Tehran University Medical Journal

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Essential hypertension is one of the risk factors of cardiovascular diseases. Hypertension etiology is not completely known, it seems that rennin-Angiotensin system has an important role in its etiology, Thus better recognition of this system and its activity changes or vascular reaction changes to different parts of this system during progressive hypertension can be more effective in better recognition of the disease progress and treatment.
Materials and Methods: In this study responsiveness of mesenteric vessels of Goldblatt two kidney- one clip (2k-lc) renovascular hypertensive rats to angiotensin / and II with and with out captopril during a time of two , four , six and eight weeks after hypertension induction was investigated and compared with control and surgical sham groups.
Results: This study shows that vascular responsiveness to angiotensin // in animals that passed four weeks of their hypertension , (p< 0.05) and in the sixth and eight week of post induction hypertension (p< 0.01 and p< 0.001) has a significant different with both sham and control groups. Also it has been observed that an increased reaction to angiotensin II with an increased significant rate of arterial hypertension in hypertensive group. In the other hand in spite of inhibition of angiotensin converting enzyme by captopril in animals that have been eight weeks hypertension , on the contrary to other groups reactive to angiotensin /.
Conclusion: Results of this study show that vessels reaction to angiotensin /and II increased due to six to eight weeks post induction renal hypertension. Captopril does not inhibite mesenteric vessels reaction to Angiotensin / in hypertensive Rats after eight weeks. Try to completely inhibit production of angiotensin II maybe a hopful way in controlling essential hypertension.

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Background: Chang in the serum K+ level may increase perioperative morbidity and mortality in kidney transplant recipients. Thus this research was done with the aim of evaluated of K+ change in kidney transplant recipients. Hence the following study was carried to evaluate the fluctuation of potassium ion in the kidney transplant recipient patients.

Materials and Methods: In a simple randomized clinical trial the serum K+ level was assessed in 40 kidney transplant candidates as following interval, pretransplantation, during renal art, anastomosis, after diuresis and post transplantation period. After hydration with 5 ml/kg normal saline all patient were undergone general anesthesia identically. They were premedicated fentanyl (2µg/kg), induction was performed by thiopental sodium (5 mg/kg). Tracheal intubation was facifitated with atracurium (0.6 mg/kg). Anesthesia was maintained with N2O + O2 50%, halothane 0.1% and fentonyl 1 µg/kg every 30 min.

Results: The least mean K+ level was during anastomosis (ie. 3.5±0.24 mmol/L) and showed a decrease in the serum K+ level compared to preoperative period (mean 4.4±0.48 mmol) (P< 0.001). The maximum serum K+ level detected preoperatively and postoperatively were 5 (mmol/ L) and 4.7 (mmol/L) respectively.

Conclusion: Despite the above results we inferred that range of serum K+ level was maintained within normal. Therefore with suitable pereoprative assessment hyperkalemia is a rare occurrence in transplant recipients.

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Background: Chang in the serum K+ level may increase perioperative morbidity and mortality in kidney transplant recipients. Thus this research was done with the aim of evaluated of K+ change in kidney transplant recipients. Hence the following study was carried to evaluate the fluctuation of potassium ion in the kidney transplant recipient patients.

Materials and Methods: In a simple randomized clinical trial the serum K+ level was assessed in 40 kidney transplant candidates as following interval, pretransplantation, during renal art, anastomosis, after diuresis and post transplantation period. After hydration with 5 ml/kg normal saline all patient were undergone general anesthesia identically. They were premedicated fentanyl (2µg/kg), induction was performed by thiopental sodium (5 mg/kg). Tracheal intubation was facifitated with atracurium (0.6 mg/kg). Anesthesia was maintained with N2O + O2 50%, halothane 0.1% and fentonyl 1 µg/kg every 30 min.

Results: The least mean K+ level was during anastomosis (ie. 3.5±0.24 mmol/L) and showed a decrease in the serum K+ level compared to preoperative period (mean 4.4±0.48 mmol) (P< 0.001). The maximum serum K+ level detected preoperatively and postoperatively were 5 (mmol/ L) and 4.7 (mmol/L) respectively.

Conclusion: Despite the above results we inferred that range of serum K+ level was maintained within normal. Therefore with suitable pereoprative assessment hyperkalemia is a rare occurrence in transplant recipients.

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Background: Ureteral obstruction, leading to urinary stasis and elevated pressure in the proximal part of urinary tract, causes progressive renal dysfunction. This study was designed to evaluate the status of oxidative stress and metabolic defect in acute unilateral ureteral obstruction (UUO).

Methods: Experiments were performed on three groups of male Sprague-Dawley rats (n=10 in each group). In the UUO group, rats were lightly anesthetized by ether and the left ureter was occluded by means of a sterile surgical procedure. Twenty-four hours after UUO-induction, both kidneys were removed and stored at -70 °C. In the sham group, anesthesia and surgery were performed without ureteral occlusion, and the control group received no surgical procedure. The kidney samples were assessed to measure the levels of ATP and ADP by the luciferin-luciferase method for determining metabolic status. In addition, the levels of malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP) of the kidneys were measured to evaluate the redox state. Data are expressed as means ±SEM per gram of kidney weight (gKW). The comparisons were performed using paired t-test for intra-group analysis, and ANOVA followed by Duncan's post-hoc test and then LSD test for inter-group analysis. Significance was taken at p<0.05.

Results: The comparisons between the UUO and sham groups indicated that 24 hours of UUO increased levels of MDA (51.42±1.86 vs. 38.64±1.02 nmol/gKW, respectively p<0.001) and ADP (0.67±0.04 vs. 0.47±0.045 µmol/gKW, respectively p<0.01), but decreased levels of FRAP (2.44±0.18 vs. 4.28±0.27 µmol/gKW, respectively), ATP (1.09±0.10 vs. 2.26±0.19 µmol/gKW, respectively) and ATP/ADP ratio (1.64±0.14 vs. 5.11±0.56, respectively) in the obstructed kidneys, all p<0.001. In the non-obstructed kidneys, the levels of ATP and ADP were higher (p<0.01 and p<0.001, respectively), while the levels of MDA and ATP/ADP ratio were equal to those of the sham group.

Conclusion: Twenty-four hours of acute UUO induces oxidative stress and reduces the aerobic metabolism in obstructed kidneys, whereas non-obstructed kidneys with a normal redox state show the higher levels of metabolism.

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Background: Kidney transplantation had been evaluated in some researches in Iran mainly with clinical approach. In this research we evaluated graft survival in kidney recipients and factors impacting on survival rate. Artificial neural networks have a good ability in modeling complex relationships, so we used this ability to demonstrate a model for prediction of 5yr graft survival after kidney transplantation.
Methods: This retrospective study was done on 316 kidney transplants from 1984 through 2006 in Isfahan. Graft survival was calculated by Kaplan-meire method. Cox regression and artificial neural networks were used for constructing a model for prediction of graft survival.
Results: Body mass index (BMI) and type of transplantation (living/cadaver) had significant effects on graft survival in cox regression model. Effective variables in neural network model were recipient age, recipient BMI, type of transplantation and donor age. One year, 3 year and 5 year graft survival was 96%, 93% and 90% respectively. Suggested artificial neural network model had good accuracy (72%) with the area under the Receiver-Operating Characteristic (ROC) curve 0.736 and appropriate results in goodness of fit test (κ2=33.924). Sensitivity of model in identification of true positive situations was more than false negative situations (72% Vs 61%).
Conclusion: Graft survival in living donors was more than cadaver donors. Graft survival decreased when the BMI increased at transplantation time. In traditional statistical approach Cox regression analysis is used in survival analysis, this research shows that artificial neural networks also can be used in constructing models to predict graft survival in kidney transplantation.

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Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background: The effect of ischemia/reperfusion (I/R) injury on kidney has been under investigation for many years. But the changes in liver function and oxidative stress status in renal I/R injury is not well known. Recent studies suggest a crosstalk between liver and kidneys. The aim of the present study was to assess liver changes after induction of various degrees of renal I/R injury.
Methods: This is an experimental study conducted on 20 male rats that were obtained from animal house of Physiology Department. Twenty male rats were subjected to either sham operation or ischemia (30, 45 and 60 min) followed by 60 min reperfusion periods. Blood samples were drawn post-operatively and plasma creatinine, BUN, ALT and AST were measured. Hepatic glutathione (GSH) and FRAP (ferric reducing antioxidant power) levels and the concentration of IL-10 and tumor necrosis factor (TNF) -alpha were evaluated.
Results: Both 45 and 60 min ischemia followed by 1h reperfusion periods resulted in significant increases in plasma creatinine (11.1±1.7mg/dl and 1.24±0.07mg/dl vs 0.55±0.15mg/dl, p<0.05) and BUN (34±3.85mg/dl and 35.0±2.81mg/dl vs 23.75±1.1mg/dl, p<0.05). These rats showed a significant decrease in liver GSH as well as significant increase in TNF-a & IL-10 concentrations.
Conclusion: Renal ischemia causes changes in liver function and oxidative stress status. A minimum of 45 min ischemia is needed to study the effects of renal injury on liver as a remote affected organ.

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Background: In kidney transplantation decision about the proper kidney donation is different between surgeons, but simple vasculature anatomy and a kidney without abnormalities are the most important reasons of choosing a kidney. Therefore    complete assessment of renal vessels of a live donor with noninvasive techniques is a necessity for nephrectomy. For delineation of the kidney vasculature anomalies and urinary system abnormalities, Multi-Detector CT seems to be excellent method for evaluation.
Methods: In this study 59 live donors were assessed with Multi-Detector CT Angiography. After injection of contrast media, we acquired images with 0.6 mm slice thickness. Processing and three dimentional reconstructions were done and the accessory arteries, early branching of main renal artery, the number of main renal vessels and the ureters were assessed. Findings were compared with the nephrectomy results.
Results: In Multi-Detector CT Angiography the prevalence of accessory renal artery was 3/4% with 98% accuracy, early branching of main renal artery was 8/4% with 100% accuracy. Multiplicity of renal veins was seen in 8/4% of donors with 98% accuracy. Duplicated ureter was not seen in any of the donors.

Conclusions: The accuracy of CT Angiography is 95% for depicting accessory renal artery and multiple renal artery and 100% for early branching. These results were comparable with findings in conventional angiography. Studies showed this method  more valuable than M.R. Angiography and digital subtraction angiography. It is less invasive and can be named as the gold standard method in the diagnosis of anomalies of vessels & collecting system in live donors. 

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Background: An increased risk for invasive infections with encapsulated bacteria such as Streptococcus pneumoniae has been described in patients with chronic kidney disease (CKD) or in those on dialysis. The aim of this study was to evaluate the antibody response to pneumococcal capsular polysaccharide vaccine in CKD patients. Methods: Sixty-six patients with CKD and 40 healthy individuals were vaccinated with pneumococcal polysaccharide vaccine. The serum antibody response (IgG and IgG2) to the Pneumovax antigens was determined by enzyme-linked immunosorbent assay (ELISA) prior to and four weeks after vaccination. Results: Out of 66 vaccinated patients with CKD, 14 were found to be hyporesponsive to the vaccine (Group 1). Patients with normal specific antibody response were regarded as respondents and were assigned to Group 2 (n=52). The mean post-vaccination IgG titer to the pneumococcal antigens in Group 1 was significantly lower than those in Group 2 (P=0.012 for IgG and P=0.02 for IgG2). The increased anti-pneumococcal IgG titer was significantly lower in patients in Group 1 versus Group 2 (P=0.001) or the healthy control group (P=0.005). During the follow-up period of patients, patients in Group 1 developed higher episodes of pneumococcal infections than those in Group 2 (P=0.007). Conclusion: A substantial proportion of patients with chronic kidney disease fail to mount an adequate antibody response to pneumococcal antigens and remain at significant risk for such infections. These patients should be offered other prophylactic measures to protect them against invasive pneumococcal diseases.

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Background: In a recent study, we were able to demonstrate a role for leukocyte transfer in the induction of liver damage in recipient mice after induction of IR (60 min of bilateral renal artery occlusion and 3 hrs reperfusion) injury in donors. The present study investigates the role of leukocyte transfer in the induction of kidney damage in recipient mice after induction of renal IR injury in donors.

Methods: Mice were divided into two sham and renal IR groups. After anesthesia, leukocytes were isolated from blood and were transferred to the two recipient groups: the intact recipient mice received leukocytes from the sham donor group (Sham recipient) and the intact recipient mice that received leukocytes from IR donor group (IR recipient). After 24 hrs, the recipient mice were anesthetized and blood samples and renal tissues were collected.

Results: Renal malondialdehyde (MDA) increased and glutathione and superoxide dismutase (SOD) decreased significantly in IR recipient group in comparison to sham recipient group. Although renal function tests, including BUN and plasma creatinine were significantly different between IR donor and sham donor groups, but they were not significantly different in two recipient groups. Renal tissues in IR donor group showed extensive damage compared to sham group, but in IR recipients' kidneys, they were different from IR donor tissues despite being different from their respective sham group.

Conclusion: These findings are suggestive of implication of leukocytes in renal tissue damage and oxidative stress after renal IR injury.

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Background: Sympathetic complex of over-activation kidneys is one of the main causes of primary hypertension (HTN). We aimed to assess the efficacy and safety of sympathectomy using 5Fr mariner catheter ablation on patients with refractory hypertension.
Methods: In this prospective cohort study, patients who received three or more anti-hypertensive medications with 160mmHg systolic blood pressure (BP) or more were randomly included and divided into 2 groups. Cases in the first group were undergone to renal denervation and the second group was treated by previous antihypertensive medications. Both groups were followed for six month by assessing BP and adverse effects.
Results: One hundred and seventeenth patients (54%) out of 212 screened patients were included in the first group (renal denervation) and 95 patients as the second group. The mean of BP changes in the first group was 35/15 mmHg with standard deviation of 22/11mmHg. (P<0.001) in the second group, the mean changes of BP was not statistically significant. (5/0mmHg± 22/11, P=0.79 for systolic BP and P=0.96 for diastolic BP). 92% of 117 patients in the first group had a favorable BP decrease, which was defined as a 20mmHg or more decrease in BP, in comparison with 15% of 95 patients as controls (P=0.001). There was no observed complication after denervation in the first group.
Conclusion: It seems that the sympathetic renal denervation can be an effective and safe method for treatment of refractory hypertensive patients indeed of routine medications although further studies with longer follow up duration and more cases are suggested for confirming this issue.

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Background: Renal transplantation is the preferred therapeutic method for patients with end-stage renal disease. Patients with renal failure have significant associated medical conditions, such as cardiovascular disease. The suitable anesthesia for renal transplantation requires minimal toxicity for the transplanted organ, as well as sufficient pain relief and maintenance of optimal blood pressure and intravascular volume to keep renal functions. The aim of this study was to improve our experience of spinal anesthesia in patients undergoing renal transplantation.
Methods: Sixty consecutive patients scheduled for elective renal transplantation over a period of two years who consented for spinal anesthesia were enrolled in the study. Intraoperative hemodynamic, intravenous fluids and infused blood products, duration of surgery, urine output and arterial blood gas and intensity of pain score in the recovery room were monitored. We also noted intraoperative and postoperative complications.
Results: Spinal anesthesia was satisfactory in all, but in five patients they required supplementation with general anesthesia for excessively prolonged surgery. There were no significant intraoperative hemodynamic changes. The total intravenous fluid used during surgery was 65.15±7.2 mL/kg, the mean surgical time was 170±22 min. The mean of mean arterial pressure (MAP) during the operation was 98±12 mmhg. There was no significant acidosis at the end of the operation (PH=38±0.03). Also the mean intensity of pain was 4±2 in recovery and a few of patients suffered from bladder catheter bladder discomfort in the recovery room (8 patients).
Conclusion: Spinal anesthesia is a successful regional anesthetic technique in well selected patients for renal transplantation. A successful outcome in this technique is dependent on close intra-operative monitoring, optimization of intravascular fluid volume and keep the hemodynamic status in optimal range.

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Background: Several studies indicate that gender differences exist in tolerance of the kidney to ischemia reperfusion (IR) injury. Recently, postconditioning (POC), induction of brief repetitive periods of IR, has been introduced to reduce the extent of the damage to the kidney. This method was shown to attenuate renal IR injury by modifying oxidative stress and reducing lipid peroxidation. Considering the gender effect on the results of several treatment methods, in this study, we investigated the impact of gender on the protective effect of POC on the rat kidney.
Methods: In this study, after right nephrectomy, 48 male and female rats were randomly divided into 6 groups of 8 rats: In IR group, with the use of bulldog clamp, 45 minutes of left renal artery ischemia was induced followed by 24 hours of reperfusion. In the sham group, all of the above surgical procedures were applied except that IR was not induced. In the POC group, after the induction of 45 minutes ischemia, 4 cycles of 10 seconds of intermittent ischemia and reperfusion were applied before restoring of blood to the kidney. 24 hours later, serum and renal tissue samples were collected for renal functional monitoring and oxidative stress evaluation.
Results: Postconditioning attenuated renal dysfunction considering the significant decrease in plasma creatinine and BUN compared with IR group only in male rats (P<0.05). Also, POC attenuated oxidative stress in male rats’ kidney tissues as demonstrated by a significantly reduced malondialdehyde (MDA) level and increased superoxide dismutase (SOD) activity (P<0.05). In female rats, there were no changes in functional markers and oxidative stress status in POC group compared to IR group.
Conclusion: Considering gender difference, POC had protective effect against IR injury by attenuating functional and oxidative stress markers in male rat kidneys. This protective effect was not seen in female rats.

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Background: Aspirin is the drug of the century, and is a multifunctional drug and one of the most prescribed drugs in the world. Aspirin is a safe drug at low doses but also it has life-threatening side effects when administered at high doses. This study investi-gates the effects of aspirin on renal cortical and medullary tissue in rat embryos.
Methods: In this study, 30 pregnant female rats were randomly divided into 6 groups. Control group with no intervention, sham group received 2 ml distilled water (as a sol-vent of aspirin) received from days 8 to 20 of pregnancy, and four experimental groups received different doses of 75, 100, 200 and 300 mg/kg of aspirin by gavage. Pregnant rats were sacrificed on the twenty days of pregnancy and the fetuses were removed. Weight of the fetuses and placenta and Crown-Rump length were measured. Fetal kid-neys were fixed in formalin processed, sectioned and stained with Hematoxylin- Eosin. Thickness of renal cortical and medullary tissue by using a Motic hardware and soft-ware system were measured and recorded. A significance level of 0.05 was predeter-mined for all statistical analyses.
Results: No apparent fetal anomalies were observed in experimental groups. In addi-tion, no significant differences were shown in the mean of fetal weight, placental weight, mean of Crown-Rump length in experimental groups 75, 200 and 300 mg/kg compared to control and sham groups. Mean fetal and placental weight in experimental group 100 significantly increased compared to control and sham groups. Mean ratio of renal cortex to renal medulla in experimental group 75, 100 and 300 were significantly decreased compared to control and sham groups (respectively P= 0.03, P= 0.013, P= 0.03).
Conclusion: It seems that maternal use of aspirin during pregnancy can not cause fetal abnormalities. However, it can cause some changes in renal cortical and medullary tis-sue of rat embryos.

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Background: The renal sympathetic nerve activity (RSNA) is enhanced in renal failure. Paraventricular nucleus in hypothalamus is an important central site to regulate sympathetic activity. There are angiotensin II (Ang) II receptors in this nucleus. The aim of this study was to evaluate the effects of angiotensin II in hypothalamic paraventricular nucleus (PVN) on renal ischemia-reperfusion injury and RSNA. Methods: This study was done at 2013 in Physiology department of Tehran University of Medical Sciences. One week before the induction of renal Ischemia-Reperfusion (IR) in Sprague-Dawley rats, a cannula was inserted into the right PVN for microinjection of different doses of Ang II (3, 30, and 300 ng). Then right nephrectomy was done. After one week recovery, renal IR injury was induced by clamping the left renal artery for 45 minute and then reperfusion for 3 or 24 hour. Ten minutes before the induction of renal ischemia-reperfusion, administration of different doses of angiotensin II were done in different groups. In all animals, left renal sympathetic activity was recorded before and during renal ischemia. After 3 or 24 hours reperfusion the blood, kidney and brain were collected to assay renal function and histology and oxidative stress indices Superoxide Dismutase, SOD and Malondialdehyde, MDA) in PVN. Results: Administration of different pharmacological doses of angiotensin II into PVN exaggerated the renal IR injury. Angiotensin II in different doses increased the plasma creatinine and BUN levels and renal histological markers in comparison to renal IR in-jury (P<0.05). Angiotensin II had detrimental effects on RSNA and oxidative stress in-dices Super Oxide Dismutase (SOD) and Malondialdehyde (MDA) in PVN as the dose was increased (P<0.05). Conclusion: These data showed that the PVN is a responsive site for central Ang II-induced damage in renal IR injury. We suggested the central effects of Ang II in the PVN on renal IR injury are mediated by oxidative stress in the PVN, and the peripheral effects by a sympathetic pathway.

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Background: Everolimus is an immunosuppressive agent with a novel mode of action but has a different clinical role with calcineurin inhibitors (CNI). The aim of this study was to evaluate the safety and effectiveness of everolimus compared with sirolimus and tacrolimus in preventing kidney transplantation rejection. Methods: Search was conducted for finding randomized clinical trials (RCT) until the end of 2013 in main databases include Cochrane, Medline and other related databases in February 2014. To find the ongoing trials two databases were searched (Clinicaltrial.gov and irct.ir/fa/). Two independent reviewers checked studies for quality and eligibility and finally extracted the data. Data extraction was performed using Cochrane data extraction form for clinical trial. Discrepancies were resolved via consultation with third person. The studies examined in term of heterogeneity with I2 and Chi-square test. The mata-analysis was carried out using RevMan 5.2 (Wintertree Software Inc, Ontario, Canada) when there was homogeneity. Results: Finally, seven reports from six RCTs included in this study. All reports were in english language and total numbers of participant in these studies were 824. No studies were found in comparison of everolimus and sirolimus and all seven reports were combination of everolimus, tacrolimus and other relative drugs. Follow up time of studies were different from 6 to 36 months. Due to the heterogeneity of included studies, only two studies were entered into meta-analysis. The recorded mean values for glomerular filtration rate, serum creatinine and creatinine clearance were between 60-80 ml/min, 50 to 80 ml/min and 1.2 to 1.9 mg/dl respectively. The results of meta-analysis in three outcomes include serum creatinine, creatinine clearance and glomerular filtration rate were significantly in favor of low dose tacrolimus plus everolimus. Conclusion: In general, everolimus showed better results in combination with tacrolimus. Given the available evidence in this study, everolimus in combination with low dose tacrolimus showed better safety and effectiveness in preventing kidney transplantation rejection.

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Background: The goal of Induction therapy is to prevent acute rejection during the early posttransplantation period by providing a high degree of Immunosuppression at the time of transplantation. Induction therapy is often considered essential to optimize outcomes, especially in patients at high risk for poor short-term outcomes. The optimal prophylactic induction immunosuppressive therapy to prevent kidney transplant rejection remains controversial and historically, immunosuppressant selection was solely based on efficacy in preventing rejection. Methods: In a cross-sectional retrospective study, 410 cases of renal graft recipients were reviewed in the Hasheminejad Hospital, Tehran, Iran from March 2008 to March 2011. The adult patients with induction therapy with age over 18 years were studied for the indication, results and adverse effects of Induction therapy. Results: From 66 transplanted patients with induction therapy, 44(66.7%) patients were male. The mean age±SD of patients with induction therapy was 39.9±13.2 years. The most common cause of Induction therapy was cadaveric transplantation (45.5%), other causes was the prior history of transplantation (24.2%), without risk factor of rejection, panel reactivity test (PRT)>20% and delay graft function. Anti-thymocyte globulin (rabbit) is the most commonly used agent (97%) for induction therapy. The rate of acute rejection was 16.7% percent (11 patients), that the most of them related to the panel positive patients. The most common adverse effect of anti-thymocyte globulin was thrombocytopenia (15.2%) and the rate of New Onset Diabetes mellitus After transplantation (NODAT) and leukopenia was 10.6%, 1.5%, respectively. The urine culture was positive in 6 (9.1%) patients with induction therapy and positive blood culture was seen in one patient (1.5%). The viral and fungal infections were not seen. Conclusion: No standard Induction immunosuppressive regimen exists for patients undergoing renal transplantation. Anti-thymocyte globulin with low dose regimen is the most commonly used agent. The PRT>20% had the most association with acute allograft rejection. The most common side effect of induction therapy was thrombocytopenia.

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Thymoglobulin is a purified polyclonal immunoglobulin that has been used widely over the last decades in the prevention and treatment of rejection following renal transplantation. This immunoglobulin works against human thymocytes. Since thymoglobulin does not contain the nephrotoxic properties therefore it can be used in induction therapy especially in patients with higher risk of graft rejection such as patients who receive graft from cadavers. Recent research showed also its beneficial role in cross-match-positive transplantation, a role that is mediated through conjunction with inhibitors of terminal complement activation. This immunoglobulin has also been used for treatment of rejection following renal transplantation. Thymoglobulin can have various effects on various Immune system cells including T cells, B cells and also plasma cells. Thymoglobulin also affects the Tcell surface antigens, natural killer-cell antigens, B cell antigens, plasma cell antigens, adhesion molecules and chemokine receptors. Diverse effects of thymoglobulin on the immune system includes: T cell depletion, induce apoptosis in B cell lineage and interference with dendritic cell functional properties. Thymoglobulin can cause acute complications, delayed complications as well as infectious complications. Acute reaction events includes: anaphylaxis, fever, chills, dyspnea, nausea, vomiting and diarrhea. Thymoglobulin also induces cytokine release syndrome manifested by high grade fevers and chills and treated by steroid therapy. Delayed reactions events usually present as serum sickness and infections. Infectious complications are more important and include cytomegalovirus (CMV) infection, sepsis, candidiasis, herpes simplex and urinary infections. Thymoglobulin can also induce cytokine release syndrome. It has been thought that thymoglobulin increases the risk of post-transplant lymphoproliferative disorder (PTLD), however, debate still exists whether such an association is present when lower dosing regimens are used. In this review, we aimed to present first a brief history of thymoglobulin development and its mechanism of action and then assess the most recent published data regarding the role of thymoglobulin in following issues: immunological tolerance, ischemia-reperfusion injury, delayed graft function, prevention and treatment of acute allograft rejection, live donor transplantation, graft and patient survival and posttrans-plant lymphoproliferative disorder. This review can help specialist in transplant domain to appropriately used thymoglobulin in transplant patients.

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Background: Autosomal recessive polycystic kidney disorder (ARPCKD) is one of the most prevalent hereditary disorders in neonates and children. Its frequency is between 1/6000 to 1/55000 births. In the most severe cases, it can be diagnosed prenatally by the presence of enlarged, echogenic kidneys and oligohydramnios. However, in the milder forms, clinical manifestations are usually detected in neonatal and childhood period. PKHD1 gene located on chromosome 6 is linked with this disorder. About half of detected mutations in this gene are missense ones. The largest protein product of this gene is called the FPC/polyductin complex (FPC). It is a single-membrane spanning protein whose absence leads to abnormal ciliogenesis in the kidneys.

Case presentation: Here we present a 5-year-old female patient affected with ARPCKD. She has been born to a non-consanguineous healthy Iranian parents. No similar disorder has been seen in the family. Prenatal history has been normal. In order to find the genetic background, DNA was extracted from patient's peripheral blood lymphocytes. PKHD1 gene exons and exon-intron boundaries were sequenced using next generation sequencing platform. Two novel variants have been detected in compound heterozygote state in the patient (c.6591C>A, c.8222C>A). Bioinformatics tools predicted these variants to be pathogenic.

Conclusion: In the present study, we detected two novel variants in PKHD1 gene in a patient with ARPCKD. The relatively mild phenotype of this patient is in accordance with the missense mutations found. Molecular genetic tools can help in accurate risk assessment as well as precise genotype-phenotype correlation establishment in families affected with such disorder to decrease the birth of affected individuals through preimplantation genetic diagnosis or better management of disorder.

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