Overview of kidney transplant

renal transplant kidney transplant for non nephrologist
basics of kidney transplant overview of transplant

1. “An overview of Renal transplant for Non- Nephrologist ” Dr. Lalit K. Agarwal Consultant Nephrologist Woodlands Multispeciality Hospital Kolkata

2. Benefits of Transplantion Improve life expectancy Cardio-vascular benefits Improve Quality-of-life Socio-economic benefits

3. History of Kidney Transplantation 1950’s First successful kidney transplant-1954 TBI and Steroids 1960’s Azathioprine 1970’s Polyclonal anti-bodies – ATG and ALG Allograft survival rate 50% at 1 year and pt mortality rate was 10% to 20%

4. History of Kidney Transplantation 1980’s- significant improvement of graft survival 90% Cyclosporine - “triple drug therapy” Monoclonal antibody - OKT3 in 1985 199 0’s - reduce AR with ≈ graft and pt. survival Tacrolimus and MMF - Basiliximab and Daclizumab-IL2RAntibody Thymoglobulin Sirolimus 1999/ Everolimus 200 0’s Several new chemicals and biologic agents Alemtuzumab,Rituximab , IVig,Belatacept,Bortezomib

5. The Transplantation Process Pre-transplant evaluation Legal compliance The operation Immunosuppression Complications Short and long term follow up

6. Recipient Selection For Kidney Transplantation All patients with ESRD are candidates for KT unless - contraindications Systemic malignancy. Chronic infection. Severe cardiovascular disease. Neuropsychiatric disorder. Extremes of age (relative). ABO incompatibility and sensitized recipient

7. Kidney Donor Living related. Living unrelated (altruistic). Deceased/Cadaveric (Brain-dead ). Beating and non-beating heart.

8. CRITERIA FOR LIVING DONOR SELECTION Blood relative. Highly motivated . ABO blood group-compatible. HLA-identical or haploidentical with negative cross-match. Excellent medical condition with normal renal function.

9. Medical Conditions That Exclude Living Kidney Donation Renal parenchymal disease. Conditions that may predispose to renal disease History of stone disease History of frequent UTI Hypertension D.M . Conditions that increase the risks of anaesthesia and surgery. Recent malignancy.

10. Does Donation Of A kidney Pose A long-term Risk For The Donor? Following nephrectomy , compensatory hypertrophy and increase in GFR occur in the remaining kidney. Slight risk of poteinuria and hypertension. Meta-analysis of data from donors followed for >20y confirmed safety of kidney donation.

11. Human organ Transplant Act 1994 (Amended in 2008 and 2011) Regulate removal ,storage and transplantation of Human organs for therapeutic purpose To prevent commercial dealings in organs CHAPTER I PRELIMINARY CHAPTER II  AUTHORITY FOR THE REMOVAL OF HUMAN ORGANS CHAPTER III REGULATION OF HOSPITALS CHAPTER IV APPROPRIATE AUTHORITY CHAPTER V REGISTRATION OF HOSPITALS CHAPTER VI OFFENCES AND PENALTIES CHAPTER VII  MISCELLANEOUS       

12. CRITERIA FOR CADAVER DONOR SELECTION Irreversible brain damage. Normal renal function appropriate for age. No evidence of preexisting renal disease. No evidence of transmissible diseases. ABO blood group-compatible. Negative cross-match. Best HLA match possible, particularly at the DR and B loci.

13. Matching between Recepient And Donor A- Tissue typing Determined by 6 antigens located on cell surface encoded for by the HLA gene located on the short arm of chromosome 6. Class I antigens (HLA-A and HLA-B) are expressed on the surface of most nucleated cells. Class II antigen (HLA-DR) are expressed on surface of APC and activated lymphocytes. These 6 antigens are referred to as major transplant antigens. The match between donor and recipient can range from 0 to six.

14. Matching between Recepient And Donor B- Cross matching A laboratory test that determines weather a potential transplant recepient has preformed antibodies against the HLA antigens of the potential donor. (Donor Lymphocytes + Recepient Serum) C- Compatible ABO blood group.

15. Effect Of HLA Matching On The Graft Outcome Data from large registries indicate that, the better the HLA-match, the better the long-term survival of the allograft. The benefits of matching are particularly noteworthy in recipients of kidneys from donors with zero mis -match. The benefits of lesser degrees of matching have become less obvious with the use of newer and more potent immunosuppressive drugs. Matching for DR antigens are more favorable than others.

16. The beneficial effect of HLA B and DR matching in patients with and without the benefit of cyclosporine.

17. Surgical Procedure Surgical implantation into right or left iliac fossa , most often on the right . Generally, donor kidney is flipped antero-posteriorly before being placed in the iliac fossa to facilitate the vascular anastomosis and ensure correct orientation of the ureter .

18. Vascular Hookup Due to its lower incidence of renal artery stenosis, an end renal artery – to – side external iliac artery anastomosis is preferred over end renal artery – to – end internal iliac artery. End – to – side anastomosis between the renal vein and the external iliac vein.

19. Ureter Anastomosis with anti-reflux technique and DJ stenting

20. The Final Look

21. WHAT YOU SHOULD EXPECT FOLLOWING TRANSPLANT SURGERY SURGERY IS 3 – 4 HOURS UNDER G.A. HOSPITAL STAY 7 – 10 DAYS AFTER SURGERY: FOLEY CATHETER WITH UROMETER DRAIN TUBE CENTRAL VENOUS PRESSURE LINE (CVP ) AND IVF STAPLES/DRESSING HOLDING WOUND TOGETHER POD # 1 : BEDREST POD # 2: START EATING POD # 3: WALKING AS TOLERATED POD # 5: DRAIN REMOVAL POD # 7: FOLEYS REMOVAL

22. Surgical Complications Vascular Complications: arterial, venous Ureteric complications : urine leak/obstruction Perigraft Fluid Collections: Seroma & Hematoma Abscess Urinoma Lymphocele Wound infection Delayed graft function

23. Medical Complications of Transplantation Acute rejection - Acute cellular rejection - Antibody-mediated rejection-C4d NODAT/PTDM Infectious complications - Cytomegalovirus - BK virus - Post op infections Malignancy-PTLD and Skin Carcinoma common Chronic allograft dysfunction(r/o reversible factors)

24. Elevation of Creatinine (allograft dysfunction) Exclude pre-renal and post renal factors Volume depletion-less intake and excessive diuresis ( Diretics , Hyperglycemia and hypercal ) CNI toxicity, rarely Thrombotic microangiopathy Rejections: Cellular and antibody mediated CMV and BKV ACEI and ARB Sepsis

25. Fever in the Transplant Patient Commom problem spectrum of infection in transplant pts is different from the general population Classical presentation may be modified by immunosuppressive medication. Remember that fever may be non-infectious .

26. Infections time line 1 st month causes : by allograft/residual infection 95% of the infections are the surgical wound, urinary, pulmonary, vascular access, drain related 1 st month onward : Viral and opportunistic infect CMV, BKV, EBV and P carini , Aspergillus,Listeria monocytogenes 6 st month onward same as community acquired

27. Principles underlying current immunosuppressive treatment 1- The benefits of a successful transplant outweighs the risks of chronic immunosuppression . 2- Immunosuppressive therapy is required indefinitely. 3- Multidrug regimens are generally employed. 4- Large doses of immunosuppressant drugs are used in the early transplant period.

28. Immunosuppressive Medications Induction: Corticosteroids Anti- thymocyte globulin (ATG) IL-2 receptor antagonists - Basiliximab Maintenance: Corticosteroids Calcineurin inhibitors (CNIs) mTOR inhibitors Antimetabolites

29. Trends in Immunosuppression Steroid sparing regimens, and steroid avoidance Reducing calcineurin inhibitor dose after critical post transplant period Calcineurin inhibitor avoidance Single drug regimens

30. Induction Immunosuppressive therapy During the first 1-3 weeks post transplant. Usually refer to use of anti-T-cell antibodies - polyclonal ( thymoglobulin). - Monoclonal ( Simulect ). Helpful to delay use of calcineurin drugs, may decrease acute rejection and improve graft outcome (debatable). Expensive, risk of infection and malignancy Better used in selected patients.

31. Risks associated with chronic Immunosuppression 1- Infection 2- Malignancy 3- Side effects of different drugs (Steroids, CsA , Tacrolimus , MMF, Sirolimus … )

32. What are the common causes of Patients death after KT Cardiovascular disease Infections Malignancy Allograft failure after KT Chronic rejection Damage by both immunologic and non- immunologic mechanism Death with a functioning kidney(40-50%) Patients and Graft survival after kidney transplant depends on a large number of variables .

33. Renal Allograft Rejection 1- Hyperacute . 2- Acute. 3- Chronic.

34. Acute Rejection Acute cellular rejection mediated by activated T-lymphocytes. Activations of T-cells occurs after recognition of graft antigen either directly or after being processed and presented by APC. This usually occur during the first 6 months. It manifest as increase in creatinine with or without oliguria .

35. Histology of acute cellular rejection

36. How Common is acute Rejection ? At least one episode of acute rejection occurs in 62% in patients treated by CsA , Aza and steroids. With Newer immunosuppressants drugs rates are less. CSA, Aza , Steroid+Simulect is 36% Tacro,MMF,Steroid+Simulect is 18 %

37. Treatment of Rejection: Corticosteroids Anti- thymocyte globulin Intravenous Immunoglobulin (IVIG) Rituximab Plasmapheresis More than 90% of acute rejection episodes occuring in the first 6 months can be reversed.

38. Chronic allograft Rejection Manifest clinically by a slow and gradual decline in renal function, usually more than 6 months after transplant and typically accompanied by moderate to heavy proteinuria . Histologically , characterized by glomerulo -sclerosis, interstitial fibrosis, and obliteration of arteriolar lumina . Treatment is unsatisfactory.

39. Chronic rejection with tubulointerstitial lesions.

40. Management of Chronic allograft rejection Target at immunologic and non-immunologic mechanism Switch from calcineurin inhibitor. ACEIs or ARBs. Statins . Increasing immunosuppression ? Others

41. Present Indian Scenario About 100,000 patients needs kidney transplant each year Approximately 5000 transplants performed each year 95 percent living & 5 percent cadaver donors 60-70 % live donors are LRD 30-40% are LURD (Varies from time to time and place to place)

42. In conclusion, renal transplantation should be recommended as the preferred mode of RRT for most patients with ESRD in whom surgery and subsequent immuno -suppression is safe and feasible.