Design and implementation of the European-Mediterranean Postgraduate Programme on Organ Donation and Transplantation (EMPODaT) for Middle East/North Africa countries.

This prospective study reports the design and results obtained after the EMPODaT project implementation. This project was funded by the Tempus programme of the European Commission with the objective to implement a common postgraduate programme on organ donation and transplantation (ODT) in six selected universities from Middle East/North Africa (MENA) countries (Egypt, Lebanon and Morocco). The consortium, coordinated by the University of Barcelona, included universities from Spain, Germany, Sweden and France. The first phase of the project was to perform an analysis of the current situation in the beneficiary countries, including existing training programmes on ODT, Internet connection, digital facilities and competences, training needs, and ODT activity and accreditation requirements. A total of 90 healthcare postgraduate students participated in the 1-year training programme (30 ECTS academic credits). The methodology was based on e-learning modules and face-to-face courses in English and French. Training activities were evaluated through pre- and post-tests, self-assessment activities and evaluation charts. Quality was assessed through questionnaires and semi-structured interviews. The project results on a reproducible and innovative international postgraduate programme, improvement of knowledge, satisfaction of the participants and confirms the need on professionalizing the activity as the cornerstone to ensure organ transplantation self-sufficiency in MENA countries.

Effect of losartan on the recoverability of renal function in anuric and oliguric patients with a solitary obstructed kidney: a double-blind randomized placebo-controlled trial.

OBJECTIVES: To assess the role of the angiotensin receptor blocker losartan on the recoverability of renal function after de-obstruction in patients with anuria and oliguria. MATERIALS AND METHODS: This was a double-blind randomized placebo-controlled trial in anuric or oliguric patients with calcular obstruction of solitary kidney. Patients with an anomalous kidney or those with an American Society of Anesthesiology score of >3 were excluded. After relief of obstruction, patients were allocated to receive either losartan potassium 25 mg or placebo for 3 months. Serum creatinine (sCr) and renographic glomerular filtration rate (GFR) were measured at nadir and after 3 months. Changes in sCr and renographic GFR were calculated by subtracting the values at nadir from those at 3 months. Improvement, stabilization or deterioration of sCr and renographic GFR were defined as percentage increase or decrease from nadir ≥10%, while changes <10% were considered as stabilization. RESULTS: A total of 76 patients completed 3 months of follow-up. Demographics and peri-operative data were comparable in the two groups. The median (range) sCr change was -1.05 (-1.8, 0.4) and -0.5 (-1.3, 0.1) mg/dL in the losartan and placebo, groups, respectively (P = 0.07). In the losartan group, renographic GFR had improved in 26 (59.1%) and deteriorated in six (13.6%) patients, while, in the placebo group, it had improved in eight (25%) and deteriorated in 10 patients (31.3%; P = 0.01). Losartan also enhanced renographic GFR improvement vs placebo by a median (range) of 6.9 (-9, 44) vs 1.4 (-10, 32) mL/min (P = 0.004). CONCLUSIONS: In patients with anuria and oliguria, losartan treatment contributes to renal function recoverability after relief of calcular obstruction of the solitary kidney.

Gingerol-derivatives: emerging new therapy against human drug-resistant MCF-7.

Cancer chemotherapies have been improved dramatically over the last two decades. In the case of human breast cancer, the combination chemotherapeutic protocol, cyclophosphamide (CPA), doxorubicin (DOX), and 5-fluorouracil (5-FU) (CDF), is often used. Nevertheless, the clinical usefulness of CDF is limited by its remarkably low therapeutic window and frequent eruption of resistance. These limitations prompted our search for a more effective and safe drug candidate that may raise the therapeutic benefits for breast cancer patients. Gingerols' wide therapeutic indices as well as their high efficacy in the suppression of carcinogenesis are well established. However, no thorough study to date has profiled their antibreast cancer activities in depth. Therefore, the aims of the present study are to evaluate the antibreast cancer activities of gingerols in comparison to CDF and to gain insight into the structure activity relationships (SARs) responsible for the observed effect using a breast cancer cell model, MCF-7. Our data revealed that 6-gingerol showed the highest anticancer potency that is superior to that of CDF with IC50 = 30.4 µM. Guided by these results, semisynthetic modifications of 6-gingerol have been carried out to characterize 6-gingerol's SARs. The obtained results showed that the acquisition of free hydroxyl group in the aliphatic side chain of 6-gingerol is essential for the antibreast cancer activity. Likewise, the length of aliphatic side chain in 6-gingerol is optimum for its anticancer activity because any decrease in the side chain length resulted in a dramatic loss of anticancer activity. Additionally, allylation of phenolic group has shown antibreast cancer activity superior to that of 6-gingerol per se. Conversely, methylation or isoprenylation of phenolic group has led to a potential decrease in the anticancer activity, whereas loss of aromaticity resulted in a complete loss of 6-gingerol's cytotoxic activity. Collectively, the present results would simplify drug design to allow safer and more effective antibreast cancer pharmaceuticals to be designed.

Possible role of nitric oxide in hepatic injury secondary to renal ischemia-reperfusion (I/R) injury.

Hepatic injury secondary to renal I/R injury has been documented in several studies. This study aimed to investigate the role of NO in hepatic injury secondary to renal I/R in rat model. Sprague-Dawley rats (n = 48) were divided into 4 equal groups; sham-operated, I/R injury group (45 min of bilateral renal ischemia), L-arginine group (I/R with 300 mg/kg L-arginine, 20 min before ischemia), L-NAME group (I/R with 50 mg/kg L-NAME, 20 min before ischemia). L-NAME (NO synthase inhibitor) caused significant elevation in serum creatinine, BUN, liver enzymes, liver histopathological damage score (p ≤ 0.05) and MDA production (p ≤ 0.001); on the other hand significantly decreased NO and GSH levels (p ≤ 0.05). L-arginine significantly decreased serum creatinine, BUN and GSH (p ≤ 0.05) and caused significant elevation in liver enzymes and NO (p ≤ 0.05), and also in MDA levels (p ≤ 0.001) in liver tissues. We conclude that endogenous NO might have protective effect against hepatic injury induced by renal I/R injury and inhibition of this endogenous NO by L-NAME or exogenous administration of NO (by L-arginine) might be harmful.

Impact of CD 28, CD86, CTLA-4 and PD-1 genes polymorphisms on acute renal allograft rejection and graft survival among Egyptian recipients.

To study the impact of four gene polymorphisms on acute renal allograft rejection (AR) and graft survival among Egyptian population. These 4 gene polymorphisms include: (1) CD 28 (rs3116496), (2) CD86 (rs1129055), (3) CTLA-4 (rs3087243), (4) PD-1 (rs2227982). This is a non-concurrent cohort study including 50 kidney transplant recipients diagnosed histopathologically as (AR) [study group] and another 50 matched allograft recipients without AR [control group]. Blood samples were taken from both groups and subjected to genotyping for the selected four genetic polymorphisms by TaqMan genotyping assay. The difference in genotypic distribution of CD 28: rs3116496 and CD86: rs1129055 wasn't statistically significant between the study and control groups (P = 0.22 and 0.33 respectively) and also both polymorphisms had no effect on graft survival (P = 0.36 and 0.74 respectively) while the addition of C allele to IVS3 +17T/C polymorphism in CD28 gene showed a protective effect against AR (P = 0.03). CTLA-4: rs3087243 AG genotype showed a protective effect against AR as it was more frequent in no rejection group compared to those with AR (P = 0.001) with a statistically significant impact on graft survival (P < 0.001), while PD-1: rs2227982 AG genotype was equally distributed between both groups (variant of unknown significance). There was no detected association between CD86 polymorphism: rs1129055 and CD 28 polymorphism: rs3116496 with the development of AR. However, C allele of CD 28 IVS3 +17T/C polymorphism and CTLA-4 polymorphism: rs3087243AG genotype both demonstrated a protective effect against AR.

Management of pre-renal transplant secondary hyperparathyroidism: parathyroidectomy versus cinacalcet.

Background: Secondary hyperparathyroidism is a common consequence of end-stage renal disease. Despite the efficacy of kidney transplantation in treating renal failure, many transplant recipients still suffer from persistent or tertiary hyperparathyroidism. Furthermore, the impact of secondary hyperparathyroidism therapy choices on other renal transplant outcomes is poorly understood. Methods: We retrieved the clinical data of 334 patients who received a kidney allograft between January 2007 and December 2014 at the Sheffield Teaching Hospitals, NHS Foundation Trust, United Kingdom. We identified three groups: parathyroidectomy group (34 patients), including patients who had parathyroidectomy before transplantation; cinacalcet group (31 patients), including patients who received cinacalcet before transplantation; and control group (269 patients), including patients who receive a transplant in the same period but did not have any evidence of hyperparathyroidism. We reviewed the demographic data, biochemical parameters and graft survival of all groups. Results: Patients who underwent parathyroidectomy before transplantation had significantly better post-transplant calcium and parathyroid hormone levels than patients in the cinacalcet group (p=0.003). In addition, a significantly lower number of patients had tertiary hyperparathyroidism in the parathyroidectomy group than in the cinacalcet group at 1 year of follow-up (p=0.001). However, short-term and long-term graft survival was comparable in all groups. Conclusions: Renal allograft survival was comparable in all groups. However, tertiary hyperparathyroidism was less likely to occur in patients who underwent parathyroidectomy than in those who were administered cinacalcet.

Renal replacement therapy for critically ill patients with COVID-19-associated acute kidney injury: A review of current knowledge.

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly evolved into a global pandemic. A significant proportion of COVID-19 patients develops severe symptoms, which may include acute respiratory distress syndrome and acute kidney injury as manifestations of multi-organ failure. Acute kidney injury (AKI) necessitating renal replacement therapy (RRT) is increasingly prevalent among critically ill patients with COVID-19. However, few studies have focused on AKI treated with RRT. Many questions are awaiting answers as regards AKI in the setting of COVID-19; whether patients with COVID-19 commonly develop AKI, what are the underlying pathophysiologic mechanisms? What is the best evidence regarding treatment approaches? Identification of the potential indications and the preferred modalities of RRT in this context, is based mainly on clinical experience. Here, we review the current approaches of RRT, required for management of critically ill patients with COVID-19 complicated by severe AKI as well as the precautions that should be adopted by health care providers in dealing with these cases. Electronic search was conducted in MEDLINE, PubMed, ISI Web of Science, and Scopus scientific databases. We searched the terms relevant to this review to identify the relevant studies. We also searched the conference proceedings and ClinicalTrials.gov database.

Torque Teno Virus Polymerase Chain Reaction Titer: A Promising Immunometry.

Solid-organ transplant is the treatment of choice for all patients with end-stage diseases. Long-term graft function and survival rely on suitable immunosup-pressive treatment to prevent rejection. Besides this desired effect, a reduced immunocompetence in the transplant recipient increases the risk of developing infectious diseases and malignancies. An ideal biomarker should be sensitive, allow early visibility, be accessible in peripheral blood, and be associated with a known mechanism. Torque teno virus or transfusion transmitted virus is a virus that has gained attention as a possible marker of immune function. This virus rarely causes disease in healthy individuals, but torque teno viral load in immunosuppressed patients is shown to be higher than in healthy controls. Replication of torque teno virus is inversely correlated with number and especially functions of T lymphocytes. Torque teno virus could join the current list of predictive biomarkers in transplantation to detect whether the patient is over- or under-immunosuppressed. More studies are needed to confirm or disprove this possibility.

Does timing of post-renal transplant diuresis affect graft survival in live-donor renal transplants?

OBJECTIVE: To study the effect of timing of diuresis on short and long term graft survival in live-donor (LD) renal transplants. METHODS: Between 1976 and 2005, 1747 consecutive LD renal transplants were performed in a single institution. Patients were classified according to timing of diuresis after vascular de-clamping; group 1 included patients with diuresis within 10 min; group 2 started diuresis between 10 and 60 min after de-clamping; group 3 started diuresis between 1 and 24 h after de-clamping; and group 4 started diuresis > 24 h after de-clamping. Patients' data were stored on an electronic database and were reviewed for risk factors and clinical relevance of timing of diuresis. RESULTS: Groups 1-4 comprised 1598 (91.5%), 87 (5%), 44 (2.5%) and 18 (1%) patients, respectively. By multivariate analysis, vascular thrombosis was the significant risk factor for delayed diuresis. Delayed diuresis was significantly associated with the occurrence of acute tubular necrosis (ATN), and acute and chronic rejection. Graft and patient survival rates were significantly affected by the timing of diuresis. The 1-year graft survival rates were 93.8, 83.0, 83.6 and 55.6%, and the 5-year graft survival rates were 77.4, 59.4, 69.4 and 35.7% in groups 1, 2, 3 and 4, respectively (P < 0.001). The 1-year patient survival rates were 96.5, 84.4, 90.7 and 61.1% and the 5-year patient survival rates were 87.1, 72.0, 78.1 and 52.4% in groups 1, 2, 3 and 4, respectively (P < 0.001). CONCLUSION: Delayed diuresis is a rare event after LD renal transplantation, which has an adverse effect on short- and long-term graft and patient survival.

Association and prognostic impact of persistent left ventricular hypertrophy after live-donor kidney transplantation: a prospective study.

AIM: Persistent or de novo left ventricular hypertrophy (LVH) is a risk factor for cardiovascular diseases and congestive heart failure following renal transplantation (RT). Our aim was to determine the associations and impact of persistent LVH on RT outcome. MATERIALS AND METHODS: We included 72 live-donor renal allograft recipients with mean age of 28.5 years who had evidence of LVH at time of transplantation and had stable functioning grafts 1 year after transplantation. Cardiac status of all recipients was assessed before transplantation and at 1 year after transplantation by echocardiography. Recipients were subdivided into two groups according to persistence or regression of LVH 1 year after transplantation. The first group included 33 patients who had persistent LVH. The second group included 39 patients in whom LVH had regressed (control group). Both groups were closely followed for 10 years. RESULTS: Univariate analysis showed that persistent LVH 1 year after RT was significantly associated with high serum creatinine, higher incidence of medical infection, and acute and chronic rejection. Chronic rejection and infection were the only valid associations on multivariate logistic regression analysis. Patient and graft survival were significantly lower in the persistent LVH group (P = 0.012). CONCLUSION: Persistent LVH may be associated with higher incidence of medical infection and chronic rejection that worsen the prognosis for renal transplant recipients.

CYP3A5 Gene-Guided Tacrolimus Treatment of Living-Donor Egyptian Kidney Transplanted Patients.

BACKGROUND: Tacrolimus is an approved first-line immunosuppressive agent for kidney transplantations. Part of interindividual and interethnic differences in the response of patients to tacrolimus is attributed to polymorphisms at CYP3A5 metabolic enzyme. CYP3A5 gene expression status is associated with tacrolimus dose requirement in renal transplant recipients. MATERIALS AND METHODS: In this study, we determined the allelic frequency of CYP3A5*3 in 76 renal transplanted patients of Egyptian descent. Secondly, we evaluated the influence of the CYP3A5 gene variant on tacrolimus doses required for these patients as well on dose-adjusted tacrolimus trough-concentrations. RESULTS: The CYP3A5*3 variant was the most frequent allele detected at 85.53%. Additionally, our results showed that, mean tacrolimus daily requirements for heterozygous patients (CYP3A5*1/*3) were significantly higher compared to homozygous patients (CYP3A5*3/*3) during the first year after kidney transplantation. CONCLUSION: This is the first study in Egypt contributing to the individualization of tacrolimus dosing in Egyptian patients, informed by the CYP3A5 genotype.

Does posttransplant anemia at 6 months affect long-term outcome of live-donor kidney transplantation? A single-center experience.

BACKGROUND/AIMS: Posttransplantation anemia (PTA) frequently occurs. We aimed to assess the prevalence of anemia at 6 months of transplantation in patients under different protocols of immunosuppression, and to determine the impact of anemia on long-term patient and graft survival. METHODS: We included 832 renal transplant recipients who were categorized at 6 months according to hemoglobin (Hb) level into two groups: the first group, with Hb >13 g/dl in males and >12 g/dl in females (group I, 385 cases); and the second group, with Hb <13 g/dl in males and <12 g/dl in females (group II, 447 cases). We compared the two groups regarding posttransplant complications as well as patient and graft survival. RESULTS: Although there was no significant difference between the two groups regarding acute rejection episodes, chronic allograft nephropathy was significantly higher in the anemic group. Other posttransplant medical complications were comparable in both groups. Graft survival was significantly higher in the nonanemic group. However, no difference in patient survival was detected. CONCLUSION: From this study, we can conclude that prevalence of PTA is high, especially in females and those receiving calcineurine inhibitors (CNI) and mycophenolate mofetil (MMF), and that it was associated with poorer graft outcome but with no effect on patient survival.

Value of donor-specific antibody detection in first-graft renal transplant recipients with a negative complement-dependent cytotoxic crossmatch.

OBJECTIVES: The clinical significance of pretransplant donor specific antihuman leukocyte antigen antibodies that occur despite negative cytotoxicity crossmatches is still unclear. In this study, we assessed the impact of those antibodies on the outcome of renal transplants. MATERIALS AND METHODS: Our study subjects consisted of 153 living-donor kidney transplant recipients whose pretransplant sera were available. All subjects had a negative complement-dependent cytotoxic crossmatch and were retrospectively evaluated for antihuman leukocyte antigen antibodies and their donor specificities by means of LABScan 100 Flow analyzer (Luminex Corporation, Texas, USA). The follow-up data of all subjects were reviewed. RESULTS: Antihuman leukocyte antigen antibodies were detected in 49 patients, donor nonspecific antihuman leukocyte antigen antibodies were found in 33, and donor specific antihuman leukocyte antigen antibodies were identified in 16. There was a trend toward more acute rejection in the patients with antihuman leukocyte antigen antibodies (22%) than in those without antihuman leukocyte antigen antibodies (17%), but that difference had no statistical significance (P = .378). Patients with donor specific antihuman leukocyte antigen antibodies had a significantly higher incidence of acute cellular rejection (19% vs 6%, respectively) and vascular rejection (25% vs 6%, respectively) than did patients with donor nonspecific antihuman leukocyte antigen antibodies (P = .04). CONCLUSIONS: Our results suggest that there is a higher incidence of acute rejection in patients with donor specific antihuman leukocyte antigen antibodies and a negative complement-dependent cytotoxic crossmatch; however, those factors had no statistically significant impact on patient or graft survival.

Detection of Hepatis C Virus-Related Immunologic Markers and Their Impact on Outcomes of Living-Donor Kidney Transplant Recipients.

OBJECTIVES: Liver disease is an important cause of morbidity and mortality among recipients of transplanted organs. In addition to the liver, hepatitis C virus infection has a significant prevalence among recipients of kidney transplant and is related to worse graft and recipient survival as the kidney is an important component of the hepatitis C virus clinical syndrome. MATERIALS AND METHODS: This retrospective single center study included 336 patients with end-stage renal disease who received a kidney transplant at the Mansoura Urology and Nephrology Center from January 1992 to December 1995. Of 336 patients, 63 were excluded, and the remaining 273 patients were divided into 3 groups: viremic active (72 patients), viremic inactive (108 patients), and nonviremic (93 patients). Division of patients was based on hepatitis C virus RNA complement level (C3 and/or C4 consumption), circulating cryoglobulins, and rheumatoid factor detection. RESULTS: Our study showed insignificant differences regarding patient characteristics and demographic data among the study groups but significantly higher incidence of transaminitis in viremic (active and inactive) patients. Nonsignificant differences were found regarding proteinuria among the 3 groups, including among those who had levels in either nephrotic or nonnephrotic ranges. Biopsy-proven acute rejection episodes among the 3 groups of recipients were statistically comparable, with significantly higher frequency of chronic rejection episodes among viremic active patients. Nonviremic recipients had significantly lower serum creatinine levels than viremic (active and inactive) recipients. Patient and graft survival results were comparable among the groups. CONCLUSIONS: Presence of hepatitis C virus immunologic markers does not have a significant effect on patient and graft survival; however, it may be a clue for long-term incidence of chronic rejection.

Refractory CD20 Positive Cellular Rejection in Living Kidney Transplant: A Case Report and Review of Literature.

Transplant is the optimal therapy for patients with end-stage renal disease. Acute cellular rejection refractory to treatment remains a major risk factor for graft loss and poor outcomes. In this study, we describe a 39-year-old man who received a living-related kidney transplant. Two days after transplant, the patient displayed acute deterioration of graft function. Conventional anti-rejection therapy was initiated, but graft function did not improve. Biopsy revealed acute cellular rejection (grade IIA), and C4d and HLA antibodies were negative. Immunohistochemistry phenotyping revealed clusters of CD20-positive lymphocytes, with 80% being CD3 positive. Rituximab was prescribed, and graft function improved dramatically. After 1 week, a second graft biopsy was done due to lagging of graft function, shown by serum creatinine of 2.1 mg/dL. Biopsy revealed regenerating acute tubular necrosis with disappearance of the CD20-positive lymphocyte cluster infiltrates. Two year, after transplant, the patient's graft function maintained stable. Phenotyping of the cellular infiltrate is important as it may lead to a proper selection of immunosuppression and consequent improvement of graft outcome.

Long-term evaluation of single bolus high dose ATG induction therapy for prophylaxis of rejection in live donor kidney transplantation.

BACKGROUND/AIMS: The long-term evaluation of single bolus high dose antithymocyte globulin (ATG) induction therapy has not been adequately studied. We aimed to evaluate its long-term effects in the living related donor kidney transplantation. METHODS: Eighty adult recipients with their first kidney allograft were randomized into two equal treatment groups, one group received intraoperative single bolus rabbit ATG in a dose of 9 mg/kg and the second group served as a control. All patients were maintained on triple immunosuppressive therapy (steroids, calcineurin inhibitor and antiproliferative agent). We followed them thoroughly for minimum of 5 years. RESULTS: ATG significantly reduced the proportion of patients who experienced acute rejection episodes in the first year (9/40) when compared to the control group (26/40) and in 5 years (11/40) when compared to (30/40) in controls. The cumulative steroid dose used throughout the study was significantly lower in the ATG group. The overall incidence of posttransplant complications was comparable among the two treatment groups. There was no significant difference in patient and graft survival: 5 year survival was 100% and 85% for the ATG group, and 95% and 92.5% in the control group, respectively. CONCLUSION: Although routine single bolus ATG induction significantly reduces the incidence of acute rejection, its long-term beneficial effects on graft function and patient and graft survival are not evident.

Impact of Sex Disparities on Outcomes of Living-Donor Kidney Transplant in Egypt: Data of 979 Patients.

OBJECTIVES: Renal transplant is the criterion standard for treatment of end-stage renal disease. The effects of disparities between men and women on renal transplant outcomes have been evaluated in many studies but with debatable results. It has been suggested that female kidney donors have poor outcomes after transplant compared with male kidney donors, especially when implanted in a male recipient. The aim of the study was to evaluate the effects of sex on living-donor kidney transplant outcome. MATERIALS AND METHODS: The data of 979 patients who underwent living-donor kidney transplant from January 2000 to December 2010 at a single center were reviewed retrospectively. The patients were divided into 4 groups according to recipient and donor sex: male donor-to-male recipient (n = 307), male donor-to-female recipient (n = 132), female donor-to-male recipient (n = 411), and female donor-to-female recipient (n = 129). We compared the demographic characteristics, posttransplant rejection and complications, and graft and patient survival rates among the groups. RESULTS: Male recipients were older than female recipients, whereas male donors were younger than female donors (P < .001). No statistically significant differences were shown regarding recipient body mass index, ischemia time and time to diuresis, and acute and chronic rejection rates between the groups. Graft (P = .947) and patient (P = .421) survival rates were comparable between groups. CONCLUSIONS: Donor and recipient sex had no significant effect on outcomes of living-donor renal allograft recipients.

Management of sensitized patients awaiting renal transplantation: does sequential therapy of intravenous immunoglobulin and simvastatin offer a solution?

The value of intravenous immunoglobulin and simvastatin as potential modalities for the treatment of sensitized patients was studied. We aimed to test their efficacy as solo agents to inhibit anti-human leukocyte antigen (HLA) antibodies. We tested samples from 11 adult hemodialysis patients who were waiting for renal allotransplantation at our center, all of whom had persistently positive crossmatches with their living related donors and panel reactive antibody titers more than 20%. All patients received intravenous immunoglobulin (500 mg/kg/day on alternate days for 6 doses). Panel reactive antibody titer measurement and crossmatch testing were carried out after each dose and before each subsequent one. Two months later, 8 patients received simvastatin (20 mg/day) for 2 months. Panel reactive antibody measurement titer and crossmatch testing were carried out every 2 weeks. Only 4 patients showed an insignificant reduction in panel reactive antibody activity (P=0.36). None of them attained a negative crossmatch. Furthermore, simvastatin also resulted in an insignificant reduction of HLA antibodies in 3 patients (P=0.32). We concluded that intravenous immunoglobulin or simvastatin alone cannot effectively inhibit preformed anti-HLA antibodies to allow successful renal transplantation. Further trials of the use of intravenous immunoglobulin and simvastatin with other modalities to desensitize these patients may be warranted.

Intercellular adhesion molecules in systemic lupus erythematosus patients with lupus nephritis.

Cardiovascular events are markedly increased in systemic lupus erythematosus (SLE), and the mechanism of atherogenesis remains poorly understood. Several methods have been employed to assess endothelial function, among these is the measurement of biomarkers of endothelial activation and dysfunction [intercellular adhesion molecule (ICAM-1)]. It has been reported that such biomarkers play a more important role than traditional risk factors in cardiovascular disease. The objectives of this study were to determine the level of ICAM-1 as markers of endothelial dysfunction in 40 Egyptian patients who have SLE with various degrees of activity and to investigate their relationship to disease activity. Sixty people (40 with SLE and 20 healthy as the control group) were the subject of this study; their clinical disease activity was scored according to the SLE disease activity index (SLEDAI), and serum sampling was obtained for ICAM-1 level assay. Renal biopsy was carried out and examined by light microscopy by a pathologist blinded to the clinical activity. The mean level of ICAM-1 was significantly higher in SLE patients with active disease (826.05 +/- 367.1 Pg/ml) compared to those with inactive disease (441.33 +/- 225.19 Pg/ml) and the healthy control volunteers (111.5 +/- 17.36 Pg/ml). There was a positive correlation between serum ICAM-1 and SLEDAI (r = 0.66). A high concentration of soluble ICAM-1 in SLE patients with nephritis is reported in this paper. Our finding of increased concentrations of ICAM-1 in SLE patients with nephritis underlines the importance of inflammation and endothelial involvement in this disease, but their predictive value in the disease monitoring need to be further studied.

Is it worth using daclizumab induction therapy with mycophenolate mofetil-based immunosuppressive regimens in live related donor kidney transplantation? A long-term follow up.

BACKGROUND/AIMS: The aim of this work is to determine the long-term therapeutic benefit(s) of daclizumab induction therapy with triple immunosuppressive protocols including prednisolone, cyclosporine microemulsion (CsA), and mycophenolate mofetil (MMF) in the living related donor kidney transplantation. METHODS: Twenty-one adult recipients of their first kidney allograft were allocated to receive daclizumab with triple immunosuppressive therapy (steroids, CsA, and MMF). They were compared to 50 recipients of their first grafts who received a maintenance triple immunosuppressive therapy (steroids, CsA, and azathioprine). The patients were followed up for 5 years. RESULTS: Daclizumab group significantly experienced a marked reduction of acute rejection (7/21) when compared to the control group (31/50) with subsequent significant reduction of cumulative steroids doses at the end of 5 years. The overall incidence of post-transplant complications was comparable among the two treatment groups. There was no significant difference in patients and graft survival; 5-year patient and graft survival were 95.3%, 85.7% for daclizumab and 96%, 88% for control group, respectively. CONCLUSIONS: Although prophylactic daclizumab with triple immunosuppressive protocol including MMF have drastically reduced the incidence of acute rejections, the graft and patient survival are unchanged in this long-term follow up.