Islet and Pancreas Transplantation

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1 Islet and Pancreas Transplantation Julie Wardle Specialist Nurse Coordinator

2 Indication for Transplant Treatment option for a select groups of patients with type 1 diabetes Aged 18 years or over Recurrent life threatening hypoglycaemia despite optimal intervention

3 Types of Transplant Islet Transplant Alone (ITA) Islet Transplant after Kidney (IAK) Pancreas Transplant Alone (PTA) Simultaneous pancreas kidney transplant (SPK) Pancreas after Kidney Transplant (PAK)

4 Goals of Transplantation PTA Restores normoglycaemia Insulin independence Stabilisation of progressive diabetic complications Islet Transplant Prevent recurrent life threatening hypoglycaemia and restore optimal glycaemic control Attain HbA1c <7.0% Reduce exogenous insulin requirements Both confer risks with increased morbidity and mortality associated with PTA

5 Criteria for ITA and PTA Recurrent severe hypoglycaemia >1 episode requiring 3 rd party assistance per year >2 episodes in the last 2 years or 1 episode in the last year Evidence of impaired awareness of hypoglycaemia Marked glycaemic lability Ryan Lability Index Continuous subcutaneous glucose monitoring profile

6 Criteria for IAK Functional renal transplant, clinically stable on immunosuppression with prednisolone dose 5mg daily GRF < 40ml/min/1.73m/serum creatinine,175mmol/l Patients experiencing Severe hypoglycaemic or altered hypoglycaemic awareness HbA1c >7% Evidence of marked glycaemic lability

7 Assessment for Transplant Central to the assessment is informed choice Insulin dependence for 5 years C peptide negative Review of current diabetic management Hypoglycaemic severity and frequency Concordance Glucose testing 3 times daily Evidence of education and self management Optimised insulin regimen

8 Assessment for Transplant Cont Absence of insulin resistance islet transplant < 0.7units/Kg/day to achieve an HbA1c < 9 BMI < 28 for Islet transplant BMI < 30 for PTA Renal function Baseline creatinine Isotopic GFR >90mls/in/1.73m mls/in/1.73m2 discussed with Nephrologist 24 hour urine collection for proteinuria (ACR < 300mg/24hrs)

9 Assessment for Transplant Cont Cardiology review ECG Stress echo +/- coronary angiogram CXR Liver ultrasound Blood profile Malignancy screen Dental review Assessment of diabetic foot disease Evaluation of autonomic impairment Psychology review

10 National Allocation Scheme Pancreas allocation scheme Equity of access for all patients waiting for islet or whole vascularised graft NHS Blood and Transplant (NHSBT) NHSBT organ specific advisory groups 9 pancreas transplant centres 6 islet transplant centres 3 isolation centres Organs retrieved by national organ retrieval service (NORS)

11 7 Type 1 patients with severe hypoglycaemia metabolic instability Islets purified without animal proteins immediate transplantation 2-3 donors for each recipient Successful but very expensive to set up in all transplant centres

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16 UK Islet Transplant Outcomes 24 islet transplant recipients ( ) Data from 20 recipients 80% recipients has graft function at 24 months Severe hypoglycaemia reduced from 20 episodes pre transplant to 0.3 episodes per patient per year 60% of recipients experienced no recurrent severe hypoglycaemia over 24 months post transplant Hypoglycaemic awareness improved (Gold score) Target HbA1c <53mmol/mol achieved in 70% of recipients 45% recipients achieved insulin independence (9 recipients of which 3 maintained independence at 24 months)

17 Pancreas Transplant Procedure Intraperitoneal Vascular management Arterial Conduit to common iliac artery Venous Portal vein to common iliac vein inferior vena cava Exocrine secretions Enteric drainage to loop jejunum

18 Pancreas transplants Pancreas transplant type Pancreas & liver PTA PAK SPK Year

19 % graft survival One-year pancreas survival, DBD, % patient survival Graft survival Log-rank p< Kidney only: 93% Patient survival Log-rank p= N Survival (%) 95% CI SPK (K) (94 98) SPK (P) (82 91) PTA (41 76) PAK (36 76) Months post-transplant N Survival (%) 95% CI SPK (92 98) PTA (70 99) PAK ( ) Newcastle Months upon Tyne post-transplant Hospitals

20 Transplant Associated Risks Procedure related Islet transplant <1% risk of mortality 4% risk of portal vein thrombosis 10% risk of haematoma 20-30% risk of fatty infiltration in the liver PTA 3% mortality 30% morbidity 6-12% graft thrombosis

21 Transplant Associated Risks Cont Immunosuppression therapy Opportunistic infection Malignancy Nephrotoxicity Side effects of medication

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23 Offers the potential of significant improvement in quality and quantity of life Select group of patients with type 1 diabetes Transplantation confers a degree of risk to a potential recipient Hypoglycaemia versus burden of immunosuppression

24 Any Questions

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