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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

This study compared the effects of lower- versus higher-intensity isometric handgrip exercise on resting blood pressure (BP) and associated clinical markers in adults with hypertension. Thirty-nine males were randomly assigned to one of three groups, including isometric handgrip at 60% maximal voluntary contraction (IHG-60), isometric handgrip at 30% IHG-30, or a control group (CON) that had been instructed to continue with their current activities of daily living. The volume was equated between the exercise groups, with IHG-60 performing 8 × 30-s contractions and IHG-30 performing 4 × 2-min contractions. Training was performed three times per week for 8 weeks. Resting BP (median [IQR]), flow-mediated dilation, heart rate variability, and serum markers of inflammation and oxidative stress were measured pre- and post-intervention. Systolic BP was significantly reduced for IHG-60 (−15.5 mmHg [−18.75, −7.25]) and IHG-30 (−5.0 mmHg [−7.5, −3.5]) compared to CON (p < 0.01), but no differences were observed between both the exercise groups. A greater reduction in diastolic BP was observed for IHG-60 (−5.0 mmHg [−6.0, −4.25] compared to IHG-30 (−2.0 mmHg [−2.5, −2.0], p = 0.042), and for both exercise groups compared to CON (p < 0.05). Flow-mediated dilation increased for both exercise groups versus CON (p < 0.001). IHG-30 had greater reductions in interleukin-6 and tumor necrosis factor-α compared to the other groups (p < 0.05) and CON (p = 0.018), respectively. There was a reduction in Endothelin-1 for IHG-60 compared to CON (p = 0.018). Both the lower- and higher-intensity IHG training appear to be associated with reductions in resting BP and improvements in clinical markers of inflammation and oxidative stress.

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.

Metal-Organic Frameworks (MOFs) are a new class of crystalline porous structures which can be used as a novel structure in diverse fields of medical science. Several studies have shown that chromium supplementation can be effective in amelioration of biochemical parameters of diabetes and its renal complications. Therefore, a chromium-containing MOF (DIFc) was synthetized by nanochelating technology in the present study and then its effect on biochemical indices in diabetic rats was evaluated. Diabetes was induced by high-fat diet consumption and streptozotocin (35 mg/kg) injection and then the treatment started 8 weeks after disease induction and continued for 8 weeks. The results showed that DIFc treatment decreased HOMA-IR index, blood urea nitrogen, uric acid and malondialdehyde in plasma samples. This nano MOF also reduced albumin, malondialdehyde and 8-isoprostane in urine specimen, while it increased creatinine clearance. In conclusion, DIFc MOF demonstrated promising results in the present study, indicating that it can be developed and evaluated in future investigations with the aim of designing a novel agent for management of diabetes and its renal complications.

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.

Introduction: Nephrotoxicity as a side effect caused by the immunosuppressive drug, cyclosporine-A (CsA), can be a major problem in transplant medicine. Oxidative stress may play an important role in the CsA-induced nephrotoxicity. It has been shown that the antihypertensive drug, valsartan (Val), has also renoprotective effects but, its molecular mechanism is largely unknown. In the present study, it was aimed to evaluate the Val effect in the alleviation of CsA nephrotoxicity via probable renal glutathione peroxidase (GPx) upregulation and oxidative stress decrease. Methods: Thirty-two Sprague-Dawley rats were divided into four groups based on CsA and/or Val administration: group A (Control, 1 mL/kg/day of olive oil as vehicle), group B (CsA, 30 mg/kg/day), group C (CsA+Val, 30+30 mg/kg/day), and group D (Val, 30 mg/kg/day). After the administration period (six weeks), renal GPx expression was evaluated by real-time polymerase chain reaction (PCR). Plasma levels of GPx and 8-Hydroxydeoxyguanosine (8-OHdG) were measured by enzyme-linked immunosorbent assay (ELISA). Malondialdehyde (MDA) and protein carbonyl groups (PCG) were measured by spectrophotometer. Plasma levels of urea and creatinine were measured by an autoanalyzer. Results: CsA treatment led to the decrease in renal expression and plasma levels of GPx in comparison to other study groups. Rats received CsA were detected to have significantly (p

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

Objectives: To investigate the effect of lovastatin therapy and withdrawal on paraoxonase 1 (PON1) and arylesterase (ARE) activities, and low-density lipoprotein cholesterol (LDL-C) susceptibility to oxidation in people with type 2 diabetic nephropathy (T2DN). Design and methods: Lovastatin (20 mg/day) was administered to 30 people with T2DN for 90 days and then withdrawn for 30 days. PON1 and ARE activities were measured by the spectrophotometric method. Susceptibility of LDL-C to oxidation was determined as the production of conjugated dienes. Results: After 90 days of lovastatin intervention, PON1 and ARE activities and LDL-C lag phase were significantly increased (p = 0.004, 0.002, and

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

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.