| Abstract|| |
The renal transplant program at the Jeddah Kidney Center (JKC), The King Fahd Hospital, Jeddah commenced in November 1990. Since then, 746 patients have undergone renal transplantation in this center. Post-transplantation immunosuppresion in our patients comprised of prednisolone, azathioprine and cyclosporin. More recently, mycophenolate in place of azathioprine and tacrolimus in place of cyclosporine has been used in select groups of patients. Following surgery, delayed graft function was encountered in 131 (17.6%) of our renal transplant patients. Of them, 101 (77.1%) recovered completely while 30 (22.9%) either recovered partially or lost their graft completely and returned to dialysis. We encountered 94 (12.6%) acute rejection episodes. All these patients were treated with methylprednisolone administered in a dose of 250-500 mg intravenously on three consecutive days. Forty-seven (50%) responded favorably while the remaining 47 patients proved to have steroid-resistant rejection. Complete recovery with recovery of normal graft function occurred in 70 cases (74.5%), while 24 cases (25.5%) remained with mild renal impairment. Post-transplant diabetes mellitus was diagnosed in 126 patients (16.8%). Post-transplant hypertension was diagnosed in 399 patients, a prevalence of 53.4%, which agrees with the figures of previous reports. Post-transplant hyperlipidemia was reported in 355 patients (47%). We encountered 12 cases of urine leak and obstruction while lymphoceles were diagnosed in 20 patients. Urinary tract infections were the most prevalent infection in the first month post-transplant and occurred in 59 patients (7.9%). The other common infections in the early post-transplant period were wound infection and infection of subcutaneous collections /hematomas which occurred in 22 patients (2.9%).Overall, the 3, 5 and 10-year graft survival rates are 92%, 90% and 84% respectively. The patient survival after 1, 3, 5 and 10-years post-transplant is 98%, 96%, 90% and 90% respectively. Our results and outcome data of our renal grafts and patients show that renal transplantation is a highly successful modality of renal replacement therapy in our hospital.
|How to cite this article:|
Shaheen FA, Basri N, Mohammed Z, Abdullah K, Haider R, Awad A, Nasser A, El Gabarty A. Experience of Renal Transplantation at the King Fahd Hospital, Jeddah, Saudi Arabia. Saudi J Kidney Dis Transpl 2005;16:562-72
|How to cite this URL:|
Shaheen FA, Basri N, Mohammed Z, Abdullah K, Haider R, Awad A, Nasser A, El Gabarty A. Experience of Renal Transplantation at the King Fahd Hospital, Jeddah, Saudi Arabia. Saudi J Kidney Dis Transpl [serial online] 2005 [cited 2020 May 31];16:562-72. Available from: http://www.sjkdt.org/text.asp?2005/16/4/562/32848
| Introduction|| |
Renal transplantation is the optimal treatment for patients with end-stage renal disease (ESRD) and offers marked improvement in the quality of life of patients who undergo this form of treatment. Physical and psychosocial well-being scores, among patients who have undergone renal transplantation, reach levels comparable to those found in the general population.  The renal transplant program at the Jeddah Kidney Center (JKC), The King Fahd Hospital, Jeddah commenced in November 1990. Since then, 746 patients have undergone renal transplantation in this center. These transplantations have been performed using kidneys from living related donors (LRD) or cadaveric donors (CD). In this report, we present the overall experience of renal transplantation at the JKC between November 1990 and December 2004. We describe our protocols for donor and recipient evaluation as well as immunosuppression used, the results and complications encountered after transplantation.
| Patients and Methods|| |
The total number of transplanted subjects evaluated was 746. There were 486 males and 260 females. Details regarding age, sex and nationality are presented in [Table - 1].
| Renal Transplant Recipient Evaluation|| |
We evaluate the potential transplant candidates to ascertain that they are free from major organ diseases that may contraindicate renal transplantation. Also, attempt is made to identify medical, surgical and/or psychosocial factors that may adversely affect patient and graft survival.
All potential renal transplant candidates are subject to evaluation of the cardiovascular status by obtaining detailed history and physical examination, electrocardiogram (ECG) and echocardiography. It is reported that the prevalence of cardiovascular disease (CVD) is particularly high in patients with ESRD older than 50 years of age and those with diabetes. , Therefore, such patients are subject to initial non-invasive screening for inducible ischemia e.g. exercise electrocardiogram or thallium scintigraphy (with diphyridamole). Some patients are further evaluated with angiography to define the extent of ischemic heart disease and the need for revascularization before renal transplantation.
Diabetics with evidence of peripheral vascular disease are referred to the vascular surgeon for evaluation. Routine aortic and iliac vessel angiography is performed in all such candidates before transplantation. Similarly, all diabetics with diabetic retinopathy are referred for management by an ophthalmologist before transplantation.
Hepatitic C Virus (HCV) infection is highly prevalent in Saudi Arabian hemodialysis patients. Because HCV-positive patients are at high-risk for chronic active hepatitis, a liver biopsy is part of our pre-transplantation evaluation of all HCV-positive patients. Also, in order to stratify a patient's risk of progression and looking for evidence of active liver disease, a liver biopsy is routinely performed in hepatitis B surface antigen (HBsAg) positive patients regardless of whether liver enzymes are elevated.  Liver biopsy, HbeAb status and HBV-DNA studies are part of our evaluation in all HBsAg positive patients before transplant. Clinically active hepatitis with hepatic cirrhosis in either HCV or HBsAg positive patients or, patients with infection with both viruses, are both considered an absolute contraindication to transplantation in our center.
Our pre-transplantation work-up includes screening for urinary tract infection, nephrolithiasis and prostate hypertrophy as well as vesicouretral reflux. All urological disorders are corrected before transplantation.
Also included in our evaluation of a potential renal transplant candidate are possible conditions that might be exacerbated by the immunosuppressive therapy including an ongoing infection (tuberculosis, CMV, Brucellosis More Details, dental or ENT infection), peptic ulcer disease, gall bladder disease, chronic liver or lung disease. Thus, all potential recipients are routinely investigated with the following: chest radiography, PPD skin test, endoscopy, abdominal ultrasound and screening for CMV and Brucella More Details antibodies, dental and ENT evaluation. If tuberculosis is proven, anti-tuberculous therapy is given for six months before transplantation. In high-risk patients or patients with positive tuberculin test, we give isoniazid prophylaxis after transplantation for six months. If a patient has got peptic ulcer disease, we treat with proton pump inhibitors and/or medications for Helicobacter pylori ection before transplantation and we continue with either proton pump inhibitors or H 2 - receptor antagonist prophylactically after transplantation. All CMV-positive recipients receiving kidneys from either a CMV-negative or positive donors are given pre-emptive prophylactic therapy after transplantation.
In our pre-transplant evaluation, we also look for renal diseases with potential for recurrence in the graft, e.g. inherited renal diseases or glomerulonephritis with known tendency to recur in the graft.
| Kidney Donor Evaluation|| |
Evaluation of Live Donors
The potential donors undergo complete psychosocial evaluation to ensure voluntary donation. We exclude a potential live donor under the following circumstances:
- Age < 18 years or > 60 years.
- Presence of hypertension
- Presence of diabetes mellitus
- Morbid obesity
- Impaired renal function or pathological hematuria and/or proteinuria.
- Family history of hereditary nephritis or polycystic kidney disease.
- Presence of HIV, HBV or HCV infection. All appropriate investigations are performed to evaluate the suitability of the donor.
Cadaver Donor Evaluation
The potential cadaver donor is screened for presence of infectious diseases and malignancy. The laboratory tests performed include blood group, HLA screening, complete blood count, renal function tests, liver function tests, serology for HIV, HBV and HCV, CMV, urinalysis and blood, urine and sputum cultures.
| Results|| |
Of the 746 transplants performed in our unit, 576 were from living donors and 170 from cadaveric donors. The immunosuppression protocols are adjusted to suit a given patient. The protocols followed in our center are as under:
| Induction Immunosuppressive Therapy|| |
Triple Drug Induction Therapy
This is the most commonly used protocol and includes methylprednisolone in a dose of 500 mg, given intravenously (i.v.) intra-operatively at the time of vascular anastomosis, followed by daily dose of 250 mg for three days postoperatively to be tapered to a daily dose of 20 mg of prednisolone (Pred) by the end of second week. Azathioprine (Aza) in a dose of 2 mg/kg/day is commenced two days before transplant and continued thereafter. Of late, mycophenolate mofetil (MMF) in a dose of 1 gm twice daily is used instead of Aza in certain cases of known HCV infection with chronic hepatitis (no.= 245). The third drug is cyclosporin (CyA) (microemulsion) given initially in a dose of 5 mg/kg/day, which is given two days before transplantation, and is then increased to a dose of 8 mg/kg/day post-operatively after ensuring satisfactory graft function. Tacrolimus (Tac) (prograf FK 506) in a dose of 0.1-0.15 mg/kg/day is given instead of CyA in special group of patients e.g. children, female patients and those who develop CyA-related side effects (no.= 120).
Quadruple Drug Induction Therapy
In the immunologically high-risk recipients (cadaveric donor transplant, second renal trans-plant and patients with high PRAs) quadruple therapy is used in one of two protocols:
- Simultaneous time-related therapy: Low dose CyA or Tac combined with low-dose Aza or MMF, Pred and ATG in a dose of 3-5 mg/kg/day for 7-10 days is used. Once there is satisfactory recovery of the renal graft and serum creatinine reaches to 3 mg/dl, the ATG is discontinued and the doses of CyA (or Tac) and Aza (or MMF) are adjusted (no. = 40).
- Sequential kidney function related therapy: ATG, Pred and Aza (or MMF) are used in the immediate post-operative period until there is recovery of renal allograft function following which, ATG is replaced by CyA (no. = 130).
Maintenance Immunosuppressive Therapy
Our maintenance triple therapy protocol includes Pred at a dose of 5-10mg/day, Aza at a dose of 1-2 mg/kg/day and CyA microemuslion in a dose of 3-5 mg/kg/day adjusted according to the following levels recommended by the manufacturer:[Table - 2]
Mycophenolate Mofetil (Cellcept)
Recently, we included in our protocol the use of MMF in a dose of 1 gm twice daily instead of Aza in transplant patients with HCV infection and chronic hepatitis. The dose is adjusted according to the patient's tolerance and development of gastrointestinal, hepatic or bone marrow side effects (no. = 245).
The new calcineurin inhibitor (Tac, Prograf) has proven efficacy and currently in our center, this drug is used instead of CyA microemulsion in certain groups of patients e.g. children, ladies and patients with CyA-related side effects (no. = 120).
The drug dose is adjusted according to the following levels recommended by the manufacturer:[Table - 3]
| Complications Encountered in Our Series|| |
Delayed Graft Dysfunction (DGF)
We encountered this situation in 131 (17.6%) of our renal transplant patients. These patients required dialysis for a period of 2-3 weeks post-operatively. Of the 131 patients of DGF, 101 (77.1%) recovered completely while 30 (22.9%) either recovered partially or lost their graft completely and returned to dialysis.
We encountered 94 (12.6%) acute rejection episodes. All these patients were treated with methylprednisolone administered in a dose of 250-500 mg intravenously on three consecutive days Forty-seven (50%) responded favorably while the remaining 47 patients proved to have steroid-resistant rejection. All these patients were treated with ATG, with 11 cases requiring plasmapheresis and five cases receiving OKT3 in addition. Complete recovery of normal graft function occurred in 70 cases (74.5%), while 24 cases (25.5%) remained with mild renal impairment.
Diabetes Mellitus (DM) Post-Renal Transplantation
Post-transplant diabetes mellitus was diagnosed in 126 patients (16.8%) in our center. This prevalence rate is comparable to the prevalence of DM in the general population in Saudi Arabia (16.8% vs 16.4%).  This may be an indication that the variables that accompany the present day renal transplantation per se do not seem to be diabetogenic.
Hypertension Post-Renal Transplant
In our center, hypertension post-renal transplantation was diagnosed in 399 patients, a prevalence of 53.4%, which agrees with the figures of previous reports. Different antihypertensive medications were used in our patients with a higher tendency to use calcium channel blockers, beta blockers as well as angiotensin converting enzyme inhibitors.
Hyperlipidemia is common after renal transplantation. In our center, hyperlipidemia post-transplantation was seen in 355 patients (47%). These patients showed elevated levels of both triglycerides and total cholesterol which required treatment with HMG-COA reductase inhibitors, fibric acid analogues besides dietary therapy.
Surgical and non-surgical complications of kidney transplantation may present with similar clinical picture. Graft dysfunction, graft tenderness, and drop in urine output may all be due to acute rejection, urine leak, ureteral obstruction or vascular complications. Urinary leak: We encountered 12 cases of urine leak and obstruction in our series. Endo-urological intervention was tried initially but all cases required surgical exploration and reimplantation of the ureter. Lymphocele: In our center, lymphoceles were diagnosed in 20 patients. Most of them were small and asymptomatic requiring no specific therapy and regressed spontaneously. Large lympoceles which caused compression on the graft or on the ureter or caused leg swelling and required surgical drainage or marsupialization occurred in (no. = 8) patients and all recovered completely after surgical intervention. Vascular Complications: This complication occurred rarely in our renal transplant patients. Only three cases had thrombosis of the renal vessels and by the time the diagnosis was made it was too late to salvage the graft and nephrectomy was required in all the cases. We also encountered two cases of renal artery aneurysm, which also required graft nephrectomy. Two cases of graft renal artery stenosis were diagnosed in our center; one was managed by angioplasty and the other required surgical reconstruction of the graft renal artery.
Post-Renal Transplant Infection
Urinary tract infection was the most prevalent infection in our post transplant patients in the first month and occurred in 59 patients (7.9%). The other common infections in the early post-transplant period in our center were wound infection and infection of subcutaneous collections/hematomas which occurred in 22 patients each (2.9%). These infections were managed successfully with appropriate antibiotics and minimal surgical intervention including aspiration or drainage in certain cases. Respiratory infections occurred in 14 patients (1.8%). Septicemia secondary to wound, urinary or respiratory infections occurred in 21 patients (2.8%) in our center. After the first month posttransplantation the important causes of infection with significant morbidity are due to CMV and EB viruses and opportunistic infections due to Pneumocystis carinii, Listeria monocytogenes and Aspergillus fumigatus. In our center, the rate of CMV infection and disease was very low and occurred in 16 patients (2.1%).
Malignancy Post-Renal Transplantation
Malignancies are common after renal transplantation. In general, the long-term use of immunosuppressive therapy increases the risk of malignancy by 100-fold. In our center, we encountered six cases of Kaposi's Sarcoma, two cases of Non-Hodgkins lymphoma and one case of hepatocellular carcinoma. The overall prevelance of malignancy post-renal transplant in our center is very low (9 out of 746, 1.2%).
Graft and Patient Survival
In our center, the overall one-year graft survival is 96.3%. The 3, 5 and 10-years graft survival are 92%, 90% and 84% respectively. The patient survival rates after 1, 3, 5 and 10-years posttransplant were 98%, 96%, 90% and 90% respectively.
| Discussion|| |
Triple drug immunosuppressive therapy with Pred, Aza and CyA was the commonest induction protocol in our center. Maintenance therapy was with low doses of each drug, which is based on the rationale that the side effects of each drug (particularly calcineurin inhibitors' nephrotoxicity) administered in low doses are minimal and that chronic rejection is better controlled by the synergistic or additive effect of these three drugs.,
There appears to be a synergistic affect of MMF with CyA and with its introduction in clinical practice, studies have shown great benefit in both induction and maintenance therapy. ,,
The new calcineurin inhibitor (Tac, Prograf) has also been shown to cause improvement in renal graft survival. ,
| Complications of Renal Transplantation|| |
Delayed Graft Function (DGF)
We encountered this situation in 131 (17.6%) of our renal transplant patients. Delayed graft function (DGF) occurring in the immediate post-transplant period has a frequency of as low as 10% and as high as 50%  and most patients with DGF require dialysis for varying periods of time.
Acute rejection occurs most typically between the first week and the first three months after transplantation.  The features of acute rejection besides drop in urine output are rising serum creatinine levels, rise in blood pressure, large tender kidney and fever. Many rejection episodes are asymptomatic and present with elevated creatinine upon routine testing. Doppler ultrasound shows graft enlargement and elevated resistance index. The gold standard diagnostic tool for acute rejection is kidney biopsy. Our clinical approach to such cases is to start therapeutic intervention empirically on the basis of clinical and laboratory findings.  The incidence of acute rejection in our center is lower than that reported in the literature. The reason could be that most of our transplant patients received kidneys from good HLA matched donors and that all our high-risk patients received induction therapy with ATG.
Post-Transplant Diabetes Mellitus
Diabetic nephropathy has become an increasingly important cause of end-stage renal failure.  Diabetes Mellitus accounts for 2530% of new patients requiring treatment in USA and Europe , and 30-45% in Saudi Arabia.  Despite improvement in the overall survival of post-transplant patients and grafts, post-transplant diabetes is a major cause of cardiovascular morbidity.  The etiology of post-transplant diabetes was earlier attributed to the large dose of steroids used in the early days of transplantation. In the CyA era, the percentage of patients developing diabetes post-transplant decreased with the use of reduced doses of steroids. , However, recent studies indicate that the incidence of post-transplant diabetes mellitus is higher in renal transplantation patients on Tac compared to CyA. ,
Hypertension is an important risk factor for cardiovascular disease [24 as well as for the progression of chronic renal disease.  The etiology of post-transplant hypertension is multifactorial, the common risk factors being presence of family history, obesity, nature of native kidney disease and presence of hypertension before transplantation.  Renal graft dysfunction and immunosuppressive medications are the two important risk factors for hypertension after renal transplantation.  We defined hypertension in this paper based on the criteria set by the 7 th Joint National Committee (JNC - VII).  The incidence of hypertension after renal transplantation reported in literature has varied from 50 to 80%. 
The prevalence of post-transplantation hyperlipidemia ranges from 16 to 78%.  Reported changes in serum lipid levels include elevation of levels of both triglycerides and total cholesterol. The correlation between high lipid levels and cardiovascular mortality is well established in the general population. 30 There is increasing evidence that post-transplant lipoprotein abnormalities may contribute to the development of cardiovascular and peripheral vascular disease. ,
Post-Transplant Surgical Complications
We encountered 12 cases of urine leak and obstruction in our series. Urinary leak may occur at the level of the bladder, ureter or renal calyx. The most common causes of urinary leak are avulsion of the ureter at its insertion to the bladder or ureteric necrosis. Some cases can be managed by endo-urologic techniques while others require early surgical exploration and repair.
In our center, lymphoceles were diagnosed in 20 patients. Lymphoceles may present by producing ureteral obstruction, by compressing the iliac vein leading to deep vein thrombosis or leg swelling, or as an abdominal mass. Small asymptomatic lymphoceles do not need any intervention. Large lymphoceles, which cause ureteral obstruction, require drainage either externally with or without instillation of sclerosing agent, or internally by marsupialization into the peritoneal cavity. 
Vascular complications occurred rarely in our renal transplant patients. Arterial or venous thrombosis generally occurs within the first two to three days after transplantation, although it may occur as long as two months after transplantation. The reported incidence varies widely from 0.5 % to as high as 8 %.  Venous thrombosis may present with severe graft swelling, tenderness and gross hematuria. Sudden cessation of urine output and rapid rise in serum creatinine should alert the transplant physician to rule out the presence of vascular thrombosis by Doppler ultrasound or isotope flow scan. These techniques help distinguish thrombosis from other causes of acute anuria such as rejection or obstruction. Confirmed thrombosis usually requires graft nephrectomy.
Post-Renal Transplant Infection
The observation that more than 50% of transplant recipients have evidence of active infection in the first year post-transplantation is of great significance, since the impact of infection in these patients goes far beyond and causes great morbidity and mortality in affected patients. There is a temporal pattern that defines when different infections occur after transplantation. More than 90% of the infections that occur in the first post-transplant month are due to technical problems related to the surgery and the management of devices such as the endotracheal tube, drains, catheters and the vascular access.  Also, urinary tract infections remain an important cause of post-transplant morbidity.
After the first month post-transplantation, the important causes of infection with significant morbidity are due to CMV and EB viruses and opportunistic infections due to Pneumocystis carinii, Listeria monocytogenes nes and Aspergillus fumigatus. The overall frequency of CMV infection after renal transplantation varies from 50-80% of patients, whereas CMV disease is observed in 30-60% of recipients.  The protocol we follow in our center is that all CMV sero-positive recipients receive prophylactic treatment with oral acyclovir, and all high-risk patients who receive biological agents such as ATG or OKT3 are given gancyclovir prophylactically.  All our recipients with documented CMV disease received gancyclovir, given initially i.v. for two weeks, followed by oral gancyclovir for a longer duration. , This protocol might be the reason for the low prevalence of CMV infection we encountered in our center, despite the very high prevalence of CMV sero-positivity in our donors and recipients.
Malignancies are common after renal transplantation. In general, the long-term use of immunosuppressive therapy increases the risk of malignancy by 100-fold. The incidence of development of certain cancers e.g. skin squamous cell carcinoma, non-Hodgkin's lymphoma, carcinoma of the cervix, vulva and perineum is markedly increased after transplantation. 
Skin cancer, the commonest in transplant patients as a whole, is estimated to occur in 4070% of patients after 20 years of transplantation. It has some features that differ from skin cancer in the general population; it tends to have multiple sites, occurs in younger age-group and is more aggressive and recurrent. Also, the squamous cell type is more common than basal cell carcinoma. 
Lymphoproliferative disorders are the second commonest type of malignancy after transplantation. They account for 21% of all posttransplant malignancies in the West compared to 5% in the general population. 
Graft and Patient Survival
There is some evidence to suggest that patients who have received transplants enjoy a survival advantage over patients who continue to undergo dialysis.  Graft survival (and specifically one-year graft survival) has improved significantly over the years. The overall oneyear graft survival ranges form 87 to 96% depending on the source of the kidney i.e. cadaveric donor versus HLA identical sibling donor. The long-term survival of renal transplants as measured by the half-life is 8.6 years for cadaveric allografts, 12.1 years for living related donor allografts and 23.6 years for HLA identical siblings donor allografts. 
The outcome data derived from the three large databases, the Eurotransplant, the United Network for Organ Sharing and the Collaborative Transplant Study have divided their results into 1, 5 and 10 years patient and graft survival. These registries have shown patient survival at 1, 5 and 10 years ranging between 97 and 99%, 92 and 96% and 83 and 89% respectively while graft survival at 1, 5 and 10 years ranged between 94 and 96%, 83 and 87% and 67 and 77% respectively. The results of transplant at our center match these survival rates with a 3, 5 and 10 years graft survival of 92%, 90% and 84% respectively while the patient survival after 3, 5 and 10 years post-transplant were 96%, 90% and 90% respectively.
| Summary|| |
Renal transplantation at the King Fahd Hospital, Jeddah commenced in November 1990 and until December 2004, 746 renal transplant operations have been carried out. In this report, we have summarized our policies and protocols pertaining to renal transplantation. The medical and surgical complications encountered have been discussed. Our results and outcome data of our renal grafts and patients show that renal transplantation is a highly successful modality of renal replacement therapy in our hospital.
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Faissal AM Shaheen
Department of Nephrology, Jeddah Kidney Center, The King Fahd General Hospital, P.O. Box 11076, Jeddah 21453
[Table - 1], [Table - 2], [Table - 3]