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The expanded criteria donor is any donor over the age of 60 years or a donor over the age of 50 years with 2 of the following 3 items: (1) history of high blood pressure, (2) serum creatinine ≥1.5 mg/dL, and (3) death due to stroke. To accept an expanded criteria donor kidney may significantly decrease the amount of time a person waits for transplant but requires written informed consent from the recipient. Although expanded criteria donor kidneys have predictably shorter outcomes than standard criteria donors, the exact risk is unknown. At 5 years follow-up, 50% of expanded criteria donor kidneys are still working. Regardless of donor status of these kidneys as expanded criteria or standard criteria, the transplant recipients have higher survival rates compared with candidates who remain on the wait list. The success rate may be increased when a perfusion pump is used to preserve the kidneys. Sometimes the function of a single kidney from an expanded criteria donor is deemed insufficient. In this situation, a pair of marginally functioning kidneys may be transplanted as a dual-kidney transplant. This dual transplant option offers acceptable outcomes as good as a single-kidney transplant with normal function and can effectively address the shortage of donor organs. The use of a perfusion pump allows the clinician to decide whether or not to use a particular expanded criteria donor kidney. Expanded criteria donors may be justified by meticulous selection of each donor for recipients, along with more sophisticated surgical techniques to maximize the kidney donor pool.

Cisplatin is a therapeutic drug widely used to treat various solid tumors. Nephrotoxicity is a well-known side effect in patients treated with cisplatin. Falcarindiol (FAD), natural polyacetylene compound greatly found in Apiaceae family, has anti-cancer, -bacterial, -inflammatory and -oxidant activity which is utilized in the present study. Thirty male C57BL/6 mice were randomly divided into five groups of six each; sham, cisplatin (15 mg/kg), cisplatin + FAD (50 and 100 mg/kg/day), and FAD (100 mg/kg/day). Cisplatin administration elevated the concentrations of BUN and creatinine, as well as kidney histopathologic damage. On the other hand, FAD treatment attenuated cisplatin-induced injury, and also down-regulated mRNA levels of TNF-α and IL-1β together with protein expression of p-NF-kB p65. Moreover, FAD induced the protein expression of p-AMPK and nuclear Nrf2 accompanied by its respective target genes such as NQO-1 and HO-1 in a dose-dependent manner. In conclusion, the findings collectively characterize FAD as a drug candidate to treat cisplatin-induced nephrotoxicity thorough down-regulation of NF-kB signaling pathway in mice

The wait list for organ transplant exceeds the rate of organ donation, especially in children. The solid-organ transplant rate has remained stable over time, despite increased demand. Although donation after cardiac death has helped to expand the donor organ pool for the adult population, this option remains scarce for children in need of transplant. Because long-term graft survival is more important in the pediatric group than in adults, we should reconsider the common notion that donation after cardiac death is inferior to donation after brain death. Herein, we review the literature to extract and analyze data regarding donation after cardiac death for solid-organ transplant in children.

Background One common feature of chronic diseases, such as cancer, diabetes and chronic kidney disease (CKD), is the disruption of iron metabolism and increase in labile iron pool, which can result in excessive production of harmful oxidative stress. The proper management of iron metabolism in this situation can be a valuable tool to ameliorate pathological events. Materials and methods In the previous studies, the anti-neoplastic effects of BCc1, a nanochelating-based nanomedicine with iron-chelating property, were demonstrated in cell culture, animal models and clinical trials. In the present study, the therapeutic effects of BCc1 in animal model of diabetic kidney disease (DKD), induced by streptozotocin injection (35 mg/kg) and high-fat diet consumption, were evaluated. Results The results showed that BCc1 significantly decreased HOMA-IR index, uric acid, blood urea nitrogen, malondialdehyde and 8-isoprostane. In addition, it reduced urinary albumin excretion rate and albumin-to-creatinine ratio in comparison to DKD control rats. This nanomedicine had no negative impact on liver iron content, hemoglobin level, red blood cell count, hematocrit and mean corpuscular volume, while it significantly decreased aspartate aminotransferase and alanine aminotransferase compared to DKD control group. Moreover, the histopathological assessment indicated that lesser glomerular basement membrane and wrinkling, mesangial matrix expansion and pathological changes in proximal cortical tubules were seen in the kidney samples of BCc1-treated rats. Conclusion In conclusion, BCc1 as an iron-chelating agent shows promising impacts in DKD animal model, which can ameliorate biochemical and pathological events of this disease.

Monitoring allograft function after kidney transplant has routinely relied on the use of nonspecific markers, such as serum creatinine, glomerular filtration rate, proteinuria, and donor-specific antibodies. These traditional markers have low sensitivity and fail to detect subclinical changes. Diagnosis of renal allograft dysfunction still requires an allograft biopsy, as it remains the criterion standard for assessment of graft status. However, renal biopsy is an invasive procedure, and sampling errors may result in misdiagnosis, perhaps causing graft failure. New biomarkers have been developed to monitor allograft function, although many are not yet routinely used. Other shortcomings, such as lack of standardization and high cost, should be solved before their widespread application in the clinic. A recipient's immune status could be monitored by use of urine or blood samples. These include functional cell-based assays and the evaluation of molecular expression at the messenger RNA or protein levels. Molecular technologies, including molecular microscope diagnostic systems, have been recently developed to improve the yield of histologic evaluation of the allograft biopsy. Prospective, interventional trials are required to demonstrate whether these new biomarkers improve patient or transplant outcomes. Implementation of these technologies into standard clinical practice remains challenging until their generalizability, cost, ease of interpretation, and the identification of patients who may benefit from more than standard-of-care surveillance can be determined. These biomarkers could allow immunosuppressive therapy to be individualized for patients.

Recent developments have been achieved for better matching in solid-organ transplantation by epitope matching. HLA matching remains a standard immunologic strategy to determine organ compatibility for recipients. Advancements in tissue typing have introduced HLA matching at the epitope level. For this, B cells are able to recognize polymorphic amino acid configurations, which are named epitopes. However, antibody production against these epitopes may be a leading cause of rejection. Although data to support the added clinical benefit of epitope matching over traditional antigen matching are still lacking, there are at least 2 theoretical reasons for epitope matching: (1) to avoid future allosensitization with the development of anti-HLA antibodies and (2) to allow selection of a suitable allograft for highly sensitized patients through virtual crossmatch. Sensitive antibody tests with a comprehensive panel of single alleles have yielded informative, donor-specific antibody reactivity patterns that can be analyzed with a computer algorithm. This program (HLAMatchmaker) uses structurally defined eplets to describe epitopes that can react with specific antibodies. Although low mean fluorescence intensity levels by Luminex (Austin, TX, USA) assay are usually considered low risk for solid organ transplant, it could be important in posttransplant humoral rejection. Thus, specific shared eplets should always be investigated with respect to previous transplant mismatches. Epitopes are present on a single HLA (private epitope) or shared by multiple antigens (public epitope). The phenomenon of crossreactivity in HLA testing, often explained as crossreactive groups of antigens with antibody, can be clearly explained now by public epitopes, an antibody targeting an epitope that shows positive reaction with all antigens sharing the epitope. A better understanding of the immunogenicity and structural characteristics of HLA epitopes will guide us to consider epitope matching as an important parameter for donor selection in kidney transplant in the near future.

Allopurinol is an inhibitor of xanthine oxidase (XO) enzyme. This drug is a reducer of uric acid in the body and one of the golden drugs with worldwide administration. XO is an important biological source of free radical generation. Allopurinol as an antioxidant, has direct and indirect antioxidant activity on these free radicals such as hydroxyl radical and superoxide anion. The purpose of this paper is to determine the impact of allopurinol on some aspects of renal disturbances such as renal ischemia/reperfusion injury (IRI), nephrotoxicity and contrast-induced nephropathy (CIN).

To avoid the ethical issues of embryonic stem cells, genome engineering has focused on inducible pluripotent stem cells, which can develop into all 3 germ layers. The ability to detect methylation patterns in these cells allows research into pluripotency markers. The recently developed CRISPR system has allowed widespread application of genome engineering techniques. The CRISPR-Cas9 system, a potent system for genome editing, can be used for gene knockout or knock-in genome manipulations through substitution of a target genetic sequence with a desired donor sequence. Two types of genome engineering can be initiated: homologous or nonhomologous DNA repair by the Cas9 nuclease. Delivery of the CRISPR-Cas9 and target donor vectors in human pluripotent stem cells can be accomplished via viral and nonviral delivery methods. Nonviral delivery includes lipid-mediated transfection and electroporation. It has become the most common and efficient in vitro delivery method for human pluripotent stem cells. The CRISPR-Cas9 system can be combined with inducible pluripotent stem cells to generate single or multiple gene knockouts, correct mutations, or insert reporter transgenes. Knockouts can also be utilized to investigate epigenetic roles and targets, such as investigation of DNA methylation. CRISPR could be combined with human pluripotent stem cells to explore genetic determinants of lineage choice, differentiation, and stem cell fate, allowing investigators to study how various genes or noncoding elements contribute to specific processes and pathways. The CRISPR-Cas9 system can also be used to create null or nucleasedead Cas9, which has no enzymatic activity but has been utilized through fusion with other functional protein domains. In conclusion, RNA-guided genome targeting will have broad implications for synthetic biology, direct perturbation of gene networks, and targeted ex vivo and in vivo gene therapy.

Background: Diabetes is the leading cause of end stage renal disease (ESRD) worldwide. Objectives: We compared the clinical outcomes in diabetic patients on hemodialysis (HD) with non-diabetics. Patients and Methods: Adult maintenance HD patients (N= 532) from 9 HD facilities were enrolled to this prospective cohort study in September 2012. Causes of death, hospitalization, and HD exit were recorded in a median 28 months follow up period. Results. Forty-one percent of patients were diabetic. Diabetic patients compared to non-diabetics had significantly higher age (62.2 ± 11.2 versus 53.1 ± 16.7 years), lower dialysis duration (median: 23 versus 30 months), more cardiovascular comorbidities (64% versus 28%) , higher C-reactive protein (CRP) levels (median: 3.80 versus 2.25 mg/L), lower serum albumin (3.86 ± 0.35 versus 3.93 ± 0.35 g/dL), lower intact parathyroid hormone (iPTH) (median: 272 versus 374 ρg/mL), higher serum triglyceride (167 ± 91 versus 139 ± 67 mg/dL) and low density lipoprotein (LDL) (82.5 ± 24.5 versus 77.5 ± 23.8 mg/dL), and worse short form health survey (SF36) score (45.7 ± 20.9 versus 52.7 ± 20.5). Annual admission rate was higher in diabetics (median: 0.86 versus 0.43) and diabetic foot involved 16% of their admissions. Transplantation rate was 4 and 9 per 100 patient years in diabetics and non-diabetics, respectively. Death rate was two folds higher in diabetics (24 versus 12 per 100 patient years). Cardiovascular diseases ( ± infections/other causes) comprised 80.5% of death in diabetics and 54.5% in non-diabetics. In Cox regression proportional hazard multivariate analysis, hazard risk of death in diabetics was 1.9 times higher than non-diabetics. Conclusions: Clinical outcomes and health related quality of life (HRQOL) are much worse in diabetic compared to non-diabetic HD patients mainly due to more frequent of cardiovascular diseases (CVDs).

CONTEXT AND OBJECTIVE: Red grape seed extract (RGSE) contains oligomeric proanthocyanidin complexes as a class of flavonoids. These compounds are potent antioxidants and exert many health-promoting effects. This study aimed to determine the effects of RGSE on serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apo-AI) levels and paraoxonase (PON) activity in patients with mild to moderate hyperlipidemia (MMH). DESIGN AND SETTINGS: A randomized double-blind placebo-controlled clinical trial was conducted at Shahid-Modarres Hospital (Tehran, Iran) and Tabriz University of Medical Sciences. Seventy MMH patients were randomly assigned to receive treatment (200 mg/day of RGSE) or placebo for eight weeks. RESULTS: Significant elevation in serum levels of apo-AI (P = 0.001), HDL-C (P = 0.001) and PON activity (P = 0.001) and marked decreases in concentrations of TC (P = 0.015), TG (P = 0.011) and LDL-C (P = 0.014) were found in the cases. PON activity was significantly correlated with apo-AI (r = 0.270; P < 0.01) and HDL-C (r = 0.45; P < 0.001). Significant differences between the RGSE and control groups (before and after treatment) for TC (P = 0.001), TG (P = 0.001), PON (P = 0.03), apo-AI (P = 0.001) and LDL-C (P = 0.002) were seen. CONCLUSION: It is possible that RGSE increases PON activity mostly through increasing HDL-C and apo-AI levels in MMH patients. It may thus have potential beneficial effects in preventing oxidative stress and atherosclerosis in these patients.

Empagliflozin, a SGLT-2 inhibitor, improves diabetic nephropathy through its pleiotropic anti-inflammatory effects. The present study aims to evaluate empagliflozin effects on renal and urinary levels of tubular epithelial cell injury markers in streptozotocin-induced diabetic rats. Empagliflozin at 10 mg/kg (p.o.) was administered for 4 weeks, beginning 8 weeks after induction of diabetes. Renal function as well as markers of renal tubular epithelial cell injury were assessed in kidney tissue homogenates and urine. Empagliflozin was able to ameliorate diabetes induced elevations in serum cystatin C levels. It also alleviated renal KIM-1/NGAL levels and urinary albumin, α-GST, and RBP excretions. In addition to decreasing urinary levels of cell cycle arrest indices i.e. TIMP-2 and IGFBP7, empagliflozin mitigated acetylated NF-κB levels in renal tissues of diabetic rats. As a whole, these findings reveal empagliflozin capability in improving diabetic nephropathy via ameliorating indices of renal inflammation, injury, and cell cycle arrest on streptozotocin-induced diabetic rats.

Background: Increasing evidence implies that Adipocytokines may result in cardiovascular disease (CVD) events and metabolic changes in the general population and also increase graft failure rate in the renal transplant recipient. Objectives: To compare the serum levels of Adipocytokines and lipid profiles in renal transplant recipients with healthy individuals. Methods: In a case-control study undertaken from the beginning of 2015 to December 2016; 30 renal transplant recipients, with stable conditions, whose renal transplant at least survived well over six months, were randomly selected to be the case group. Besides, 30 healthy individuals who referred to the transplantation clinic as the patientsâ�� attendants were considered as the control group. The serum levels of IL-1, IL-6, TNF-I±, Adiponectin, Visfatin, Leptin, and the Lipid profiles were measured after 12 hours of fasting and were compared between the two groups. Results: The serum levels of Adipocytokines including IL-1, IL-6, TNF-I±, Visfatin, and Leptin were significantly higher in renal transplant recipients than in healthy individuals (P

Background: The aim of this study was to evaluate the management of mineral and bone disorders (MBD) in patients with chronic kidney disease (CKD) in Iran and the extent to which KDIGO goals were met. Methods: This multi-centre observational studywasconductedonpatients withCKDstages 4, 5, and5D. Data were collectedfroma total of 209patients withnosurgical or medical conditions that precluded their participation. This study assessed the frequency of measurements, serum levels of phosphorus (P), calcium (Ca), and parathyroid hormone (PTH), the achievement of the targets recommended by the 2009 KDIGO guidelines, and the presence of vascular/valvular calcification. Results: The KDIGO targets for P, Ca, and iPTH, were achieved in 47, 51, and 18 of the patients with stage 4 + 5 and in 63, 50, and 44 of the patients with stage 5D, respectively. The serum PTH level of 18 of the patients with CKD stage 4 + 5 was within the recommended range, while it was higher than the recommended level in other patients. Among patients with CKD stage 5D, the serum PTH level was within, below, and above the recommended range in 44, 39, and 17 of the patients, respectively. The frequency of the measurement of the blood levels of Ca, P, and PTH were based on the 2009 KDIGO guidelines in 88 of patients. Forty-six percent of cases were screened for vascular/valvular calcification, 30 of whom had calcification at least in one site. Conclusions: The current status is far from the targets recommended by the current guidelines in the management of CKD-MBD. © 2017, Nephro-Urology Monthly.

Nontraditional risk factors for cardiovascular disease (CVD), including mineral disorder, high fibroblast growth factor 23 (FGF23), low klotho, and low soluble TWEAK could predict the incipient risk of CVD in chronic kidney disease (CKD). The present study evaluates the effect of sevelamer on soluble tumor necrosis factor-like weak inducer of apoptosis (TWEAK), and klotho levels in adenine-induced CKD rats.Normal control rats without sevelamer were compared with 3 groups of adenine-induced CKD rats, including CKD rats without sevelamer, CKD rats treated with 3% sevelamer, and rats receiving adenine and 3% sevelamer concurrently. After 4 weeks of sevelamer treatment, serum levels of klotho and soluble TWEAK were measured, along with biochemical parameters related to kidney function.Sevelamer significantly reduced serum levels of phosphate and increased serum levels of klotho and soluble TWEAK. Decreased levels of phosphate were negatively correlated with elevated levels of klotho and soluble TWEAK (r = -0.70, P = .003; r = -0.58, P = .02; respectively) in serum.Sevelamer successfully reduced serum levels of phosphate, and meanwhile, it led to an elevation in serum levels of klotho and soluble TWEAK in rat models of CKD.

Cardiovascular disease, as the leading cause of patient death with chronic kidney disease, could be predicted by carotid atherosclerosis. The aim of the present study was to evaluate a possible relationship between serum soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and Vitamin D levels with mean right/left carotid intima-media thickness (cIMT), in the hemodialysis (HD) patients. In this cross-sectional study, serums were obtained from 50 stable chronic HD patients and 39 healthy controls. The serum levels of sTWEAK, Vitamin D, intact parathyroid hormone (iPTH) in both groups, and cIMT were determined in HD patients by standard methods. Serum levels of sTWEAK were higher [808.8 (521.6–5032.4) pg/ml vs. 664.4 (487.4–2955.8) pg/ml (p = 0.006)] and Vitamin D levels were lower [13.4 (2.5–153) ng/ml vs. 27.8 (18.4–59.0) ng/ml (p = 0.001)] in the hemodialysis patients than in the healthy control. No important correlation was found between sTWEAK Vitamin D levels (r = 0.010/p = 0.946), and mean right(r = −0.194/p = 0.178) and left (r = 0.061/p = 0.673) cIMT in the HD patients. Our study shows that sTWEAK levels are elevated in HD patients. This elevation has no association with the cIMT.

Statins are widely used drugs for their role in decreasing cholesterol in hypercholesterolemic patients. Statins through inhibition of Hydroxy Methyl Glutaryl-CoA Reductase (HMGCR), the main enzyme of the cholesterol biosynthesis pathway, inhibit mevalonate pathway that provides isoprenoids for prenylation of different proteins such as Ras superfamily which has an essential role in cancer developing. Inhibition of the mevalonate/isoprenoid pathway is the cause of the cholesterol independent effects of statins or pleotropic effects. Depending on their penetrance into the extra-hepatic cells, statins have different effects on mevalonate/isoprenoid pathway. Lipophilic statins diffuse into all cells and hydrophilic ones use a variety of membrane transporters to gain access to cells other than hepatocytes. It has been suggested that the lower accessibility of statins for extra-hepatic tissues may result in the compensatory induction of mevalonate/isoprenoid pathway and so cancer developing. However, most of the population-based studies have demonstrated that statins have no effect on cancer developing, even decrease the risk of different types of cancer. In this review we focus on the cancer developing "potentials" and the anti-cancer "activities" of statins regarding the effects of statins on mevalonate/isoprenoid pathway in the liver and extra-hepatic tissues.

Background: Patients on hemodialysis (HD) generally display a significant decrease in the quality of life owing to comorbidities, malnutrition, and inflammation. Methods: In this multicenter prospective study, the SF36 (short form with 36 questions scored between 0 and 100) and relevant demographic data and comorbidities (charlson comorbidity index); nutritional factors, and C-reactive protein (CRP) were evaluated in 416 HD patients in September 2012. Hospitalization and mortality were assessed in a median of a 28 month follow-up. Results: The SF36 score in survived patients was 53.6 ± 19.3 versus 41.6 ± 22.4 in the non-survived patients (P 3.60 - 3.85, > 3.85 - 4.00, > 4.00 - 4.20, > 4.20 (reference) g/dL was respectively 3.69 (1.98 - 6.89), 2.08 (1.10 - 3.94), 1.91 (0.97 - 3.85), 1.10 (0.76 - 1.49). Serum albumin revealed a strong association with mortality such that hazard ratio for every 1 g/dL decrease in serum albumin was 6.28 (95% CI: 3.80 - 10.42; P < 0.001). Conclusions: In patients with hemodialysis, SF36 shows significant association with serum albumin, comorbidities, inflammation, and clinical outcome.

The aim of the present study was to evaluate the osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B ligand (RANKL), oxidant, and antioxidant status in untreated active pulmonary tuberculosis patients (PTB). Serum was obtained from 42 patients with different forms of untreated active PTB and 41 healthy subjects, as the control group. The serum levels of OPG, RANKL, tumor necrosis factor alpha (TNFα), malondialdehyde (MDA), total antioxidant capacity (TAC), and the lipid profiles were determined using standard methods. Patients with PTB were detected to have significantly higher plasma MDA, TNFα, OPG, and RANKL levels, and lower TAC levels, when compared to the healthy controls(p

Hyperlipidemia can lead to atherosclerosis by lipoprotein deposition inside the vessel wall and oxidative stress induction that leads to the formation of atherosclerotic plaque. Oxidized low-density lipoprotein particles (Ox-LDL) have a key role in the pathogenesis of atherosclerosis. The lipid-lowering properties and antioxidants of the grape seed can be beneficial in atherosclerosis prevention. We conducted a randomized double-blind placebo-controlled crossover clinical trial. Fifty-two mildly hyperlipidemic individuals were divided into two groups that received either 200 mg/day of the red grape seed extract (RGSE) or placebo for 8 weeks. After an 8-week washout period, the groups were crossed over for another 8 weeks. Lipid profiles and Ox-LDL were measured at the beginning and the end of each phase. RGSE consumption reduced total cholesterol (-10.68±26.76 mg/dL, P=.015), LDL cholesterol (-9.66±23.92 mg/dL, P=.014), and Ox-LDL (-5.47±12.12 mg/dL, P=.008). While triglyceride and very low-density lipoprotein cholesterol were decreased and high-density lipoprotein cholesterol was increased by RGSE, the changes were not statistically significant. RGSE consumption decreases Ox-LDL and has beneficial effects on lipid profile-consequently decreasing the risk of atherosclerosis and cardiovascular disorders-in mild hyperlipidemic individuals.

Background: Abnormal mineral metabolism is common among hemodialysis patients and has been associated with higher morbidity and mortality rates. Methods: A cohort of 532 hemodialysis patients was selected from nine hemodialysis centers in September 2012 and were prospectively followed-up for a median of 28 months. Unadjusted and adjusted (in terms of age, gender, dialysis vintage, body mass index, albumin level, and comorbidities) hazard ratios (HRs) of mortality associated with serum phosphorus, calcium, and parathyroid hormone (PTH) levels were calculated, using Cox proportional hazards model. Results: In the unadjusted model, HRs of mortality for serum phosphorus < 4 mg/dL (reference: 4 - 6) and iPTH < 200 pg/mL (reference: 200 - 600) were 1.61 (95% CI: 1 - 2.46) and 1.55 (95% CI: 1.06 - 2.27), respectively. After adjustment, the foregoing values were no longer significant, and HRs for serum phosphorus level ≥ 6 mg/dL (reference: 4 - 6), calcium level ≥ 10 (reference: < 10), and iPTH ≥ 600 (reference: 200 - 600) were calculated to be 1.56 (95% CI: 1.09 - 2.22), 2.34 (95% CI: 1.21 - 4.51), and 1.59 (95% CI: 1.03-2.45), respectively. Meanwhile, significant adjusted correlates of iPTH were serum alkaline phosphatase (r = 0.49), phosphorus (r=0.24), dialysis vintage (r = 0.21), age (r = -0.20), diabetes (r = -0.16), and serum calcium level (r = -0.13). Conclusions: While high serum PTH, calcium, and phosphorus levels could determine the mortality risk in hemodialysis patients, decreased serum phosphorus and PTH levels were in association with malnutrition and comorbidities and were not independent risk factors for mortality.

In solid-organ transplant, cell therapy is used as an immunomodulation therapy or as a functioning graft (bioengineering medicine). Before such treatment can be more accepted among transplant societies, some uncertainties should be clarified. These include: why is such therapy mandatory? What are the indications for this therapy, and what are the mechanism(s) of actions? What types of cells are involved and what are their routes of actions? Finally, what is known about the safety? In general, the risks associated with intravenous administration of immunoregulatory cell products are similar to those encountered with conventional blood transfusions. The adverse effects of immunosuppressive drugs, such as infections, cardiovascular disease, metabolic complications, and malignancies, would be decreased with cell therapy. Immunoregulatory cells act when necessary and through multiple mechanisms through different targets. Immunoregulatory cells are not only passive inhibitors such as drugs, but they have active functions. Treatment would only be once or perhaps a few times but not indefinitely, which is in contrast to immunosuppressive drugs; therefore, complications involving immunosuppressive drugs are no longer present. Cell therapy in solid-organ transplant is indicated for treatment of ischemic-reperfusion injury, prevention of chronic allograft nephropathy, minimization of immune suppression, and induction of long-term allograft tolerance. Many cell types have being investigated as potential cell-based immunotherapies for use in solid-organ transplant, including mesenchymal stromal cells, regulatory macrophages, tolerogenic dendritic cells, regulatory T cells, and regulatory B cells. Efficacy and safety of each group of cells should be clarified before widespread clinical use. The landscape of transplant science would be at least partially, if not totally, changed with cell therapy.

Cardiovascular and noncardiovascular mortality and morbidity rates of hemodialysis patients are high despite improvement in dialysis delivery.Hemodialysis patients (n = 532) from 9 hemodialysis facilities were enrolled in this cohort study in September 2012. Causes of death, hospitalization, and hemodialysis exit were recorded during a 28-month follow-up period. A Cox proportional hazard model was used to predict death adjusting for case-mix variables, nutrition variables, bone mineral variables, Kt/V, vascular access, and Charlson comorbidities index.Patients were 56.0 ± 15.4 years old (57% men). A total of 161 patients (30%) died (17 per 100 patient years), and the most common causes of death were cardiovascular diseases (42%) and infections (25%). Transplantation rate was 7 per 100 patient years and hospitalization frequency was 0.76 per patient year. Based on the multivariable Cox proportional hazard model, the mortality hazard ratio was 1.03 (95% confidence interval [CI], 1.01 to 1.05; P = .007) for age (years), 0.21 (95% CI, 0.11 to 0.40; P.001) for serum albumin (g/dL), 1.21 (95% CI, 1.03 to 1.42; P = .02) for serum phosphorus (mg/dL), 1.001 (95% CI, 1.0005 to 1.002; P = .001) for serum intact parathyroid hormone (pg/mL), 1.58 (95% CI, 1.01 to 2.51; P = .047) for hemodialysis catheter (compared to arteriovenous fistula), and 1.75 (95% CI, 1.59 to 1.94; P.001) for the Charlson score.Nutritional factors, comorbidities, vascular access, and abnormal mineral metabolism are the main determinants of mortality and morbidity in hemodialysis patients.

RESUMO Objetivos: A taxa de mortalidade de pacientes com doença renal crônica (DRC), que tenham sido submetidos à terapia de substituição renal, é muito elevada devido a doenças cardiovasculares (DCV). Alguns estudos indicaram que a ciclosporina A (CsA), um medicamento utilizado para prevenir a rejeição de transplante, está associada à perda óssea após o transplante. Além disso, ela tem um efeito oxidante sobre os lipídeos circulantes. Seu efeito pró-oxidante nas membranas celulares provoca a liberação de cálcio. Este estudo teve como objetivo analisar se o transplante renal pode ou não resultar em melhora no estresse oxidativo (EO); e avaliar a associação entre a LDL oxidada (LDL-ox) e algumas variáveis na predição do risco de DCV em pacientes transplantados renais (TR), comparados com o grupo controle. Materiais e Métodos: Um total de 30 pacientes com DRC foram recrutados para avaliação das alterações dependentes do tempo no biomarcador de EO antes e após TR. Foram avaliados: LDL-ox, parâmetros do metabolismo dos lipídeos, a CsA, creatinina, cálcio e fosfato tanto antes do TR, 10 dias e 6 meses após o TR, em comparação com o grupo controle (n = 30). Resultados: após 6 meses, a concentração de LDL-ox mudou de 79,7 ± 9,7-72 ± 7 mU/ml (p < 0,009). O nível de fosfato de cálcio foi positivamente correlacionado com a concentração de LDL-ox (R = 0,467, p = 0,011) e ciclosporina (r = 0,419, p = 0,024) 6 meses após o transplante. Conclusão: Os resultados indicaram que a restauração da função renal pelo transplante, melhora o estresse oxidativo induzido pela uremia. O produto de fosfato de cálcio, como um fator de risco independente para DCV, correlaciona-se com o LDL-ox antes do TR e 6 meses após o TR. O produto de fosfato de cálcio também se correlaciona com a ciclosporina no grupo TR. ABSTRACT Objectives: The mortality rate of chronic kidney disease (CKD) patients that have undergone renal replacement therapy is very high due to cardiovascular diseases (CVD). Some studies have indicated that cyclosporine A, a drug used to prevent transplant rejection, is associated with bone loss following transplantation. Furthermore, it has an oxidative effect on circulating lipids. Its prooxidant effect on cell membranes causes calcium release. This study aimed to examine whether or not renal transplantation result in improvement in oxidative stress and to assess the association between oxidized LDL (ox-LDL) and some variables in the prediction of CVD risk in Renal Transplantation (RT) patients that were compared with the control group. Material and Methods: A total number of 30 CKD patients were recruited to evaluate time dependent changes in biomarker of OS before and after RT. The ox-LDL, lipid metabolism parameters, CsA, creatinine, calcium and phosphate were assessed both before RT, 10 days and 6 months after RT in comparison with the control group (n = 30). Results: Over 6 months, ox-LDL concentration changed from 79.7 ± 9.7 to 72 ± 7 mU/mL (p < 0.009). calcium phosphate level was positively correlated with the concentration of ox-LDL (R = 0.467, p = 0.011) and cyclosporine (R = 0.419, p = 0.024) 6 months after transplantation. Conclusion: The findings indicated that restoring renal function by transplantation, improves uremia induced oxidative stress. calcium phosphate product, as an independent risk factor for CVD, correlates with ox-LDL before RT and 6 months after RT. Calcium phosphate product correlates with cyclosporine in the RT group, too.

Calcineurin inhibitor nephrotoxicity is major problem after organ transplantation. It is multifactorial, but oxidative stress may have an important role in this process. It has been shown that angiotensin II receptor blockers have renoprotective effects but their molecular mechanism is largely unknown. Antioxidative effect is an important role of the recently known anti-aging protein, klotho. This study aimed to evaluate effect of valsartan in alleviation of cyclosporine A nephrotoxicity via a probable increase in serum klotho levels or decreasing oxidative stress.Thirty-two Sprague-Dawley rats were divided into 4 groups to receive 1 mL/kg/d of olive oil as control; 30 mg/kg/d of cyclosporine; 30 mg/kg/d of cyclosporine and 50 mg/kg/d of valsartan; and 50 mg/kg/d of valsartan. After the 6 weeks of administration period, serum levels of klotho and 8-hydroxydeoxyguanosine were measured using an enzyme-linked immunosorbent assay. Serum malondialdehyde level was measured spectrophotometrically.The mean serum level of klotho was significantly lower in the cyclosporine group compared with control and valsartan groups. Klotho level in the valsartan group was significantly higher than those in the other groups. The cyclosporine group was detected to have significantly higher serum 8-hydroxydeoxyguanosine and malondialdehyde levels compared with the other study groups. The levels of klotho were negatively correlated with 8-hydroxydeoxyguanosine and malondialdehyde levels.Administration of valsartan may lead to attenuation of the nephrotoxic side effect of cyclosporine via enhancing klotho and decreasing oxidative stress levels.

Background: The most important surgical complications of renal transplantation are stenosis and obstruction of the ureterovesi- cal anastomosis. Routine use of ureteral stents can prevent this complication, but the optimal time for ureteral stent use is still controversial. Objectives: The purpose of this study is to compare the benefits and complications of early and delayed stent removal after surgery. Early ureteral stent removal can decrease some complications, such as urinary tract infections (UTIs), bladder irritation symptoms, persistent hematuria, and the risk of stent crusting; its benefits include easier stent removal and shorter hospitalization time. Patients and Methods: All patients who underwent kidney transplantation from May 2011 until March 2012 in Modarres Hospital were included in this study. We classified the patients into three groups, based on time of stent removal (10, 20, and 30 days after transplantation). Results: Ninety-one patients were studied; urologic complications (hydroureteronephrosis and urinoma) in these three groups were analyzed and showed no statistical significant dierence. Conclusions: We can remove the ureteral stent earlier after kidney transplantation with no increase in the prevalence of surgical complications.

Please cite this paper as: Tavana et al. (2011) Influenza vaccination in patients with pulmonary sarcoidosis: efficacy and safety. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750-2659.2011.00290.x. Background Sarcoidosis is an inflammatory, granulomatous disorder of unknown etiology. The role of cellular and humoral immune systems in this disease is unclear, whereas dysregulation of the immune system is suggested. Patients with sarcoidosis show diverse responses while exposed to various antigens. Although influenza vaccination is recommended in pulmonary sarcoidosis, its efficacy and safety has not been investigated. Objectives To evaluate safety and immunogenicity of influenza vaccine in patients with sarcoidosis. Patients/Methods Influenza vaccination was performed in 23 eligible patients with sarcoidosis (SP) and 26 healthy controls (HC). Antibody titers against H1N1, H3N2, and B influenza virus antigens were evaluated just before and 1 month after vaccination. Patients were followed for 6 months to assess vaccine safety. Results Serological response and magnitude of changes in antibody titers against influenza vaccine antigens were comparable between SPs and HCs. Women showed a better serological response against B antigen (P = 0·034) than men. Twenty-four-hour urine calcium was associated with antibody response against H1N1 [correlation coefficient (CC) = 0·477, P = 0·003] and H3N2 (CC = 0·352, P = 0·028) antigens. Serum angiotensin-converting enzyme correlated negatively with antibody response against B antigen (CC = −0·331, P = 0·040). Higher residual volume was associated with fewer rises in antibody titer against H3N2 antigen (CC = −0·377, P = 0·035). No major adverse events or disease flare-up was observed during follow-up. Conclusions In this study, influenza vaccination did not cause any major adverse event in SPs, and their serological response was equal to HCs. Studies with larger sample size and a broader selection of subjects could help validate the results of this study.

OBJECTIVE: The objectives of this study were to determine the effects of zinc supplementation on dietary intake, symptoms of eating problems, and serum zinc levels in hemodialysis patients. METHODS: Thirty-nine patients who received chronic maintenance hemodialysis were randomized to experimental (n 21) and placebo (n 18) groups given a daily supplement of 100 mg elemental zinc and corn starch, respectively, for 60 days. Dietary intake, body composition, and eating problems were assessed using 2-day dietary records, bioelectric impedance tests, and a questionnaire, respectively. Serum zinc levels were determined by atomic absorption before and after intervention. RESULTS: The mean daily macro- and micronutrients intakes and percentage of body fat in the supplemented group increased insignifi cantly. Administration of zinc improved appetite loss, dry mouth, nausea, and hypogeusia, while incidence of these symptoms increased in control group. A signifi cant increase (p 0.01) was observed in the mean serum zinc levels in the experimental group (102 4 vs. 76 3 g/dL) while changes in the placebo group were not signifi cant. CONCLUSIONS: Despite observed improvement in symptoms of eating problems and serum zinc levels in the supplemented group, more study over a longer period must be carried out to achieve clearer results.

Background: Age-related macular degeneration (AMD) is the most common cause of elderly irreversible vision loss in the world. Since C-reactive protein (CRP) is a potential risk factor that has been known to induce AMD, this study was designed to explore the relationship between AMD and serum levels of high sensitivity C-reactive protein (hsCRP), and endothelin-1 (ET-1). Methods The subjects were 48 males with AMD (28 with wet type and 20 with dry type) having a mean age of 69.4 ± 9.6 years and a matched group of 45 apparently healthy control subjects. The AMD was diagnosed using a slit-lamp with super filled lens, fundus photography and fluorescein angiography. Levels of hsCRP and ET-1 were determined using ELISA methods. Results: hsCRP (6.96 ± 5.15 vs. 3.64 ± 4.67 mg/l, P

Purpose: To evaluate the effects of onion juice on sodium-selenite induced cataract formation. Materials and Methods: Thirty-two 10-day-old Wistar-albino rat pups were divided into four equal groups. Group 1 received only subcutaneous saline injection. In Group 2, sodium-selenite (30 nmol / g body weight) was injected subcutaneously. In Group 3, subcutaneous sodium-selenite was injected and one drop 50% diluted fresh juice of crude onion was instilled every 8 h into the right eye for 14 days; the left eye received no treatment. Group 4 rats were similar to those of Group 3, the only difference being that of undiluted fresh juice of crude onion. The development of cataract was assessed. Rat lenses were analyzed for total antioxidant (TA) level, and for activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD). Results: Both eyes of all rats in Group 1 did not exhibit cataract formation . In Group 2, all rats developed Grade 3 cataract in the lenses of both eyes. The difference in exhibited cataract in the lens of the right eyes in all rats between Group 2 and any eyes of groups 3 or 4 were significant ( P = 0.001). The mean TA level and mean activities of SOD and GPX in Group 2 rat lenses were significantly lower than the values in lenses of all rats in Group 1 ( P = 0.001, 0.003, 0.001), and in the lenses of the right eyes of rats in Groups 3 and 4 ( P = 0.001, 0.020, 0.001). Conclusion: Instillation of onion juice into the rat eyes can effectively prevent selenite-induced cataract formation. This effect was associated with increased TA level, SOD and GPX activities in the lens.

Disturbances in metabolism of lipo-proteins and oxidative modification of low-density lipoprotein contribute to cardiovascular disease and development of oxidative stress in patients under renal replacement therapy (hemodialysis and renal transplant). This study was designed to compare oxidized low-density lipoprotein levels and lipid profiles in renal transplant recipients and hemo-dialysis patients.We investigated the concentration of oxidized low-density lipoprotein in hemodialysis (n = 38) and renal transplant (n = 59) patients who had no active inflammatory disease, liver disease, or malignancy, and results were compared to a control group (n = 30).Renal transplant recipients had hypercholesterolemia, hypertriglyceridemia, and increased oxidized low-density lipoprotein levels (P = .019) compared with the control group. Hemodialysis patients had moderate hypertriglyceridemia (not significant), hypercholesterolemia, decrease in high-density lipoprotein, and increase in oxidized low-density lipoprotein levels (P.0001) compared with the control group. In the renal transplant group, oxidized low-density lipoprotein level had a negative correlation with the duration after transplant (r = -0.407; P = .026), positive association with cyclosporine level (r = 0.288; P = .04), and negative correlation with high-density lipoprotein level (r = -.30; P = .05); oxidized low-density lipo-protein/high-density lipoprotein ratio also had a positive correlation with cyclosporine level (r = 0.309; P = .027) and negative correlation with high-density lipoprotein level (r = -0.72; P.001) in the renal transplant group and high-density lipoprotein in the hemodialysis group (r = -0.87; P.001). Multiple stepwise regression analyses showed that oxidized low-density lipoprotein only was associated with cyclosporine level (R2 = 0.155; β=0.393; P = .024).History of cardiovascular disease is the most important factor associated with end-stage renal disease, and high oxidized low-density lipoprotein level, oxidized low-density lipo-protein/high-density lipoprotein ratio, and high-density lipoprotein level may affect cardiovascular disease.

To explore the probable association of serum hepcidin and haemoglobin levels with iron and inflammation statuses in patients of chronic kidney disease stage 4 with anaemia.The cross-sectional study was conducted at Tabriz University of Medical Sciences, Iran, from March 2011 to October 2012, and comprised patients of chronic kidney disease stage 4 with anaemia. Serum biochemical factors as well as hepcidin, ferritin, interleukin 6, high sensitivity C-reactive protein and iron levels were measured using standard methods. Statistical correlations were established using regression analysis and Pearson's correlation coefficient.There were 40 patients among whom 15(37.5%) were males and 25(62.5%) were females with an overall mean age of 55.68±14.4 years. There was a significant inverse relationship between hepcidin and haemoglobin levels (p0.05). There were significant correlations between hepcidin with iron status, nutritional and inflammatory markers such as ferritin, Total iron binding capacity, albumin and interleukin 6 (p0.05 each).Hepcidin had negative correlation with haemoglobin level in stage 4 chronic kidney disease patients with adequate iron stores, which could be effective in the development of anaemia in such patients.

Background High serum phosphate and fibroblast growth factor-23 (FGF-23) levels are well-recognized independent risk factors of mortality and morbidity in patients with chronic kidney diseases (CKDs). Sevelamer, as a phosphate chelating agent, reduces serum phosphate and FGF-23 levels produced by bone osteocytes. This study aimed to determine the best dose at which sevelamer could successfully reduce serum phosphate and FGF-23 levels in rat models of adenine-induced CKD. Methods CKD was induced using adenine. Healthy and CKD-induced rats were divided into 6 groups as follows: healthy controls; CKD controls; rats treated with 1%, 2%, and 3% sevelamer for CKDs; and healthy rats administered 3% sevelamer. Biochemical factors and serum FGF-23 levels were measured using spectrophotometry and enzyme-linked immunosorbent assay methods. Results Serum phosphate levels were best decreased in rats receiving 3% sevelamer in their diet (5.91±1.48 mg/dL vs. 8.09±1.70 mg/dL, P

Background aims Chronic kidney disease (CKD) attributed to cisplatin is well documented. Mesenchymal stromal cells (MSCs) are proven to be renotropic. Although they have been shown to improve function in CKD and reduce fibrosis in different experimental rodent models, their efficiency in primates is unknown. The present study aimed to evaluate the prevention of CKD and reduction of fibrosis in monkeys treated with MSCs after cisplatin nephrotoxicity. Methods We induced CKD in adult rhesus Macaca mulatta monkeys by means of intravenous administration of cisplatin. Autologous MSCs were transplanted by means of intrarenal arterial injections to assess the adverse effects of cisplatin in two CKD models: preventative and stable. Preventative CKD monkeys ( n = 3) underwent cell transplantation 4 days after the cisplatin injection. The stable CKD monkeys ( n = 2) underwent cell transplantation 6 months after the cisplatin injection. Non-treated ( n = 4) and normal saline–injected animals ( n = 3) comprised the control and vehicle groups, respectively. We followed the animals for survival rate, serum biochemistry, urine analysis and histopathological indices. Results In the preventive CKD model, MSC transplantation tended to improve some renal functions but significantly reduced the histopathologic score compared with the vehicle and control groups. In the stable CKD model, MSCs did not ameliorate renal function or pathological score. Conclusions These results suggest that MSCs tend to delay progression of CKD and fibrosis but do not reduce established interstitial fibrosis in this unique primate model of cisplatin-induced nephrotoxicity.

Background: Endotheline-1 (ET-1), an endothelial mediator, influences on mineral metabolism; especially vascular calcification in uremic patients. Objectives: The aim of the present study was to evaluate of ET-1, high-sensitivity C-reactive protein (hs-CRP) and mineral metabolites as the main factors for vascular calcification and inflammation in hemodialysis (HD) patients. Patients and Methods: In this cross-sectional study, 46 chronic stable HD patients were selected from nephrology departments of Tabriz University of Medical Sciences affiliated hospitals and classified based on phosphorus (P), Ca-P product (Ca × P) and intact Parathyroid Hormone (iPTH) levels. We evaluated fasting serum ET-1and hs-CRP levels by the standard methods and compared with 46 healthy control subjects. Results: The levels of serum hs-CRP and ET-1 were significantly higher in the patient’s group compared with controls (4.40 ± 1.26 vs. 1.38 ± 1.61, P < 0.0001, and 2.31 ± 0.87 vs. 0.75 ± 0.48, P < 0.0001, respectively) and with regard to Ca × P product cut-off point (3.99 ± 0.78 vs. 5.33 ± 1.64, P < 0.0001, and 2 ± 0.73 vs. 3.04 ± 0.73, P < 0.0001 respectively). ET-1 was correlated significantly with hs-CRP level (r = 0.776, P < 0.0001). Serum P, Ca × P and iPTH levels directly and Ca indirectly were correlated with serum ET-1 in HD patients (r = 0.932, P < 0.0001, r = 0.766, P < 0.0001, r = 0.514, P < 0.0001, r = -0.538, P < 0.0001 respectively). Multiple regression analysis demonstrated that serum P were independently associated with ET-1 levels (β = 0.932, P < 0.0001). Conclusions: Serum P and iPTH levels were independently associated with ET-1 and those may play a role in development of endothelial dysfunction in chronic kidney disease.

Plasma protein growth arrest-specific 6 (GAS6) and matrix Gla protein (MGP) are crucial mediators of vascular calcification and are involved in the development of vascular complications in chronic kidney diseases. This study was set out to investigate the relationship between plasma GAS6 levels and MGP in patients with end-stage renal disease on maintenance hemodialysis.Forty-six hemodialysis and 46 healthy individuals with normal kidneys were recruited. Plasma GAS6 and MGP concentrations and related biochemical factors were quantified as well as collection of data on clinical characteristics.Plasma GAS6 levels were significantly higher in the hemodialysis patients as compared with the control group (763.52 ± 187.91 pg/mL versus 421.63 ± 189.91 pg/mL, P.001). Plasma MGP concentration was significantly lower in the hemodialysis patients than the control group (52.35 ± 12.35 ng/mL versus 6.60 ± 19.54 ng/mL, P.001). The levels of GAS6 were inversely associated with MGP (r = -0.341, P = .02) in the hemodialysis patients.Increased GAS6 and decreased MGP levels in hemodialysis patients, as mediators of induction or prevention of vascular calcification, and their inverse correlation may suggest that there might be a role in increased calcification process in hemodialysis patients or only as a secondary phenomenon of advanced kidney failure. Their direct role on vascular calcification needs further studies in the future.

Low fetuin-A and 1,25-hydroxyvitamin D3 (vitamin D) levels accompanied with high intact parathyroid hormone (PTH) contents are associated with cardiovascular disease in dialysis patients. The aim of present study was to evaluate the relationship between vitamin D receptor (VDR) gene FokI and ApaI polymorphisms with serum levels of fetuin-A, vitamin D, and intact PTH in hemodialysis patients.Serum was obtained from 46 stable chronic hemodialysis patients and 43 healthy controls. Serum levels of intact PTH, fetuin-A, vitamin D, calcium, and phosphorus were measured. Genotyping of the VDR gene was performed using standard methods.Serum fetuin-A and vitamin D levels were significantly lower, whereas serum levels of PTH, calcium, and Phosphorus were higher in the hemodialysis patients than in the healthy controls. The FokI genotypes were more frequent in the hemodialysis patients than the control group (P = .004). With respect to FokI genotypes, intact PTH level was higher among the hemodialysis patients compared to the controls (P = .02). In contrast, vitamin D level was lower in the hemodialysis patients with ApaI genotypes compared to the control group (P = .04).Our study shows that increased serum level of PTH and decreased fetuin-A and vitamin D levels may increase susceptibility of atherosclerosis in patients with hemodialysis through VDR gene FokI and ApaI polymorphisms.