Prevalence of Transfusion-transmitted Virus (TTV) Infection and its Association with Renal Post-transplantation Complications in Iran.

BACKGROUND: Transfusion-transmitted virus (TTV) is a single-stranded DNA virus. Renal transplant patients have a higher risk of TTV infection. OBJECTIVE: To evaluate the prevalence of TTV and its correlation with post-renal transplantation complications in a population of Iranian patients. METHODS: A cross-sectional study was performed on 120 renal transplant recipients. TTV infection in the peripheral blood samples was detected by semi-nested polymerase chain reaction (semi-nested PCR). Then, the relationship between TTV and renal post-transplant complications was examined. RESULTS: 34.2% renal transplant recipients were positive for TTV. There was a significant correlation between the presence of TTV and diabetes, acute transplant rejection, and urinary tract infection. We did not find any direct correlation between the presence of TTV infection and hypertension, hyperlipidemia, respiratory tract infection, and cytomegalovirus infection. CONCLUSION: We found an increased rate of TTV infection in renal transplant recipients associated with post-transplantation complications. TTV may be an important risk factor for some post-renal transplantation complications.

The Incidence of Cytomegalovirus Glycoprotein B Genotypes in Kidney Transplant Recipients in Iran.

BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic viral infection in kidney transplant recipients. CMV classification is usually based on its glycoprotein B (gB) genotypes, which divides the virus into 4 strains (gB1-4). OBJECTIVE: To determine the incidence of CMV genotypes in Iran and their relation to various clinical factors. METHODS: We studied 80 renal transplant recipients admitted to our transplant referral center between 2014 and 2015. All of the studied patients were monitored every 1-2 weeks for CMV infection by immunofluorescence method. There were 34 CMV-infected patients whose sera were studied with sequencing technique to identify the 4 CMV genotypes. All patients were followed up to 6 months after transplantation. RESULTS: gB1 was the most common genotype (35.3%); it was followed by gB3 and gB4 (each with 17.6 %), gB2, and mixed gB1,3 and gB1,2 (each with 14.7%). Age (p=0.037), time of infection after transplantation (p=0.011), and biopsy-proven rejection (p=0.012) were associated with CMV genotype. After adjusting for covariates, significant associations were found between genotype gB1 and family relationship (p=0.047) as well as HLA mismatch (p=0.014); genotype gB3 and family relationship (p=0.011); and genotype gB4 and age (p=0.019). CONCLUSION: The most common CMV gB genotype in CMV-infected kidney transplant recipients in Iran was gB1. We recommend considering related therapeutic applications in the management of such patients.

Kidney Allograft Stone after Kidney Transplantation and its Association with Graft Survival.

BACKGROUND: It is said that renal transplantation lithiasis is rare. However, literature has some different frequencies in this field and most of the studies related to this issue are case reports. Also the exact effect of this complication on the graft survival rate is not clear. OBJECTIVES: To determine the prevalence of nephrolithiasis among kidney transplant recipients and evaluate its association with the graft survival. METHODS: We conducted a retrospective study to determine the prevalence of renal stone among 574 kidney transplant patients aged ≥18 years who had undergone renal transplantation in Baqiyatallah Transplant Center between 1990 and 2010. Cox regression analysis was used to determine the effect of renal stone on the graft survival. RESULTS: The mean±SD follow-up time was 55±53 months. Kidney stones were diagnosed in 31 (4.4%) of all 574 kidney transplants studied. Cox regression analysis revealed that nephrolithiasis after transplantation had no significant effects on the survival of the transplanted kidney (OR 1.04, CI: 0.708-1.54). CONCLUSION: For the first time, we showed that nephrolithiasis in recipients does not have a significant effect on the transplant survival.

Evaluation of ganciclovir resistance in cytomegalovirus infection of renal transplant recipients in Tehran.

BACKGROUND: Human cytomegalovirus (CMV) infection is a major issue in solid organ transplant recipients. Although development of prophylaxis and preemptive procedures have presented significantly improved consequences in CMV infection, increasing incidence of antiviral resistance has raised virologists' concern. METHODS: The present study focused on kidney transplant recipients with high quantities of CMV load after antiviral therapy. We collected 5 mL blood from each of 58 patients. DNA extraction was performed with the use of the QIAamp DNA Mini kit (Qiagen), in accordance with the manufacturer's instructions. RESULTS: Our population study was 38% female and 62% male. CMV DNA was observed in 50 specimens (86%) with the range of 1.9 × 10(3) to 11 × 10(7) copies/mL serum. All of these patients had received ganciclovir for >3 months. Sequencing showed 18 mutations in 10 patients. Among these, 16 mutations were associated with Ul97 and the rest with Ul54 gene. Forty CMV-positive patients did not show any mutations. CONCLUSIONS: The consequences of long-term ganciclovir resistance could not be determined.

Prevalence and risk factors of hyperuricemia among kidney transplant recipients.

Hyperuricemia is common in renal transplant patients (RTRs), especially those on cyclosporine (CsA)-based therapy. We conducted a retrospective study to determine the prevalence of hyperuricemia and its risk factors among RTRs. A total of 17,686 blood samples were obtained from 4,217 RTRs between April 2008 and January 2011. Hyperuricemia was defined as an uric acid level of ≥7.0 mg/dl in men and of ≥6 mg/dl in women that persisted for at least two consecutive tests. Majority (68.2%) of RTRs were normouricemic. Hyperuricemia was more frequent in younger and female RTRs. On multivariate logistic regression, we found high trough level of cyclosporine to be a risk factor for hyperuricemia. In addition, female gender, impaired renal function, and dyslipidemia (hypercholesterolemia, hypertriglyceridemia, and elevated LDL) were also associated with higher probability of hyperuricemia. Hyperuricemia is a common complication after renal transplantation. Risk factors implicated in post-transplant hyperuricemia include high trough level of cyclosporine, female gender, renal allograft dysfunction, and dyslipidemia.

Association of nonalcoholic fatty liver disease (NAFLD) with urolithiasis.

OBJECTIVE: The NAFLD is related to metabolic disorders and is negatively associated with kidney function. Renal stone disease (urolithiasis) is an increasing form of a common renal disease that is a multifactorial disorder influenced by both intrinsic and extrinsic, mainly environmental factors. The association between the fatty liver and renal calculi, as a specific underlying risk factor, has received no attention, so far. Therefore, in this study, a possible relationship between fatty liver with renal calculi and urolithiasis is investigated. METHODS: In a cross sectional study, a total of 11245 ultrasonography reports revealing the condition of fatty liver, kidney stones (urolithiasis), or a combination of both of them, were categorized and evaluated statistically. Descriptive statistics determined the number (frequency and percentage) of each condition. The statistical significance of the association between fatty liver and kidney stone, and vice versa, was evaluated using McNemar's test. The Chi Square Test assessed the relationship between genders. Odds ratios and 95% confidence intervals (95% CI) assessed the likelihood of characteristics of urolithiasis for fatty liver patients. RESULTS: We found 8% frequency of urolithiasis among subjects with healthy liver. NAFLD was identified in 30%, while urolithiasis in 11% subjects from all individuals studied. The present study diagnosed urolithiasis in 17% of patients with fatty liver. Its occurrence was more common in men than women. Data revealed more common diagnosis of fatty liver (48%) in patients with urolithiasis, which was also higher in males than females. The higher NAFLD was linked with urolithiasis, indicating a greater chance of their association. Interestingly, the detection frequency of urolithiasis in the patients with NAFLD was also markedly higher (odds ratio: 2.4, 95% CI 2.1-2.7). The NAFLD appears to be an independent variable as a risk factor for stone formation. CONCLUSIONS: The present study indicates that the prevalence of urolithiasis is significantly higher in the NAFLD than healthy subjects. This result suggests that NAFLD may be involved in the mechanism of the onset of the urolithiasis. It is suggested that lipid peroxidation, oxidative stress and changes in the urinary constituents in the NAFLD may be considered as a risk factor in the progression of stone formations.

Dynamic Changes of IFN-γ-producing Cells, TGF-ß and Their Preidctive Value in Early Outcomees of Renal Transplantation.

BACKGROUND: A growing body of evidence demonstrated an immune etiology as well as nonimmune mechanisms for episodes of clinical acute rejection and long-term allograft dysfunction. OBJECTIVE: To investigate the correlation of IFN-γ-producing cells and TGF-ß with incidence of clinical acute rejection in living-related and unrelated kidney allogarft recipients during the first post-transplant year. METHODS: This multi-center study was performed on 57 kidney allograft recipients from living-related (n=20) and unrelated (n=37) donors between April 2011 and September 2012 and who were followed prospectively for a mean period of one year. Peripheral blood samples were collected from all patients pre-transplantation and at days 14, 30 and 90 after transplantation; PBMCs were used as responding cells in enzyme-linked immunosorbent spot (ELISPOT) assay to measure the frequency of IFN-γ-producing cells after stimulation with donor lymphocytes. Additionally, TGF-ß levels were measured in cell culture supernatants of ELISPOT assay. RESULTS: During the follow-up period, 45 (79%) patients were diagnosed with stable graft function (group A); 12 (21%) experienced clinical acute rejection episodes (group B). The frequency of IFN-γ-producing cells was significantly (p<0.001) higher in the rejection group in all three times after transplantation. Also, post-transplantation comparison for TGF-ß showed a significantly (p<0.001) higher contents in group A vs. group B. Comparing the post-transplantation levels of TGF-ß and mean numbers of IFN-γ- producing cells between groups A and B demonstrated a continuous increment in TGF-ß and decreasing frequencies of IFN-γ-producing cells in group A vs. group B. CONCLUSION: Serial post-transplantation monitoring of IFN-γ-producing donor reactive cells during the first months is a clinically feasible approach for identification of kidney allogarft recipients at risk for ongoing immune-mediated graft damage and later graft loss.

National strategies of ophthalmic education in iran.

BACKGROUND: Academic medicine is in a state of dramatic transformation. For this reason strategic thinking is the most essential part of educational planning. The main purpose of the present study was developing the strategic educational planning of Ophthalmology in Iran from 2007 to 2010 METHODS: A qualitative investigation using focus group discussion has been implemented successfully for developing educational planning. Six to twelve representatives of key stakeholders in the ophthalmic education of Iran participated to this study. RESULTS: Strengths, weaknesses, opportunities and threats of ophthalmology education in Iran were analyzed. Strategic goals in education, research, and health service providing domains were being developed. Educational goals were defined as training of human resources in accordance with the community needs at the level of general practitioner, specialist, and fellowships in ophthalmology. Research goals of the program were defined as scientific inter-departmental and international communications, in order to promote the level of education, research, and treatment in the country. Also, in the field of health services according to the community needs, providing services by the means of advanced and cost effective methods were defined as strategic objectives. CONCLUSION: Based on this strategic plan in the last three years ophthalmic education in Iran shall be many changes in educational, research and health care provision for social accountability.

Hyperuricemia beyond 1 year after kidney transplantation in pediatric patients: Prevalence and risk factors.

Hyperuricemia is frequent among adult renal transplant recipients; however, data among pediatric kidney recipients are scarce. This study is designed to estimate the prevalence and risk factors of late post-transplant hyperuricemia in pediatric recipients. A retrospective observational multicenter study on 179 pediatric renal recipients (5-18 years) was conducted between April 2008 and January 2011 from five kidney transplant centers of Tehran, Iran. All recipients were followed up for more than 1 year (5.9 ±3.3 years) after transplantation. A total of 17686 blood samples were obtained for serum uric acid (SUA). The normal range of SUA was defined as SUA 1.86-5.93 mg/dl for children between 2 and 15 years in both genders; 2.40-5.70 mg/dl for girls aged >15 years; 3.40-7.0 mg/dl for boys aged >15 and more than 6 and 7 mg/dl in boys and girls older than 15 years old. The median age of the children was 13 years. Male recipients were more popular than female (male/female 59/41%). Hyperuricemia was detected in 50.2% of patients. Mean SUA concentration was 5.9±1.7 mg/dl and mean SUA concentration in hyperuricemic patients was 7.7±1.2 mg/dl. While at multivariate logistic regression elevated serum creatinine concentration (P<0.001) and the time span after renal transplantation (P=0.02) had impact on late post-transplant hyperuricemia. High cyclosporine level (C0 and C2) was not risk factor for huperuricemia. Late post-transplant hyperuricemia was found in about half of pediatric renal recipients, and was associated with impaired renal allograft function.

Cytomegalovirus Infection following Kidney Transplantation: a Multicenter Study of 3065 Cases.

BACKGROUND: Cytomegalovirus (CMV) infection is a common complication following kidney transplantation. OBJECTIVE: To assess the incidence and risk factors of CMV infection among renal transplant recipients. METHODS: In a retrospective multicenter study, 3065 renal transplant recipients from 17 transplant centers of Iran were studied between April 2008 and January 2011. Kidney transplant patients were routinely monitored by sequential blood samples drawn for use in the CMV-pp65 antigenemia assay, and for hematological and biochemistry tests. RESULTS: 63% of studied patients were males; the mean±SD age of participants was 38±15 years. The majority of cases (81%) received a kidney from a living unrelated donor (LURD), 9% from living related donor (LRD), and 10% from deceased donors. 671 patients experienced CMV viremia. The incidence of CMV infection was 21.9% (95% CI: 20.4%-23.4%). The rate was higher in the first 6 months after transplantation (p<0.001); in recipients with higher level of cyclosporine (p<0.001); in those with lower hemoglobin concentration (p=0.02); patients with elevated ALT (p<0.001); those with increased fasting blood sugar (p=0.005); recipients with dyslipidemia (p<0.05); deceased kidney recipients (p=0.006); and patients with kidney graft impairment (p=0.01). In multivariate regression analysis, time since kidney transplantation (p<0.001) and renal allograft failure (p<0.001) were the only risk factors associated with CMV infection. CONCLUSIONS: CMV infection was a common complication in the first 6 months of kidney transplantation, particularly among patients with kidney graft impairment.

Electrolytes Disturbance and Cyclosporine Blood Levels among Kidney Transplant Recipients.

BACKGROUND: Kidney transplantation is associated with various biochemical abnormalities such as changes in serum blood level of sodium (Na), potassium (K), calcium (Ca), and phosphorous (P). Although cyclosporine (CsA) is used commonly, the prevalence of its side effects, including electrolytes disturbance, is not well understood. OBJECTIVE: To find the prevalence of electrolytes disturbance and its relation to CsA blood levels. METHODS: In a retrospective study, 3308 kidney transplant recipients transplanted between 2008 and 2011 were studied. We evaluated the relation between serum Ca, P, Na, K and CsA trough (C0) and 2-hour post-dose (C2) levels. RESULTS: The mean±SD age of recipients was 37±15 years; 63% of patients were male. Overall, C2 levels had correlation with Ca blood level (p=0.018; OR: 1.13, 95%CI: 1.02-1.25), C0 levels had also correlation with blood levels of P and Cr (p<0.001; OR: 1.83, 95% CI: 1.59-2.11). CONCLUSION: Electrolyte disturbances are prevalent. Higher serum levels of CsA can worsen the allograft function by disturbing the serum P and Ca levels.

Is the lower cyclosporine concentration at 2 hours after dosing safe in kidney transplant recipients?

OBJECTIVE: To determine the correlation between cyclosporine blood concentration at 2 hours after dosing (C2) and renal allograft function. MATERIALS AND METHODS: From 2008 to 2010, 1191 kidney transplant recipients (718 male and 473 female patients) were studied. The correlation between serum creatinine concentration and C2 blood concentration was stratified as 400, 600, 800, and 1000 ng/mL. RESULTS: The mean (SD) C2 was 620 (235) ng/mL, and serum creatinine concentration was 1.49 (0.68) mg/dL. At multivariate regression analysis, no significant correlation was observed between serum creatinine concentration and C2 blood concentrations of 600, 800, or 1000 ng/mL (P=.18, .57, and .76, respectively); however, it was associated at 400 ng/mL (P=.03). Moreover, 36.1% of 3159 samples demonstrated satisfactory renal allograft function despite low C2 blood concentration between 400 and 600 ng/mL. CONCLUSION: During maintenance therapy, C2 blood concentration between 400 and 600 ng/mL is effective and safe for providing prophylaxis against rejection, and can improve long-term survival by decreasing cyclosporine toxicity.