In vitro osteogenic differentiation potential of the human induced pluripotent stem cells augments when grown on Graphene oxide-modified nanofibers.

Due to the several limitations that surgeons are faced during bone tissue implantation there are daily increases in introducing new cell-co-polymer composites for use in bone tissue engineering approaches. In this study tried to develop a suitable nanostructured bio-composite for enhancing osteogenic differentiation of the human induced pluripotent stem cells (iPSCs). Polyvinylidene fluoride-Graphene oxide (PVDF-GO) nanofibers was fabricated by electrospinning and then characterized using scanning electron microscope, tensile and viability assays. After that osteogenic differentiation of the iPSCs was investigated in three groups, including PVDF, PVDF-GO and tissue culture plate as a control group. Alkaline phosphatase activity and calcium content of the iPSCs cultured on PVDF-GO were significantly higher than those cultured on other groups. In addition, Runx2, osteocalcin and osteonectin genes were up regulated in iPSCs cultured on PVDF-GO significantly higher than those cells cultured on PVDF and control. Finally, osteocalcin and osteopontin proteins expression evaluated and the results confirmed higher osteoinductivity of the PVDF-GO nanofibers in comparison with the PVDF nanofibers. According to the results, it was demonstrated that PVDF-GO nanofibers have a great osteoinductive potential and taking together iPSCs-PVDF-GO nanofibrous construct can be an appropriate bio-implant to use for bone tissue engineering applications.

Kidney Failure Due to Abdominal Compartment Syndrome Following Snakebite.

Treatment of snakebite complications is challenging, as it is difficult to distinguish what kind of antivenins should be used. Kidney failure as a result of rhabdomyolysis or hemolysis may happen due to accumulated fluids that increase the pressure in the abdomen. This case report describes acute kidney failure probably due to intra-abdominal hypertension following an unknown bite.

Prevalence of HCV, HBV, and HIV Seropositivity among Cadavers Referred to Autopsy Hall of Legal Medicine Bureau of Tehran, Iran.

A large number of dead bodies are referred to forensic autopsy halls for medicolegal examination. They can be a source of transmission of infectious diseases through direct contact or autopsy tools. The main aim of this study was to estimate the virus infection rates in the dead bodies. One thousand consecutive dead bodies that had been referred to autopsy hall of Legal Medicine Bureau of Tehran, Iran, during 2016, were included. The blood samples were analyzed in the laboratory for detection of HBs Ag, HBs Ab, HIV Ab, and HCV Ab, after providing informed consent from legal next of kin of the dead bodies. The general characteristics of the dead bodies were also collected by a checklist. Forty-seven cases of HIV seropositivity, 80 cases of HBs Ag seropositivity, and 97 cases for HCV Ab seropositivity were found. Among them, 27 cases of HIV, 40 cases of anti-HBC positive, and 94 cases of RIBA testing positive for HCV were proved through confirmatory tests. In other words, 2.6% of the dead bodies were infected with HIV, 3.8% with HBV, and 9% with HCV. The total infection rate was 15.5%. This is a worrying risk for pathologist and autopsy technicians.

The impact of acute rejection in kidney transplantation on long-term allograft and patient outcome.

BACKGROUND: Patients with end stage renal disease (ESRD) can be sustained with dialysis therapy. OBJECTIVES: In this study, we followed up the effect of early acute and late acute rejections on survival rates of patients' grafts. PATIENTS AND METHODS: We investigated the timing and frequency of acute rejection episodes related to long-term patient-graft survival in Taleghani hospital between 1990 and 2011. Recipients were divided into three groups as Group-1 (no rejection), Group-2 (early acute rejection [EAR]: less than 3-months) and Group-3 (late acute rejection [LAR]: after 3 months of transplant). RESULTS: One and five-year patient's survival rates were 94.87% and 93.8%, and graft survival (GS) rates were 92.6% and 81.9%. EAR and LAR occurred in 125 (18.8%) and 77 (11.7%) patients, respectively. Graft and patient survival rates at one and five years were as follows; Group-1 (Graft 96.7% and 94.5% patient: 97.4% and 96.8%), Group-2 (Graft: 72% and 61%, patient: 85.6% and 84%), Group-3 (Graft: 84.4% and 36.8%, patient: 92.2% and 89.4%). Recipient age, type and length of dialysis, number of transplantations and the status of panel reactivity antibody (PRA) had no effect on the type of rejection. LAR was more commonly associated with males (P = 0.001) and donors' age was associated with rejection (P = 0.0002). Five-year GS rate among the three groups was lower in the LAR group (P < 0.0001). CONCLUSIONS: LAR had a negative impact on long-term renal allograft survival and the risk of chronic graft dysfunction increased in patients with a history of LAR.

Association between metabolic syndrome and coronary heart disease in patients on hemodialysis.

BACKGROUND: The metabolic syndrome (MeS) is a common risk factor for coronary heart disease (CHD) in the general population. OBJECTIVES: We examined the association between MeS and its risk in terms of CHD in patients on hemodialysis (HD). PATIENTS AND METHODS: This study was conducted on 300 patients on HD in six HD centers during March 2012. Patients were divided in two groups regarding presence of MeS. The rate of CHD were evaluated in each group and compared with each other. RESULTS: A total of 300 patients on HD, 173 males and 127 females with mean age of 61.7 ± 14.2, were enrolled in the study. Prevalence of MeS was 50.3%; hypertension, 83.7%; diabetes mellitus, 52%; high triglyceride level, 34%, low HDL cholesterol, 48.3%; and abdominal obesity, 41.3%. During the study, the CHD was more frequent in patients with MeS (27.8%) than was in those without MeS (14.1%) (P = 0.004). In addition, stroke happened more frequently in the MeS group than in those without MeS (30.5% vs. 17.4%; P = 0.008). The mean number of criteria for MeS was not significantly associated with mortality causes (CHD, 2.7 ± 1.3; stroke, 2.8 ± 0.9; other causes, 2.9 ± 1.3 P = 0.78). However, hypertension (89.3%) and diabetes mellitus (53.8%) were associated with increased risk for mortality. In the group of MeS, CHD were not significantly associated with serum albumin, calcium, phosphate, blood urea nitrogen, creatinine, ferritin, C-reactive protein, and KT/V; but there was significant association with white blood cells count (P < 0.0002). CONCLUSIONS: These findings suggested MeS might be an important risk factor for CHD, but not for mortality due to CHD in patients on HD.

Does living donor hyperoxia have an impact on kidney graft function after transplantation?

BACKGROUND: Improvement in the outcome of organ transplantation is related to advances in patient selection criteria, organ preservation, operative techniques, perioperative care and efficacy of immunosuppressive agents. OBJECTIVES: We aimed to evaluate the effects of higher levels of arterial PaO2 in donors on DGF (delayed graft function). PATIENTS AND METHODS: Forty patients over 18 years old with stage 4-5 chronic kidney disease (CKD) who received a kidney from living donors were enrolled. They were randomly grouped in to the case (n = 17) and control (n = 23) groups and were followed for 2 weeks after transplantation. Donors were exposed to 60% oxygen for at least 2 hours with a face-mask (venture mask) for 2 consecutive days before transplantation until arterial oxygen pressure increased in arterial blood gas to 200 mmHg. Neutrophil gelatinase associated lipocalin (NGAL), Interleuk-18 (IL-18), tumor necrosis factor- α (TNF-α) and transforming growth factor-ß (TGF-ß) could be good biomarkers for early diagnosis of kidney injury in renal transplant recipients; we assessed kidney function with these biomarkers. RESULTS: Forty living kidney transplantations including 17 cases and 23 controls were performed; female gender was more prevalent in recipients (n = 16, 40%). The mean age of recipients was 36.1 ± 12.4 (18-67) years old. DGF was detected in 2 (5.95%) individuals, from whom one was in the case group and the other one in the control group. In the univariate analysis, there was no significant correlation between age and biomarkers in urine and serum unless for the second serum NGAL (P = 0.02, r = -0.06) and second urine IL 18 (P = 0.03, r = -0.5) which had a negative correlation, and first urine TNF α (P = 0.02, r = 0.7) which had a positive correlation. CONCLUSIONS: Oxygen therapy in the case group had no significant impact on protection from DGF.

Investigation of the efficacy of a biogeneric recombinant human erythropoietin alfa in the management of renal anemia in patients on hemodialysis: a multi-center clinical trial.

BACKGROUND: Recombinant human erythropoietin (rHuEPO) is the cornerstone therapy for anemia associated with chronic kidney disease. However, not all patients with renal anemia receive sufficient doses of rHuEPO due to its high cost. The present trial aimed to evaluate the efficacy of Epolyrec, a biogeneric rHuEPO, in the management of renal anemia in patients on hemodialysis. METHODS: Seventy-two patients with end stage renal disease (ESRD) who were receiving hemodialysis were assigned to receive Epolyrec subcutaneously at a dose of 40-80 IU/Kg in 2-3 divided doses after each dialysis session for 12 weeks. Hemoglobin, hematocrit, and CBC/DIFF together with biomarkers of iron status, renal function, and trace elements were evaluated at baseline and during the course of trial. RESULTS: Hemoglobin concentrations and hematocrit progressively increased from baseline (8.45 +/- 1.42 mg/dL and 27.05 +/- 4.64% for hemoglobin and hematocrit, respectively) to the end of trial (10.56 +/- 1.93 and 34.06 +/- 6.70) (p < 0.001). RBC count (p = 0.026), reticulocyte count (p = 0.045), and MCV (p < 0.001) were also significantly increased at the end of trial (3.86 +/- 0.91x10(6)/microL, 0.78 +/- 0.31%, and 93.50 +/- 10.90 fL for RBC count, reticulocyte count, and MCV, respectively) compared to baseline (0.98 +/- 3.38, 0.18 +/- 0.63, and 89.75 +/- 9.35). Serum iron and ferritin were decreased while creatinine and phosphorous increased by the end of trial. No significant change was observed in WBC count, RDW, MCH, MCHC, BUN, PTH, Na, Ca, K, and Mg (p > 0.05). The frequencies of evaluated side effects were generally low and < 10%. CONCLUSIONS: Epolyrec is clinically efficacious in the elevation of hemoglobin and hematocrit in anemic ESRD patients receiving hemodialysis. Future comparative trials are warranted to compare the efficacy and safety of Epolyrec to those of innovator products.

Delayed graft function, allograft and patient srvival in kidney transplantation.

INTRODUCTION: Delayed Graft Function (DGF) is a common complication of renal transplants and the long-term relation between DGF and survival of patients and grafts is not well established. METHODS: This is a historical cohort study of transplanted patients in Taleghani Hospital of Shahid Beheshti University in Iran between 1994 and 2010. Patients who required dialysis during the first week after transplantation were considered to have DGF. The patients' conditions were updated to determine existing graft function, graft loss or patients' death at one year and five years post transplantation in relation to the presence or absence of DGF. RESULTS: DGF complicated 67/385 transplants (17.4%). Causes included acute tubular necrosis (58.2%), accelerated rejection (29.9%), transplant renal artery thrombosis (9%) and renal vein thrombosis (3%). More kidneys in the DGF group were procured from cadaveric donors (6% versus 0.9%, P = 0.02). At hospital discharge, patients with DGF had significantly higher mean creatinine level (4.4 ± 2.8 versus 2.0 ± 1.7; P = 0.001) compared to other patients. They also had more early acute rejection episodes and more late acute rejection episodes (34.3% versus 2% and 16.4% versus 3%, respectively; P = 0.0001) compared to other patients. The proportion of functioning grafts was significantly lower in the DGF group at 1-year (53.7% versus 95.3%, P = 0.0001) and 5-years (22.4% versus 61.6%, P = 0.001) compared to patients without DGF. CONCLUSION: The DGF group had a significantly higher acute rejection rate and an increased risk of graft loss at one and five years.

The effect of allopurinol on lowering blood pressure in hemodialysis patients with hyperuricemia.

BACKGROUND: Hyperuricemia has been associated with the development of high blood pressure (BP). We studied the effects of allopurinol therapy in hyperuricemic hemodialysis (HD) patients with high BP. MATERIALS AND METHODS: This single-blind, randomized cross-over clinical study involved 55 HD patients with serum uric acid level > 6.5 (men) and > 5.5 mg/dL (women). They were randomly divided in two groups, each of which went through two phases. Group-1 in phase-1 received 100 mg/day orally of allopurinol for three months; while Group-2 was given whatever medication they received prior to the study. After two months of washing period, the groups were crossed-over. The BP levels were measured before and after HD during the eight months study period. RESULTS: Fifty-three patients completed the study (33 men and 20 women, with mean age of 55.8 years). Uric acid levels decreased significantly during the12 weeks of allopurinol therapy (7.71 ± 1.53 to 5.2 ± 1.2 P < 0.005). Overall, after the 12 weeks of allopurinol therapy, systolic and diastolic BP also significantly decreased in allopurinol group, 15.8% (139 to 117, P < 0.0005) and 8.6% (81 to 74, P <.0005), respectively. There were not significant changes in body mass index, blood urea nitrogen, creatinine, albumin, cholesterol, triglyceride, hemoglobin, liver enzymes and serum electrolytes level after treatment. Patients treated with allopurinol had a significant increase in the quality of dialysis (KT/V) (P: 0.043). CONCLUSIONS: In HD patients, allopurinol treatment reduced BP. The results indicate a new potential therapeutic approach for controlling BP in HD patients.

Association between helicobacter pylori infection and body mass index, before and after eradication of infection in hemodialysis batients.

BACKGROUND: In dialysis patients, chronic infections have been associated with cachexia and anorexia. OBJECTIVES: This study was carried out to determine the association between Helicobacter pylori (HP) infection and body mass index (BMI) in hemodialysis (HD) patients. PATIENTS AND METHODS: Ninety eight patients were divided into two groups of negative (group 1) and positive (group 2), for HP. BMI of all patients was measured at the beginning and in group2 after six months following eradication of HP. Before dialysis, various paraclinical parameters were checked at the same intervals. RESULTS: Fifty-nine patients were enrolled in group 1 and 39 patients in group 2. The means of BMI in groups 1 and 2 were 23.4±3.7 and 25.8±4.4kg/m², respectively. Prior to the study, there was no significant difference for BMI, duration of HD and paraclinic data between two groups. Group 2 took anti HP therapy and eradication occurred in 30 of them. In this group six months after eradication of HP, the BMI was significantly decreased from 25.02±4.4 to 24.4±4.0 kg/m² (P = 0.001). Also six months following the eradication of HP, the mean of serum albumin level was significantly declined from 4.2 to 3.7 g/L (P<0.001). There was also significant decrease in cholesterol (P=0.001), blood urea nitrogen (P=0.005) and calcium (P=0.02). However, significant increase in hemoglobin level was also seen (P=0.03). CONCLUSIONS: The results of this study show that eradication of HP has an impact on BMI. The results need to be investigated with larger cases.

Two decades of experience in mucormycosis after kidney transplantation.

BACKGROUND: Invasive mucormycosis is a very rare infection after kidney transplantation. Here, we report 25 renal transplant recipients with mucormycosis; to our knowledge, this is the largest reported population of mucormycosis in these patients. MATERIAL/METHODS: In a retrospective study, we collected all kidney transplants with mucormycosis from 9 Transplant Centers of Iran from 1990 to 2010. The definitive diagnosis of mucormycosis was established by obtaining a biopsy specimen of the involved tissue. RESULTS: The most form of disease was rhino-cerebral (n =13), followed by pulmonary (n=7). Overall mortality rate was 52% (n=13), particularly in recipients with pulmonary infection (100%); however, the mortality rate in rhino-cerebral form of disease was low (30.8%). There was no statistically significant difference in mortality rate between male and female (P=0.8). In addition, no significant differences were seen in mortality rate with age of patients (p=0.8) and time of diagnosis since transplantation (p=0.3). Pulmonary infection was more seen in recipients received azathioprine compared to those on mycophenolate mofetil (p=0.006). CONCLUSIONS: Mucormycosis after renal transplantation has a poor prognosis, particularly patients with pulmonary involvement.

Prevalence of metabolic syndrome in a hemodialysis population.

INTRODUCTION: The role of metabolic syndrome (MS) in hemodialysis population has not been thoroughly studied. This study aimed to determine the prevalence of MS and to identify its correlates among hemodialysis patients. MATERIALS AND METHODS: This cross-sectional study was conducted on patients in a hemodialysis center. The MS was defined according the Adult Treatment Panel III criteria. Clinical data of the patients were collected and blood samples were studied to measure fasting blood glucose and lipid profile. RESULTS: Eighty hemodialysis patients, including 47 men (58.8%) and 33 women (41.2%) with a mean age of 55.6 ± 15.6 years, were enrolled in this study. Metabolic syndrome was diagnosed in 23 patients (28.7%). Hypertension was present in 55 patients (68.8%). Fifteen patients (18.8%) were diabetic, 24 (30.0%) had a high serum triglyceride, 22 (27.5%) had a low high-density lipoprotein cholesterol, and 20 (25.0%) had evidence of abdominal obesity. Patients with MS had significantly higher body mass indexes (P < .001), fasting blood glucose levels (P < .001), and triglyceride levels (P = .004). Metabolic syndrome was not associated with gender, age, and duration of hemodialysis. Men showed significant abnormality in glucose metabolism (P = .008). Prevalence of low high-density lipoprotein cholesterol was significantly higher in the women than in the men (P = .02). CONCLUSIONS: The prevalence of MS in our hemodialysis patients was relatively high, with the most common element being hypertension. We suggest that there needs to be a new set of criteria defined for MS in hemodialysis patients.

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

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

Ramadan fasting in kidney transplant recipients with normal renal function and with mild-to-moderate renal dysfunction.

BACKGROUND: Fasting during Ramadan is prescribed for every healthy Muslim after the age of puberty. However, many patients ask their physicians whether it is safe for them to fast. AIM: The aim of this study was to evaluate the influence of voluntary Ramadan fasting on patients with transplanted kidneys. METHODS: We conducted a prospective study on 41 kidney transplant recipients who chose to fast during Ramadan and 41 recipients who had not fasted at five transplant centers in the month of Ramadan (September-October 2007). All 82 recipients underwent transplantation at least 1 year prior to the study, and all had had stable renal function for at least 6 months prior to the study. RESULTS: The mean ages of the fasting and control groups were 42 +/- 12 years and 43 +/- 12 years, respectively, and the corresponding duration since transplantation was 10-210 (average: 65) months and 11-180 (average: 69) months. Our results showed that estimated GFR did not significantly change during Ramadan for either group (mean estimated GFRs pre- and post-Ramadan were 72.8 +/- 27.8 and 73.1 +/- 29.3 ml/min in the fasting group, and 73.4 +/- 18.8 and 73.1 +/- 18.5 ml/min in non-fasters, respectively). In patients with GFR < 60 ml/min, renal function remained stable during Ramadan. CONCLUSION: The results did not show any adverse effects of fasting, especially on allograft function, in kidney recipients who had normal as well as mild to moderate impaired but stable renal function prior to fasting.

Kaposi's sarcoma following living donor kidney transplantation: review of 7,939 recipients.

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.

Posttransplant lymphoproliferative disorders in kidney transplant recipients: an Iranian multicenter experience.

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.