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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.

Cisplatin is a broadly prescribed anti-tumor agent for the treatment of diverse cancers. Therapy with cisplatin, however, is associated with various adverse effects including nephrotoxicity and ototoxicity. AMP kinase (AMPK), an evolutionarily conserved enzyme, functions as the fundamental regulator of energy homeostasis. While AMPK activation protects normal tissues against cisplatin-induced toxicities, its impact in cancer is context-dependent and there is no single, uniform role for AMPK. On one hand, some report that AMPK activation augments cisplatin-induced apoptosis in cancer, while on the other hand, few reports indicate that AMPK activation rescues cancer cells from the cytotoxicity induced by cisplatin. Here we review the most salient signaling pathways regulated by AMPK with an emphasis on their relation to cisplatin toxicity and yet discuss context-dependent functions of AMPK in cancer.

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.

Receptor for advanced glycation end-products (RAGE) is involved in the pathogenesis of diabetic nephropathy. FPS-ZM1, a selective RAGE inhibitor, in combination with valsartan were investigated for their protective potentials on the renal markers of tubular injury in streptozotocin-induced diabetic rats. Rats were assigned into groups of receiving FPS-ZM1 (1 mg/kg/day), valsartan (100 mg/kg/day), and FPS-ZM1 plus valsartan (1 mg/kg/day and 100 mg/kg/day, respectively) for one month. Kidney histology, renal inflammation and oxidative stress, and renal and urinary markers of tubular injury were investigated. FPS-ZM1 and valsartan in combination more significantly attenuated renal expressions of tumor necrosis factor-alpha and interleukin-6 genes and reduced urinary levels of interleukin-6. Moreover, the combination elevated renal NAD+/NADH ratios and Sirt1 activities, and mitigated nuclear acetylated NF-κB p65 levels. In addition to alleviating indices of oxidative stress i.e. malondialdehyde, superoxide dismutase and glutathione peroxidase, the combination of FPS-ZM1 and valsartan more effectively upregulated the renal levels of master antioxidant proteins Nrf2, heme oxygenase-1, and NAD(P)H:quinone oxidoreductase-1. Additionally, this dual therapy ameliorated more efficiently the indices of renal tubular injuries as indicated by decreased renal kidney injury molecule-1 levels as well as reduced urinary levels of cystatin C, retinol binding protein, and beta-2-microglobulin. While FPS-ZM1 alone had no appreciable effects on the renal fibrosis, the combination treatment ameliorated fibrosis better than valsartan in the kidneys. Collectively, these findings underline the extra benefits of FPS-ZM1 and valsartan dual administrations in obviating the renal tubular cell injury in streptozotocin-induced diabetic rats partly by suppressing renal inflammation and oxidative stress.

Post-transplant ischemic acute kidney injury (AKI), secondary to ischemia reperfusion injury (IRI), is a major problem influencing on the short and long term graft and patient survival. Many molecular and cellular modifications are observed during IRI, for example, tissue damage result production of reactive oxygen species (ROS), cytokines, chemokines, and leukocytes recruitment which are activated by NF-κB (nuclear factor kappa B) signaling pathway. Therefore, inhibiting these processes can significantly protect renal parenchyma from tissue damage. Klotho protein, mainly produced in distal convoluted tubules (DCT), is an anti-senescence protein. There is increasing evidence to confirm a relationship between Klotho levels and renal allograft function. Many studies have also demonstrated that expression of the Klotho gene would be down regulated with IRI, so it will be used as an early biomarker for acute kidney injury after renal transplantation. Other studies suggest that Klotho may have a renoprotective effect for attenuating of kidney injury. In this review, we will discuss pathophysiology of IRI-induced acute kidney injury and its relation with klotho level in renal transplantation procedure.

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).

Hydroxy-Methyl-Glutaryl-CoA reductase (HMGCR) – the main enzyme of the cholesterol biosynthesis pathway – is mostly inhibited by statins in hepatocytes. In spite of the other tissues, liver utilizes cholesterol in different ways such as the synthesis of bile acids, excretion in to the intestine and synthesis of lipoproteins. Therefore, statins theoretically alter these pathways; although, there have not been such effects. In this review, we aim to show the roles of extra-hepatic tissues, in particular intestine, adipose and cutaneous tissues in providing the cholesterol after reduction of the whole body cholesterol content by statins.

Hyperlipidemia and oxidative stress are indispensable features of chronic kidney disease (CKD) that favor the development of atherogenic plaques and cardiovascular disease (CVD). A number of vasoactive mediators including proprotein convertase subtilisin-kexin type 9 (PCSK9), endothelin-1, nitric oxide, and angiotensin II have fundamental roles in the pathophysiology of atherosclerotic events; moreover, their levels are affected by dyslipidemia and oxidative stress due to renal dysfunction. Therefore, therapeutic measures aimed at correcting dyslipidemia and alleviating oxidative stress could potentially protect against CVD in CKD patients. In this review, we discuss the relation between dyslipidemia, oxidative stress, and vasoactive mediators as well as the available treatment options against these disturbances in CKD patients.

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.

Background The growing morbidity and mortality rate of chronic kidney disease (CKD) has forced researchers to find more efficient strategies for controlling this disease. Studies have proven the important role of alteration in iron, zinc and selenium metabolism in CKD pathological process. Nanotechnology, through synthetizing nano metal-organic framework (NMOF) structures, can be employed as a valuable strategy for using these trace elements as the key for modification and improvement of CKD-related pathological events. After proving the anti-diabetic property of DIBc NMOF (which contains selenium and zinc) in the previous study, the impact of this NMOF on some important biochemical and pathological parameters of CKD was evaluated in the current study. Methods Knowing that diabetic nephropathy (DN) is the leading cause of CKD, male wistar rats were selected and given a high fat diet for 2 weeks and then were injected with streptozotocin (35 mg/kg) to induce DN. Six weeks after streptozotocin injection, DIBc or metformin treatment started and continued for 8 weeks. Results Eight weeks of DIBc treatment decreased plasma fasting blood glucose, blood urea nitrogen, uric acid, malondialdehyde (MDA) and HOMA-IR index compared to DN control and metformin groups. This NMOF significantly reduced urinary albumin excretion rate, MDA and 8-isoprostane, while it increased creatinine clearance in comparison to the above-mentioned groups. Renal histo-pathological images indicated that DIBc ameliorated glomerular basement membrane thickening and wrinkling, mesangial matrix expansion and hypercellularity and presence of intra-cytoplasmic hyaline droplets in proximal cortical tubules of kidney samples. Conclusion The results showed the therapeutic effect of DIBc on important biochemical and histo-pathological parameters of CKD, so this NMOF could be regarded as a promising novel anti-CKD agent.

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.

Diabetic nephropathy is one of the most frequent micro-vascular complications both in type 1 and type 2 diabetic patients and is the leading cause of end-stage renal disease worldwide. Although disparate mechanisms give rise to the development of diabetic nephropathy, prevailing evidence accentuates that hyperglycemia-associated generation of advanced glycation end products (AGEs) plays a central role in the disease pathophysiology. Engagement of the receptor for AGE (RAGE) with its ligands provokes oxidative stress and chronic inflammation in renal tissues, ending up with losses in kidney function. Moreover, RAGE activation evokes the activation of different intracellular signaling pathways like PI3K/Akt, MAPK/ERK, and NF-κB; and therefore, its blockade seems to be an attractive therapeutic target in these group of patients. By recognizing the contribution of AGE-RAGE axis to the pathogenesis of diabetic nephropathy, agents that block AGEs formation have been at the heart of investigations for several years, yielding encouraging improvements in experimental models of diabetic nephropathy. Even so, recent studies have evaluated the effects of specific RAGE inhibition with FPS-ZM1 and RAGE-aptamers as novel therapeutic strategies. Despite all these promising outcomes in experimental models of diabetic nephropathy, no thorough clinical trial have ever examined the end results of AGE-RAGE axis blockade in patients of diabetic nephropathy. As most of the AGE lowering or RAGE inhibiting compounds have emerged to be non-toxic, devising novel clinical trials appears to be inevitable. Here, the current potential treatment options for diabetic nephropathy by AGE-RAGE inhibitory modalities have been reviewed.

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

Despite the effectiveness of renin-angiotensin blockade in retarding diabetic nephropathy progression, a considerable number of patients still develop end-stage renal disease. The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor of receptor for advanced glycation end products (RAGE), alone and in combination with valsartan, an angiotensin receptor blocker, against glomerular injury parameters in streptozotocin-induced diabetic rats. FPS-ZM1 at 1 mg/kg (i.p.), valsartan at 100 mg/kg (p.o.), and their combination were administered for 4 weeks, starting 2 months after diabetes induction in rats. Tests for kidney function, glomerular filtration barrier, and podocyte slit diaphragm integrities were performed. Combined FPS-ZM1/valsartan attenuated diabetes-induced elevations in renal levels of RAGE and phosphorylated NF-κB p65 subunit. It ameliorated glomerular injury due to diabetes by increasing glomerular nephrin and synaptopodin expressions, mitigating renal integrin-linked kinase (ILK) levels, and lowering urinary albumin, collagen type IV, and podocin excretions. FPS-ZM1 also improved renal function as demonstrated by decreasing levels of serum cystatin C. Additionally, the combination also alleviated indices of renal inflammation as revealed by decreased renal monocyte chemoattractant protein 1 (MCP-1) and chemokine (C-X-C motif) ligand 12 (CXCL12) expressions, F4/80-positive macrophages, glomerular TUNEL-positive cells, and urinary alpha-1-acid glycoprotein (AGP) levels. These findings underline the benefits of FPS-ZM1 added to valsartan in alleviating renal glomerular injury evoked by diabetes in streptozotocin rats and suggest FPS-ZM1 as a new potential adjunct to the conventional renin-angiotensin blockade.

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.

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.

BACKGROUND Nephrotoxicity side effect of the immunosuppressive drug, cyclosporine A (CsA), can be a major issue in transplantation medicine. Cyclosporine A-induced nephrotoxicity is multifactorial but oxidative stress has a critical role in this process. It has been demonstrated that Valsartan (Val) as an angiotensin receptor blocker has renoprotective effects, but the molecular mechanisms responsible for the renal protection, independent from its blood pressure lowering effect, have not yet been fully understood. The present study is aim at evaluating the Val effect in alleviation of CsA nephrotoxicity by probable increase in renal Klotho expression and/or reducing oxidative stress. METHODS Thirty-two Sprague-Dawley rats were divided into 4 groups based on the administration of CsA and/or Val: group A (control, 1 mL/kg per day of olive oil as vehicle), group B (CsA, 30 mg/kg per day), group C (CsA + Val, 30 + 30 mg/kg per day), and group D (Val, 30 mg/kg per day). Real-time polymerase chain reaction and Western blotting were used to evaluate Renal Klotho expression. Serum Klotho level was measured by enzyme-linked immunosorbent assay. 8-Hydroxy-deoxy guanosine and malondialdehyde levels as markers of oxidative stress were measured by enzyme-linked immunosorbent assay and spectrophotometrically, respectively. RESULTS Cyclosporine A treatment reduced renal expression and serum levels of Klotho, improved malondialdehyde and 8-hydroxy-deoxy guanosine levels, and also deteriorated renal function. Valsartan prevented CsA-induced oxidative stress as well as Klotho downregulation and could alleviate CsA-induced renal histological changes and function. CONCLUSIONS Administration of Val might lead to amelioration of CsA nephrotoxicity by probably diminishing CsA-induced renal Klotho downregulation and oxidative stress.

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

One of the important factors in the occurrence of acute kidney injury (AKI) among renal transplant patients (RTPs) is ischemia reperfusion injury (IRI). The current study aimed at determining the anti-inflammatory and anti-oxidative effects of melatonin on the complications of IRI and the level of Klotho expression in these patients.A total of 40 renal transplant candidates were randomly assigned into placebo or melatonin group receiving the same dose of 3 mg/day. In order to measure serum melatonin levels, inflammatory and oxidative stress factors, renal function biomarkers, and Klotho gene/protein expression, venous blood samples were taken from patients over two different time points, i e, 24 h before the transplantation and at discharge from hospital.Melatonin was associated with improvement in renal transplantation, since the serum level of neutrophil gelatinase-associated lipocalin, as a renal functional marker, significantly decreased (P .001). The effect of melatonin as a suppressor of inflammation and oxidative stress was also evident in the melatonin group due to a significant reduction in the serum levels of MDA, CP, 8-OHdG, and TNF-α markers (P .001).Reduction in serum levels of renal function and oxidative stress/inflammatory markers in the melatonin group indicates that melatonin can inhibit IRI outcomes in RTPs through its anti-oxidant and anti-inflammatory properties. However, these properties do not appear as a result of influence on the level of Klotho gene/protein expression.

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.

BackgroundArteriovenous fistula (AVF) is the optimal vascular access in hemodialysis (HD) patients because of its lower complication rates and better longevity compared to arteriovenous graft (AVG) and central venous catheter (CVC).MethodsA cohort of 532 HD patients from nine HD facilities were recruited in September 2012 and prospectively followed for a median of 28 months. Unadjusted and fully adjusted hazard ratios (HR) of mortality for vascular access were calculated using Cox proportional hazards model.ResultsSeventy-two percent of patients had AVF, 7% AVG, 21% CVC. Overall, AVF failure was 43 per 1000 patient-years and AVF creation 19 per 1000 patient-years. In logistic regression analysis, odds ratio of having non-AVF access for age was 1.02 (95% CI: 1.01-1.03), female gender 1.97 (95% CI: 1.30-3.01), and Charlson comorbidity index (CCI) 1.17 (95% CI: 1.02-1.36). Total number of deaths was 17 per 100 patient-years. Two percent of death was because of pure catheter infection and 10.5% more mortality happened due to catheter infection complicated by underlying cardiovascular diseases. In unadjusted and full adjustment Cox models, HR of death for patients with CVC (reference: AVF patients) was, respectively, 2.17 (95% CI: 1.51-3.11) and 1.58 (95% CI: 1.01-2.51). Access problems of insertion-repair accounted for 24% of hospitalization, and catheter infection explained 10% of total admissions.ConclusionsCatheter use in HD patients was associated with higher mortality and morbidity despite extensive adjustment for covariates. Risk factors for higher usage of non-AVF access are older age, female gender, and underlying comorbidities.

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.

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.

Serum receptor activator of nuclear factor-κ B ligand and osteoprotegrin are mediated to vascular calcification in the general population. Our knowledge is very sparse in hemodialysis and renal transplant patients. Receptor activator of nuclear factor-κ B ligand, osteoprotegrin, intact parathyroid hormone, calcium, and phosphorus were measured in blood samples of 45 hemodialysis and 45 age-matched renal transplant patients. Osteoprotegrin (P = 0.001) and intact parathyroid hormone (P = 0.001) levels in the hemodialysis patients were higher than the renal transplant recipients. Osteoprotegrin had positive correlation with duration of dialysis and age in the hemodialysis (r = 0.88, P = 0.001 and r = 0.34, P = 0.02, respectively) and renal transplant patients (r = 0.92, P = 0.001 and r = 0.46, P = 0.001, respectively). Hemodialysis patients have higher osteoprotegrin levels than the renal transplant recipients. It may act as a protective factor for renal osteodystrophy or only as a secondary phenomenon of advanced renal failure.

Objective The aim of the present study was to evaluate of Fetuin-A and Pentraxin3 (PTX3) as the main factors for vascular calcification and inflammation in hemodialysis (HD) and renal transplant (RT) patients. Method Serum was obtained from 45 stable chronic HD patients and 44 stable RT recipients. Biochemical factors, intact Parathormone, high-sensitive C-reactive protein (hsCRP), Fetuin-A and PTX3 levels were determined by standard methods. Results In the RT recipients PTX3 level was significantly higher than the HD patients [5.78(1.09–20.36) ng/mL vs. 1.65(0.24–7.89) ng/mL, p ≤ 0.001]. Serum Fetuin-A concentration was significantly higher in the HD compared to RT group [43.39(27.75–81.48) ng/mL vs. 38.76(22.26–89.07) ng/mL, p = 0.020]. hsCRP level was also higher in the HD than the RT group [2.90(0.1–8.50) mg/L vs. 1.1(0.1–7.9) mg/L, p = 0.003]. Conclusion Although our study shows that serum PTX3 is increased and Fetuin-A is decreased after successful RT, their direct role on atherosclerosis needs further studies in the future.

PURPOSE Disequilibrium between oxidative stress and antioxidant levels has been proposed as an important case of exudative age-related macular degeneration (AMD). The aim of the present study was to investigate homocysteine (Hcy) level and antioxidant paraoxonase 1 (PON1) activity within its phenotypes together with oxidized low-density lipoprotein (OX-LDL) levels in the patients with exudative AMD. METHODS Serum PON1 activity and plasma Hcy and OX-LDL levels were analyzed in 45 exudative AMD patients and compared with 45 healthy controls. Paraoxonase 1 activity was measured in serum using paraoxon and phenylacetate as substrates. The PON1 phenotype was determined using double-substrate method. Homocysteine and OX-LDL levels were determined by enzyme-linked immunosorbent assay method. RESULTS The distribution of PON1 phenotypes was significantly different between the patients with exudative AMD and control subjects (chi-square = 6.17, P = 0.01). AA phenotype with low activity was significantly more frequent in exudative AMD patients compared with healthy subjects (62.2% vs. 35.6%, respectively). Other phenotype frequencies in the patients compared with controls were as AB phenotype (intermediate activity) 28.9% versus 46.7% and BB phenotype (high activity) 8.9% versus 17.8%, respectively. Except in BB phenotype (P = 0.2), patients with AA and AB phenotypes had higher plasma Hcy levels in comparison to those of controls (P = 0.02 and P = 0.03, respectively). The mean OX-LDL levels, in all 3 phenotypes (P < 0.05), and OX-LDL/high-density lipoprotein ratio, in AA and AB phenotypes (P = 0.001, P = 0.1, respectively) but not in BB (P = 0.1), were significantly higher in the patients than controls. No significant differences in comparison of Hcy and OX-LDL levels between 3 PON1 phenotypes in both control (P = 0.6 for Hcy, P = 0.7 for OX-LDL) and patients (P = 0.8 for Hcy, P = 0.6 for OX-LDL) were found CONCLUSION Increased plasma OX-LDL levels and ratios of OX-LDL/high-density lipoprotein, as biomarkers of lipoprotein oxidative stress, higher levels of Hcy, as oxidant agent, and more common low or intermediate PON1 activity in patients with exudative AMD, compared with controls, indicate that PON1 activity is insufficient to explain the increased oxidative stress observed in exudative AMD.

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.

Due to the association of oxidative stress and telomere shortening, it was aimed in the present study to investigate the possibility whether cyclosporine-A exerts its nephrotoxic side effects via induction of oxidative stress-induced renal telomere shortening and senescent phenotype in renal tissues of rats. Renal oxidative stress markers, 8-hydroxydeoxyguanosine, malondialdehyde, and protein carbonyl groups were measured by standard methods. Telomere length and telomerase activity were also evaluated in kidney tissue samples. Results showed that cyclosporine-A treatment significantly (P < 0.05) enhanced renal malondialdehyde, 8-hydroxydeoxyguanosine, and protein carbonyl groups levels, decreased renal telomere length, and deteriorated renal function compared with the controls. Renal telomerase activity was not affected by cyclosporine-A. Renal telomere length could be considered as an important parameter of both oxidative stress and kidney function. Telomere shortening and accelerated kidney aging may be caused by cyclosporine-induced oxidative stress, indicating the potential mechanism of cyclosporine-induced nephrotoxicity.

Objective Soluble receptor activator of nuclear factor-kappa B ligand (sRANKL) to osteoprotegerin ratio is designated as a bone metabolism equation in many rheumatologic disorders and would be modified with fish oil (FO) supplementation. Design and methods Eighty-three females with rheumatoid arthritis were divided randomly to 40 and 43 patients treated with (1 g/day) or without FO for 3 months accompanied with conventional drugs, respectively. Osteoprotegerin, sRANKL, tumor necrosis factor alpha (TNFα) serum levels were measured before and after treatment. Results Serum levels of osteoprotegerin increased, although sRANKL, TNFα and sRANKL/osteoprotegerin ratio decreased with FO therapy. A significant positive correlation was observed between sRANKL/osteoprotegerin ratio and TNFα levels ( r = 0.327 , p = 0.040) in the FO-treated group. Conclusions FO could decrease the inflammatory response by lowering of serum TNFα levels and sRANKL/osteoprotegerin ratio.

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.

Objective. Lipoprotein a [Lp(a)] is a strong biochemical risk factor that predicts posttransplant atherosclerosis. In this study we measured the ankle to arm blood pressure index (AAI) as a predictor of clinical atherosclerosis and assessed its relationship to serum Lp(a) values among 60 renal transplant recipients. Materials and Methods. After measuring the AAI in a recumbent position, biochemical factors including cholestrol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and Lp(a) were measured by commercial kits in 60 renal transplant and 30 healthy subjects. Results were analyzed using SPSS. Results. Lp(a) concentrations were significantly higher among transplant recipients compared with the control group (P .05). AAI was similar between the kidney transplant recipients and controls, showing no significant correlation of Lp(a) concentration with AAI. Conclusion. Increased serum Lp(a) in renal transplant recipients, a potent biochemical risk factor for atherosclerosis, was not associated with abnormal AAI.

As renin-angiotensin system (RAS) activity may affect the severity of oxidative stress and inflammatory markers, we assessed the effects of enalapril (E) and/or losartan (L) on these markers in renal transplant recipients with RAS polymorphisms.After determination by PCR of RAS genotypes, consisting of the angiotensin-converting enzymes (ACE I/D), angiotensinogens (AGT M235T) and angiotensin II type 1 receptors (ATR1 A1166C), 76 recipients were recruited randomly and assigned 4 groups. The first (n = 17) and second (n = 24) groups were treated with E (E(+): 10 mg/d) and L (L(+): 50 mg/d) alone, respectively. The third positive control group (n = 17) received E + L (E(+)L(+): 10 mg/d + 50 mg/d) and the fourth negative control group (n = 18) received no medication (E(-):L(-)). High-sensitivity C-reactive protein (hs-CRP) and total antioxidant (TA) inflammatory and antioxidative markers were measured after 2 months. After a 2-week washout period, the E(+) group was changed to L(+) and vice versa in a crossover design. They were followed for another 8 weeks before retesting hs-CRP and TA. A value of Por = .05 was considered significant.After 2 and 4 months of treatment with the drug regimen, hs-CRP and TA levels were significantly decreased and consequently increased among the E(+)L(+), L(+) and E(+) groups (P.05). On analyzing the relationship between RAS polymorphisms and baseline hs-CRP or TA levels, CC genotype of ATR1 showed lower hs-CRP levels (P = .04). However, none of the RAS polymorphisms predicted the antioxidant and anti-inflammatory response rates to the drugs (P.05).Although hs-CRP was lower in the CC genotype patients of ATR1 polymorphisms E and/or L reduced hs-CRP and increased TA regardless of the RAS genotype.

Aims: We aimed to assess humoral immune response to the influenza vaccine in adult kidney transplant recipients (KTRs) subjected to two immunosuppressive regimens containing either mycophenolate mofetil (MMF) or azathioprine (Aza). Methods: 40 eligible KTRs (24 treated with Aza [KTRs-Aza] and 16 treated with MMF [KTRs-MMF]) and 40 matched healthy controls (HCs) were administered the trivalent 2006–2007 anti-influenza vaccine. Antibody (Ab) titers were measured before (pre-vacc) and 1 month after (post-vacc) vaccination. The proportion of protective Ab titers (i.e. ≧1:40), the serological response (i.e. ≧4-fold rise in titers) rates, and the magnitudes of change in titers were evaluated. Results: KTRs and HCs were similar in serologic responses, magnitudes of change in Ab titers, and proportions of acquired protective titers against all antigens. Whereas KTRs-MMF and KTRs-Aza were identical in magnitude of rise in titers as well as in serologic responses, KTRs-MMF did poorer in developing post-vacc-protective titers against A/H1N1 (p < 0.05). The function of the transplanted kidney has not deteriorated after vaccination. Conclusions: Anti-influenza vaccination was safe in KTRs and evoked Ab responses comparable to those of HCs. KTRs-MMF and KTRs-Aza responded almost equally to the vaccine. Annual anti-influenza vaccination can be recommended to all stable KTRs.

Objectives. Vascular complications are common after renal transplantation. In this study we correlated Doppler sonographic indices and transplant kidney function. Methods. We reviewed data on 244 renal transplant patients. Doppler ultrasonographic evaluation was performed during the first 2 weeks after renal transplantation. We determined resistive index (RI) and pulsatility index (PI) in the interlobar arteries and thrombosis of renal and lower limb veins. Serum creatinine (Cr) and cyclosporine levels were evaluated prior to sonographic assessment. Results. The mean age of the 142 male and 102 female patients was 36.31 ± 3.30 years. Prevalence of real artery stenosis was 9.5%. In these patients the mean serum Cr level (2.21 ± 1.83 mg/dL) was significantly higher than among patients with patent renovascular tributary (1.49 ± 1.00 mg/dL; P = .03). RI and PI were also significantly correlated with serum Cr(P = .05 and .001, respectively). There was no relationship between cyclosporine level or panel-reactive antibody with RI and PI. Retransplant patients showed higher RI than first renal allograft recipients (0.72 ± 0.16 vs 0.63 ± 0.11; P = .006). Serum Cr level was higher among renal allograft recipients with Doppler evidence of thrombosis of the lower limb veins (3.1 ± 0.98 mg/dL versus 1.56 ± 1.13 mg/dL; P = .04). Conclusions. RI and PI are two valuable Doppler ultrasonographic markers to determine renal allograft function and related vascular complications.

Aims: Following carnitine administration a decrease in plasma levels of triglyceride (TG) and increase in total high-density lipoprotein cholesterol (HDL-C) has been reported. Our hypothesis was that it also improves the HDL2/HDL3 ratio, symptomatic intradialytic hypotension, and anemia in hemodialysis (HD) patients. Methods: Forty HD patients with a mean (± SD) age of 53 ± 13 years were treated with 500 mg/day carnitine taken orally for 2 months. Patients were used as their own controls (before treatment). Lipid and lipoproteins were determined by Alcyon Abbott autoanalyzer. HDL subclasses were measured by magnesium precipitation after fractionation with dextran sulfate. Hemoglobin, hematocrit and serum albumin were measured by standard methods. The results were analyzed by SPSS 11.05. Results: We found a significant decrease in serum TG (2.22 ± 0.99 vs. 1.93 ± 1.07 mmol/l, p < 0.01) and VLDL-C (0.93 ± 0.36 vs. 0.81 ± 0.34 mmol/l, p = 0.01) and a marked increase in HDL-C (0.9 ± 0.16 vs. 1.06 ± 0.24 mmol/l, p < 0.05), HDL2-C (0.17 ± 0.06 vs. 0.27 ± 0.14 mmol/l, p < 0.05) and albumin (37 ± 4 vs. 42 ± 5 g/l, p = 0.01) levels. The serum levels of total cholesterol (4.61 ± 0.89 vs. 4.5 ± 0.95 mmol/l, p = 0.1), LDL-C (2.78 ± 0.85 vs. 2.6 ± 0.89 mmol/l, p > 0.05), HDL3-C (0.73 ± 0.1 vs. 0.79 ± 0.17 mmol/l, p > 0.05), hemoglobin, hematocrit, and intradialytic blood pressure did not change after the treatment. Conclusion: Treatment with 500 mg/day carnitine taken orally for 2 months reduces serum levels of TG and VLDL-C, and increases HDL-C, HDL2-C and albumin in HD 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.

Atherosclerosis may be evaluated by structural or functional changes of the main arteries. We sought to investigate the probable associations of static and dynamic arterial changes with lipoprotein (a) and homocysteine levels, the two risk factors for atherosclerosis. Intima-media thickening and vasodilatory responses to nitroglycerine of the common carotid artery and the renal transplant artery were studied by color Doppler sonography in 75 renal transplant recipients and 30 controls. At 3, 5, and 10 minutes after 0.4 mg of sublingual nitroglycerine are measured resistive index and peak systolic velocity of the common carotid artery and renal transplant artery. Intima-media thickening in renal transplant recipients and controls were 0.86 +/- 0.34 mm and 0.74 +/- 0.14 mm (P = .05), respectively. Although intima-media thickness did not correlate with the duration of renal transplantation, it was significantly higher in older renal transplant recipients. Peak systolic velocity of common carotid artery was significantly decreased by nitroglycerine in the controls (81.8 +/- 16.7 m/s to 73.2 +/- 12.8 m/s, P = .03). This decrement was more obvious in renal transplant recipients, especially at 10 minutes (69.6 +/- 18.5 m/s vs 59.3 +/- 2 m/s, P = .01). These reductions did not correlate with intima-media thickening, latter of which also did not correlate with homocysteine concentrations, which were higher among renal transplant patients with creatinine more than 1.8 mg/dL. Basal resistive indices of the common carotid artery and renal transplant artery were higher among graft recipients with dysfunction than recipients with good function, (0.7 vs 0.59, P = .003). In conclusion, neither homocysteine nor lipoprotein(a) concentrations predict static and dynamic vascular properties.

Peritoneal dialysis offers several advantages such as better clearance of intermediate/large molecules and better preservation of renal residual function when compared with hemodialysis. However, dialysis adequacy is one of the subjects of concern of this modality. There are some drugs that are capable of influencing solute transport in the peritoneum, such as acetyle co-enzyme inhibitors (ACE-I) medications and calcium channel blockers. Captopril and Verapamil are often mentioned, but their use has shown varying conclusions and initial studies were performed with the intra-peritoneal administration of these drugs and there are only a few studies on the effect of the oral administration of these drugs. This study was undertaken with the aim to evaluate the effects of oral administration of Verapamil and Enalapril among continuous ambulatory peritoneal dialysis (CAPD) patients. The results of this study showed that Verapamil and Enalapril do not have any effects on glucose, creatinine, sodium, potassium and urea clearance (during the 4-h peritoneal equilibration test (PET) test). However, it was shown that Enalapril significantly increased the peritoneal urea Kt/V and caused a meaningful decrease in the diastolic and mean blood pressures. Therefore, we feel that Enalapril may be administered as an anti-hypertensive medication of choice in CAPD patients, which can also result in better dialysis adequacy. However, further studies with larger sample sizes are needed in the future.

Project The aim of this study was to determine the effects of zinc supplementation on serum zinc and leptin levels as well as on anthropometric status and some biochemical parameters in hemodialysis (HD) patients. Procedure In this randomized, double-blind, and placebo-controlled trial, sixty HD patients were randomly divided into groups to receive a daily supplement of 100 mg elemental Zn (supplemented group) or placebo (control group) for 60 days. Anthropometric measurements were taken using standard calibrated instruments. Serum zinc and leptin levels were determined by atomic absorption and ELISA method respectively before and after intervention. Results Zinc supplementation resulted in significant increase in the mean serum zinc level in the experimental group while changes observed in the placebo group were not significant. The mean serum leptin in women part of the experimental group was decreased significantly after supplementation. After adjusting for age, BMI, body fat (%), serum zinc and dietary Zn intake, a negative and significant association was observed between serum zinc and leptin levels in all subjects (β = −0.33, P = 0.03) as a result of Zn supplementation. Conclusions More studies are needed to clarify the mechanisms by which serum leptin level is influenced as a result of zinc supplementation in HD patients.

This paper1 was simultaneously submitted by the authors to "Transplantation" journal under the title "The Effects of Valsartan on Renal Klotho Expression and Oxidative stress in Alleviation of Cyclosporine Nephrotoxicity" and was accepted for publication in that journal. On the basis of BioImpacts policy in accordance with the Committee on Publication Ethics (COPE), any duplicate submission is considered as an ethical misconduct. The accepted manuscript in Transplantation shared considerable overlapping text and data (identical images and materials) with the published paper1 in BioImpacts. The Editor-in-Chief of BioImpacts, Prof. Y. Omidi, was alerted by the Editor-in-Chief of Transplantation, Prof. Jeremy R. Chapman, on such duplication. A comprehensive investigation through comparison of both papers was conducted by the editorial office of BioImpacts along with the Ethics Committee of Tabriz University of Medical Sciences (TUOMS) under Prof. M. R. Rashidi, who also acts as Director-in-Charge of BioImpacts and TUOMS Vice Chancellor of Research and Technology Affairs. As a result, they decided to retract this paper in line with the COPE recommendations. The authors were informed and advised on this serious ethical breach. Therefore, the paper is retracted at the request of authors, the aforementioned committee and the Editor-in-Chief of BioImpacts, even though the corresponding author believed that two papers were different in their aims, studied animals, and factors. By the way, they apologize for any inconvenience this may have caused. One of the conditions of submission of a paper to BioImpacts is that authors declare explicitly that "This manuscript has been exclusively submitted to this journal and is not under review or accepted for publication elsewhere". As such, this paper represents abuse of the scientific publishing system. As a peer-review multidisciplinary international "Publish Free" and "Access Free" journal, BioImpacts strongly adheres to the "Publication Ethics", and its foremost goal is to preserve the integrity of the scientific reports in the highest standards, therefore the journal takes all issues of publication misconduct seriously.

Patients on maintenance hemodialysis (HD) face an increased risk of atherosclerosis, a crucial problem and the leading cause of cardiovascular morbidity and mortality. This study was designed to evaluate the effects of zinc supplementation on paraoxonase (PON) enzyme activity in patients on HD.This double-blind randomized controlled trial was conducted from June 2005 to June 2007. Sixty HD patients were enrolled and divided into two groups: treatment (case) and control. The treatment and control groups were treated with 100 mg/day zinc or placebo, respectively, for 2 months. Serum zinc concentration was measured by atomic absorption spectrophotometry. PON activity was evaluated by spectrophotometric method. Lipid profile was determined using commercial kits, and apolipoprotein AI (Apo-AI) and B (Apo-B) levels were measured by commercial immunoturbidimetric kits.In the case group, there was no significant change in the serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and Apo-B levels, while the serum levels of high-density lipoprotein (HDL), Apo-AI, and PON activity were significantly increased (p = 0.02). In the control group, although significant increases were observed in the serum levels of TC, TG, and Apo-B (p = 0.009, 0.019, and 0.001, respectively), the serum PON activity was significantly decreased (p = 0.025) and the serum levels of HDL, LDL, and Apo-AI were not changed. At the end of intervention period, the serum level of Apo-AI and PON activity were significantly higher in the case group.Zinc supplementation increased both the activity of PON and the serum level of Apo-AI in the HD patients.