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Objectives: Widespread and prolonged therapy with ganciclovir (GCV) may result in the emergence of GCV-resistant mutations in human cytomegalovirus (HCMV) genome. The aim of this study was to detect the UL97 mutations associated with GCV resistance in kidney transplant recipients., Methods: Forty-nine kidney recipients with positive HCMV DNAemia, who received GCV therapy were included in this study. A 707 bp fragment of UL97 gene spanning codons (436 to 655) was amplified by nested PCR and sequenced., Results: Thirteen (26.5 %) out of 49 recipients contained mutations associated with amino acid changes. Two UL97 mutations related to GCV resistance were detected in 2 recipients (4 %), including alanine to valine (A594V) and proline to leucine (P521L). The D605E mutation was identified in 8 out of 49 (16.3 %) recipients. Silent mutations G598G, G503G, L553L, L634L, D456D and G579G were commonly observed., Conclusion: Our results indicate that mutations in the UL97 gene associated with GCV resistance may occur in 1 in 25 recipients treated with GCV. In addition, a higher mutation rate of D605E was detected in our recipients. This study provides the first evidence of the prevalence and pattern of GCV related mutations in Iranian Turkish recipients (Tab. 2, Fig. 1, Ref. 28).

Surgical site infection (SSI) is one of the most common and debilitating complications of surgery. The risk of SSI rises if the patient has underlying health-related risk factors. This article reports on the complicated case of 61-year-old female with a history of obesity and diabetes. She was diagnosed with end-stage renal disease (ESRD) and had been receiving haemodialysis since 2012. She underwent a kidney transplant and developed a multidrug-resistant Pseudomonas aeruginosa SSI following surgery. She experienced delayed wound healing with a partially dehisced incision. Despite conventional wound care, there was no progress in wound healing. The authors combined sharp debridement, irrigation and antibiotic therapy with a silver-containing antimicrobial dressing for 1 month. Her SSI improved significantly and she returned to theatre for wound closure. The patient recovered well and was discharged from the hospital after suture removal. Wound care professionals can use combination therapies to manage SSIs effectively and reduce patient and healthcare costs.

Background: Drug-laboratory (lab) interactions (DLIs) are a common source of preventable medication errors. Clinical decision support systems (CDSSs) are promising tools to decrease such errors by improving prescription quality in terms of lab values. However, alert fatigue counteracts their impact. We aimed to develop a novel user-friendly, evidence-based, clinical context-aware CDSS to alert nephrologists about DLIs clinically important lab values in prescriptions of kidney recipients., Methods: For the most frequently prescribed medications identified by a prospective cross-sectional study in a kidney transplant clinic, DLI-rules were extracted using main pharmacology references and clinical inputs from clinicians. A CDSS was then developed linking a computerized prescription system and lab records. The system performance was tested using data of both fictitious and real patients. The "Questionnaire for User Interface Satisfaction" was used to measure user satisfaction of the human-computer interface., Results: Among 27 study medications, 17 needed adjustments regarding renal function, 15 required considerations based on hepatic function, 8 had drug-pregnancy interactions, and 13 required baselines or follow-up lab monitoring. Using IF & THEN rules and the contents of associated alert, a DLI-alerting CDSS was designed. To avoid alert fatigue, the alert appearance was considered as interruptive only when medications with serious risks were contraindicated or needed to be discontinued or adjusted. Other alerts appeared in a non-interruptive mode with visual clues on the prescription window for easy, intuitive notice. When the system was used for real 100 patients, it correctly detected 260 DLIs and displayed 249 monitoring, seven hepatic, four pregnancy, and none renal alerts. The system delivered patient-specific recommendations based on individual lab values in real-time. Clinicians were highly satisfied with the usability of the system., Conclusions: To our knowledge, this is the first study of a comprehensive DLI-CDSS for kidney transplant care. By alerting on considerations in renal and hepatic dysfunctions, maternal and fetal toxicity, or required lab monitoring, this system can potentially improve medication safety in kidney recipients. Our experience provides a strong foundation for designing specialized systems to promote individualized transplant follow-up care.

Candidiasis is a major challenge among renal transplant recipients (RTRs) worldwide and is associated with high morbidity and mortality rates. Fluconazole is the most commonly used agent for Candida infections. However, frequent relapse and treatment failure are still reported among patients affected with this infection. In the present study, Candida species obtained from RTRs were characterized based on conventional and molecular assays. Furthermore, the antifungal susceptibility profiles of these species were determined. This study was conducted on a total of 126 RTRs within 2012-2016. The patients were categorized according to the referenced diagnostic criteria. The identification of Candida species was accomplished based on conventional examination, assimilation profile test, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The minimum inhibitory concentrations (MICs) of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and caspofungin were determined based on the guidelines of Clinical and Laboratory Standards Institute. The patients with Candida infection were diagnosed with urinary tract candidiasis (n = 17), peritonitis (n = 8), intra-abdominal candidiasis (n = 6), candidemia (n = 4), hepatosplenic candidiasis (n = 3), and Candida pneumonia (n = 3). A total of 41 Candida isolates, including C. albicans (n = 18), C. famata (n = 8), C. kefyr (n = 4), C. tropicalis (n = 4), C. parapsilosis (n = 3), C. glabrata (n = 2), and C. lusitaniae (n = 2), were isolated from 32.5% (41/126) renal transplant recipients. Fluconazole-resistance was observed in seven isolates, entailing C. albicans (n = 6) and C. tropicalis (n = 1). Fluconazole MIC for C. lusitaniae isolates was above the epidemiologic cut-off value (4-16 μg/ml). Furthermore, MIC range values of fluconazole against C. famata and C. kefyr were obtained as 4-32 μg/ml and 4-8 μg/ml, respectively. Posaconazole exhibited potent activity against Candida isolates, followed by caspofungin. The identification of Candida species, together with susceptibility testing, provides important data about the geographic trends of the fluconazole-resistance profiles of Candida species. It is necessary to maintain a consistent method for the implementation of early diagnosis and adoption of treatment regimen., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Receiving a kidney transplant from donors with multiple renal arteries (MRAs) is suggested to be associated with higher risk of vascular and urologic complications and poor allograft outcomes compared to the donors with single renal artery (SRA). We evaluated survival rates in the recipients from donors with MRAs compared to those from donors with SRA., Materials and Methods: In a retrospective study on 115 kidney allograft recipients, demographic characteristics and the outcomes of kidney transplantation were compared between the recipients from donors with MRAs compared to those from donors with SRA. These included acute tubular necrosis, acute allograft rejection, hypertension, vascular complications, urologic complications, kidney function indicators, and allograft survival at 1 year., Results: There was no significant difference in the recipients' age, sex distribution, and weight, donors' age, donor-recipient familial relation, urologic complications, and duration of hospitalization between the two groups. However, MRA was significantly associated with a higher likelihood of right-side kidney donation, longer warm and cold ischemia times, and lower glomerular filtration rate and higher serum creatinine concentrations at discharge and 12 months after transplantation, as compared to SRA transplants. No significant difference was seen in late complications including hypertension and renal artery stenosis. One-year graft survival was slightly poorer in the MRA group than the SRA group., Conclusions: Our results demonstrate that kidney allografts with MRAs are associated with risks but have acceptable outcomes during the 1st year after transplantation, as compared to SRA kidney allografts.

Kaposi's Sarcomas (KS) have been associated with many conditions and also known as a typical complication of immunosuppression. It should be considered as an important differential diagnosis in skin lesions of patients after solid organ transplantation. This is a report of a 61-year-old man, who presented with disseminated KS and a history of renal transplantation. We suggest systemic evaluation and visceral assessment in patients with Cutaneous KS.

After renal transplantation approximately forty percent of patients with membranous glomerolunephritis (MGN) had a recurrence, most commonly during the first year.We present two cases with recurrent MGN after kidney transplantation who successfully treated with ritoximab.

Chronic Myelogenic Leukemia (CML) is a rare malignant disorder after solid organ transplantation, especially in renal transplant recipients. Imatinib Mesylate is currently approved as first line treatment of CML. Most reports on CML are from kidney recipients who received azathioprine  in combination with cyclosporine and prednisolone as immunosuppressive therapy. We report a case with CML who was treated with Mycophenolate Mofetil.

Posttransplant lymphoproliferative disorder (PTLD) is a well-documented complication that arises as a result of immunosuppression in the setting of solid organ or bone marrow transplantation. The disorder may be subtle and/or extranodal. We report a patient with extranodal lymphoma following kidney transplantation who had successful treatment with surgery and chemotherapy.

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.

Decreased bone mineral density is a common problem after kidney transplantation. Osteoporosis has a major role in morbidity in these patients. We evaluated the incidence of osteoporosis and determined risk factors in 77 patients aged 17 to 50 years who had undergone renal transplantation 6 months to 2 years previously. Bone mineral densitometry was performed using dual-energy x-ray absorptiometry. The incidence of osteoporosis was 26% (20 of 77 patients). Mean (SD) age of affected patients was 34.6 (8.7) years. The most common sites of osteoporosis were the hip (osteoporotic in 19 patients [24.7%] and osteopenic in 42 [54.5%]) and the spine (osteoporotic in 6 patients [7.8%] and osteopenic in 52 [67.5%]). There was a significant relationship between posttransplantation creatinine concentration and hip osteoporosis (P = .01). No relationship was observed between osteoporosis and age, sex, body mass index, duration of hemodialysis therapy, cumulative dosage of any drugs, or use of pulsed methylprednisolone therapy. A hip or spine z score of 1 or less had no relationship to the number of steroid pulse sessions but was significantly related to the total dosage of cyclosporine (P < .001), prednisolone (P < .001), and mycophenolate mofetil (P < .05). A hip z score of less than 1 was related to the posttransplantation period (P = .02). In conclusion, osteoporosis is a frequent complication that requires detection and treatment to reduce morbidity.

Objectives: Full activation of T cells requires 2 distinct but synergistic signals. The first is the T-cell antigen receptor, which is antigen specific, and the second is activation of co-stimulatory signals. Active vitamin D (1, 25-dihydroxyvitamin D3) decreases T-cell activation and proliferation, inhibits differentiation and maturation of dendritic cells, and induces tolerogenic dendritic cells. These immunoregulatory effects may be due, at least in part, to changes in cytokine secretion and expression of co-stimulatory molecules. The use of active vitamin D has been reported to improve allograft survival, decelerate loss of allograft function, and prevent acute rejection. This study was conducted to assess the effect of active vitamin D on the expression of co-stimulatory molecules and HLA-DR in renal transplant recipients., Materials and Methods: In this prospective study, we enrolled 24 renal transplant recipients who had undergone a transplant 6 to 18 months earlier, had stable allograft function, and were without episodes of allograft dysfunction or febrile illness in the previous 2 months. Participants were administered oral calcitriol 0.5 micrograms daily for 4 weeks. Expression of HLA-DR, CD28, CD86, and CD40 in peripheral blood leukocytes was assessed by flow cytometry before and after calcitriol administration., Results: Compared to baseline levels, expression of HLA-DR decreased by 16.8%; expression of CD28, by 30%; of CD40, by 31.2%; and of CD86, by 36.7%., Conclusions: In renal transplant recipients, decreased expression of co-stimulatory and HLA-DR molecules occurred after treatment with active vitamin D. Such changes may be involved in increasing allograft survival.

Introduction: Kaposi's sarcoma (KS) is one of the most common tumors to occur in kidney recipients, especially in the Middle East countries. Limited data with adequate sample size exist about the development of KS in living kidney recipients., Methods: Therefore, we made a plan for a multicenter study, accounting for up to 36% (n = 7,939) of all kidney transplantation in Iran, to determine the incidence of KS after kidney transplantation between 1984 and 2007., Results: Fifty-five (0.69%) recipients who developed KS after kidney transplantation were retrospectively evaluated with a median follow-up of 24 (1-180) months. KS occurred more often in older age when compared to patients without KS (49 +/- 12 vs. 38 +/- 15 years, P = 0.000). KS was frequently found during the first 2 years after transplantation (72.7%). Skin involvement was universal. Furthermore, overall mortality rate was 18%, and it was higher in patients with visceral involvement compared to those with mucocutaneous lesions (P = 0.01). However, KS had no adverse affect on patient and graft survival rates compared to those without KS. Forty-four patients with limited mucocutaneous disease and four with visceral disease responded to withdrawal or reduction of immunosuppression with or without other treatment modalities. Renal function was preserved when immunosuppression was reduced instead of withdrawn in patients with and without visceral involvement (P = 0.001 and 0.008, respectively)., Conclusion: The high incidence of KS in this large population studied, as compared to that reported in other transplant patient groups, suggests that genetic predisposition may play a pathogenetic role.

Introduction: Limited data with adequate sample size exist on the development of posttransplant lymphoproliferative disorder (PTLD) in living donor kidney recipients. We conducted a retrospective cohort study on the data of 10 transplant centers to identify the incidence of PTLD in Iran., Materials and Methods: Data of 9917 kidney transplant recipients who received their kidneys between 1984 and 2008 were reviewed. Fifty-one recipients (0.5%) who developed PTLD were evaluated with a median follow-up of 47.5 months (range, 1 to 211) months., Results: Patients with PTLD represented 24% of all posttransplant malignancies (51 out of 211 cases). There was no relationship between PTLD and sex (P = .20). There were no statistically significance differences considering the age at transplantation between patients with and without PTLD. The late-onset PTLD (70.6%) occurred more frequently compared to the early form. There was no signification relationship between early-onset and late-onset groups in terms of clinical course and outcome. In patients who received azathioprine, PTLD was more frequent when compared to those who received mycophenolate mofetil (P < .001). The lymph nodes were the predominantly involved site (35.3%), followed by the gastrointestinal tract, brain, kidney allograft, lung, ovary, vertebrae, and palatine. Age at diagnosis and the time from transplantation to diagnosis were comparable for various involvement sites of PTLDs. The overall mortality in this series of patients was 51.0%., Conclusions: Posttransplant lymphoproliferative disorder is a rare but devastating complication and long-term prognosis can be improved with early recognition and appropriate therapy.

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.

Background: Current immunosuppressive therapies are effective to prevent acute rejection episodes (ARE) and graft loss following renal transplantation. Newer agents now make it possible to develop equally efficacious but better tolerated, less toxic strategies. We compared the efficacy of early low- versus high-dose cyclosporine (CsA) induction therapy in living donor renal transplantation., Methods: In this single-center study, 90 consecutive recipients of living donor kidney transplants between November 2002 to October 2003 including 51 females and mean average age of 48.23 years were treated with either CsA (5 mg/kg/d) plus mycophenolae mofetil (MMF; 30 mg/kg/d) and prednisolone (1 mg/kg/d; group 1; n=42); or CsA (8 mg/kg/d) plus MMF (30 mg/kg/d) and prednisolone (1 mg/kg/d; group 2; n=48). The 2 groups were matched with respect to age, sex, underlying renal diseases, pretransplantation dialysis period, number of transplantations, and panel-reactive antibody tests. CsA dose tapering was initiated in the 2 group 3 months after transplantation. At the end of the first year, the CsA dose was 3.5 +/- 0.65 mg/kg in group 1 and 3.4 +/- 0.34 mg/kg in group 2. Prednisolone was tapered within the first 2 months, reaching 10 mg/d in all patients. The MMF dose remained unchanged. The 2 groups were compared with respect to ARE, patient and graft survivals, and clinical outcomes within 2 years after transplantation., Results: There were no significant differences between the 2 groups with respect to clinical outcomes, including 2-year patient survival (97.62% vs 97.92%; P=.76), 2-year graft survival (80.32% vs 80.41%; P=.82), ARE (47.61% vs 52.08%; P=.09), or length of immediate postsurgical hospital stay, number of readmissions, total hospitalization days, posttransplantation diabetes mellitus, and infectious, cardiovascular, gastrointestinal, and hematologic complications. There was more hypertension (67.5% vs 50.23%; P=.007), hypertriglyceridemia (45.5% vs 32.64%; P=.005), and elevated liver enzymes in group 2 (12.5% vs 7.14%; P=.018)., Conclusions: Compared with 8 mg/kg CsA induction therapy, the lower doses of CsA were effective, well tolerated, and safe with relatively fewer side effects.

Introduction: Renal transplantation recipients are at a high risk of developing tuberculosis (TB) following transplantation, especially in developing countries, with high incidences of morbidity and mortality. In this report, we examined the risk factors and impact of TB on the outcome of kidney transplantation., Patients and Methods: Among 1350 living donor Iranian kidney transplantations, 52 (3.9%) had TB diagnosed in various organs. Of these, 7 (13.5%) had TB pretransplantation and 40 (76.9%) were men. The overall mean age was 32.6 +/- 10.5 years., Results: The interval between transplantation and diagnosis was 54.6 +/- 48.23 (range 4 to 140) months. In 34 (65.6%) patients TB was diagnosed after the first year posttransplantation. Pleuro/pulmonary TB was the most common form (68%). All posttransplant TB patients received a quadriple antituberculosis therapy; pyrazinamide, rifampicin, ethambutol, and isoniazide). Hepatotoxicity was seen in 16 (30%) patients, including 12 mild cases with normalization after temporary withdrawal of isoniazide and rifampicin, and four were severe, but mortality was not attributable to hepatocellular failure. Twelve patients (23%) died. Chronic allograft dysfunction occurred in 34 (65%) patients, 19 (37%) with graft loss. Pre-TB patients showed comparable posttransplant courses., Conclusion: TB is a common infection among renal transplant recipients in developing countries. The peak incidence is after the first year of transplantation and mortality is considerable. Hepatoxicity is a considerable risk of treatment, possibly as a result of additive toxic effects of immunosuppressive drugs. Chronic allograft nephropathy is a serious complication that has a negative impact on the graft survival.

The long-term risk of malignancy among renal transplant patients is approximately 100 times that of the general population. Unlike North America and many European countries, Kaposi's sarcoma is the most common cancer after renal transplantation in most series reported from the Middle East. Human herpes virus-8 (HHV-8) has a major role in the pathogenesis of Kaposi's sarcoma. The risk of posttransplantation Kaposi's sarcoma is 23% to 28% among seropositive patients compared with 0.7% among seronegative patients. This study was conducted to investigate the seroprevalence of HHV-8 among our transplant recipients. The sera from 100 renal transplant recipients were examined by indirect immunofluorescence against latent nuclear antigen. Sixty of 100 patients were males. The overall mean age was 41.1 years (range, 17-74 years) with 17 patients older than 55 years. The mean transplantation duration was 41.6 months. Twenty-five percent of patients were seropositive for HHV-8. There was statistically significant seropositivity for HHV-8 among recipients older than 55 years (P=.02). Eight of 17 patients older than 55 years were seropositive (47%), whereas 17/83 patients younger than 55 years were seropositive (20%). There were no significant differences for HHV-8 seropositivity regarding sex, transplantation duration, and immunosuppressive regimen, including dose of immunosuppressive drugs and cyclosporine blood levels. In this study, we showed seropositivity for HHV-8 among a significant percentage of our renal transplant recipients, a finding which may render them at risk to develop Kaposi's sarcoma. Seropositive and seronegative patients were followed for 16 months. One HHV-8 seropositive patient (1/25) developed Kaposi's sarcoma.

Despite numerous studies, the precise role of Th1/Th2 cytokines in acute renal allograft rejection remains unclear. To provide insight into the role of cytokines in acute allograft rejection, we measured serum T-cell cytokine concentrations for correlation with clinical events after renal transplantation in adults. Serum Th1 (interleukin-2 [IL-2] and interferon-gamma [IFN gamma] and Th2 (IL-4, IL-10) cytokine concentrations were measured in 60 consecutive living donor kidney transplant recipients namely, 40 males, overall mean age 38.82 years), on the day before as well as 7 and 14 days posttransplantation using ELISA. Patients were stratified based upon acute rejection episode (ARE) in the first month after transplantation. Immunosuppression consisted of cyclosporine, mycophenolate mofetil, and prednisolone. ARE was diagnosed based on an increased plasma creatinine of more than 50%, sonographic analysis, radioisotope scan, pathologic findings, or measured cyclosporine blood levels. Twelve ARE were diagnosed among patients (20%). There was no significant difference between the 2 groups with respect to the mean serum concentration values of IL-2, IL-10, IL-4, and IFN gamma on the day before or 7 or 14 days after transplantation. This study showed that there was no correlation between the Th1/Th2 serum cytokine profiles and early ARE in living donor kidney transplantation.