| Abstract|| |
The Kidney Transplant Program at the King Faisal Specialist Hospital and Research Center (KFSH&RC), Riyadh was launched in 1981 when the first living-donor (LD) kidney transplant was performed in the center. The first deceased-donor (DD) kidney transplant was performed in 1982, and the first simultaneous kidney-pancreas (SPK) in 2004. As of February 2005, more than 1,000 kidney transplants (654 living-donor and 347 deceased-donor) have been performed. The Renal Transplant Program at KFSH&RC underwent a major transformation in the year 2001 with the introduction of the concept of designated Renal Transplant Physicians and the emphasis on multi-disciplinary teamwork. This core team of highly qualified, experienced and dedicated physicians worked along side their colleagues, the Renal Transplant Surgeons, to pursue state-of-the-art kidney and pancreas transplantation. A new theme of true collaboration and shared vision was born. This fundamental change has resulted in tripling of the size of the program and in expanding its scope of services to include high-risk patients (immunological and surgical). The above achievements were coupled with outstanding outcome data. The Kidney Transplant Program at KFSH&RC is now a leading transplant center in the region in terms of size and scope of services and it measures up to the top 10% of the leading kidney transplant centers in the world in terms of size, scope of services, and outcome measures. The current program is a multi-disciplinary program composed of three Consultant Surgeons, two Consultant Renal Transplant Physicians, one Associate Consultant Surgeon, two Assistant Consultant Surgeons, two Assistant Consultant Transplant Physicians, two Clinical Co-ordinators, one Nurse Clinician, one Administrative Co-ordinator, one Clinical Pharmacist, one Health Educator, one Social Worker and a qualified Immunologist with HLA/Immunopathology staff.
|How to cite this article:|
Al Meshari K. The Kidney Transplant Program at King Faisal Specialist Hospital and Research Center. Saudi J Kidney Dis Transpl 2005;16:586-97
|How to cite this URL:|
Al Meshari K. The Kidney Transplant Program at King Faisal Specialist Hospital and Research Center. Saudi J Kidney Dis Transpl [serial online] 2005 [cited 2021 Apr 15];16:586-97. Available from: https://www.sjkdt.org/text.asp?2005/16/4/586/32850
| Scope of Services|| |
The Kidney Transplant Program at the King Faisal Specialist Hospital and Research Center (KFSH&RC), Riyadh, Saudi Arabia was launched in 1981 when the first living-donor (LD) kidney transplant was performed in the center. The first deceased-donor (DD) kidney transplant was performed in 1982, and the first simultaneous kidney-pancreas (SPK) in 2004. As of February 2005, more than 1,000 kidney transplants (654 livingdonor and 347 deceased-donor) have been performed. In addition to the standard LD and deceased donor DD kidney transplantation, the scope of services offered by the Program extends to several other services of highly specialized and high-risk nature. These services include:
a) Pediatric kidney transplantation, especially low body-weight children: body weight (BW) ≤ 10.0 kg (high surgical/ immunological risk).
b) Kidneys with multiple renal arteries, small kidneys (≤ 6cm), and en-bloc kidneys (high surgical risk).
c) Extended criteria donor (ECD) kidneys from a DD (high immunological risk).
d) Highly sensitized patients with positive cross-match from living related donor (high immunological risk).
e) Simultaneous pancreas and kidney transplantation (SPK) (high surgical/ immunological risk)
| Referrals, Initial Evaluation, Follow-up Evaluation|| |
The initial evaluation of potential renal or renal/pancreas transplant candidates is done in the pre-transplant clinic. The evaluation process involves interviews with the social worker, health educator as well as full history and physical examination by the renal transplant physician. During this phase, the potential candidates are provided with educational booklets that detail the basic principles and advantages of kidney transplantation, the benefits of pre-emptive kidney transplantation (transplantation prior to initiation of dialysis), a special emphasis on living donation, and the importance of compliance with medical advice and immunosuppressive medications.
A separate renal transplant physician, health educator and social worker interviews all potential living donors. One of the most important parts of the evaluation is the assurance that donation is altruistic and free of coercion on the one hand, and the understanding by the potential donor that our team is his best advocate on the other hand.
Potential donors are also provided with educational booklets detailing benefits of living donor kidney transplantation and the description of the surgical procedure and its morbidity. The goal of the work-up phase is to conclude the evaluation by six weeks.
Once the evaluation of potential renal or renal/pancreas transplant candidates and their potential donors (in case of living donor kidney transplant) is complete, they are all presented at the Renal Transplant Conference Meeting (a multi-disciplinary weekly group meeting) for approval by consensus for listing on cadaver waiting list (CWL) (in case of candidates for cadaver kidney, or kidney/pancreas transplantation), or for scheduling for operation (in case of living donor kidney transplantation).
| Cadaver Transplant Waiting Lists|| |
At present, the program has three CWLs: a) Adult CWL for kidney transplantation b) Pediatric CWL for kidney transplantation c) Adult CWL for SPK transplantation
All these lists are arranged according to blood group categories (O, A, B, AB), and due to the current shortage in cadaver organ donation, a ceiling has been established for each blood group. Only a fixed number of potential candidates can be listed in each of the four blood groups, after approval by the Renal Transplant Conference.
The management of CWL is quite intense and dynamic, and is done by the Clinical and Administrative Co-ordinators and is supervised by Renal Transplant Physicians/ Surgeons. Candidates who remain on the list longer than one year without transplantation are re-evaluated yearly. A kidney/pancreas organ procurement team, consisting of renal/ pancreas transplant surgeons and renal transplant coordinator, is available at all times for harvesting kidney/pancreas from deceased donors.
Following successful renal or renal/pancreas transplantation and upon discharge, the patient is given appointments in the short-term postrenal transplant clinic. During the short-term follow-up (the first six months post engraftment), the recipients are intensely monitored for signs of rejection, infection, graft dysfunction, drug toxicity, weight gain, diabetes and hypertension.
This intense monitoring is ensured by frequent clinic visits, whereby patients are fully assessed by renal transplant physicians and surgeons; the patients are encouraged to report to the "walk-in" post-transplant clinic at any time if they do not feel well, as well as encouraging patients to contact the staff in the clinic for any inquiries. The post-renal transplant clinic is provided with a procedure room for renal allograft biopsy. In addition to renal allograft biopsy for clinical indications, protocol biopsies at certain time points post engraftment, are done on all DD and high-risk LD kidney transplant recipients.
| Delayed Graft Function (DGF) / Slow Graft Function (SGF) Prophylaxis|| |
DGF is defined as dialysis dependency during the first week of engraftment. SGF is defined as non-dialysis requiring, significant renal allograft dysfunction during the first week of engraftment. DGF and SGF have both been associated with subsequent poor graft function and increased risk for acute rejection. Our goal is to minimize DGF and SGF [Table - 1].
[Table - 1]: Measures to minimize the incidence of delayed and slow graft function (DGF/SGF)
a) Limit cold ischemia time to 0 24 hours.
b) Limit warm ischemia time to 030 minutes.
c) For patients on dialysis, maintain body weight at 1.5 to 2.0 kg above the estimated dry weight (EDW) one day prior to surgery
d) Aggressive fluid "repletion" intra-operatively (at least 3-4 liters)
e) Allow moderate hypertension (HTN) prior to surgery.
f) Treat anemia.
g) Infuse Thymoglobulin (when indicated) intra-operatively prior to reperfusion of the renal allograft.
| Uniformity of Approach and Utilization of Resources|| |
Immunosuppressive and supplementary protocols are developed to unify the approach to the use of immunosuppressive and other medications between members of the Renal Transplant Program. The protocol is revised every two years and the revision process is guided by evidence-based approach as well as local experience.
Clinical pathways are also developed to guide the management of hospitalized kidney donors and kidney or kidney/pancreas transplant recipients. The ultimate goal is to optimize their medical/surgical care, and to reduce the length of hospital stay.
| Immunosuppressive Protocol|| |
The immunosuppressive protocol for renal transplant recipients consists of induction and maintenance protocols. The induction protocol is designed for a select group of renal transplant recipients who are at intermediate high-risk for immunologic injury or, are at risk for DGF or SGF.
Maintenance protocol is Calcineurin-Inhibitor-based drug regimen with adjuvant agents.
Induction therapy is defined as the use of polyclonal (lymphocyte-depleting) or monoclonal (non-lymhocyte-depleting) antibody preparations in the pre- and the early post-transplant phases of kidney transplantation.
The choice of the induction preparation is based on the immunological risk stratification of the potential recipients (intermediate or high-risk) as follows:
| High Immunologic Risk Candidates (LD and DD)|| |
a) Highly sensitized [panel reactive antibodies (PRA) ≥ 50%], sensitized re-transplant or, re-transplant with a history of early graft loss due to immunologic causes
b) Historically positive, currently negative cross-match
c) DD transplants
d) Patients with DGF or SGF
e) Simultaneous pancreas and kidney transplantation
| Intermediate Immunologic Risk Candidates (LD)|| |
a) Sensitized: PRA ≥10% - < 50%
b) Non-sensitized re-transplant, or re-transplant who did not have a history of early graft loss due to immunologic causes
c) Children (< 14 years of age) and adolescents (14-18 years of age)
d) > 3-antigen mismatches
f) Child to mother, husband to wife, male to female.
| Candidates at Risk for DGF/SGF Deceased Donor Recipients|| |
a) Non-heart-beating donor, expanded criteria donor
b) Donor requiring vasopressors for hemodynamic support
c) Donor with ATN
d) Cold ischemia time (CIT) of 0 24 hours
| Living Donor Recipients|| |
a) Vascular anastomosis time of > 30 minutes
b) Diabetes as cause of ESRD
c) Prolonged hypotension during engraftment
| Induction Protocol for High-Risk Patients|| |
Three to ten doses, the first dose to be infused prior to reperfusion of the renal allograft.
| Induction Protocol for Medium-Risk Patients|| |
Two doses, at 0 and 4 days of engraftment.
| Maintenance Protocol for Intermediate High Risk Patients|| |
Recipients with intermediate/high-immunologic risk receive tacrolimus** + mycophenolate mofetil (MMF) or rapamycin* + prednisone * Rapamycin is avoided in the following circumstances:
- Patients at risk for micro-vascular thrombosis
- Patients at risk of impaired wound healing (e.g. obese, elderly, thin/frail abdominal wall, etc.)
- Patients with severe hyperlipidemia
- Patients with acute tubular necrosis or at risk for DGF
**In case of DGF or SGF, tacrolimus is introduced only once when the serum creatinine is ≤ 300 µmol/L and/or polyuria (> 3 L/24 hours) occurs, along with a decline of serum creatinine levels (>100 µmol/L/day).
| Low Immunologic Risk|| |
Low immunologic risk patients are adult recipients who do not belong to the intermediate/ high-risk groups, and have the following characteristics:
a) First (primary) transplant
b) ≤ one haplotype (3-antigen) mismatch
c) PRA < 10%
d) Elderly (> 60 years of age)
| Maintenance Protocol for Low-Risk Patients|| |
LD recipients who do not have intermediate/ high immunologic risks (low-risk patients) will not receive induction therapy and will be placed on maintenance, calcineurin inhibitorbased double or triple immunosuppressive regimen. This regimen will be further individualized according to age, gender, underlying kidney disease, HLA-antigen match, and cardiovascular risk profile as follows:
a) All adult female renal transplant recipients between the ages of 18-35 will receive tacrolimus-based double or triple immuno suppressive regimen as follows: Tacrolimus + Prednisone (LD recipients with zero antigen mismatch) Tacrolimus + MMF or Rapamycin + Prednisone (other recipients)
b) All adult recipients of zero-antigen mismatched LD kidneys receive tacrolimus + prednisone
c) All adult recipients of LD kidneys with high cardio-vascular risk profile receive tacrolimus + MMF + Prednisone
d) Recipients with de-novo, or at risk for, recurrent hemolytic uremic syndrome receive tacrolimus + MMF + prednisone
e) All other adult recipients receive cyclosporine A (CsA) + MMF + prednisone
f) Elderly recipients (≥ 60 years) receive CsA + MMF + prednisone (Elderly recipients receive lower doses of immunosuppressants, as compared with those of younger age groups).
| Crossover to Other Immunosuppressants|| |
Crossover from MMF to rapamycin and conversely from rapamycin to MMF is done under the following situations:
a) Development of rejection, despite maximum doses of either drug, and/or a therapeutic calcineurin inhibitor level.
b) Development of severe side effects to either drug.
c) Crossover from CsA to tacrolimus is done when an acute rejection episode occurs despite the presence of therapeutically adequate CsA level.
| Drugs|| |
Adults and pediatrics: 1.5 mg/kg/day given as an IV infusion through a central line, AV fistula/ graft, or peripheral line. The first dose is to be given intraoperatively prior to reperfusion. The total number of doses ranges from three to a maximum of ten doses, and it is guided by lymphocyte counts and/or lymphocyte receptor counts.
Adults: 20 mg IVPB, one dose immediately prior to reperfusion and the second dose on the 3 rd post-operative day.
Children: 10 mg IVPB, one dose immediately prior to reperfusion and the second dose on the third post operative day.
Adult: (BW > 25 kg) LD and DD recipients receive Corticosteroids according to the following schedule:
Pediatric (BW < 25 kg) LD and DD recipients receive Corticosteroids according to the following schedule:
Tacrolimus (FK - 506)
- Adults and pediatrics: initial dose of 0.15 - 0.3 mg/kg in two divided doses (po): LD recipients with low immunological risks receive four doses (1800, 0600, 1800, 0600 hours) prior to transplant surgery.
- Recipients who are destined to receive induction therapy will start the first dose following engraftment.
- The post-operative dose will be similar to pre-operative dose and will be adjusted according to Tacrolimus trough level.
Cyclosporine (CsA) Microemulsion (Neoral):-
- Initial dose: 5-7 mg/kg/day in two divided doses:
- LD recipients who are Hepatitis C negative receive four doses at 1800, 0600, 1800, 0600 hours, prior to transplant surgery (total of 7 mg/kg/day). The post-operative dose will be similar to the pre-operative dose and will be adjusted according to AUC and C2 profiling.
- LD recipients who are Hepatitis C positive receive four doses at 1800, 0600, 1800, 0600 hours, prior to transplant surgery (total of 5 mg/kg/day). The post-operative dose will be similar to the pre-operative dose and will be adjusted according to the AUC and C2 profiling.
- CsA total dose can be given in 3 divided doses for the following patients:
- C1 = C max (rapid metabolizers)
- Patients requiring a total dose 10 mg/kg/ day to achieve a therapeutic drug level (optimal CsA exposure)
Mycophenolate Mofetil (MMF)-
Adults: Initial dose: 2.0 gm in two divided doses po.
- LD recipients receive two doses prior to transplant (the day before at 2100 hrs and the morning of transplant at 0600 hrs). - DD recipients receive one dose prior to transplant surgery
- Decrease MMF dose if side-effects occur (diarrhea, leukopenia, thrombocytopenia).
In case of Tacrolimus/MMF combination, give MMF 2-3 hours after Tacrolimus and may reduce the dose to 1.5 gm/day (due to PK interaction) Pediatrics: Initial dose: 600 mg/m 2 po BID:
- LD recipients receive two doses prior to transplant (the day before at 2100 hrs. and the morning of transplant at 0600 hrs.)
- DD recipients receive one dose prior to transplant surgery
- The dose can be spread to a three times daily schedule if gastrointestinal symptoms develop early.
- Decrease MMF dose if side-effects occur (diarrhea, leukopenia, thrombocytopenia).
Rapamycin (Rapamune, Sirolimus)
- Loading dose: 6-15 mg po followed by 2-6 po once daily.
- Give Rapamycin 4-5 hours after CsA.
- Monitor serum lipids, as 0 70% of patients will require lipid-lowering agents.
- Decrease Rapamycin dose if side effects occur (thrombocytopenia, leukopenia)
| Therapeutic Drug Monitoring|| |
Cyclosporine levels (adults only) [Table - 2],[Table - 3]
Area under the curve (AUC) 0-4 hours will be measured once on all patients receiving Cyclosporine 5 days after commencement of CsA. Further monitoring will be based on C2 level in patients whose C2 = Cmax. In patients where C2 is not Cmax, AUC is the preferred method for monitoring, and it may need to be repeated at a suitable interval, especially in those who are slow absorbers as described below.
The lower end of the above target ranges are aimed for HCV-positive patients and the higher ends are aimed for HCV-negative patients.
A small proportion of patients can have markedly delayed absorption of CsA (i.e. extended time to peak concentration). These patients are referred to as slow absorbers. Increasing the CsA dose according to C2 levels in these patients may lead to excessive CsA exposure.
Target AUC level is 4400 - 5500 ng.h/ml for the first 6/12 months post transplant.
For patients on CsA/Rapamycin combination, [Table - 4] a therapeutic C2 is not yet established and C0 is the preferred method for monitoring.
| Antimicrobial Prophylactic Protocol|| |
CMV Prophylaxis (Selected Prophylaxis):
- CMV negative kidney transplant recipients of CMV positive kidneys receive IV Gancyclovir 1.25 - 5 mg/kg/day (adjusted to renal function) for one week, followed by oral #Valgancyclovir 900 mg/day for three months.
- CMV positive renal transplant recipients (especially those receiving CMV positive kidneys) and requiring antilymphocyte antibodies (Thymoglobulin), receive intra venous Gancyclovir (1.25 - 5 mg/kg/day) adjusted to renal function for the duration of antilymphocyte antibody therapy. This will be followed by #Valgancyclovir 900 mg orally once daily for three months.
CMV positive renal transplant recipients who are treated with three drug immunosuppressive regimen consisting of FK-506 + MMF + Prednisone or receiving multiple treatments for acute rejection, will receive #Valgancyclovir 450 mg, once daily, for three months.
#Pediatric patients receive oral gancyclovir instead of oral valgancyclovir.
| Anti-bacterial Prophylaxis|| |
Trimethoprim-Sulfamethoxazole (Septra, Bactrim)
- LD and DD recipients receive one single strength Trimethoprim-sulfamethoxazole tablet po everyday for 6 months. (Patients on Rapamycin require longer periods of prophylaxis: 9 months).
- Patients with chronic rejection or recurrent urinary tract infections receive Septra or other antibiotic prophylaxis for the duration of the graft survival.
| Tuberculosis Prophylaxis|| |
LD and DD recipients who are PPD skin test positive or LD PPD negative recipients of kidneys from PPD positive donors receive INH 300 mg po along with Vitamin B6 25 mg po everyday for 6 - 9 months.
Calcineurin-inhibitor levels and doses are carefully monitored and adjusted respectively to maintain therapeutic drug levels.
| Antifungal Prophylaxis|| |
This is aimed predominantly at Mucocutaneous Candida infection during multiple high dose steroid therapy and/or prolonged courses of antimicrobial therapy. Patients at risk of Mucocutaneous Candida infection receive Mycostatin swish and swallow or Clotrimazole trouches for the duration of high dose steroid or antimicrobial therapy.
Antihypertensive, Antihyperlipedemic, and Supplementary Drugs Antihypertensive
- Amlodipine or Adalat LA
- *Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensine Receptor Blockers (ARB)
- Vitamin D
* ACE and ARB are used beyond the first six months of engraftment and in patients with proteinuria.
| Desensitization Protocol|| |
Pillars of Desensitization Protocol at KFSH&RC
- Cytotoxic antibody depletion
- T and B lymphocyte depletion
- Immunomodulation of activated T and B lymphocytes
- An allograft from a living donor with good HLA match
- Effective antimicrobial and antiviral prophylaxis
The above outcome data should be viewed in the context of significant proportion of patients with high risk for graft loss.
| References|| |
|1.||American Journal of Transplantation, Volume 5, Issue 4, Part 2, 2005 Clinical Transplant, 2001, 2002, 2003. |
Khalid Al Meshari
Director, Renal Transplant Program, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, Riyadh 11211
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6], [Table - 7], [Table - 8], [Table - 9], [Table - 10], [Table - 11], [Table - 12], [Table - 13], [Table - 14]