T-regulatory cells in chronic rejection versus stable grafts.

OBJECTIVES: Studying regulatory T cells in kidney allograft acceptance versus chronic rejection may help in the understanding of more mechanisms of immune tolerance and, in the future, may enable clinicians to induce immune tolerance and decrease the use of immunosuppressive drugs. The aim of the current study was to evaluate regulatory T cells in kidney transplant patients with stable graft versus transplant with biopsy-proven chronic rejection. MATERIALS AND METHODS: The 3 groups that were studied included: kidney transplanted patients with no rejection episodes (n = 43); transplanted patients with biopsy-proven renal rejection (n = 27); and healthy age-matched nontransplanted individuals as controls (n = 42).The percentage of regulatory T cells (CD4+CD25+Foxp3+) in blood was determined by flow cytometry. RESULTS: The regulatory T cell percentage was significantly lower in chronic rejection patients than control or stable graft groups. No significant difference was observed in regulatory T cell percentage between the stable graft and control groups. In the stable graft group, patients on rapamycin had a significantly higher regulatory T cell percentage than patients on cyclosporine. No effect of donor type, infection, or duration after transplant was observed on regulatory T cell percentage. CONCLUSIONS: The results of the current study are consistent with previous studies addressing the function of regulatory T cells in inducing immunotolerance after kidney transplant. Considering the established role of regulatory T cells in graft maintenance and our observation of high regulatory T cell percentage in patients receiving rapamycin than cyclosporine, we recommend including rapamycin when possible in immunosuppressive protocols. The findings from the current study on the chronic rejection group support ongoing research of having treatment with regulatory T cells, which may constitute a novel, efficient antirejection therapy in the future.

Human leukocyte antigen G and renal allograft transplant.

OBJECTIVES: Studying immune tolerance induced by HLA-G in kidney allograft acceptance may help understanding of its mechanisms, hoping in the future to boaster it and decrease the immunosuppressive drugs given that are well known to have serious adverse effects. MATERIALS AND METHODS: The current study sought to evaluate soluble HLA-G in 3 groups: kidney transplanted patients with no rejection episodes, transplanted patients with biopsy-proven renal rejection, and healthy age-matched non transplanted individuals. Three groups were studied: kidney transplanted patients with no rejection episodes (n = 43); transplanted patients with biopsy-proven renal rejection (n = 27); healthy, age-matched, nontransplanted individuals as controls (n = 42). Soluble HLA-G level was measured in the serum by a quantitative sandwich enzyme linked immunosorbent assay. RESULTS: sHLAG level was significantly higher in the transplanted patients compared with the control. Prograf and not cyclosporine or Rapamune had positive effects on sHLAG levels. Patients with chronic rejection had a significant lower level of sHLAG compared with a graft stable group. No effect of donor type, infection or duration posttransplant, on sHLAG levels was found. CONCLUSIONS: The results of the current study are consistent with previous studies addressing the role of sHLAG in inducing immunotolerance postkidney transplant. The findings from the current study on the chronic rejection group, supports the on-going research of having a treatment with HLA-G/or derivate, which may constitute in the future a novel efficient antigraft rejection therapy.

Immunological aspects of biopsy-proven lupus nephritis in Bahraini patients with systemic lupus erythematosus.

Lupus nephritis (LN) is a frequent and potentially serious complication of systemic lupus erythematosus (SLE) that may influence morbidity and mortality. Immunological investigations are aiding tools to the kidney biopsy findings in early diagnosis, in addition to monitoring the effect of therapy. The aim of the present study is to highlight the role of these investigations in a group of Bahraini patients and to determine whether there is any positive association between these findings and the outcome of LN. The current study is a retrospective case-control study of randomly selected 88 SLE patients, 44 with biopsy-proven LN and 44 without, acting as controls. All renal biopsies performed during the period from 1996 to 2012 were classified according to the World Health Organization classification. Immunological investigations analyzed are: Antinuclear antibodies (ANA), anti-ds DNA, anti-ENA, anti-cardiolipin antibodies (abs) and complement components C3, C4. Human leukocyte antigen (HLA) typing class II was performed on selected cases. All patients had positive ANA (100%). A significantly high frequency of anti-Smith abs among the non-LN group (43.18%) compared with the LN group (18.18%) was found (P <0.001). On the other hand, the anti-Ro/SSA abs in the non-LN group was also found at a statistically higher frequency (20.45%) compared with that in the LN group (4.54%) (P <0.01). Anti-ds-DNA abs were found to be higher in the LN group (84.09%) compared with the non-LN group (70.45%), but the difference was not statistically significant (P = 0.082). There was a positive association of ANA positivity and low C3 and or C4 in the studied group. In our study, 88.2% of the HLA typed patients had HLADR2, DR3 or both. In conclusion, in our Arabic Bahraini SLE patients, the presence of anti-Smith, anti-Ro/SSA and anti-RNP antibodies and the absence of anti-dsDNA antibodies are independent predictive markers for renal involvement. However, more prospective studies with a larger number of patients are essential to ascertain those findings.

Sirolimus-based calcineurin inhibitor withdrawal immunosuppressive regimen in kidney transplantation: a single center experience.

BACKGROUND/AIM: This observational study was conducted to evaluate the safety and efficacy of the conversion from calcineurin inhibitors (CNIs) to sirolimus (SRL)-based immunosuppressive therapy in kidney transplantation. MATERIALS AND METHODS: Sixty-four kidney recipients of mean age 38.3 +/- 14.6 years were converted to SRL. The main reasons for conversion were elective in 45 (70.3%) and biopsy-proven chronic allograft nephropathy in 11 (17.2%). The primary CNI used was cyclosporine A in 51 patients. Mean time to conversion was 50.5 months. After conversion, 61 patients received mycophenolate mofetil. We evaluated the impact of conversion on renal function for 5 years post-conversion. The overall mean follow-up time was 72.8 months. RESULTS: The analysis showed significant improvement in renal function at month 3 post-conversion (P < 0.05) with stabilization thereafter. Lipid parameters and blood sugar levels were similar pre- and post-conversion. Abnormal liver function test was transient in 12.8%. Reasons for SRL discontinuation were nephrotic range proteinuria in two patients and mouth ulceration in one. We compared patients with serum creatinine <140 micromol/l and those with serum creatinine > or = 140 micromol/l, and found that serum creatinine was an independent risk factor for chronic allograft dysfunction (P = 0.02). Graft loss occurred in three patients because of cardiovascular death in two and an acute rejection episode in one. CONCLUSIONS: We concluded that conversion from CNIs to SRL is an option and of benefit without significant acute rejection episodes or chronic allograft dysfunction especially in well-selected kidney transplant recipients with good graft function.

Soluble Fas: a useful marker of inflammation and cardiovascular diseases in uremic patients.

BACKGROUND: Inflammation has been associated with atherosclerotic cardiovascular disease (CVD) and anemia in patients with end-stage renal disease (ESRD) which may lead to left ventricular impairment via myocardial hypertrophy and/or ischemia. We therefore sought to investigate serum levels of sFas in uremic patients and its correlation with known markers of inflammation and CVD. METHODS: The study included 30 patients on hemodialysis, 30 patients with chronic kidney disease (CKD), and 30 normal control subjects. We measured serum levels of sFas, C-reactive protein (CRP), and albumin. We also investigated the association of serum sFas levels with the presence of CVD by echocardiographic assessment before and after 1 year. RESULTS: Levels of sFas were elevated in CKD and ESRD patients compared to controls. sFas levels correlated positively with serum creatinine and negatively with serum albumin. In the dialysis patients, we observed that sFas levels were higher among those with CVD. Compared with baseline, after 1 year of follow-up there was a significant decrease in left ventricular (LV) ejection fraction, increases in LV end-diastolic dimension and LV end-systolic dimension, and myocardial ischemic changes. CONCLUSIONS: These results suggest that sFas may be a marker of inflammation in CKD and ESRD patients.

A single-center experience of renal transplantation in elderly patients.

BACKGROUND: We retrospectively reviewed the results of renal transplantation in patients over 60 years of age at our center. MATERIAL/METHODS: A retrospective study was conducted of 212 Bahraini patients receiving renal transplants from January 1979 to December 2007. All medical records were reviewed for demographic data, graft function and survival. Patient and graft survival was compared for patients above and below the age of 60. RESULTS: Seventeen patients >60 years with a mean age of 64.1+/-3.6 years at the time of transplantation. Diabetic nephropathy (52%) was the most common causes of end-stage renal disease. Mean donor age was 26+/-6 years and most of them were unrelated (82%). Of the elderly patients, 4 died: 3 with a functioning graft, 1 within one year of transplantation. Cardiovascular causes (3 patients, 75%) were the most common cause of death. Causes of graft loss were death with a functioning graft (4) and chronic rejection (1). Cox's proportional-hazards regression analysis showed on univariate analysis that pre-transplant hypertension, diabetes mellitus and vascular surgery (CABG) before transplant significantly affected the dependent variable of graft loss. Multivariate analysis did not show these variables to be significant. Kaplan Meier patient survival curves showed statistically significant differences between study (>60 years) and control (18-59 years) patients (p=0.04) at 10 year. CONCLUSIONS: We conclude that Patients older than 60 yr of age can be transplanted safely and successfully, especially when they are properly screened for the presence of significant risk factors such as severe cardiovascular disease and diabetes.

Safe conversion of mycophenolate mofetil to azathioprine in kidney transplant recipients with sirolimus-based immunosuppression.

AIM: Mycophenolate mofetil (MMF) is a powerful immunosuppressive drug with established efficacy and safety. The long-term use of MMF may bring increased risk of for infection and malignancy and also increased cost of transplantation. The search for minimization of immunosuppressive protocol has led to an open randomized clinical trial of conversion from MMF to azathioprine (AZA). METHODS: A total of 50 kidney allograft recipients treated with prednisone, sirolimus and MMF were randomized into two groups: converted (AZA group) and continuing (MMF group). The average duration of MMF therapy prior to conversion was 43 months in each group. Inclusion criteria included: patients with serum creatinine levels of less than 200 micromol/L; no past history of acute vascular rejection or recent acute rejection 6 months before randomization; and normal liver function tests. RESULTS: Baseline demographics were similar in the two groups. During the 12 month observation period, there were no acute rejection episodes in either group. There were no significant differences in overall patient or graft survival or function. AZA-treated patients had a lower incidence of gastrointestinal complications (P=0.03). Daily cost reduction in the AZA group was more than $US8.79/day per patient. CONCLUSION: In general, replacing MMF with AZA in stable renal transplant recipients is well tolerated and was cost effective with no increased risk of rejection. As the this study was on relatively small samples, larger and longer follow-up studies will be needed to confirm these expected advantages for the long-term outcome and to assess the long-term safety of this minimization of immunosuppressive therapy.

Long-term graft outcome in patients with chronic allograft nephropathy after immunosuppression modifications.

BACKGROUND/AIM: This retrospective study was conducted to assess the efficacy and safety of immunosuppression conversion on progression of chronic allograft nephropathy (CAN). METHODS: One-hundred and seventy-four cyclosporin (CsA)-treated renal transplant recipients were studied. Patients were included if they had a biopsy-proven CAN (mild to moderate) with serum creatinine < or =3.5 mg/dL. Patient treatment was switched to either: (A) MMF/reduced dose CsA (MMF for azathioprine (Aza); n = 132); or (B) Aza/Tac for CsA (n = 42). Patient records were checked for graft function and survival, and for co-morbidities after conversion. RESULTS: Mean follow-up before conversion was 52.2 +/- 31.1 and 47.9 +/- 27.4 months for groups A and B, respectively. There was significant deterioration of graft function in group B after five years (P < 0.5). Ten-year actuarial graft survival was 38% in group A and 19% in group B (P = 0.04). Nine patients (five patients and four patients in groups A and B, respectively) started dialysis within 12 months. Tacrolimus-treated patients had a lower insignificant incidence of hyperlipidemia (P = 0.05), but a significantly higher incidence of diabetes mellitus (P = 0.04).There was no significant change or difference in blood pressure between groups. CONCLUSIONS: Our results suggest that in patients with CAN and deteriorating allograft function, CsA minimization and addition of MMF achieved favorable efficacies in retarding the decline of graft function. Further prospective studies with larger cohorts are needed for validation.

Characteristics of patients with Banff borderline changes in renal allograft biopsies.

OBJECTIVES: The aim of this retrospective study was to characterize the patients who experienced borderline rejection. MATERIALS AND METHODS: Patients with a minimum follow-up of 2 years were enrolled in this study. Forty-seven patients out of 106 patients with borderline rejection (after exclusion of those with associated chronic interstitial fibrosis) were compared with patients with acute cellular rejection grade 1 (n = 650), and patients free of rejection episodes (n = 444) regarding the different characteristics. RESULTS: Patients aged 20 years or younger were frequently in borderline rejection group than other groups (which was statistically significant) (P = .001). Significant differences were found in recipient and donor ages, consanguinity, pretransplant blood transfusion, and immunosuppression plan. Most patients in borderline rejection group received triple immunosuppression therapy than other groups (P = .001). Univariate and multivariate regression analysis of different variables on graft survival in borderline rejection patients revealed that none of them was statistically significant. CONCLUSIONS: Borderline rejection is a frequent finding in biopsy-proven acute rejection after kidney transplant. Time of occurrence, frequency, treatment or not, and response to therapy were not predictors to graft survival.

Long-term graft outcome in patients with chronic allograft dysfunction after immunosuppression modifications.

BACKGROUND: This retrospective study was conducted to assess the efficacy and safety of immunosuppression conversion on progression of chronic allograft nephropathy (CAN). MATERIAL/METHODS: One hundred-seventy four cyclosporin (CsA)-treated renal transplant recipients were studied. Patients were included if they had a biopsy-proven CAN (mild to moderate) with serum creatinine < or =3.5 mg/dL. Patients were treated with either: (A) MMF/reduced dose CsA [MMF for azathioprine (Aza)] (n=132); (B) Aza/Tac for CsA (n=42). Patient records were checked for graft function and survival, co-morbidities after conversion. RESULTS: Mean follow-up before conversion was 52.2+/-31.1 and 47.9+/-27.4 month in-group A and B, respectively. There was a significant deterioration of graft function in-group B after 5-years (P<0.5). Ten-year actuarial graft survival was 38% in-group A and 19% in-group B (P=0.04). Nine patients started dialysis within 12 months. Tacrolimus-treated patients had a lower insignificant incidence of hyperlipidemia (P=0.05), but a significantly higher incidence of diabetes mellitus (P=0.04).There was no significant change or difference in blood pressure between groups. CONCLUSIONS: Our results suggest that in patients with CAN and deteriorating allograft function, CsA minimization and addition of MMF achieved favorable efficacies in retarding the decline of graft function. Further prospective studies with larger cohorts are needed for validation.

Immunosuppression modifications and graft outcome in patients with chronic allograft nephropathy.

OBJECTIVES: This retrospective study was done to assess the efficacy and safety of immunosuppression conversion on progression of chronic allograft nephropathy. MATERIALS AND METHODS: One hundred seventy-four cyclosporine-treated renal transplant recipients were studied. Patients were included if they had biopsy-proven chronic allograft nephropathy (mild to moderate) with a serum creatinine level of 300 micromol/L or less. The treatments groups were (1) mycofenolate mofetil and reduced-dosage cyclosporine (group MMF/CsA; n=132) and (2) azathioprine and reduced-dosage tacrolimus (group Aza/Tac; n=42). Patient records were checked for graft function, survival, and comorbidities after conversion. RESULTS: Mean follow-up before conversion was 52.2 -/+ 31.1 and 47.9 -/+ 27.4 month in groups MMF/CsA and Aza/Tac, respectively. There was a significant deterioration of graft function in group Aza/Tac after 5 years (P < .05). Ten-year actuarial graft survival in group MMF/CsA was 38%; in group Aza/Tac it was 19% (P = .04). Nine patients started dialysis within 12 months. Tacrolimus-treated patients had a lower insignificant incidence of hyperlipidemia (P = .05) but a significantly higher incidence of diabetes mellitus (P = .04). There were no significant changes or differences in blood pressure between the groups. CONCLUSIONS: Our results suggest that in patientswith chronic allograft nephropathy and deteriorating allograft function, cyclosporine minimization and addition of mycofenolate mofetil achieve favorable effects in retarding the decline of graft function. Further prospective studies with larger cohorts are needed for validation.

Characteristics of recipients whose kidney allograft has functioned for more than 20 years.

OBJECTIVES: To study the characteristics of, and predictors for, survival in renal transplant recipients with an allograft functioning for more than 20 years. MATERIALS AND METHODS: Of 144 renal transplants done between 1976 and 1985, 31 allografts were still functioning for more than 20 years (range, 21- 28.5 years). The characteristics of the patients and determinants of the outcomes were obtained by reviewing the patients' medical records. RESULTS: Fourteen patients were treated with cyclosporine, while 17 patients had primary immunosuppression with azathioprine-based regimens. Episodes of acute rejection occurred in 17 patients (58%), 7 of these experienced 2 or more episodes. At most-recent follow-up, the mean serum creatinine level was 132 +/- 44 micromol/L . Four patients were assessed by graft biopsy 15 or more years after the transplant, revealing 2 cases of mild glomerulosclerosis and 2 cases of moderate chronic allograft nephropathy. The most common complication was hypertension (54%). The independent determinants of long-term graft survival were donor age and source, hypertension both before and after renal transplant, and histopathological findings of chronic allograft nephropathy. CONCLUSIONS: Renal transplant offers a near-normal life to patients with end-stage renal disease soon after transplant and for upwards of 20 years and more. We found no significant benefit to cyclosporine-based immunosuppression on long-term graft survival.

Comparison of sirolimus with low-dose tacrolimus versus sirolimus-based calcineurin inhibitor-free regimen in live donor renal transplantation.

UNLABELLED: Between May 2001 and January 2003, 132 live donor renal allotransplant recipients were included in a prospective, randomized controlled trial where they were divided into two groups. All patients received steroids and basiliximab induction therapy. For maintenance immunosuppression, tacrolimus and sirolimus were used in group A. In group B, mycophenolate mofetil (MMF) and sirolimus were utilized. Patients were followed up for a minimum of 24 months. One-year patient and graft survival rates were not significantly different between group A (96.9%, 92.3%) and group B (100%, 98.4%), respectively. However, the incidence of biopsy-proven acute rejection was less in group B but the difference was not statistically significant (13.5% vs. 18.5% in group A). Statistically significant better renal function was encountered among group B patients at two years post-transplantation as measured by serum creatinine (1.25 vs. 1.43 mg/dl; P = 0.017) and calculated glomerular filtration rate (GFR) (94.9 vs. 79.6 ml/min; P = 0.005). One year protocol biopsies showed insignificant differences relative to chronic allograft damage index (CADI) between either group (Group A: 2.41 vs. Group B: 2.69; P = 0.436). CONCLUSION: Similar outcome was noted among patients in whom calcineurin inhibitors were not included in their immunosuppressive regimen. The long term impact of this observation on graft survival and function needs longer follow up.

Living-donor kidney retransplantation: risk factors and outcome.

OBJECTIVE: To review the results of kidney retransplantation at our centre. PATIENTS AND METHODS: Between March 1976 and January 2002, 1406 kidneys were transplanted; among these, 54 patients received a second graft (39 men, mean age 32.1 years, sd 8.6). The donors were 48 relatives (mean age 35.4 years, sd 10.1). RESULTS: The mean (sd, range) duration of the first graft was 49.1 (45.9, 1-192) months and the main cause of these grafts failing was immunological. The mean duration of graft failure was 17.3 (10.5, 5-62) months. The rate of histocompatibility leukocyte antigen (HLA)-A, -B >3 was 16.7% and of haplotype DR matching was 11%. The immunosuppression regimen was mainly based on cyclosporin (75%). There were 33 episodes of acute rejection in 23 patients. The major complications were hypertension (70%), infections (30%) and hepatitis (11%). The overall graft and patient survival was good; 15 grafts (27%) were lost during the follow-up of 1-17 years. Ten patients died, five with a functioning graft. Multivariate analysis showed that donor relationship, primary immunosuppression, duration of first graft and serum creatinine level at 1 year were predictors of graft survival. CONCLUSION: Renal retransplantation is the treatment of choice in patients who have lost their graft. The use of related living-donors and potent immunosuppression could help to improve the outcome.

Clinical features and course of Kaposi's sarcoma in Egyptian kidney transplant recipients.

The prevalence of Kaposi's sarcoma (KS) after renal transplantation varies greatly depending on geographic and ethnic backgrounds. Out of 1400 live-donor kidney transplantation, 50 patients developed malignancy in our center. Kaposi's sarcoma was diagnosed in 24 patients (48%). Twenty patients were males and the main age of the patients was 29.8 +/- 11.1 years. They developed KS at a mean interval of 33.9 +/- 27.2 months, and the main duration of follow up was 62.2 +/- 50.7 months. Nineteen patients were cyclosporinee treated while four patients were azathioprine-based. Cutaneous KS was diagnosed in 20 patients, visceral in one, and three patients had both lesions. We found that the frequency of HLA-A1, -A2 and -DR5 were significantly common in KS patients. Titrated reduction of immunosuppression was initially tried in all patients. Bleomycin injection and superficial irradiation was tried in some cases. Response to therapeutic modalities was good in cutaneous form of KS. Twelve patients died (50%), two of them with functioning graft. We conclude that KS is the most common malignancy after kidney transplantation in our locality. Patients on cyclosporine are more prone to develop KS, and certain HLA-antigens may predispose to this. Early diagnosis and interference carry a favorable outcome.

Effect of angiotensin II receptor blocker on plasma levels of TGF-beta 1 and interstitial fibrosis in hypertensive kidney transplant patients.

BACKGROUND/AIM: Transforming growth factor-beta1 (TGF-beta 1) is involved in the pathogenesis of chronic allograft nephropathy after kidney transplantation. The aim of the study was to evaluate the effect of the angiotensin receptor blocker losartan on TGF-beta 1 plasma levels and proteinuria in hypertensive transplant recipients. METHODS: A total of 162 transplant recipients were included in the study. The patients were randomized into 3 groups: group 1 received losartan; group II received an angiotensin-converting enzyme inhibitor (captopril), and group III received a calcium channel blocker (amlodipine). All the parameters were recorded at the time of therapy initiation and at 1, 4 and 12 weeks and 12 months thereafter. Graft biopsy before the start and at the end of the study was done to evaluate histopathological progression. RESULTS: Blood pressure was controlled in the 3 groups; however, the need for other antihypertensive agents was significant in groups I and II. Treatment with losartan significantly decreased the plasma level of TGF-beta1, 24-hour urinary protein and serum uric acid (p < 0.05). No significant changes were seen in the hemoglobin or serum potassium levels. The rate of histopathological progression was significantly lower in the losartan group. No patient was discharged from the study due to side effects. CONCLUSIONS: After transplantation all drugs were able to control blood pressure with good safety and tolerability. The study demonstrates that ARB significantly decreases the plasma levels of TGF-beta1, proteinuria and uric acid. These results could play an important and decisive role in the treatment and prevention of chronic allograft nephropathy.

Characteristics of long-term live-donor renal allograft survivors.

BACKGROUND/AIMS: Despite the high rate of rejection, allograft failure and patient mortality in the early years of renal allotransplantation, some patients have done-remarkably well. We report here on 62 renal transplant recipients out of 144 patients (43%) who had functioning grafts for more than 15 years (range 15-24 years). MATERIALS: Demographic and follow-up data for patients fulfilling the criteria were reviewed. These patients include 43 males and 19 females, with a mean age at transplantation of 27.5 +/- 6.6 years (range 9-43 years), and mean donor age of 30 +/- 8.6 years. The donor source was 8 parents, 49 siblings and 5 unrelated. The main causes of end-stage renal disease were chronic pyelonephritis and chronic glomerulonephritis. Twenty-nine patients were treated with cyclosporine (CsA) while 33 patients were primarily immunosuppressed by steroids and azathioprine. RESULTS: Acute rejection episodes occurred in 40 patients (64.3%), out of them 19 patients experienced two or more acute rejection episodes. Univariate analysis showed that recipient and donor age, HLA-DR matching, pre- and post-transplant hypertension, ATN, delayed diuresis and chronic allograft nephropathy are significant risk factors; while recipient age, delayed diuresis and post-transplant hypertension were still significant by multivariate analysis. CONCLUSIONS: We concluded that renal transplantation, even in its earliest years and despite the numerous complications, has provided 15 or more years of near-normal life to patients with end-stage renal disease. Certain characteristics of long-term renal allograft survivors include young donor/recipient pairs, good DR matching with less pre- and post-transplantation prevalence of hypertension.

Death with functioning graft in living donor kidney transplantation: analysis of risk factors.

BACKGROUND: Death with a functioning graft (DWF) has been reported as a major cause of graft loss after renal transplantation. It has been reported to occur in 9-30%. METHODS: From March 1976 to January 2002, a total of 1400 living donor renal transplants were performed in our center. Out of 257 reported deaths among our patients, 131 recipients died with functioning grafts after a mean period of 53.4 +/- 53.2 months. RESULTS: DWF patients account for 27% of all graft losses in our series. The mean age was 34.9 + 10.6 (range 8-62 years), 98 of them were male and 33 were female. The original kidney disease was GN in 9, PN in 24, PCK in 5 and nephrosclerosis in 8 patients. Acute rejection episodes were diagnosed in 84 patients (63.1). The post-transplant complications encountered were hypertension in 78 patients (59.5%), diabetes mellitus in 30 patients (22.9%), medical infections in 68 (51.5%), hepatic complications in 30 (22.9%) and malignancy in 17 patients (13%). The main causes of death in these patients were infections in 46 (35.6%), cardiovascular in 23 (17.6%), liver cell failure in 15 patients (11.4%) and malignancy in 8 (6.1%). The mean serum creatinine was 2 +/- 0.6 mg/dl at last follow-up before death. CONCLUSION: We conclude that the relatively higher mortality in renal transplantation is, in part, due to co-morbid medical illness, pre-transplant dialysis treatment, and factors uniquely related to transplantation, including immunosuppression and other drug effects. DWF must be in consideration when calculating graft survival.