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
1990’s - reduce AR with ≈ graft and pt. survival
 Tacrolimus and MMF -
 Basiliximab and Daclizumab-IL2RAntibody
 Thymoglobulin
 Sirolimus 1999/Everolimus
2000’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.

12. 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

13. 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.

14. 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.

15. 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.

16. 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.

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

18. 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.

19. 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.

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

23. The Final Look

24. 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

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

26. 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)

27. 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

28. 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.

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

30. 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.

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

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

33. 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.

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

35. 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.

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

37. 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.

38. Histology of acute cellular rejection

39. 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%

40. 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.

41. 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.

42. Chronic rejection with tubulointerstitial lesions.

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

45. 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)

46. 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.