Introduction to Kidney Transplantation

1. Introduction to Kidney Transplantation Dr Natasha Cook Renal Physician, Austin Health and Northern Health September 2009

2. Treatment for Kidney Failure Dialysis: Haemodialysis & Peritoneal Transplantation

3. A kidney transplant is only one type of treatment for End Stage Renal Failure. It is NOT a cure

4. Where does my new kidney go?

5. Where does my new kidney go?

6. Kidney Transplant - Advantages What are the benefits of a kidney transplant? Quality of Life: normal life No dialysis Back to work, holiday etc. Food and fluid intake less restricted Improved sexual function and fertility Improved Medical Outcome: Increased longevity in the majority of patients

7. Short Term Risks of Transplantation • Anaesthesia and surgical complications: • including infection (wound, pneumonia, urine infections), • bleeding, • clots in the legs and lungs. • death • Donors are screened thoroughly for infections and cancers, however unknown infectious agents and microscopic cancers in the donor which are not detectable may be transmitted to the recipient. This is very uncommon.

8. Risks of Transplantation • Complications from the anti-rejection medications • Infections overall and includes infectious organisms which the general population would not normally acquire (“opportunistic infections” eg. Viral, fungal, atypical – examples are Cytomegalovirus, Pneumocystis) • Cancers in general are increased in transplant recipients; especially skin cancers and lymphoid cancers • Diabetes • High blood pressure • High cholesterol and other lipids • Osteoporosis • Specific side-effects of each anti-rejection medication

9. Kidney Transplant – Other considerations Hospital stay is usually about 1 week but complications can lead to a longer stay or coming back into hospital Delayed Graft Function : You may need dialysis for a while until your kidney starts to work Rejection Infection Technical Problems with Surgery at the blood vessel or the bladder end Frequent visits to clinic, frequent blood tests. It may take some time before you feel the benefits.

10. Ongoing issues and changes to Kidney Transplantation • Supply and Demand - increasing waiting time on deceased donor waiting list (Currently about 3-6 years depending on blood group and antibody level) • Changes to Practice due donor organ shortage • Increasing Live Donor Transplantation • Transplantation of patients with “positive cross-match” • ABO incompatible transplantation • Paired exchange • Significant changes to anti-rejection therapy

11. Types of Transplants Deceased Donor Transplants Live Donor Related (genetic) Unrelated (“emotionally”) Other Live Non-directed donation Paired Exchange

12. Number and Duration of Functioning Grafts Australia 2005 All Functioning Grafts (6,269)

13. Deceased Donor Transplants

14. How are the kidneys obtained? The Donor Transplant Coordinator facilitates, coordinates and assists in the procurement of donor organs 24 hours a day. Provides the link between the donor hospital and the transplant hospital Receives referrals from Intensive Care Units who believe they may have a potential donor Attends the referring hospital to assist in organising the donation

15. Who is eligible for a transplant? For people who are Neardialysis or dialysis dependent Medically & Surgically Fit Transplant is NOTa suitable treatment for everyone

16. Age It’s not the age in years that count but how worn your body is or how many other disease you have.

17. The Transplant List • There is only ONE Transplant List which is the “Active Transplant List”– ready to be called for transplantation • Interim Patients under consideration or temporarily off the Active List do NOT appear on the active transplant list

18. Transplant Waiting List Requirements 2nd Monthly blood test for antibodies Yearly Transplant Review Review recipients due to increasing waiting time Medical & Surgical fitness Education Seminar every 2 years Update on new developments Update on Risks/Benefits of Transplantation

19. Transplant “Work Up” Transplant Doctor & Transplant Nurse in Transplant Outpatient Clinic Detailed History and Examination Blood tests X rays Heart Tests Check up by Transplant Surgeon Referrals to other specialists as needed- Cardiac, Gastroenterology, Dermatology, Liver, Psychiatrists, Vascular Surgeons

20. Tissue Typing and Cytotoxic antibodies Tissue typing identifies Transplantation or Tissue antigens Must be completed before acceptance onto the transplant list Cytotoxic Antibodies (antibody to “Transplantation or Tissue” antigen) Monthly test Patient removed from the transplant list if blood is not received regularly

21. Living Donor Transplants Donor Workup

22. Living Donor Transplants Who can donate? Parents, brothers, sisters, cousins, husbands, wives, friends.

23. Live Donor Transplants The Donor is the very important person in this situation and every possible care is taken to make sure any potential risk is minimised to acceptable levels

24. Individuals who may be excluded for living donation Age – the elderly Women who have not completed childbearing: preferably not used Diabetes – complete contraindication Obesity/overweight Renal disease complete contraindication Abnormal GFR. (The volume of urine filtered by the kidney over a set time) Protein in the urine Kidney stones Kidney surgery Reflux High Blood Pressure Blood in the urine Heart disease Lung disease Cancer Infection Inability to give consent The donation must not be coerced and must be truly altruistic.

25. Live Kidney Donor Workup Blood tests Urine tests: to check for blood and protein Special Kidney Xrays Ultrasound of kidneys and urinary tract Renal Scan CT Angiogram Review by Transplant Surgeon, Psychiatrist and Independent Renal Physician

26. Donor Nephrectomy

27. Post Transplant Follow up

28. Maximising Survival of the kidney Factors that we watch for, which may contribute to poor function: Kidney Rejection (Early and Late) Drug Toxicity Proteinuria Poorly controlled blood pressure BK virus infection

29. Post Transplant Complications • Infection • PCP pneumonia: Bactrim 3 times weekly or nebulised pentamadine for 6 mo • CMV: anti-viral treatment depending on exposure status of donor and recipient • Recurrence of kidney disease • Diabetic nephropathy • Glomerulonephritis (Primary or Secondary) • Cardiovascular disease • Diabetes (prednisolone, tacrolimus) • Cancer: Screening, Dermatology review • Osteoporosis: 2 yearly DEXA scan

30. Other Health Issues • Obesity • Smoking • Diet • Issues relating to Fertility

31. Transplantation issues in Alport Syndrome

32. Transplantation is an Excellent Treatment for End Stage Renal Failure due to Alport Syndrome

33. Anti-Glomerular Basement Membrane Antibody disease • 2-3% risk of graft loss due to formation of anti-Glomerular Basement Membrane Antibodies in male transplant recipients with Alport Syndrome

34. Anti-Glomerular Basement Membrane Antibody disease • The glomerular basement membrane in the kidney is made of Type 4 Collagen • Production of components of type IV collagen is reduced or defective in Alport Syndrome • When normal components are encountered in the new kidney by a recipient with Alport Syndrome, they are seen as foreign and antibodies can be formed • This leads to glomerulonephritis and graft loss

35. Anti-Glomerular Basement Membrane Antibody disease • Men with deafness and kidney failure before 30 years of age are more susceptible • COL4A5 deletions (The gene encoding α5 chain of Type IV collagen) are associated with higher risk • However studies generally find the risk of anti-GBM nephritis is still less than predicted • Plasma exchange, cyclophosphamide and more recently rituximab are treatment options • Difficult to treat

36. Anti-Glomerular Basement Membrane Antibody Disease • Bone marrow plus Kidney transplantation: • Recipient’s immune system is a mixture of cells from the native and donor immune system • Immune cells do not react against the kidney transplant

37. Use of Alport ‘Carriers’ with isolated haematuria as Renal Donors • One recently published study with very small numbers but follow up for 2-14 years: • Gross et al NDT May 2009: • 6 “Carrier” mothers donating to sons • 3/6 new high blood pressure • 2/6 new protein in the urine • 4/6 decline in kidney function (but kidney function still about 40% or more of normal)

38. Use of Alport ‘Carriers’ with isolated microscopic haematuria as Renal Donors • Significant risk of • New Onset Proteinuria • New Onset Hypertension • Decline in Renal function • HEARING LOSS, PROTEINURIA, HYPERTENSION, OR KIDNEY FAILURE PRIOR TO DONATION ARE ABSOLUTE CONTRAINDICATIONS

39. Use of Alport ‘Carriers’ with isolated microscopic haematuria as Renal Donors • Should be a rare event • Close follow up is required • Donors should be given ACE inhibitors (which reduce protein leak into the urine as well as blood pressure)

40. Questions?