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1 carolyn spiotta Pancreas/Kidney Transplant Recipient I feel so fortunate and thankful that I have received a second chance at life. Carolyn Spiotta, 44, Pittsburgh. Carolyn needed a new pancreas and kidney after suffering from type 1 diabetes and developing end-stage renal disease. Despite dialysis for several hours each week, Carolyn s diabetes continued to spiral out of control, leaving her exhausted and, at times, unconscious. Following a pancreas and kidney transplant, Carolyn spent just eight days in the hospital and remains, in her words, eternally grateful to her donor and her donor s family.

2 PANCREAS AND KIDNEY/PANCREAS TRANSPLANTATION 2011 Highlights In 2011, a total of 15 pancreas transplants were performed, including 11 kidney/ pancreas transplants and four pancreas-alone transplants. This brings the total number of transplants performed since the beginning of the program to 314. Clinical outcomes continue to be excellent. For patients receiving a pancreas/ kidney or pancreas-alone transplant in 2011, survival was 100 percent. The majority of pancreas transplants at Cleveland Clinic are performed to address diabetes. Research and Innovations Cleveland Clinic s Kidney and Pancreas Transplant Program actively participates in clinical and translational research activities and contributes significantly to the transplant scientific community with work presentations at national and international meetings, as well as through staff participation at academic and scientific conferences. Our research activities can be broadly divided into two major areas: 1) Translational research. There is a continuous need to develop novel biomarkers that will help clinicians better take care of patients so as to improve their outcomes. The National Institutes of Health (NIH) has dedicated significant funding to investigate novel tools that can predict transplant outcomes in various multicenter studies. Cleveland Clinic has been actively participating in the Clinical Trials in Organ Transplantation (CTOT) studies since Emilio Poggio, MD, and Robert Fairchild, PhD, are the principal investigators at Cleveland Clinic for the following CTOT studies: PANCREAS AND KIDNEY/PANCREAS TRANSPLANTATION Principal Investigators Dr. Emilio Poggio, Dr. Titte Srinivas and Dr. Robert Fairchild Clinical Trial in Organ Transplantation (CTOT-09): Immune Monitoring and CNI Withdrawal in Low Risk Recipients of Kidney Transplants. This is an NIHsponsored multicenter trial (PI: Dr. Peter S. Heeger) with the goal of developing a strategy of immune monitoring that will allow safe withdrawal of calcineurin inhibitors in kidney transplant recipients perceived to be at relatively low risk for immune injury

3 Principal Investigators Dr. Emilio Poggio and Dr. Richard Fatica Immune Tolerance Network (ITN524ST)/Clinical Trials in Organ Transplantation (CTOT-12): Associating Renal Transplantation with the ITN Signature of Tolerance (ARTIST Study). This is a multicenter NIH-ITN funded observational study to assess the prevalence of a tolerance signature in renal transplant recipients. Principal Investigator Dr. Emilio Poggio Clinical Trial in Organ Transplantation (CTOT-08): Discovery and Validation of Proteogenomic Biomarker Panels in a Prospective Serial Blood and Urine Monitoring Study of Kidney Transplant Recipients. This is an NIH-sponsored multicenter study (PI: Dr. Michael Abecassis, Northwestern University, Chicago) aimed at validating specific proteogenomic biomarker panels for acute and chronic rejection using prospective serial blood and urine monitoring in kidney transplant recipients. Principal Investigators All Cleveland Clinic Kidney and Pancreas Transplant Staff Kidney and Pancreas Transplant Program Bio-Repository. In collaboration with Cleveland Clinic s Lerner Research Institute, the Kidney and Pancreas Transplant Program has initiated collection and storage of biospecimens (blood, urine, biopsy tissue) from kidney and pancreas transplant recipients who receive an organ at Cleveland Clinic. These biospecimens are intended for use in developing and testing novel biomarkers that will eventually improve patient care. This is one of the most important endeavors currently ongoing in the research aspect of our program. 2) Clinical research. Clinical research has always been the backbone of scientific activities at Cleveland Clinic, including those in transplantation. Some of the most important ongoing research projects are listed below. 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. The purpose of this study is to learn whether ramipril, an ACE inhibitor drug, is safe and effective in minimizing the risk of proteinuria in subjects in whom the immunosuppressive regimen is switched from a calcineurin inhibitor to sirolimus (a noncalcineurin inhibitor medication). Principal Investigators Dr. Titte Srinivas, Dr. Stuart Flechner, Dr. Emilio Poggio Renal Allograft Function and Histology Following Switching from Tacrolimus- to Sirolimus (SRL)-Based Immunosuppression Clinical and Mechanistic Impact. This study will test the hypothesis that switching from a calcineurin inhibitor (tacrolimus) to sirolimus (Rapamune) in a triple-therapy regimen with MMF and steroids in living and/or deceased donor renal transplant recipients leads to improvement in allograft structure and function at two years post-transplantation.

4 Principal Investigator Dr. Titte Srinivas A Prospective Cohort Study to Describe the Evolution of Persistent Hyperparathyroidism in Kidney Transplant Recipients. This is a corporatefunded multicenter study to estimate the proportion of subjects with persistent hyperparathyroidism post-transplantation among those who remain undertreated over time. Principal Investigator Dr. Stuart Flechner A Two-Part, Phase 1/2, Safety, PK and PD Study of TOL-101, an Anti-TCR Monoclonal Antibody for Prophylaxis of Acute Organ Rejection in Patients Receiving Renal Transplantation. TOL-101 is a murine-derived IgM monoclonal antibody directed against the alpha-beta T-cell receptor on human lymphocytes. It is being developed for use as an induction agent in kidney transplantation. This multicenter U.S. trial will begin by determining the safe potential therapeutic dose of the drug, and then follow with a randomized controlled comparison with Thymoglobulin. It is hoped that TOL-101 will have a shorter effective half-life than current agents and that recipients will repopulate with tolerogenic gamma-delta T-cells. Principal Investigator Dr. Bijan Eghtesad Enhancing DCD Kidney Utilization with Thrombolytic Therapy. This is an HRSAsponsored study to determine if the potential for post-transplant complications due to delayed kidney function can be prevented or reduced by treating the donated kidney with a clot-dissolving medication. PANCREAS AND KIDNEY/PANCREAS TRANSPLANTATION 78 79

5 Survival analysis: For patients receiving their first transplant of this type between July 1, 2008, and Dec. 31, 2010, for the one-month and one-year models, and between Jan. 1, 2006, and June 30, 2008, for the three-year model. Singleorgan transplants only; re-transplants excluded. (Source: Scientific Registry of Transplant Recipients [SRTR], January 2012) Pancreas: Adult survival 1 Month 1 Year 3 Years Patient survival (percent) Graft survival (percent) Pancreas/kidney: Adult survival 1 Month 1 Year 3 Years Patient survival (percent) Pancreas graft survival (percent) Kidney graft survival (percent) Number of pancreas transplants in 2011 Organ Number Percent Pancreas Pancreas/kidney Total 15 a a Includes 3 re-transplants Pancreas transplant mortality in 2011 Hospital deaths only (within 30 days post-transplant) 0

6 Days on waiting list and post-transplant length of stay (LOS) for pancreas transplant recipients in 2011 Mean Median Number Days waiting Post-transplant LOS Median time to transplant for patients on waiting list a Pancreas Months Cleveland Clinic 14.5 United States (overall) 20.7 Pancreas/kidney Months Cleveland Clinic 12.3 United States (overall) 13.7 a For patients registered on waiting list between July 1, 2005, and Dec. 31, Source for U.S. data is Scientific Registry of Transplant Recipients (SRTR). Primary diagnoses for patients transplanted in 2011 Diagnosis Number Percent Diabetes Re-transplant/graft failure Total 15 PANCREAS AND KIDNEY/PANCREAS TRANSPLANTATION 80 81

7 Selected Publications Refer also to the list of publications on page 91 (Renal Transplantation). Gunasekaran G, Wee A, Rabets J, Winans C, Krishnamurthi V. Duodenoduodenostomy in pancreas transplantation. Clin Transplant Nov 29 [Epub ahead of print]. Schold JD, Buccini LD, Goldfarb DA, Flechner SM, Hsich E, Mason D, Fung J, Stephany BR, Krishnamurthi V, Srinivas TR. Patient participation in research among solid organ transplant recipients in the United States. Transplantation. 2011;91(12): Srinivas TR, Kaplan B. Transplantation in 2011: new agents, new ideas and new hope. Nat Rev Nephrol. 2011;8(2):74-75.

8 Leadership Phone numbers Pre-transplant Post-transplant Fast facts Venkatesh Krishnamurthi, MD Program and Surgical Director, Pancreas Transplant Staff Robin Avery, MD Richard Fatica, MD Sherif Mossad, MD Saul Nurko, MD John Rabets, MD Titte Srinivas, MD Brian Stephany, MD Alvin Wee, MD Emilio Poggio, MD Medical Director, Pancreas Transplant; Director, Renal Function Laboratory Initiated: 1985 First kidney/pancreas transplant: Oct. 23, 1985 First pancreas transplant: March 22, 1988 As of Dec. 31, 2011, 185 kidney/pancreas, 121 pancreas, 4 liver/pancreas, 3 pancreas/intestine/liver and 1 pancreas/intestine transplants have been performed at Cleveland Clinic PANCREAS AND KIDNEY/PANCREAS TRANSPLANTATION Charles Winans, MD 82 83