The impact of gender matching between donor and recipient on the outcome of kidney transplant patients: A retrospective study.

The influence of donor and recipient gender on patients postkidney transplant (KT) is still controversial, and literature data do not present unanimous conclusions. We were concerned with the gender impact on the outcome of kidney transplantation at the level of acute rejection (AR), graft function represented by serum creatinine level, delayed graft function (DGF), graft survival, and infection rate. The impact of gender matching between donors and recipients was studied in 299 KT recipients performed in the Transplantation Unit, Middle East Institute of Health, Bsalim, Lebanon, between November 1998 and September 2014. The patients were divided into the following groups: Group I (131 patients, male donor to male recipient), Group II (55 patients, male donor to female recipient), Group III (88 patients, female donor to male recipient), and Group IV (25 patients, female donor to female recipient). AR and DGF were not statistically different among the four groups. Moreover, all groups showed excellent graft survival with no statistical difference. Interestingly, human leukocyte antigen AB-DR matching (P < 0.001) and sensitization were statistically different among the four groups (P = 0.05). The number of patients with infections was statistically significantly lower in Group I (35.4%) and Group III (37.5%) (P = 0.35). Most importantly, graft function, represented by serum creatinine, showed a statistically significant difference among the four groups (P <0.004), with Group II (male to female) and Group IV (female to female) showing the best improvement in five-year survival. However, Group III (female to male) had the worst posttransplant graft function. These results revealed that gender impacts graft function, and Group II, male donor to female recipient, had the best 5-year graft function. This emphasizes that gender should be regarded as a determinant for the success of kidney transplantation.

Sex matching plays a role in outcome of kidney transplant.

OBJECTIVES: The effect of sex matching between donors and recipients was studied in 135 kidney transplant operations performed in our center between December 1998 and December 2007. MATERIALS AND METHODS: Patients were divided into 4 groups: group 1 (63 patients, male donor-male recipient), group 2 (25 patients, male donor-female recipient), group 3 (37 patients, female donor-male recipient), and group 4 (10 patients, female donor-female recipient). Except for donor age, recipient body mass index and donor-recipient HLA AB-DR matching, recipient, and donor demographics, and the immunosuppression were comparable in all groups. RESULTS: Acute rejection and the need for antithymocyte globulin Fresenius rescue therapy were comparable between the 4 donor-recipient combinations. Excellent 1-year actuarial patient and graft survival, comparable hospital stay, and incidence of delayed graft and slow graft function were comparable between the 4 groups. One death occurred, each, in groups 1 and 2; posttransplant complications being comparable. While 1-year graft survival (death censored and uncensored) were comparable, 1-year graft function (serum creatinine) showed that the worst graft function was seen in group 3 (female-to-male). Significant differences between the 4 patient groups also were seen in pretransplant and posttransplant hemoglobin levels as well as in posttransplant arterial hypertension and high-density lipoprotein cholesterol blood levels. Other metabolic indices were generally comparable between the 4 patient groups. CONCLUSIONS: These results revealed that sex mismatching (group 2, male donor to female recipient) had the best 1-year graft function but the same 1-year patient and graft survival.

Infectious complications in kidney transplant: a Lebanese perspective.

OBJECTIVES: Infections remain a frequent, potentially life-threatening complication of kidney transplant. SUBJECTS AND METHODS: Between 1998 and 2006, we evaluated the incidence of infections in 114 kidney transplant patients, with a 1-year follow-up. All patients received a posttransplant anti-infectious prophylaxis regimen. Induction therapy was given to 94 patients (82.4%), and maintenance immunosuppression consisted of calcineurin inhibitor (cyclosporin microemulsion or tacrolimus), together with mycophenolate mofetil and prednisone. RESULTS: In total, 56 patients (49.1%) developed a total of 95 infections up to 1-year after kidney transplant, including 46 in-hospital infections in 38 patients. Bacterial infections were the most frequent (97.8%), and were mainly urinary, followed by drain, central line catheter, and pulmonary infections. The most-frequent isolated bacteria were E. coli, followed by Klebsiella, Acinetobacter, and Pseudomonas. No viral infections were detected. Up to 1 year after discharge from the hospital, 49 infections occurred in 26 patients, of which 79.5% were bacterial; mainly urinary tract infections due to E. coli, in addition to 7 cases of cytomegalovirus, 1 herpes, and 2 cases of fungal infections. CONCLUSIONS: This is the first Lebanese study that deals with posttransplant infections in kidney transplant patients and underscores the importance of close patient monitoring and follow-up. Comparison with international data shows similar patterns.

Kidney transplantation in a patient with aortic bi-iliac endovascular graft: case report and literature review.

Arterial hypertension is a leading cause of both vascular diseases and chronic renal failure. With the increasing incidence of patients suffering from hypertensive vascular disease, namely aorto-iliac atherosclerosis and aneurysms, more candidates are referred for kidney transplantation (KT). Staged or simultaneous surgical repair of aorto-iliac lesions with KT have long been described and studied. In this report, we discuss the case of a patient with infrarenal abdominal aortic aneurysm, having an endovascular bifurcated aortic bi-iliac stent (EVBAIS) introduced, who underwent a KT 3 months after his vascular surgery without any postoperative complication. This case, as well as other previous studies, supports the fact that the presence of an EVBAIS does not contraindicate KT.

Effect of recipient age on the outcome of kidney transplantation.

We investigated the effect of recipient age (RA) on kidney transplantation outcome in 107 transplant patients, with a follow-up of 1 year. Patients were divided in 3 groups: Group A (RA<50 years; 72 patients), Group B (RA 50-60 years, 19 patients), and Group C (RA>60 years; 16 patients). The rate and severity of acute rejection, infection rate and type, delayed graft function, hospital stay, creatinine levels (3, 6, 12 months), incidence at 1 year of post-transplant hypertension, cholesterol and triglycerides blood levels, and the rate of post-transplant surgical complications, and 1-year graft and patient survival were comparable between the 3 groups. However, creatinine blood level at 1 month and the 1-year fasting blood sugar were significantly higher in Group B. The RA does not seem to be of a significant predictive value, good selection and pre-transplant patient workout are important factors for a better outcome.

Effect of pretransplant hemoglobin blood level on kidney transplant outcome.

OBJECTIVES: We investigated the effect of pretransplant hemoglobin level on the outcome of kidney transplant. PATIENTS AND METHODS: Patients were divided in 2 groups: group A < 10 g/dL (80 patients; PTHb < 10 g/dL), and group B > 10 g/dL (69 patients; PTHb = 10 g/dL), and were matched regarding donor age, recipient sex, blood group, donor recipient HLA, and Cytomegalovirus status. RESULTS: The frequency of acute rejection, together with the timing of rejection, the need for antithymocyte globulin Fresenius rescue therapy, infection rate, and posttransplant surgical complications were comparable between both groups. While the 1-year actuarial patient and graft survival rates, delayed graft function, and slow graft function rates were comparable between both groups, longer hospital stay was required for group B (> 10 g/dL) patients (P = .005). Mean serum creatinine levels upon discharge (P = .02), at 6 months (P = .05), and 1 year (P = .02) after discharge were higher in group B (> 10 g/dL) patients. While posttransplant hemoglobin levels were lower than pretransplant levels, they were higher in group B (> 10 g/dL) compared with group A (< 10 g/dL), (P = .019). CONCLUSIONS: Pretransplant hemoglobin level does not affect the outcome of kidney transplant, except for creatinine levels at 1 year.

Single-center experience with tacrolimus-based immunosuppressive regimens in renal transplantation.

The efficacy and safety of tacrolimus (FK506; Prograf) were determined in 28 adult kidney transplant patients (20 males and 8 females), aged 18-68 years (mean+/-S.D.: 46.9+/-4.03 years). Induction therapy was ATG-F (n=23), daclizumab (n=3), or none (n=2), and maintenance immunosuppression consisted of tacrolimus, combined with mycophenolate mofetil (MMF; n=26) or azathioprine (AZA; n=2) and prednisone (Pred). In seven patients, cyclosporine A microemulsion (Neoral) was replaced by tacrolimus for acute rejection (AR; three patients), slow graft function (SGF, two patients) and Neoral side effects (two patients). Acute rejection occurred in five patients (17.8%), three of whom were steroid-resistant treated with a second course of ATG-F. Infection occurred in 10 patients (35.7%) with a total of 15 infectious episodes, comprising bacterial (73%) and viral (27%) infections related to CMV. Other side effects related to tacrolimus were hypertension in four patients (14%) and post-transplantation hyperglycemia in nine patients (32%), three of whom required insulin therapy. In addition, hypercholesterolemia and hypertriglyceridemia occurred in six (21%) and eight patients (28.5%), respectively. The patient's hospital stay was 12.7+/-1.3 days (range: 8-24 days), and mean serum creatinine upon discharge, and at 1, 3 and 6 months following transplantation were: 2.1+/-0.5, 1.47+/-0.21, 1.41+/-0.53 and 1.23+/-0.11 mg/dl, respectively. The 6-month actuarial patient and graft survival rates were 100%. While tacrolimus is an effective calcineurin inhibitor for kidney transplantation (KT), severe acute rejection seen is related to highly sensitized patients, and the CMV infections noted were related to the presence of more CMV-negative recipients receiving kidneys from CMV-positive donors. Longer follow-up with a larger patient sample is needed to fully assess both the efficacy and safety of tacrolimus, including its metabolic effects.

Comparison of daclizumab, an interleukin 2 receptor antibody, to anti-thymocyte globulin-Fresenius induction therapy in kidney transplantation.

The efficacy and safety of daclizumab and anti-thymocyte globulin-Fresenius (ATG-F) as induction therapy in kidney transplantation (KT) were investigated in 45 KT performed in our center between March and May 2002. Group II (n=10) received daclizumab as induction therapy, and Group I (n=35) were induced with a single intraoperative bolus therapy of ATG-F. All patients were at low-risk, and the recipient and donor demographics, as well the immunosuppression regimen employed were comparable in both groups. Drug safety, assessed by the occurrence of side effects, was almost comparable in the two groups, except for more thrombocytopenia in Group II (P<0.0004). Acute rejection (AR) occurred in 10% in Group I and 11.4% in Group II (P=NS). There were more infections in Group II (42.8%) than in Group I (10%) (P<0.009). Bacterial and viral infections were more common in Group II (69 and 23%) than in Group I (10 and 0%) (P<0.05). The hospital stay was similar in both groups. Mean serum creatinine levels upon discharge, at 1, 3 and 6 months were: 1.23+/-0.11, 1.21+/-0.06, 1.25+/-0.11 and 1.35+/-0.08 in Group I and 2.18+/-0.43, 1.49+/-0.16, 1.49+/-0.16 and 1.35+/-0.08 in Group II, respectively. While better serum creatinine levels were observed in Group I upon discharge (P<0.048), this was due to the presence of more sensitized patients in Group II. The 6 months actuarial patient and graft survival were identical in both groups (100 and 100%, respectively). Although both daclizumab and ATG-F were effective and safe as induction therapy in KT, less bacterial and viral infections and lower early serum creatinine levels were noted in daclizumab-treated patients.

Intraoperative anti-thymocyte globulin-Fresenius (ATG-F) administration as induction immunosuppressive therapy in kidney transplantation.

We reviewed 43 adult kidney transplant patients (32 males and 11 females, 14-68 years of age) performed at our center between July 1999 and February 2002. Donors (39 males and 4 females) comprised two cadaverics, five living-related and 36 living-unrelated; age 18-44 years. Indications for kidney transplantation (KT) were: chronic glomerulonephritis (8), re-transplantation (4) and chronic pyelonephritis (3); kidney disease was unknown in 15 cases. ATG-F was given as a single intra-operative bolus induction therapy in 26 patients; extended ATG-F dose was given in 17 patients because of a high sensitization status, slow graft function (SGF) or development of calcineurin inhibitors toxicity. ATG-F was stopped in seven out of 17 patients because of thrombocytopenia or severe anemia. ATG-F-related fever occurred in six patients. Acute rejection (AR) occurred in eight patients (18%) 5-11 days post-KT. ATG-F was given in three steroid-resistant AR. Infection occurred in 19 patients (44%) for a total of 32 infectious episodes comprising 24 bacterial infections (nine urinary, seven catheter-related and three respiratory), six viral infections (five CMV and one herpes) and two fungal infections (one pulmonary aspergillosis and one catheter-related candidiasis). The hospital stay was 8-75 days for a median of 13 days. The mean serum creatinine upon discharge, at 1 and 6 months after KT were: 2.04+/-0.37, 1.43+/-0.16 and 1.29+/-0.08, respectively. One patient lost his graft on day 9 because of graft microthrombi related to Factor V-Leiden mutation. The 6 months actuarial patient and graft survival were 100 and 97.6%, respectively. ATG-F as a bolus therapy is an effective and safe induction treatment in KT.

Tacrolimus (FK506) versus cyclosporin A microemulsion (Neoral) maintenance immunosuppression: effects on graft survival and function, infection, and metabolic profile following kidney transplantation (KT).

We reviewed two groups of kidney transplant patients receiving neoral (Group I, 27 patients) or FK506 (Group II, 25 patients) as maintenance immunosuppression between December 1998 and May 2002. The recipient and donor demographics and induction therapy were comparable in both groups except for more highly sensitized patients in Group II. Acute rejection (AR) rate and timing were similar in both groups except for more steroid resistant AR in Group II (P=0.04). Infections rate was similar in both groups (25.9% in Group I and 36% in Group II; P=N.S.), but there were less viral infections in Group I (0%) than Group II (29%; 4 CMV). CMV infections were related to the presence in Group II of more CMV-negative recipients getting kidneys from CMV-positive donors. The metabolic profile was comparable between the two groups, except for a better HDL in Group II (48.2+/-7.6) versus Group I (45+/-2.2; P=0.021). Mean serum creatinine levels upon discharge, at 1, 3 and 6 months were: 1.62+/-0.32, 1.4+/-0.17, 1.39+/-0.14 and 1.4+/-0.14 in Group I and 2.15+/-0.5, 1.48+/-0.23, 1.41+/-0.21 and 1.23+/-0.11 in Group II, respectively. The 6 months actuarial patient and graft survival were identical in both groups (100 and 100%). Both calcineurin inhibitors are effective and safe in KT. The higher rate of AR in Group II was related to more highly sensitized patients and the higher CMV infections was due to the presence of more CMV-negative recipients receiving kidneys from CMV-positive donors. The same study will be continued to evaluate the long term effects of both drugs.

Transcriptional and post-transcriptional mechanisms of glucocorticoid antiproliferative effects.

Glucocorticoids (GCs) are used as immunosuppressive and anti-inflammatory agents in treating organ transplantation rejection, autoimmune diseases, (hematological) cancers, and inflammatory disorders. GCs exert their effects through a multitude of mechanisms, the most significant of which is inhibition of cytokine production, and for some cytokines their effects on target cells. Paradoxically, GCs also upregulate the expression of (pro-inflammatory) high-affinity cytokine receptors on target cells in the face of lost ligand (cytokine) stimulation. GC inhibition of cytokine expression occurs at both transcriptional and post-transcriptional levels. GCs acted transcriptionally by binding their cytosolic receptor (GR), thereby facilitating its nuclear translocation and subsequent binding to the promoter region of cytokine genes on sites compatible with GC response element (GRE) motifs, which in turn directly or indirectly regulated gene expression. In addition to direct DNA binding, GCs acted post-transcriptionally by: (1) antagonism of nuclear factors required for efficient gene expression either directly or through induction of the expression of specific transcription factor antagonists, (2) altered Th lineage development by favouring the generation of (anti-inflammatory) Th2 cells and suppressing the induction or the activity of established (pro-inflammatory) Th1 cells, and (3) stimulating the expression of transforming growth factor (TGF)-beta, an immunosuppressive cytokine which inhibited cytokine production. However, these mechanisms are not mutually exclusive, since GCs may utilize more than one mechanism in exerting their anti-proliferative effect.