fellowship trained in kidney and pancreatic transplantation and are employed by Cleveland Clinic. This regional transplant program is modeled after Cleveland Clinic s partnership with the Charleston Area Medical Center in West Virginia where Cleveland Clinic transplant surgeon Jeff Chueh, MD, PhD, leads the program along with four certified clinical transplant coordinators, a dietitian, social worker and attending nephrologists. David A. Goldfarb, MD Program and Surgical Director, Renal Transplant Richard Fatica, MD Medical Director, Renal Transplant R E N A L T R A N S P L A N T A T I O N The renal transplant program continues to be active in the Paired Donation Network, an innovative service for incompatible donor-recipient pairs. Awards and Achievements Emilio Poggio, MD, has been selected to join the Editorial Board of Transplantation the official journal of the Transplantation Society. Titte Srinivas, MD, organized Contentious Issues in Organ Transplantation A Colloquium at Cleveland Clinic, October 8-9, The event aimed to improve collaboration between various stakeholders in transplantation, including regulatory authorities and transplant centers. See pages for complete staff listing 68 69

3 Fast facts Initiated: 1963 First Adult Kidney Transplant: January 9, 1963 Medicare Approval: July 1, 1966 UNOS Approval: March 21, 1988 As of December 31, 2009, 3,482 kidney, 162 kidney/pancreas, 41 kidney/liver and 3 kidney/ heart transplants have been performed at Cleveland Clinic. Cleveland Clinic developed and refined dialysis techniques in the 1950s to enable survival of patients with kidney failure. We developed one of the first deceaseddonor kidney transplant programs in the world, established in We established active living donor programs for kidney (laparoscopic live donor nephrectomy) transplant. Research and Innovations The laboratory of Robert L. Fairchild, PhD, continues to focus on: mecha nisms that produce high levels of inflammation early in transplanted tissues and organs, understanding how this inflammation directs alloantigen-primed T cells and other leukocytes into allografts, and effector mechanisms leading to solid organ graft rejection. The introduction of specific solid phase assays and improved histological recognition has made the detection of antibody-mediated rejection of organ allografts more reliable. Antibody-mediated rejection is now emerging as a common cause of graft injury and loss, both early and late after transplant. Unfortunately, the treatment of antibody-mediated rejection has been limited to attempts at removal of the offending antibody from the serum or blocking its effects. Recently, bortezomib, an inhibitor of cytoplasmic proteosomes, has been shown to inhibit antibody production directly in plasma cells. We have used bortezomib in a regimen combined with plasmapheresis and intravenous gammaglobulin to reverse established antibody-mediated rejection in renal allograft recipients. During this past year, eight kidney recipients and two multiple organ recipients (liver-kidney, pancreas-kidney) have been treated with this regimen for failing grafts due to antibody-mediated rejection At six months after treatment, 87 percent of the grafts still function, and we were able to identify a reduction in the most dominant donor-specific antibody of about 75 percent. This preliminary experience has demonstrated that bortezomib can be used in a treatment regimen for antibody-mediated rejection, and is well-tolerated by most patients. While such treatment may decrease donor-specific antibody titers and prolong graft function, the long-term safety, optimum dose, length of treatment, and need for additional agents will be the topic of future studies. Other studies include: Children s Hospital First Pediatric Kidney Transplant: April 4, 1963 Three pediatric kidney transplants were performed in Principal Investigator: Dr. Emilio Poggio Kinetics of T-cell Donor Reactivity Post-Kidney Transplantation: NIH-sponsored study aimed at characterizing the cellular alloimmune response (T-cell reactivity to donor antigens) in kidney transplant candidates, and providing insight into immunological risk profiling by using noninvasive immune monitoring techniques. This study is also designed to correlate pre-transplant cellular alloreactivity with post-transplant clinical outcomes.

4 Principal Investigator: Dr. Howard Goldman Impact of Renal Transplant on Female Sexual Function: an investigatory-initiated study designed to assess the prevalence of sexual dysfunction in female subjects and their male partners prior to renal transplant and to determine if there is improvement after transplantation. It will also assess the sexual function of female kidney donors before and after donation, an understudied area. Phone Number Principal Investigator: Dr. Stuart Flechner Genomics for Kidney Transplantation: study to apply the latest technologies in genomics to advance our understanding of clinical kidney transplantation. Principal Investigator: Dr. Stuart Flechner A Randomized Placebo Controlled Double-Blind Comparative Study to Evaluate the Effect of Ramipril on Urinary Protein Excretion in Maintenance Renal Transplant Patients Converted to Sirolimus: a study to learn whether ramipril is safe and effective in preventing increased protein in the urine when the immunosuppressive regimen is switched from a calcineurin inhibitor to sirolimus (a non-calcineurin inhibitor medication). In native kidneys, drugs like ramipril are helpful in controlling the amount of protein in the urine. This study attempts to determine if the same is true in the transplanted kidney. Principal Investigator: Dr. Emilio Poggio Clinical Trial in Organ Transplantation (CTOT-09): Noninvasive Monitoring to Predict Outcome in De Novo Kidney Transplant Recipients: NIH-sponsored multicenter observational trial with the major goal to determine whether any single test or a combination of tests obtained in the first six months after renal transplantation correlates with acute rejection or graft loss in renal allograft recipients receiving commonly used immunosuppressive regimes. R E N A L T R A N S P L A N T A T I O N 70 71

5 Survival analysis: patient survival for 718 primary kidney, kidney/heart, kidney/liver and kidney/pancreas transplants Time Survival % 6 months year years 91.5 Survival analysis: kidney graft survival for 718 primary kidney, kidney/heart, kidney/liver and kidney/pancreas transplants Time Survival % 6 months year years 90.3 Survival analysis: kidney graft survival for 74 primary kidney/pancreas transplants Time Survival % 6 months year years 86.1 Number of transplants 2009 Organ Number Deceased Living/Related Living/Unrelated Kidney Kidney/pancreas Kidney/liver 6 6 Total 161

6 Waiting list and post-transplant length of stay (LOS) for kidney patients transplanted in 2009 Mean Median Number Days waiting (deceased donor) Post-transplant LOS * * 1 patient not discharged as of February 4, 2010 Primary diagnoses for kidney patients transplanted in 2009 Diagnosis Number Percent Diabetes Cystic disease Glomerular disease Re-transplant/graft failure Hypertension Multi-system disease Nephritis/interstitial disease Malignant disease Obstructive disease Congenital/hereditary disease Unknown Vascular disease Cirrhosis Others Total 161 R E N A L T R A N S P L A N T A T I O N Kidney transplant mortality 2009 Hospital deaths

7 Publications Demirjian S, Stephany B, Abu Romeh IS, Boumitri M, Yamani MH, Poggio ED. Conversion to sirolimus with calcineurin inhibitor elimination vs. dose minimization and renal outcome in heart and lung transplant recipients. Clin Transplant. 2009;23(3):351. Flechner SM. Sirolimus in kidney transplantation indications and practical guidelines: de novo sirolimus-based therapy without calcineurin inhibitors. Transplantation. 2009;87(8 Suppl):S1. Herts BR, Sharma N, Lieber M, Freire M, Goldfarb DA, Poggio ED. Estimating glomerular filtration rate in kidney donors: a model constructed with renal volume measurements from donor CT scans. Radiology. 2009;252(1):109. Poggio ED, Braun WE, Davis C. The science of stewardship: due diligence for kidney donors and kidney function in living kidney donation evaluation, determinants, and implications for outcomes. Clin J Am Soc Nephrol. 2009;4(10):1677. Poggio ED, Rule AD, Tanchanco R, et al. Demographic and clinical characteristics associated with glomerular filtration rates in living kidney donors. Kidney Int. 2009;75 (10):1079. Schold J, Srinivas TR, Sehgal AR, Meier-Kriesche HU. Half of kidney transplant candidates who are older than 60 years now placed on the waiting list will die before receiving a deceased-donor transplant. Clin J Am Soc Nephrol. 2009;4(7):1239. Schold JD, Rehman S, Kayle LK, Magliocca J, Srinivas TR, Meier-Kriesche HU. Treatment for BK virus: incidence, risk factors and outcomes for kidney transplant recipients in the United States. Transpl Int. 2009;22(6):626. Stephany BR, Boumitri M, Budev M, Alao B, Poggio ED. Absence of proteinuria predicts improvement in renal function after conversion to sirolimus-based immunosuppressive regimens in lung transplant survivors with chronic kidney disease. J Heart Lung Transplant. 2009;28(6):564. Tiong HY, Flechner SM, Zhou L, et al. A systematic approach to minimizing wound problems for de novo sirolimus-treated kidney transplant recipients. Transplantation. 2009;87(2):296. Tiong HY, Goldfarb DA, Kattan MW, et al. Nomograms for predicting graft function and survival in living donor kidney transplantation based on the UNOS Registry. J Urol. 2009; 181(3):1248.