An evaluation of kidney function after islet transplant graft failure

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1 An evaluation of kidney function after islet transplant graft failure Peixoto, EML.,Vendrame, F., Arnau, A., Fornoni, A, Padilla, N., Baidal, D.,Alvarez,A., Ricordi,C.,Alejandro, R. Nov, 07, 2015

2 A New Era in Islet Transplantation! % Insulin Independence 37% Partial allograft function EDMONTON PROTOCOL % Insulin Independence rate

3 NORTH AMERICA Islet Transplant Activity ( ) Edmonton (101) Miami (30) Minneapolis (20) Vancouver (12) U Penn, (12) Houston (11) Harvard, Boston (10) Birmingham AL (3) Northwestern, (8) St. Louis (8) U Illinois (5) Emory, Atlanta (7) Cincinnati (6) NIH (6) Seattle (6) City of Hope CA (5) Memphis (3) U Maryland (2) Columbia NY (2) U Mass (2) UC San Francisco (2) Carolina Med Center (1) Cornell NY (1) Denver (1) > 50 Institutions: > 700 patients Santiago Chili (1) San Paulo (3) Buenos Aires (11) EUROPE SOUTH AMERICA Geneva+GRAGIL (48) Milan (39) Giessen (31) Brussels/Free Univ (25) Nordic Network (25) Brussels/Louvain (20) ASIA & AUSTRALIA Zurich (12) Innsbruck (11) Lille (7) Budapest/Geneva (3) King s UK (4) Royal Free UK (3) Oxford (1) Stockholm/Giessen (2) Nantes (1) Sydney (6) Kyoto (6) Tokyo (1) Seoul (2) Chiba (1) Harbin (1) Shanghai (1)

5 Islet Isolation AJT January 2005

7 Intrahepatic Islet Transplantation PERCUTANEOUS TRANSHEPATIC CATHETERIZATION

8 Islet Infusion EMBOLIZATION OF THE PORTAL VEIN Tatiana Froud

9 Glucose variability after single donor infusion (18 month post Tx) Islet infusion Glucose Insulin Independence Date

10 Long term Islet Graft Function Edmonton Ed C-peptide positive 76% % Survival Corrected HbA1C and absence of hypoglycemia 23% Insulin Independence Time (years)

11 One Thousand Simultaneous Pancreas-Kidney Transplants at a Single Center With 22-Year Follow-Up Hans W. Sollinger, MD, PhD, Jon S. Odorico, MD, Yolanda T. Becker, MD, Anthony M. D Alessandro, MD, and John D. Pirsch, MD Annals of Surgery 250: , 2009

12 Solid Organ Allograft Survival Improvement in the United States: The Long-Term Does Not Mirror the Dramatic Short-Term Success S. A. Lodhi, K. E. Lamb and H. U. Meier-Kriesche American Journal of Transplantation 2011; 11:

13 Objective To evaluated the kidney function in a group of ITxrecipients up to 10 years post graft failure

14 Statistical analysis Data were analyzed using Excel for Windows and GraphPad Prism 6 software using the Kruskall-Wallis test with with Dunn's test correction for multiple comparisons and the Fisher exact test. Correlations were performed using the Pearson test. Results of continuous variables were expressed as means ± SD. Values of p <0.05 were considered statistically significant.

15 Methods A prospective analysis in 12 participants using demographic, anthropometrical, laboratory data, immunosuppressive and anti-hypertensive therapy. Kidney function assessed by CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) calculated estimated glomerular filtration rate(egfr); Iohexol clearance GFR and urinary albumin on spot urine samples at study time points Data was compared to collected data from before islet transplant and during immunosuppressant therapy(is).

16 Demographics N 12 Age (years) 49.5±9.3 Gender (F-M)) 6-6 Diabetes duration (years) 34.3±13.6 HbA1c (%) / mmol/mol 7.76 ± 0.8 / 61±8.7 Infusions (n) 1.9±1 Average IEQ/kg received 7407±3557 1/2 time on IS (years) 1.36±1.33 Time to Graft Failure (years) 2.71±1.57 Time from graft failure to study enrollment 6 ±1.9 Duration of follow-up (years) 10.6±2.2 Cardiovascular disease 2 Retinopathy 5 Nephropathy 2 Peripheral neuropathy 0

17 Study time points

18 Results Correlation of egfrand iohexolclearance. egfrfrom 12 islets transplants was obtained according to the CKD-EPI formula and correlated with the iohexolclearance obtained for the Miami historical cohort of 45 islet transplanted subjects. 120 r=0.53 p= egfr Iohexol Raw Clearance

19 Results Renal function at the time of islet transplant and on follow-up.

20 Results Albuminuriaat the time of islet transplantation and on follow-up.

21 Conclusions ITx recipients maintained stable renal function during post-gf follow up, despite exposure to immunosuppressants for approximately 3 years and worsening of glucose control after GF. A selection bias for ITx patients may account for the stability of renal function. The discontinuation of immunosuppressive therapy might be responsible for the regression of microalbuminuria. The rate of decline in egfr after GF is lower than before transplant although did not reach statistical significance. Comparisons with a type one diabetes control group would provide further evidence of the lack of impact on kidney function byisonthosewithgoodkidneyreserve.

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23 Framingham Winter is coming

PANCREAS, PANCREAS-KIDNEY, SEGMENT OF PANCREAS AND ISLET PANCREATIC TISSUE TRANSPLANTATION SUR703.013

PANCREAS, PANCREAS-KIDNEY, SEGMENT OF PANCREAS AND ISLET PANCREATIC TISSUE TRANSPLANTATION SUR703.013 COVERAGE: A simultaneous or combined pancreas-kidney transplant (SPK) from a cadaver donor or a simultaneous