Cellular immunity survey against urinary tract infection using pVAX/fimH cassette with mammalian and wild type codon usage as a DNA vaccine

PURPOSE: FimH (the adhesion fragment of type 1 fimbriae) is implicated in uropathogenic Escherichia coli (UPEC) attachment to epithelial cells through interaction with mannose. Recently, some studies have found that UPEC can thrive intracellularly causing recurrent urinary tract infection (UTI). Almost all vaccines have been designed to induce antibodies against UPEC. Yet, the humoral immune response is not potent enough to overcome neither the primary UTI nor recurrent infections. However, DNA vaccines offer the possibility of inducing cell mediated immune responses and may be a promising preventive tool. MATERIALS AND METHODS: In this study, we employed two different open reading frames within mammalian (mam) and wild type (wt) codons of fimH gene. Optimized fragments were cloned in pVAX-1. Expression of the protein in COS-7 was confirmed by western blot analysis after assessing pVAX/fimH(mam) and pVAX/fimH(wt). The constructs were injected to BALB/c mice at plantar surface of feet followed by electroporation. RESULTS: The mice immunized with both constructs following booster injection with recombinant FimH showed increased interferon-gamma and interleukin-12 responses significantly higher than non-immunized ones (p<0.05). The immunized mice were challenged with UPEC and then the number of bacteria recovered from the immunized mice was compared with the non-immunized ones. Decreased colony count in immunized mice along with cytokine responses confirmed the promising immune response by the DNA vaccines developed in this study. CONCLUSION: In conclusion, DNA vaccines of UPEC proteins may confer some levels of protection which can be improved by multiple constructs or boosters.

Change of cyclosporine absorption over the time after kidney transplantation

Although the immunosuppressant cyclosporine [CsA] is widely used after kidney transplantation over the long term, there is still no firm consensus on the best way to monitor of CsA blood levels. Cyclosporine [CsA] assay is critical for the management of renal transplant recipients due to inter- and intra-patient variation in CsA absorption and metabolism. Patients and In a retrospective cross sectional study, blood levels of CsA [through and 2 hours post dose] measured at least 5 times during 3 years post transplantation, in 7702 kidney transplant recipients from different transplant center of Tehran, IR Iran between 2008 and 2012. Cyclosporine absorption [CA] calculated C2/CO ratio. CA had a significant correlation with allograft function [P = 0.000, r =.0.285], this correlation was stronger than its relationship with CO and C2 blood levels [P = 0.000 and P = 0.000 as well as r = 0.033 and r = 0.090, respectively]. In univariate analysis during different times after transplantation, CO and C2 blood levels significantly decreased over three years follow up [P = 0.000], [P = 0.000]; While, CA reversely increases over the time [P = 0.000]. In linear regression model overall CA levels had correlation with lower age of recipient [P = 0.02], hypokalemia [P = 0.001], higher level of creatinine [P = 0.02] and triglyceride [P = 0.001]. The present study shows that CsA absorption changes trough the post-transplant time and appears to increases over time in long-term period after kidney transplantation

Impact of cigarette smoking on kidney transplant recipients. a systematic review

Cigarette smoking has adverse effects on kidney transplant recipients, causing cardiovascular disease, kidney function impairment, and cancer. However, there are surprisingly few studies on the impact of cigarette smoking among kidney transplant recipients and its consequences after transplantation. We performed a systematic review of the literature to identify the effects of cigarette smoking on patient and graft survival rates among kidney transplant recipients. We searched the PubMed from 1968 to 2009 to identify studies on the effect of cigarette smoking on kidney transplant recipients, using the following keywords: kidney transplantation, cigarette, smoking, tobacco, and nicotine. The electronic and manual searches yielded 357 articles, of which 39 were considered potentially relevant by titles and abstracts and were selected for full text review. Twenty-seven irrelevant reports were excluded. A total of 12 papers were selected for review, comprising of 1801 kidney transplant recipients with a history of smoking. The impact of cigarette smoking on kidney recipient survival was only evaluated by 6 studies and the relative risk of smoking for death was available in 3 reports, varying between 0.8 and 2.2. Cigarette smoking was an independent risk factor for patient death. In addition, on univariable and multivariable analyses, graft survival correlated with a history of cigarette smoking and the relative risk for graft failure ranged from 1.06 to 2.3. Cigarette smoking was associated with an increased risk of death and graft loss. Therefore, every attempt should be made to encourage kidney transplant candidates to stop smoking

[Optimization of extraction and amplification of microRNAs [mir-21, mir-141 and mir-205] in urine samples of patients with bladder cancer]

The current methods for bladder cancer diagnosis suffer from low sensitivity and specificity. Therefore, finding a novel tumor markers with high specificity and sensitivity is of great interest. MicroRNAs [miRNA, miR] are small endogenously-produced, non-coding RNAs with an important role in regulating gene expression. Recent studies show that miRNAs expression profiles represent significant tumor-specific changes that are unique for most cancers. The aim of this study was to optimize miRNA containing total RNA extraction from urine and use it as a reliable and repeatable technique for miRNA detection in urine of patients with bladder cancer. Total RNA was extracted from the urine of patients with bladder cancer and normal individuals using RNX and Trizol solutions with and without modifications of original protocols. Real-time quantitative RT-PCR was then used to detect miRNAs with a potential link to bladder tumorigenesis. RNX and the modified Trizol are practical methods for RNA extraction from urine samples. The mir-21 amplification of the extracted RNAs using modified Trizol method was more efficient than that of RNX method. It is noteworthy that, the levels of miRNAs expression were much higher in the frozen urines compared to the fresh ones. We have succeeded to set-up a protocol to easily amplify miRNAs in urine samples. Based on the data, microRNAs seem to be good biomarkers for early detection and screening of bladder cancer

impact of hepatitis C virus infection on kidney transplantation outcomes: a systematic review of 18 observational studies

Hepatitis C virus [HCV] infection occursin 0% to 51% of dialysis patients, and many HCV-positive patients are urged to undergo kidney transplantation. However, the outcome of renal transplantation in HCV-positive recipients is unknown. Our review aimed to address the outcomes of renal transplantation recipients [RTRs] following kidney transplantation. We selected studies that used the adjusted relative risk [aRR] and 95% CI of all-cause mortality and graft loss in HCV-positive compared with HCV-negative RTRs as study endpoints. Cox proportional hazard analysis was usedin all studies to calculate the independent effects of HCV infection on RTR outcomes. Sixteen retrospective cohort studies and 2 clinical trials were selected for our review. Sixteen studies were related to patient survival, and 12 examined graft survival. The combined hazard ratio in HCV-infected recipients was 1.69-fold [1.33-1.97, p< 0.0001] and 1.56 times [1.22-2.004, p < 0.0001] greater than that of HCV-negative recipients for mortality and graft loss, respectively. Although HCV-infected RTRs have worseoutcomes than HCV-negative RTRS, kidney transplantation is the preferred treatment for patients with HCV infection and end-stage renal disease

Hepatitis C virus infection and kidney transplantation. a review for clinicians

Hepatitis C virus [HCV] infection is frequent among kidney transplant recipients, and it is currently the major cause of chronic liver disease following kidney transplantation. The presence of HCV infection has been found to negatively affect the morbidity and mortality rates in patients on dialysis, as well; it seems that kidney transplantation is a reasonable treatment option after a careful pretransplant evaluation. Nevertheless, there are several questions about the indications of kidney transplantation, pretransplant evaluation, transplantation from HCV-infected donors, patient and graft survival rates, and kidney diseases associated with hepatitis C virus after kidney transplantation. This review deals with the most current information on pretransplant and posttransplant evaluations, complications, treatment, and prognosis of HCV-infected kidney transplant recipients

Socioeconomic links to health-related quality of life, anxiety, and depression in kidney transplant recipients

The impact of socioeconomic status on the chance of being a candidate of kidney transplantation and its effect on graft survival has been documented. Our aim was to investigate the association of socioeconomic status with kidney allograft recipients' health-related quality of life and level of anxiety and depression. Two hundred and forty-two kidney transplant recipients were categorized according to their monthly family income into low-income, moderate-income, and high-income groups. These groups were compared in terms of health-related quality of life [short form-36] and level of anxiety and depression symptoms [hospital anxiety depression scale]. There was a trend of higher HRQOL scores in association with a higher income, which was significant for the total HRQOL score and its subdomains of physical function and role limitation due to physical and emotional problems. A slight increase in anxiety symptom scores was also seen in kidney recipients with lower incomes; however, the depression symptom scores were not significantly different between the income groups. Logistic regression analysis showed that the impact of income on the total HRQL and anxiety symptoms scores remained significant after controlling the effect of age, sex, and time interval from transplantation. A significant proportion of our kidney allograft recipients had a low income and had a poorer health-related quality of life and a greater load of anxiety according to their perception of their status, compared to those with higher incomes. Special consideration to kidney transplant recipients with a lower income may improve their wellbeing

Posttransplant lymphoproliferative disorders in kidney transplant recipients. An Iranian multicenter experience

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. 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. 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%. Posttransplant lymphoproliferative disorder is a rare but devastating complication and long-term prognosis can be improved with early recognition and appropriate therapy

Outcome of kidney transplantation in type 1 and type 2 diabetic patients and recipients with posttransplant diabetes mellitus

We aimed to assess the effects of different types of diabetes mellitus [DM] on patients receiving living donor kidney allografts. A total of 111 kidney transplant patients with DM and 111 randomly selected kidney transplant recipients without DM were enrolled in the study. The characteristics of the kidney allograft recipients and the allograft and patient outcomes were assessed and compared between 4 groups of kidney recipients without DM and patients with type 1 DM, type 2 DM, and posttransplant DM. Of the 111 patients with DM, 36 [32.4%], 20 [18.0%], and 55 [49.6%] had been diagnosed with type 1 DM, type 2 DM, and posttransplant DM, respectively. Diabetic patients had significantly higher rates of rejection episodes [P = .049] and suffered more frequently from delayed graft function [P = .03] compared to the kidney recipients in the control group. Patient and allograft survival rates were significantly lower in the patients with DM [regardless of their DM type] compared to the nondiabetic patients [P = .03 and P = .04, respectively]. Prominently, type 1 DM had significantly adverse effects on patient and allograft survival. Patients with posttransplant DM had a relatively better patient survival compared to those with type 1 DM and type 2 DM. We found that kidney recipients with DM, especially preexisting DM, had worse patient and graft survival rates compared to the nondiabetics. These findings suggest that kidney transplant patients presenting with any type of DM should be more closely followed

Kaposi sarcoma after kidney transplantation

Skin cancers are the most common tumors among transplant recipients who receive immunosuppressive agents. Kaposi sarcoma [KS] is one of the most common malignancies to occur in kidney transplant recipients, especially in the Middle East countries. Its prevalence in comparison with other neoplasms is also relatively higher in Iran [> 35%]. The KS-associated herpesvirus or human herpesvirus 8 is a newly discovered herpesvirus found in all forms of the KS including those among immunosuppressed transplant recipients. Kaposi sarcoma usually regresses after withdrawal or reduction of immunosuppressive agents. A wide variety of therapies have been used for KS, including radiotherapy and administration of interferon and different chemotherapeutic regimens. Sirolimus exhibits antiangiogenic activity related to impaired production of vascular endothelial growth factor and limited proliferative response of endothelial cells to the stimulation by vascular endothelial growth factor. Therefore, it can inhibit the progression of KS. Accordingly, replacement of calcineurin inhibitors by a sirolimus can show promising results in the prevention of KS

Successful treatment of infective endocarditis in four kidney transplant recipients

Infective endocarditis [IE] is a serious complication in kidney transplantation, leading to graft loss and a high mortality rate. We report 4 successfully managed cases of IE in kidney transplant recipients. Blood culture revealed Enterococcus in 2 patients, group D Streptococcus in 1, and no bacteria in 1. All of the patients were diagnosed based on at least 2 major Duke criteria for diagnosis of IE. Although a mild increase in the serum creatinine level was observed in 3 out of 4 patients, no graft rejection occurred during the follow-up. Early diagnostic and therapeutic intervention, particularly intensive antibiotic therapy and surgical management can preserve the patient and the kidney allograft. Studies on previous recurrent infections and simultaneous diseases such as cytomegalovirus in these patients are warranted

Nephrology research output in Iran in a decade

We performed a bibliometric search to evaluate the number of papers written by the Iranian nephrologists. We considered all peer-reviewed articles published by nephrologists in biomedical journals quoted by the Medline database and the IranMedex [an Iranian database for indexing medical articles of local journals] between 1997 and 2007. The findings were analyzed according to the university from which the publication was originated, field of study, type of work, specialty of the first author [nephrologist or nonnephrologist], type of journal [indexed or nonindexed in Medline], total number of publications, the annual and 10-year collaboration rate of the Iranian nephrologists, and publications per faculty members of medical institutions. The total number of publications in the field kidney disease was 579 [average of 58 papers per year]. There was an increasing trend in the number of publications over the years. More than 56% of the publications [324] were in the internationally recognized journals that were indexed in the Medline. The majority of the papers were concerned with transplantation [58.3%], nephrology [20.0%], and hemodialysis [16.8%]. Of all the publications traced in this study, 67.5% were retrospective articles, whereas the proportion of clinical trials was relatively small [6.1%]. Iran's contribution to the research on kidney disease is not satisfactory in terms of the volume and quality of publications. On the other hand, the data suggest that there was a significant research activity in the field of kidney transplantation during the studied period

Prediction of rejection in renal transplantation by immune parameters

Monitoring of phenotypic characteristics of T-lymphocytes in peripheral blood is commonly performed to give the clinical parameters in the management of kidney transplant recipients. To predict rejection in renal transplantation by immune parameters. 16 non-diabetic kidney transplant candidates [4 females and 12 males, age = 20-65 yr,-first time transplant] were selected. The transplanted patients were divided into two groups based on the rejection during 3 weeks post transplant: group I [n = 9] without rejection and group II [n = 7] with a rejection episode. Immune parameters including lymphocytes subpopulations [by flowcytometry] and immunoglobulin classes [IgM, IgG, IgA and IgE by nephlometric assay] before and 45 days after transplantation were determined. The results of this investigation showed that the level of immunoglobulin IgG, IgM, IgA and IgE decreased post transplantation due to immunosuppressive drugs. CDS, CD4, CDS T cells count, CD56 NK cells count and CD20 B cells count pre- and post-transplantation did not show any significant differences. The amount of IgE [220 vs. 462 Ill/ml], CDS [62% vs. 69.7%] and CD4 [35% vs. 41.3%] cells increased in group II during rejection episode pre-transplantation. In addition, IgA increased pre-transplantation in group I those without rejection episode in comparison with group II with a rejection episode. Forty five days post transplantation IgA [209 vs. 152 mg/dl], IgG [1009 vs. 703 mg/dl] and CD20 [15% vs. 10%] increased in group 1 patients. It is suggestive that pre-transplantation increases IgE, CDS and CD4 are predictive of acute rejection