Comparing Therapeutic Efficacy and Safety of Epoetin Beta and Epoetin Alfa in the Treatment of Anemia in End-Stage Renal Disease Hemodialysis Patients.

BACKGROUND: Anemia is one of the most prevalent complications in patients with chronic kidney disease, which is believed to be caused by the insufficient synthesis of erythropoietin by the kidney. This phase III study aimed to compare the efficacy and safety of CinnaPoietin® (epoetin beta, CinnaGen) with Eprex® (epoetin alfa, Janssen Cilag) in the treatment of anemia in ESRD hemodialysis patients. METHODS: In this randomized, active-controlled, double-blind, parallel, and non-inferiority trial, patients were randomized to receive either CinnaPoietin® or Eprex® for a 26-week period. The primary endpoints of this study were to assess the mean hemoglobin (Hb) change during the last 4 weeks of treatment from baseline along with the evaluation of the mean weekly epoetin dosage per kilogram of body weight that was necessary to maintain the Hb level within 10-12 g/dL during the last 4 weeks of treatment. As the secondary objective, safety was assessed along with other efficacy endpoints. RESULTS: A total of 156 patients were included in this clinical trial. There was no statistically significant difference between treatment groups regarding the mean Hb change (p = 0.21). In addition, the mean weekly epoetin dosage per kg of body weight for maintaining the Hb level within 10-12 g/dL showed no statistically significant difference between treatment arms (p = 0.63). Moreover, both products had comparable safety profiles. However, the incidence of Hb levels above 13 g/dL was significantly lower in the CinnaPoietin® group. CONCLUSION: CinnaPoietin® was proved to be non-inferior to Eprex® in the treatment of anemia in ESRD hemodialysis patients. The trial was registered in Clinicaltrials.gov (NCT03408639).

Prophylactic fluid therapy in crushed victims of Bam earthquake.

BACKGROUND: Acute kidney injury (AKI) is a severe and preventable problem of crushed earthquake victims. Early hydration therapy started before fully removing earthquake rubbles has been claimed to play a decisive role in AKI prevention, which saves the necessity of later dialysis. However, the extent, quality, and appropriateness of its know-how are controversial. METHODS: Processing clinical and paraclinical data gathered from Bam earthquake victims older than 15 years, we tried to determine correlations between the time of being under the rubbles (TUR), the level of serum creatine phosphokinase (CPK), the delayed onset of fluid therapy (DFT), and finally the volume of intravenous fluid received per day (VFR) with the formation of AKI and the need for dialysis. RESULTS: There is a direct and significant relation between the intensity of the trauma (TUR and CPK) and DFT with the occurrence of AKI and need for dialysis (P < .001). However, as the VFR increases, the occurrence of AKI and the need for dialysis significantly decrease (P = .005). Based on multivariate analysis, the occurrence of AKI and the need for dialysis are primarily affected by CPK, TUR, and VFR; and DFT has been dropped out. The analysis showed the preventive role of VFR more than 6 L in severe rhabdomyolysis patients and of at least 3 L in moderate ones in development of AKI and dialysis. CONCLUSIONS: In the severely rhabdomyolized patients (CPK ≥ 15,000), higher volumes of prophylactic fluid (VFR >6 L) are required, whereas in less-traumatized patients, lower volumes (3-6 L) would be effective.

Approach to a target value for 2-hours post dose cyclosporine (C2) during the first week post renal transplantation.

BACKGROUND: There is not a wide consensus on whether recommended target ranges for 2-hours post dose cyclosporine (CsA) blood level (C2) are generalizeable to all kidney recipient populations worldwide. In this study we aimed to assess in which C2 level we can obtain the least acute rejection (AR) episodes in our kidney transplanted patients. MATERIAL/METHOD: In a retrospective cross-sectional study, we investigated all our renal recipients with at least a valid C2 blood level at the days between 5-9 post transplantation. All patients were under immunosuppressive therapy with CsA (Neoral), prednisolone and MMF. RESULTS: Hundred forty-four patients were eligible for inclusion in the study. Mean age of the study subjects at the time of transplantation was 36.8+/-16.6 years. 99 (69%) of the patients were male. Overall, 16 (11%) patients experienced AR during the first two weeks post-transplantation. Mean C2 blood levels for patients experiencing AR was 793+/-335 compared with 1028+/-391 for patients without AR (p=0.023). We found that none of the patients with a C2 level of higher than 1300 ng/mL experienced an episode of AR. CONCLUSIONS: According to our findings, we recommend that for minimization purpose of the incident AR episodes among LURD kidney, a C2 blood level of higher than 1300 ng/mL to be obtained during the first week post-transplantation. Alongside, approaching specific C2 targets for patients with different drug regimen or genetic polymorphisms seem necessary.

Does CMV infection increase the incidence of infective endocarditis following kidney transplantation?

BACKGROUND: Infective endocarditis (IE) is a rare but life threatening infection after renal transplantation. In addition, coinfection of CMV and IE has not been reported. Therefore, the current study was initiated to determine whether CMV infection is a risk factor for developing of IE after kidney transplantation. MATERIAL/METHODS: In a retrospectively study, we analyzed the medical records of 3700 kidney recipients at two transplant centers in Iran, between January 2000 and June 2008 for infective endocarditis. RESULTS: During the study, 15 patients with IE hospitalized in our centers were included. The predominant causative microorganisms (60%) were group D non-enterococcal streptococci and enterococci. Patient survival rate in all recipients was 66% at 6 months. Data analysis showed no significant differences in 6 months patient survival from hospitalization between both groups with and without CMV infection (P=0.2). The presentation time of infective endocarditis in recipients with CMV coinfection was more likely to be early when compared to CMV negative coinfection patients (P=0.03). CONCLUSIONS: The present study indicates that CMV infection may lead to predispose to infective endocarditis after kidney transplantation. Rapid diagnosis, effective treatment, and prompt recognition of complications in kidney transplant recipients are essential to good patient outcome.

Human leukocyte antigen (HLA) B-27 and older age are associated with augmented cyclosporine blood bioavailability in renal allograft recipients: an attempt toward individualization of immunosuppression.

BACKGROUND: Therapeutic drug monitoring of cyclosporine (CsA) blood values in renal transplant recipients is of extreme importance; hence, finding contributing factors in this issue is relevant. In this study, we aimed to evaluate potential associations of some characteristics of the recipients including their human leukocyte antigen haplotypes with their drug bioavailability. MATERIAL/METHODS: 616 patients who had a valid HLA typing result concomitant with other demographic data in our local data registry were consecutively selected. We extracted their HLA typing, age, gender, weight, cause of renal failure, first measured CsA trough level (C0) and concomitantly measured creatinine, CsA administered dosage, time duration from transplantation, routine laboratory test results, panel reactive antibodies percentage, and immunosuppression type. Bivariate and multivariate linear regressions were employed to evaluate associations of these factors with blood C0 values. RESULTS: 64.5% of patients were male. Mean age at transplantation was 40.7+/-15.8. Mean first measured C0 was 271+/-178 ng/ml. Analysis showed that the only factors which had independent association with C0 were age at transplantation, dose/weight ratio and HLA-B27. CONCLUSIONS: genetic factors as well as age of patients are two founded factors in this study which are recommended to be considered in monitoring drug administration in organ transplant recipients.

Immunogenicity of pneumococcal vaccination in renal transplant recipients and hemodialysis patients: a comparative controlled trial.

BACKGROUND: The objectives of this study were: to assess and compare the antibody responses of renal allograft recipients and dialysis patients to pneumococcal vaccination. MATERIAL/METHODS: 14 stable dialysis patients as well as 37 kidney transplant recipients were eligible for inclusion in this trial. Participated patients receive a single 0.5-mL of 23-valent vaccine Pneumovax administered intramuscularly in the upper extremities. The efficacy of vaccination was evaluated by measuring the antibody response to the whole vaccine. Sera were obtained prior to vaccination and 4 weeks, 6 months and 1 year after the vaccination. RESULTS: Prior to vaccination, mean IgG and IgG2 titers were equivalent in Dx and KTx patients (p>0.1 in both). Four weeks after vaccination, 49 out of 51 participated patients (96%) represented an increase in their anti pneumococcal IgG levels (mean 99+/-66) compared to 48 out of 51 (94%) for month 6 (mean 90+/-59), and 38 out of 45 (85%) for the first year after vaccination (mean 73+/-69). KTx patients kept significantly more serum IgG2 levels at months 6 and 12 after vaccination (p=0.001, p=0.03, respectively; Table 1). Mean IgG values for month 6 was 9+/-41 units lesser than month 1 post vaccination serum IgG levels. CONCLUSIONS: We found that patients with renal failure on hemodialysis and kidney transplantation well respond to immunization by anti pneumococcal vaccination. But, they rapidly loss their serum antibody levels during the one year after vaccination. Specifying protective levels for serum IgG and IgG2 levels in these patients would help us to more precisely follow these patients and to consider a revaccination when they failed to save the protective serum antibody level.

"Transplantation" research output by Muslim nations: current status, trends and future outlook.

Bibliometric measurement of scientific research production is one of the most practical methods for evaluating scientific situations of any nations. In this study, we assessed the number of scientific publications by authors from Muslim nations in journals indexed in Pubmed under "transplantation" subject. We found that Muslim nations have relatively very low publication rate in the field of transplantation. Moreover, except for Turkey, we did not detect an uplifting trend for the surveyed nations. Iran had quiet irregular trend with a very sharp missile like upwarding trend in 2007. In summary, Muslim nations with notable practice in transplantation should more fund and concentrate on scientific aspects of the practice for resolving local health dilemmas as well as exploring basic science for improving prognosis and quality of life of renal transplant patients.

Invasive fungal infections following renal transplantation: a review of 2410 recipients.

BACKGROUND: Organ transplant recipients, on long-term graft preserving immunosuppressive therapy, are at increased risk for life threatening opportunistic fungal infections. MATERIAL/METHODS: In order to evaluate the incidence of invasive fungal infections (IFIs) and to identify the most common fungal pathogens, we conducted a retrospective study on 2410 ESRD cases undergone living kidney transplantation in three transplant centers between 1998 and 2008. RESULTS: IFIs developed in 21 recipients (0.87%), 17 male and 4 female. Their immunosuppression was cyclosporine based. The mean age of patients was 48+/-10 (ranged from 32 to 67) years. Diagnosis was made by radiological findings, positive blood or bronchoalveolar lavage (BAL) cultures and tissue biopsies. Mucormycosis was the most common cause of IFIs in population studied (n=11), followed by disseminated candidiasis (n=4), aspergillosis (n=3), nocardiasis (n=2) and histoplasmosis (n=1). Pulmonary involvement was dominant (47.6%). The treatment was successful in only 10 patients and the rest died. CONCLUSIONS: In our large series of kidney transplant recipients, mucormycosis was found to be the most common cause of invasive fungal infection. Prompt diagnosis and treatment are necessary to avoid the life threatening complications and may greatly improve prognosis.

Lymphoma after living donor kidney transplantation: an Iranian multicenter experience.

INTRODUCTION: Post-transplant lymphoproliferative disorders (PTLD) are well-recognized complications in solid organ recipients. Limited data exist about the development of PTLDs in living kidney recipients. This study deals with a multicenter nationwide experience with kidney recipients from living donors. METHODS: We reviewed data of PTLD patients from a total population of 6,500 patients transplanted at three different transplant centers in Iran from 1984 to 2006. We also compared their data with 2,250 normal kidney recipients of Baqiyatallah Transplant Center. Data were analyzed to determine potential correlates with the occurrence of PTLD and patient outcome. RESULTS: Overall, 31 patients were diagnosed as having post-transplant lymphomas. The incidence of PTLD in our kidney transplant population comprised 0.47%. Sixteen (53%) PTLD patients were females, whereas 15 (47%) were males. The mean ages at transplantation and diagnosis were 37.1 and 41.9, respectively. Twelve (63%) patients died, and seven are alive. All deaths occurred within the 1st year after PTLD diagnosis. The mean time period from transplantation to diagnosis of PTLD was 64 (0.7-173) months. Localization of PTLD in the brain associated the worst outcome. Compared to non-PTLD patients, PTLD patients were significantly female predominated (51.6% vs. 32.2%; P = 0.03) and had lower age at transplantation (36.9 years vs. 42.9 years, respectively; P = 0.01). Patients under immunosuppressive regimens containing azathioprine were at higher risk for acquiring PTLDs compared to those with a MMF-containing regimen. CONCLUSION: PTLD is a major threat to kidney transplant recipients. Immunosuppressive agents have a significant role in developing the disease. Early detection of the disease and using more safe immunosuppresants may have beneficial effects on patient outcomes and incidence of the disease.

Cytomegalovirus disease in renal transplant recipients: an Iranian experience.

BACKGROUND: Cytomegalovirus is considered the most important infectious cause of mortality and morbidity in organ transplant recipients. In the current study, we evaluate the potential impact of cytomegalovirus infection and cytomegalovirus disease on the outcomes of renal allograft recipients under different conditions. MATERIALS AND METHODS: We retrospectively analyzed the data from 48 renal transplant recipients who had undergone a transplant at the Baqiyatallah Hospital in Tehran, Iran, between 1984 and 2007. We included all patients with valid laboratory test results for cytomegalovirus infection. Values for P less than .05 were considered statistically significant. RESULTS: Overall, 48 patients (2.1%) were documented as developing cytomegalovirus disease. From these, 1 patient (2%) died, and 3 (6%) lost their allograft function. Compared with mycophenolic-acid-based triple immunosuppressive therapy, azathioprine was less likely to induce cytomegalovirus disease and also promised better survival (P < .0001 and P < .001). Being negative for the anti-cytomegalovirus IgG antibody and receiving an allograft from a positive donor also were associated with cytomegalovirus disease development and poorer patient survival (P = .03 and P < .0001). CONCLUSIONS: Cytomegalovirus infection induces unfavorable outcomes in renal allograft recipients, especially when the infection occurs early on in the posttransplant phase. We suggest close monitoring of cytomegalovirus-positive patients and the use of less-intensive immunosuppressive treatments. Future prospective studies seem necessary.

Associations of Human Leukocyte Antigen (HLA) haplotypes with risk of developing lymphoproliferative disorders after renal transplantation.

BACKGROUND: Genetic susceptibility to lymphomas associated with human leukocyte antigens (HLA) has been broadly reported for many years. In this study, we aimed to evaluate the potential impact of various HLA antigens on the incidence of lymphoproliferative disorders in renal allograft recipients. MATERIAL/METHODS: In this retrospective cross-sectional study, we analysed data of PTLD patients from two of the major Iranian transplant centers and compared them with 1155 normal kidney recipients. Potential impact of previously reported relevant HLA antigens was assessed. For assessing independent impact of various factors, we used a multivariate proportional hazard analysis using Cox regression. RESULTS: Patients in the two groups were similar in their age at transplantation. PTLD group was significantly female predominated (61% vs. 33%). chi(2) showed a higher frequency of HLA-BW22 in the PTLD group. HLA-A2, HLA-A11, HLA-B5 and HLA-B35 concomitant with azathioprine based immunosuppression were significantly associated with PTLD occurrence. CONCLUSIONS: Our findings can further alert us toward the initial signs of PTLDs in high risk kidney allograft recipients. Future prospective studies with larger patient population seem necessary for confirming our findings.

Early hyperglycemia after allogenic kidney transplantation: does it induce infections.

BACKGROUND: Although impact of diabetes mellitus after solid organ transplantation is a broadly investigated issue, a potential impact of early hyperglycemia after renal transplantation has not received enough consideration. In this study, we aimed to evaluate the potential impact of early hyperglycemia on the hazards of infections development leading to re-hospitalization. MATERIAL/METHODS: We evaluated 1931 non diabetic renal allograft recipients, undergone renal transplantation at the Baqiyatallah Hospital, Tehran from 1984 to 2006. Level of hyperglycemia was defined at 126 mg/dL. Patients who had at least two glucose concentration results over the mentioned level in two different days during their early post transplantation period were determined as hyperglycemic. RESULTS: Overall, 7.6% of patients were determined as having early post transplant hyperglycemia. Multivariable hazard analysis using Cox regression model showed that early post transplantation hyperglycemia has an independent impact on rehospitalization of non-diabetic kidney allograft recipients for developing infectious diseases. CONCLUSIONS: Regarding findings of our study and previous studies we conclude that renal transplant recipients who develop hyperglycemia during their early post transplantation period should receive higher amount of attention over their follow up periods.

Epidemiologic aspects of the Bam earthquake in Iran: the nephrologic perspective.

BACKGROUND: Acute renal failure is a serious, preventable, and potentially reversible midterm complication after mass disasters. In 2003, an earthquake struck Bam, Iran. This article studies the epidemiologic aspects of the earthquake from a nephrologic perspective. METHODS: A questionnaire was sent to the reference hospitals. The resulting database of 2,086 traumatized patients hospitalized in the first 10 days was analyzed. RESULTS: Mean age was 29.0 +/- 15.6 years. Compared with the resident population, the percentage of patients was lower among children and teenagers younger than 15 years and higher among young and middle-aged adults (P < 0.001). There was no significant difference between mean ages of patients with acute renal failure and other patients. Time under the rubble was longer for patients with acute renal failure (6.2 +/- 4.1 versus 2.1 +/- 3.9 hours; P < 0.001). These patients were hospitalized later (3.1 +/- 2.8 versus 1.5 +/- 1.7 days after the disaster; P < 0.001) and longer (16.7 +/- 12.8 versus 12.5 +/- 11.3 days; P < 0.001). Sepsis (11.6% versus 0.5%), disseminated intravascular coagulation (7.3% versus 0.3%), adult respiratory distress syndrome (9.1% versus 1.4%), fasciotomy (38.9% versus 1.9%), amputation (6.1% versus 0.5%), and death (12.7% versus 1.9%) were markedly more frequent among patients with acute renal failure (P < 0.001 for all). CONCLUSION: Hospitalized patients were mostly young and middle-aged adults. Patients with acute renal failure were entrapped longer and hospitalized later and for longer periods. Medical complications, surgical procedures, and mortality were greater in the latter group. Early extrication and quick hospitalization with appropriate multidisciplinary care are cornerstones to prevent acute renal failure and its subsequent mortality in earthquake conditions.

Infective endocarditis after renal transplantation.

BACKGROUND: Infective endocarditis (IE) is a serious complication in immunosuppressive patients that has adverse effects. OBJECTIVES: The aim of this study was to define the characteristics, outcomes, and correlating factors of mortality in renal transplant recipients. PATIENTS AND METHODS: Infective endocarditis was diagnosed in 22 patients from three renal transplant centers in Iran between 2000 and 2010. Modified Duke criteria were applied to confirm the diagnosis. RESULTS: Twenty-two renal transplant patients with IE were evaluated. Blood culture results were positive in 81%. Enteroccous and group D non-enterococcal were the causative microorganisms in 31% and 25% of patients, respectively. In-hospital and 12-month mortality was 41% and the mortality rate was higher in older patients in comparison to younger patients. Overall, the rates of one-year disease-free patient and graft survival were 49% and 88%, respectively. CONCLUSIONS: Despite the availability of different and potent antibiotics, the mortality caused by IE remains considerably high. These patients are significantly prone to endovascular infections that affect the mortality and survival.

Incidence of malignancy after living kidney transplantation: a multicenter study from iran.

Malignancy is a common complication after renal transplantation. However, limited data are available on post-transplant malignancy in living kidney transplantation. Therefore, we made a plan to evaluate the incidence and types of malignancies, association with the main risk factors and patient survival in a large population of living kidney transplantation. We conducted a large retrospective multicenter study on 12525 renal recipients, accounting for up to 59% of all kidney transplantation in Iran during 22 years follow up period. All information was collected from observation of individual notes or computerized records for transplant patients. Two hundred and sixty-six biopsy-proven malignancies were collected from 16 Transplant Centers in Iran; 26 different type of malignancy categorized in 5 groups were detected. The mean age of patients was 46.2±12.9 years, mean age at tumor diagnosis was 50.8±13.2 years and average time between transplantation and detection of malignancy was 50.0±48.4 months. Overall tumor incidence in recipients was 2%. Kaposis' sarcoma was the most common type of tumor. The overall mean survival time was 117.1 months (95% CI: 104.9-129.3). In multivariate analysis, the only independent risk factor associated with mortality was type of malignancy. This study revealed the lowest malignancy incidence in living unrelated kidney transplantation.

Melioidosis: It is not Far from here.

In the modern world, with developed traveling facilities, tourism is an important factor in emerging new infectious diseases in non-endemic areas. Therefore, the epidemiology of infections is a considerable issue for physicians and should be taken into account. We report a case of melioidosis in a 69-year-old Iranian man during his trip to Southeast Asia. On admission, he was febrile with tachycardia and tachypnea and had diabetes mellitus and hypertension since eleven years ago. Bronchoscopy and bronchoalveolar lavage (BAL) were performed. Blood and BAL cultures revealed heavy growth of Burkholderia pseudomallei. According to the aforementioned culture results, the patient was treated with meropenem and TMP-SMX, while other antibiotics were discontinued. After 3 weeks, the patient was discharged with stable status and normal pulmonary function; and eradication therapy with TMP-SMX continued for about 3 months. The control lung CT scan after one month demonstrated significant improvement.

Assessment of sleep disturbance in renal transplant recipients and associated risk factors.

Sleep disturbances are highly prevalent in ESRD patients. In this study we sought to evaluate the associations of poor sleep with several genetic, laboratory, treatment and demographic factors in renal allograft recipients using a validated sleep quality questionnaire. A cross-sectional study was conducted on renal transplant patients over 18 years of age with stable current stable graft function. All patients completed PSQI and Ifudu questionnaires for assessment of sleep quality and morbidity measures. Kolmogorov-Smirnov test was used for evaluation of distributions besides Student's t-test, and Fisher's exact test for analyses. Mean total PSQI score for the whole patients was 6.5 +/- 2.6. Overall 26 (67%) of patients were diagnosed as "poor sleepers" (PSQI total score > or =5) and the reminding 13 (33%) were "good sleepers". Compared to "good sleepers", "poor sleepers" significantly had higher serum phosphate levels and ESRD duration (P = 0.05). Hematological disorders were more seen in "poor sleepers" and musculoskeletal disorders had a significant worsening impact on PSQI total score (beta = 0.28, P = 0.05). In conclusion our study showed that sleep disturbance is common in renal transplant patients is surprisingly common, and ESRD duration prior to transplant was significantly associate with sleep quality. Future studies with larger sample sizes are necessary for confirming our results.

Skin cancer after renal transplantation: Results of a multicenter study in Iran.

BACKGROUND: Incidence and risk factors for skin tumors following renal transplantation can vary geographically; therefore, a retrospective study was performed to determine the incidence of and potential risk factors for skin cancer at 14 Transplant Centers in Iran between 1984 and 2008. MATERIAL/METHODS: We enrolled 11,255 kidney transplant recipients who were examined for all skin tumors. All skin cancers were established by histological examination. The data collection included the patient's age and sex, immunosuppressive regimen before and after diagnosis of tumor, rejection episodes, post-transplant latency period, other concurrent neoplastic problems, renal allograft function and outcome. RESULTS: One hundred and twenty-eight (1.14%) renal recipients had skin tumor, representing half of all post-transplant malignancies (128 out of 245 cases). Kaposi's sarcoma was the most common post-transplant cancer compared with other skin tumors. Male recipients had more tumors than did females (P=0.04); the male-to-female ratio in the affected patients was 2.5:1. The age at transplantation of patients with skin tumor was higher compared to RTRs without skin tumor (47±11 vs. 38±15 years, P=0.000), and individuals older than 45 years were at higher risk (odds ratio=3.8, 95%CI 2.6-5.5) of skin cancers. Patients consuming azathioprine were at risk more of skin cancer compared with those were on MMF (odds ratio =2.9, 95%, CI 2.0-4.2). The overall mortality was low (7.8%) in cases with skin cancer. CONCLUSIONS: This study showed that male sex, increased age, prolonged immunosuppression and azathioprine increased the risk of skin tumors after renal transplantation.

Is pulmonary histoplasmosis a risk factor for acute renal failure in renal transplant recipients?

Prolonged use of immunosuppressive medication is associated with an increased susceptibility to viral, bacterial and fungal infections. This paper reports a 42 year old kidney transplant recipient with 10 years of stable allograft function who developed pulmonary histoplasmosis and consequently lost his kidney. This report corroborates the previously proposed threat of infection with H. capsulatum for kidney allograft rejection.

Mycophenolate sodium increases cyclosporine blood levels in renal transplant recipients.

Cyclosporine is an immunosuppressive agent that displays a broad intra- and inter-individual pharmacokinetic variability. To evaluate the factors, which significantly influence cyclosporine blood levels in our renal transplant recipients, we studied 611 consecutive patients transplanted from living donors in Baqiyatallah hospital, Tehran, Iran from 1984 to 2005. The patients were divided into two groups: Group I included patients treated with mycophenolate sodium (MS) as an adjunctive immunosuppressive agent and Group II treated with azathioprine (AZA) as an adjunctive agent. Measurements of cyclosporine blood tough levels (C0) were performed 12 hours after the morning dose (just before the night dose). The mean age of the study population at time of transplantation was 38.7 +/- 13.7 years and males formed 67% of it. Univariate analysis and multivariable linear regression model showed that older age at transplantation, treatment with MS, and time interval from time of transplantation were significantly related with higher C0 levels. We conclude that there is an interaction of immunosuppressive agents in renal transplant patients with higher cyclosporine levels in the recipients of MS.