This document provides an overview of kidney transplantation. It discusses the history and benefits of kidney transplantation. It outlines the evaluation and screening process for both living donors and recipients. Key aspects of the transplantation surgery and post-operative immunosuppressive regimens are described. Complications like delayed graft function and acute rejection are also summarized. The document aims to provide medical personnel with essential information on kidney transplantation.

1. Presentation by
Name : Joseph Ndanji Muleba
B.Sc dialysis therapy & technolody
student
Email: josephnmuleba@gmail.com
Instagram: muleba joseph
Twitter : Joseph N Muleba

2. note
• This presentation is for medical personnel , paramedics and knowledge
seeker in similar fields
• Its not to be used for self diagnosis and/or self prescription of drugs…

3. Introduction
• The first successful kidney transplant was performed in 1954 following
initial experiments dating back to World War II.
• Kidney transplantation emerged as a viable treatment for end stage renal
disease (ESRD) only with the introduction of the drug azathioprine in the
early 1960s.
• The situation was transformed in the early 1980s with the introduction of
(cyclosporine).
• the standard immunosuppressive regimen consisted of cyclosporine and
prednisone, often combined with azathioprine, now used as an adjunctive
agent in what was called triple therapy.
• In 1985, OKT3, the first monoclonal antibody was introduced based on its
capacity to treat first acute rejection episodes.
Note
The annual survival rate in the post transplant period is as high as 97.6%
compared to 77.8% in patients on maintenance hemodialysis.

4. Benefits of kidney transplant
• Despite the increased risk of death from the surgical procedure and
immunosuppressive therapy in the early post transplant patient
experience significant survival benefit, transplant period.
Other benefits
1. To consume a nutritious and relatively unrestricted diet
2. Travel without need of dialysis support
3. Become pregnant and bear children
4. Engage in strenuous training for athletic competition
5. Enjoy a life free of the limitations imposed by dialysis

5. Effects of prolonged dialysis
• Patients on dialysis are subject to a number of complications, either
as direct effect of the procedure or because dialysis does not
replace all of the functions of a normal kidney.
 Cardiovascular disease (for example diabetes and hypertension).
 vascular calcification.
 Anemia (HD related)
 renal osteodystrophy
 uremic neuropathy
 B2M amyloidosis
NOTE
o Patients on maintenance dialysis are also at increased risk for cancer,
especially of the kidney and urinary tract.
o A significamount of dialysis related morbidity is related to vascular
access failure.

6. Eligibility for transplant
 Irreversible renal disease
look for all the acute and reversible factors before considering a
patient renal transplant
 Age
although renal transplant can be performed at any age, however
usual range is from 5 years to 65 years.
 Cardiac status
The ejection fraction on echocardiography should be 30% or more
Waiting time on dialysis
In a paired kidney analysis 5 and 10 year survival rates were
significantly worse for kidney transplant recipients who were on
dialysis for more than 24 months (58% and 29%, respectively)
compared with patients who were on dialysis, for less than 6 months
78% and 63% respectively.

7. Contraindications of kidney
Transplantation
• Active malignancy or metastatic cancer
• Cirrhosis
• Severe myocardial dysfunction or peripheral vascular disease
• Other severe, irreversible extra renal disease.
• Chronic infection or untreated current infection.
• Persistent non adherence to treatment.
• Active substance abuse- Active substance abuse.
• Primary oxalosis (In this rare autosomal recessive disorder, deficiency in a
hepatic enzyme causes nephrocalcinosis, which leads to renal failure.)
• Active mental illness, Schizophrenia and other mental illnesses that preclude
and understanding of the risks of transplantation or limit adherence to an
immunosuppressive drug regimen generally contraindicate transplant.
NOTE
HIV infection does not rule out transplant if the patient has an undetectable viral load and
normal CD4 count.

8. Pre-transplant Screening
Routine Selective
a) Complete history and physical
examination
b) CBC, LFT
c) thyroid functions.
Biochemistry panel
a) PT and aPTT
b) Blood grouping
c) HBV and HCV serology
d) HIV screening
e) Cytomegalovirus (CMV) test
f) Pelvic exam and Pap smear
g) Chest X-ray
h) Electrocardiogram (ECG)
i) 2D ECHO
j) HLA tissue
Vaccination of Recipient and donor
Every potential recipient and
donor should be vaccinated with
Hepatitis B vaccine pneumococcal
vaccine and varicella vaccine
a) Voiding cystourethrogram
b) Pharmacologic or exercise stress test
c) ECG
d) Coronary angiogram
e) Mammogram
f) Noninvasive vascular study
g) Abdominal ultrasound
h) Upper gastrointestinal (GI) series
and upper endoscopy
i) Barium enema and lower endoscopy
j) Prostate-specific antigen (PSA) test
k) Immunoelectrophoresis
l) Epstein-Barr virus (HSV) titer
m) Varicella zoster virus (VZV) test
n) Toxoplasmosis titer
o) Lipid profile
p) Purified protein derivative (PPD)
tuberculin test
.

9. Sources of Transplantable Kidneys
• Decreased donors
• Living donors
Note
Over the past few years, paired donor exchange programs have emerged
as another way to increase transplantation opportunities for live donor/
recipient pairs mismatched for ABO compatibility or with positive cross
match.

10. Evaluation of Living Donors
• Pre-transplant evaluation is designed to identify contraindications and
abnormalities, which may increase risk.
• Initial steps to screen for donor suitability may be undertaken in more than
one individual and include:
 Discussion of the risks and benefits involved with donation
 ABO blood type compatibilities
 HLA tissue type of cross match
 Complete history and physical, including family history
 Psychological of kidney function
 Determination of kidney function
 Tests to exclude malignancy, infectious contraindications

11. Potential contraindications to
donation
 Age ( 65 to 70 years)
 Hypertension (>140/90mmHg or need for medication)
 Diabetes
 Kidney or urologic disease
 Urologic abnormalities
 Significant medical illness
 History of thrombosis or thromboembolism
 Strong family history of kidney disease, diabetes, or hypertension
 Psychiatric conditions
 Active substance abuse
 Pregnancy

12. Routine work up of a potential
donor includes
Blood Group U/S Kidney / Bladder X-Ray Chest - PA
• CBC
• BUN
• Creat
• SGOT
• SGPT
• Na+ & K+
• Sugar - F
• Urine R/E
• Urine C/S
• 24 hrs Urine Protein&
Ccr )
• DTPA scan of kidn
• HbsAg
HIV
HCV
CMV IgG & IgM
• EKG
• IVU
• Echo Cardiography
Must tests
 Tissue Typing/cross mat
 Renal Angiography
 Final Cross match

13. Matching Donor and Recipient
• In determining whether a potential donor is a good match for
a transplant candidate, the first step involves ABO blood type.
 donor specific antibody(DSA)
 HLA
 Cross-match
 panel reactive antibody (PRA)
Note
How well the donor and recipient are matched can affect the
 risk of acute rejection
 the amount of immunosuppressive drugs needed to prevent
rejection,
 ultimately the outcome of the transplant.

14. HLA matching
• HLA matching
 involves three groups of proteins located on the surface of white blood
cells and other tissues.
 The number of HLA mismatches has a substantial effect on the
likelihood of graft survival in deceased- donor transplants.
 HLA mismatches have a smaller effect on outcomes in living – donor
transplants.
 A negative cross match is desired, as a positive cross match increase
the risk of rejection.
 Antibodies can developed at any time so repeat cross match testing is
required immediately before the transplant.
•The cross match assesses whether the recipient has anti
HLA antibodies to the potential donor as a result of
 previous blood transfusions
 pregnancy
 transplants.

15. Desensitization for incompatible
kidney grafts
• Many times, a family member or friend is willing to serve as live donor for
a patient needing a kidney transplant, but an ABO blood type
incompatibility or positive cross match exists between the potential donor
and recipient.
• pre conditioning or desensitization protocols allow successful
transplantation in many cases of ABO blood type incompatibility or
positive cross match.
• Desensitization protocols involve
Plasmaphersis
Splenectomy (bypassed in most of current protocols)
Rituximab
Antigen specific immuno-adsorption

16. Evaluation of recipient
High risk transplant
• Current PRA > 30%
• Peak PRA > 50%
• Positive donor specific antibody.
• Previous history of blood transfusion
 Moderate risk
• Less than haplomatch
• Previous transplant
• Spouse as a donor
 Lowrisk
• Haplomatch or
more
• First transplant

17. The Kidney transplant surgery
• Donor kidney is transplanted in the right or left iliac fossa most commonly on
the right.
• Generally donor kidney is flipped antero-posteriorly before being placed in the
right iliac fossa to facilitate vascular anastomosis and ensure correct orientation
of the ureter.
• 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 side-
internal iliac artery anastomosis.
• End to side anastomosis between renal vein and external iliac vein is made.
• Donor kidney ureter is anastomosed to the native bladder by modified Lich
Gregoir technique along with a D-J stent.

19. Immunosuppressive Regimen.
• Immunosuppressive regimen can be broadly divided into induction
and maintainence immune suppressive drugs.
INDUCTION REGIMEN
a) 1L - 2 receptor antagonists
b) Baciliximab → 20 mg on day 0 and day 4
c) Daclizumab → 1 mg/kg on day 0 and day 14
d) Anti-thymocyte globulin (ATG) Two doses of 1 mg/kg (pre & post-
operative day 1) with prior medication with antihistamines, steroid
and paracetamol. Three doses are used if there is > 3 antigen
mismatch.

20. Maintenance regimen
Standard regimen is steroids, tacrolimus / cyclosporine and MMF/Azathioprine.
 Steroid dosing
 Methylprednisolone (Solumedrol)= 125 mg I.V. 12 hourly pre surgery (500 mg in
adult and 30 mg/kg in children is given intra-operatively)
 Prednisone 0.5mg/kg q24h POD# 3-14
 Tacrolimus dosing
 Tacrolimus ( FK 506) 0.1mg/kg q 12h starting evening of OR POD#1
 If diltiazem is used then tacrolimus dose is decreased to 0.05mg/kg q 12h
 Cyclosporine dosing
 Substitute for tacrolimus in patients who are either intolerant of the drug or at
high risk of developing diabetes
 Cyclosporine (Neoral) 6 mg/kg q12h starting evening of OR POD#1
 If diltiazem is used then cyclosporine dose is decreased to 3mg/kg q 12h
 MMF dosing
 Mycophenolate Mofetil (Cellcept, MMF) 500mg q6h starting evening of OR or
POD#1
 If well tolerated may change dose to 1g q12h
 Sirolimus may be considered as an alternate to MMF Dosing 2-6 mg/dy,

21. Delayed Graft function
Common causes:
Pre-renal
• Hypovolemia
• Post –Op complications (pulm
embolus, MI, etc)
• Tacrolimus / Cyclosporine
toxicity
• Other meds NSAIDSs, ACE
inhibitors
• Renal artery embolus or
thrombosis
Renal:
• Post- ischemic ATN
• Hyperacute or accelerated
rejection
Post-renal:
• Ureteric stricture
• Lmyphocele or urinoma
• Hematoma
Investigations
• Assess volume status
• Check tacrolimus or
cyclosporine levels
• Check pre – op cross match
• Obtain transplant ultrasound
with Dopplers and resistive
indices
• Consider transplant biopsy
Management
• Ensure adequate effective
circulating volume
• Hold any nephrotoxic drugs if
possible
• Reduce tacrolimus/ cyclosporine
levels and substitute basiliximab
20mg IV days 1 and 4 –
• Address any specific post-renal
complication or rejection

22. Risk factors for post – ischemic ATN
 Prolonged cold – ischemia time (>24h)
 Prior sensitization in a prior transplant - Increased donor age
 Nephrotoxic agents (pressors, contrast dye) in donor
 Subarachnoid hemorrhage in donor
 Vasculopathy in donor or recipient

23. Acute renal failure in transplant
patients
• COMMON CAUSES WEEKS 1-12
– Acute rejection
– Tacrolimus / cyclosporine toxicity
– Hypovolemia
– Urinary obstruction (ureteric
stricture or fluid collection)
– CMV infection
– Recurrence of primary disease
(esp. FSGS and HUS/ TTP)
• COMMON CAUSES AT >3 MONTHS:
– Hypovolemia
– Tacrolimus / Cyclosporine toxicity
– Acute rejection
– Recurrence of primary disease
– BK virus nephritis
– Post – transplant
lymphoproliferative disorder
– De novo renal disease
• INVESTIGATIONS:
– History focusing on medication
changes and adherence, history of
CMV or EBV mismatch, and recent
illness or volume loss
– Physical examination focusing on
volume status
– Labs including urine electrolytes,
urine dip and microscopy for
sediments, serum tacrolimus or
cyclosporine levels and routine
blood work
– Transplant ultrasound with
Doppler.

24. Treatment Guidelines For Acute
Allograft Rejection

25. Reasons for rejection
• Inadequate immunosuppressive regimen
• Decreased tacrolimus / cyclosporine levels
• Non-adherence to medications
• Drug interactions with immunosuppressant

26. Conclusion
• Kidney transplantation has evolved into a routine and successful
procedure and is now the treatment of choice for patients with ESRD.
• Surgical technique is largely standardized. Newer research in
immunosuppressive agents is transforming the transplant arena in
reducing the episodes of rejection and achieving the final goal of immuno-
tolerance