Enzyme-Linked Immunosorbent Spot (ELISpot) monitoring of cytokine-producing cells for the prediction of acute rejection in renal transplant patients.

The purpose of this study was to evaluate T-cell immunity markers using serial post-transplantation monitoring of cytokine-producing cells during the first post-transplant months for the prediction of acute rejection and potentially chronic rejection of kidney allograft. We followed 57 kidney allograft recipients for meanly 3 years post-transplantation. Blood samples were collected pre-transplant, 2, 4 and 12 weeks post-transplant. The frequencies of IL-10-, IL-17- and IFN-γ-producing cells were determined in all time-points using ELISPOT assay. The results of ELISpot monitoring and levels of IL-23 and TGF-ß were compared between recipients with acute (n = 12) or chronic rejection episodes and patients with stable graft function (n = 45). In all post-transplant time-points, significantly high frequencies of IFN-γ- and IL-17-producing cells and low frequency of IL-10-producing cells were observed in rejection group versus patients with stable graft function (P < 0.0001). The ROC curve analysis for determining the reliability of cytokine-producing cells for the prediction of acute rejection revealed that AUC was 0.046 for IL-10 (P < 0.001), 0.927 for IL-17 (P < 0.001) and 0.929 for INF-γ-producing cells (P < 0.001). Our results indicate that analyzing the frequencies of INF-γ/IL-10/IL-17-producing cells may define a reliable panel for the prediction of acute rejection within the first post-transplant year which could also be applicable for the prediction of chronic rejection episodes.

Protective Effects of L-Carnitine Against Delayed Graft Function in Kidney Transplant Recipients: A Pilot, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

OBJECTIVE: Delayed graft function (DGF) is an early complication after deceased donor kidney transplantation with significant adverse effects on graft outcomes. Ischemia-reperfusion injury during transplantation is a major cause of DGF. Tissue concentrations of carnitine, an antioxidant and regulator of cellular energy supply, decrease in the kidney following ischemia-reperfusion insult. Based on promising animal data, this study evaluated the possible protective effect of L-carnitine against DGF. DESIGN: This study is a pilot, randomized, double-blind, placebo-controlled clinical trial that was conducted on kidney transplantation patients in kidney transplant ward of Imam Khomeini hospital complex affiliated to Tehran University of Medical Sciences, Tehran, Iran. SUBJECTS: Patients older than 14 years old undergoing their first kidney transplantation from a deceased donor were evaluated for eligibility to take part in this study. Fifty-six patients were randomly assigned to L-carnitine or placebo groups. INTERVENTION: During this trial, 3 g of oral L-carnitine or placebo was administered in 3 divided doses each day for 4 consecutive days starting the day before kidney transplantation (i.e., days -1, 0, 1, and 2). MAIN OUTCOME MEASURE: The need for dialysis within the first week after transplantation, serum creatinine and urine output were assessed daily. After hospital discharge, patients were followed for 3 months regarding organ function. RESULTS: DGF incidence did not differ between the L-carnitine and placebo groups (18.51% vs. 23.8%, respectively; P = .68). Total allograft failure within 3 months after kidney transplantation happened in 6 patients in the placebo and 1 patient in the L-carnitine group (P = .05). CONCLUSION: This study showed no protective effects of oral L-carnitine supplementation against DGF occurrence recipients; however, 3-month graft loss was lower in the L-carnitine supplemented group.

Effectiveness of N-acetylcysteine for preserving residual renal function in patients undergoing maintenance hemodialysis: multicenter randomized clinical trial.

BACKGROUND: To investigate the efficacy and safety of oral N-acetylcysteine (NAC) for preserving residual renal function in patients undergoing hemodialysis. METHODS: Randomized, multi-center, parallel-group, open-label clinical trial (Registration No. IRCT 2014071418482N1). 54 patients who have been undergoing hemodialysis for at least 3 months and had residual urine volume >100 ml/24 h were randomly allocated to NAC or no medication. Residual renal function evaluated by (1) estimated glomerular filtration rate (GFR), (2) 24 h urine volume, and (3) renal Kt/V. GFR and Kt/V was determined at baseline and after 3 months. 24 h urine volume was measured at baseline, after 1, 2, and 3 months. RESULTS: Intention-to-treat analysis was performed on 47 patients (NAC = 26, control = 21). GFR in patients receiving NAC improved, whereas in the control arm a decline of 1.0 ml/min/1.73 m2 was recorded (3.59 vs. 2.11 ml/min/1.73 m2, effect size = 17.0 %, p = 0.004). For 24 h urine volume, the between-group difference after 1 month was significant (669 vs. 533 ml/24 h, effect size = 15.4 %, p = 0.004). After 3 months, 24 h urine volume in the NAC arm was on average 137 ml higher than in the control group, and the difference reached near significance (673 vs. 536 ml/24 h, p = 0.072). In the follow-up visit, Kt/V was higher in the NAC arm but the difference did not reach statistical significance (0.81 vs. 0.54, p = 0.152). CONCLUSION: Three months treatment with NAC appears to be effective in preserving renal function in patients undergoing hemodialysis and the medication is generally well-tolerated.

Rituximab-Related Late-Onset Neutropenia in Kidney Transplant Recipients Treated for Antibody-Mediated Acute Rejection.

OBJECTIVES: Kidney transplant is a new area for use of rituximab, which is being used to treat acute antibody-mediated rejection or as an induction agent in ABO- or HLA-incompatible grafts. We report on late-onset neutropenia in rituximab-treated kidney transplant recipients with antibody-mediated rejection. MATERIALS AND METHODS: This observational prospective study was performed on kidney transplant recipients with clinically suspicious or biopsy-proven antibody-mediated rejection treated with plasmapheresis plus intravenous immunoglobulin with (cases) or without (controls) rituximab. RESULTS: Compared with none of the controls, 4 of 6 patients (66.7%) in the rituximab-treated group experienced late-onset neutropenia 35 to 93 days after the last dose of rituximab. The course of neutropenia was complicated by endocarditis in 1 patient, resulting in his death just because of a lack of valvular surgery. CONCLUSIONS: Increased use of rituximab to treat antibody-mediated rejection among kidney transplant recipients requires attention to its late-onset adverse event, neutropenia. Although asymptomatic in some patients, kidney transplant recipients treated concomitantly with plasmapheresis and mycophenolate mofetil are predisposed to hypogammaglobulinemia, and monitoring of patients for infections is required.

Prevention of Contrast-induced Nephropathy With Oxygen Supplementation: a Randomized Controlled Trial.

INTRODUCTION: The aim of the study was to investigate the efficacy of nasal oxygen as a supplementation to hydration therapy in reducing the risk of developing contrast-induced nephropathy (CIN). MATERIALS AND METHODS: In a randomized controlled trial, 348 patients scheduled to undergo elective coronary angiography were randomly allocated to standard hydration plus 2 L/min to 3 L/min nasal oxygen (from 10 minutes before the procedure until the end of the procedure) (n = 176) or standard hydration alone (n = 176). The primary outcome measure was development of CIN defined as either an increase of 25% or more in serum creatinine concentrations or an increment of at least 0.5 mg/dL in serum creatinine concentrations 48 hours after catheterization. RESULTS: Of the 348 patients who completed the study, 105 developed CIN (30.2%; 95% confidence interval, 25.4% to 35.0%). A diagnosis of CIN was made in 32 (18.6%) and 73 (41.5%) patients in the nasal oxygen and control arms, respectively (P < .001). In the intervention arm, creatinine concentrations postcontrast remained relatively constant (average change, 2.7%), whereas a significant increase of 17.3% was recorded in the control arm (P < .001; effect size, 11.8%). CONCLUSIONS: Supplementation with nasal oxygen in addition to standard hydration appears to be an effective strategy in reducing CIN. The effect size for this intervention seems to be moderate.

Potential Effects of Omega-3 Fatty Acids on Insulin Resistance and Lipid Profile in Maintenance Hemodialysis Patients: a Randomized Placebo-Controlled Trial.

INTRODUCTION: Insulin resistance (IR), a risk factor for cardiovascular disease and all-cause mortality, is prevalent among maintenance hemodialysis patients. Effects of omega-3 fatty acids on IR in hemodialysis patients have not been well understood. This study aimed to determine the effects of omega-3 fatty acids on IR and serum lipids of hemodialysis patients. MATERIALS AND METHODS: Fifty-four adult patients on hemodialysis were randomly assigned to receive either 1800 mg of omega-3 fatty acids or placebo daily for 4 months. Serum concentrations of glucose, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, C-reactive protein, insulin, leptin, and adiponectin were measured at baseline and after 4 months of the intervention. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance and 2 adipokine-based measures of IR, including the leptin-adiponectin ratio and homeostasis model assessment corrected by adiponectin. RESULTS: Mean differences of serum C-reactive protein, insulin, leptin, and adiponectin concentrations did not show significant difference between the two groups following 4 months of intervention. Fasting serum glucose and low-density lipoprotein cholesterol were not significantly influenced by omega-3 supplementation, either. Serum triglyceride, total cholesterol, and high-density lipoprotein cholesterol levels significantly decreased in the omega-3 group (P = .02, P = .03, and P < .001, respectively). None of the indirect indexes of IR showed significant changes at the end of the study in either the omega-3 or placebo group. CONCLUSIONS: Supplemental use of omega-3 fatty acids showed some beneficial effects on lipid profile of hemodialysis patients without any improvement in IR.

Association of low vitamin D levels with metabolic syndrome in hemodialysis patients.

Low vitamin D levels have been linked to metabolic syndrome in the general population. In the present study, the relationship between inadequate serum concentrations of vitamin D and metabolic syndrome in patients with end-stage renal disease undergoing hemodialysis was explored. In a cross-sectional setting, 145 patients undergoing maintenance hemodialysis were enrolled. Metabolic syndrome was defined using the International Diabetes Federation criteria. Serum concentration of 25(OH) vitamin D was determined by a commercially available enzyme immunosorbent assay method. The prevalence of metabolic syndrome was 53.1%. The prevalence rate of severe vitamin D deficiency (<5 ng/mL) was 3.4%, mild vitamin D deficiency (5-15 ng/mL) 31.0%, vitamin D insufficiency (16-30 ng/mL) 36.6%, and vitamin D sufficiency (>30 ng/mL) 29.0%. With the increasing number of metabolic abnormalities, vitamin D levels significantly decreased (P for trend = 0.028). Among the components of metabolic syndrome, vitamin D deficiency was significantly associated with central obesity (odds ratio [OR], 95% confident interval [CI] = 2.80, 1.11-7.04, P = 0.028). A positive, but nonsignificant association between vitamin D deficiency and raised fasting plasma glucose was noted (OR, 95% CI = 2.40, 0.94-6.11, P = 0.067). Both vitamin D deficiency and insufficiency were significantly associated with an increased likelihood of having metabolic syndrome (P < 0.05). In a final model controlling for age, sex, and parathyroid hormone levels, vitamin D deficiency increased the odds of having metabolic syndrome by more than threefold (OR, 95% CI = 3.26, 1.30-8.20, P = 0.012). Low levels of vitamin D are frequent among hemodialysis patients and are associated with the metabolic syndrome.

Carotid artery corrected flow time measurement via bedside ultrasonography in monitoring volume status.

PURPOSE: The purpose of this study is to investigate the possible correlation between corrected flow time (FTc) in carotid artery and changes in volume status. MATERIALS AND METHODS: Ninety-three patients with end-stage renal failure who underwent fluid removal via hemodialysis were enrolled prospectively. The volume of fluid removed as well as prehemodialysis and posthemodialysis measures of FTc in the carotid artery, heart rate, and mean arterial pressure was evaluated. All imaging measurements were performed with patients at supine position, 15 minutes before and after the hemodialysis session, by evaluating the right common carotid artery at the level of the lower border of thyroid cartilage. RESULTS: The mean FTc before fluid removal was 345.07±37.19 milliseconds. This measure decreased significantly after the volume removal with a posthemodialysis mean of 307.77±31.76 milliseconds (P<.0001). There was a statistically significant and negative association between the volume of fluid removed by hemodialysis and the changes in FTc (Pearson correlation, -0.39; P<.0001). CONCLUSION: The assessment of changes in FTc of carotid artery via Doppler waveform analysis may predict the changes in intravascular volume. The use of this diagnostic modality may be an accurate and noninvasive alternative to currently available methods.

Regulatory T cell subtypes and TGF-ß1 gene expression in chronic allograft dysfunction.

BACKGROUND: Regulatory T cells have been suggested to have a protective role against acute rejection in allograft recipients. However, there is little information available about their contribution to chronic rejection process. The role of transforming growth factor-beta 1 (TGF-ß1) as a profibrogenic and/or immunoregulatory cytokine in renal allografts is also controversial. OBJECTIVES: To evaluate the frequency of CD4+CD25+CD127- and CD3+CD8+CD28- regulatory T cells in chronic allograft dysfunction (CAD) and to investigate the expression of TGF-ß1 in renal allografts. METHODS: Thirty biopsy-proven CAD patients were pair-matched with 30 stable graft function patients and a third group of healthy volunteers. Flowcytometry was performed on PBMCs to determine the frequency of CD3+CD8+CD28- and CD4+CD25+CD127- regulatory T cells in lymphocyt population. TGF-ß1 gene expression was assessed by Real Time PCR. RESULTS: The percentages of CD3+CD8+CD28- Tregs among renal allograft recipients was higher than healthy controls (p<0.001) since stable graft patients showed the most rates. The frequency of CD4+CD25+CD127- Tregs was lower in CAD patients than stable recipients (p=0.024) and healthy group (p=0.015). TGF-ß1 gene expression was greater in CAD patients compared to healthy group (p=0.03) but there was no significant difference between gene expression of stable graft patients and healthy volunteers. CONCLUSION: The negative association between the frequency of regulatory T cell subtypes and chronic allograft dysfunction proposes these cells as probable candidates for promoting allograft survival. Moreover, despite the immunoregulatory capacity of TGF-ß1, it is likely to be implicated in chronic damages of allograft tissue.

Infective endocarditis after renal transplantation.

BACKGROUND: Infective endocarditis (IE) is a serious complication in immunosuppressive patients that has adverse effects. OBJECTIVES: The aim of this study was to define the characteristics, outcomes, and correlating factors of mortality in renal transplant recipients. PATIENTS AND METHODS: Infective endocarditis was diagnosed in 22 patients from three renal transplant centers in Iran between 2000 and 2010. Modified Duke criteria were applied to confirm the diagnosis. RESULTS: Twenty-two renal transplant patients with IE were evaluated. Blood culture results were positive in 81%. Enteroccous and group D non-enterococcal were the causative microorganisms in 31% and 25% of patients, respectively. In-hospital and 12-month mortality was 41% and the mortality rate was higher in older patients in comparison to younger patients. Overall, the rates of one-year disease-free patient and graft survival were 49% and 88%, respectively. CONCLUSIONS: Despite the availability of different and potent antibiotics, the mortality caused by IE remains considerably high. These patients are significantly prone to endovascular infections that affect the mortality and survival.

Bone mineral metabolism and subsequent hospitalization with poor quality of life in dialysis patients.

BACKGROUND: Significant impairment in health-related quality of life (HRQOL) among dialysis patients could be partly explained by some co-morbid disorders, such as chronic kidney disease-mineral and bone disorder (CKD-MBD). Also disturbance in calcium and phosphorus metabolism would increase mortality and morbidity. Therefore, further efforts to treat these abnormalities may improve the survival. OBJECTIVES: We designed a large multicenter population-based study in Iran to describe and assess the relation between HRQOL, hospitalization, and bone metabolism markers. PATIENTS AND METHODS: We enrolled a total of 5820 dialysis patients from 132 dialysis centers in different parts of the country whom were volunteers to cooperate between October 2010 and August 2011. The Iranian adapted version of the Kidney disease quality of life-short form (KDQOL-SF(TM)) version 1.3 questionnaire was used to assess the health related quality of life. The clinical and demographic characteristics were gathered from patients' data files. RESULTS: The mean (SD) age of patients was 54.88 (16.36) years, and the range was 2 to 99 years. Of all patients, 43.1% were female. The scores of kidney disease component summary (KDCS), physical component summary, mental component summary, and total quality of life were significantly higher in the lower quartile of corrected serum calcium and higher quartile of serum parathyroid hormone (PTH) levels (P < 0.05). In a regression analysis of multilevel data, while corrected serum calcium level was associated with total KDCS and short form health survey (SF-36) scores after adjusting for other variables, hospitalization was directly correlated with serum phosphorus level and had reverse correlation with dialysis duration and quality of life. CONCLUSIONS: In the current study, quality of life was correlated with serum calcium level, calcium-phosphate product, and serum PTH level, while hospitalization was correlated only with serum phosphorus level. However, quality of life was inversely correlated with hospitalization.

Comparing the frequency of hypertension determined by peri-dialysis measurement and ABPM in hemodialysis patients.

Controlling blood pressure in hemodialysis patients is crucial but not always easy. The most common blood pressure measurement method is peri-dialysis measurement, but due to interdialytic blood pressure fluctuations, we are unsure if it is the proper way for evaluating blood pressure. Some studies have shown the superiority of 24-h ambulatory blood pressure monitoring over peri-dialysis blood pressure measurement. We aimed to compare the consistency of these methods in determining hypertension among hemodialysis patients. We studied 50 patients (mean age: 55.8 years) on regular hemodialysis in Imam Khomeini University Hospital, Tehran, Iran. Peri-dialysis blood pressure and interdialytic 24-h ambulatory blood pressure monitoring were recorded for each patient. Patients' demographic data and peri-dialysis weight were recorded too. All data were analyzed using the PASW Statistics 18.0, SPSS Inc. (Chicago, IL). There was a significant difference between pre-dialysis mean systolic blood pressure (146.1 ± 23.3 mmHg) and mean systolic blood pressure recorded by ambulatory blood pressure monitoring (135.3 ± 19.3 mmHg) (p = 0.001). There was also a significant difference between pre-dialysis mean diastolic blood pressure (83 ± 14 mmHg) and mean diastolic blood pressure recorded by ambulatory blood pressure monitoring (77.3 ± 10 mmHg) (p = 0.003). But the frequencies of hypertension measured with both methods were significantly consistent and the Kappa agreement coefficient was 0.525 (p = 0.001). Considering ambulatory blood pressure monitoring as the gold standard for blood pressure measurement, our recommendation for the best cutoff point to diagnose hypertension, with the highest sensitivity and specificity would be 135/80 mmHg for pre-dialysis blood pressure and 115/70 mmHg for post-dialysis blood pressure.

Cardiac troponins in patients with chronic kidney disease and kidney transplant recipients without acute cardiac symptoms.

INTRODUCTION: Cardiovascular diseases are the most common causes of death in chronic kidney disease (CKD) and kidney transplant patients. This study aimed to evaluate cardiac troponins in transplant recipients and CKD patients without cardiac symptoms. MATERIALS AND METHODS: Two groups of patients (CKD and kidney transplant recipients) were evaluated for troponins T and I levels. These values were associated with renal replacement therapy and demographic and clinical characteristics of the patients. RESULTS: Eighty CKD patients and 80 kidney transplant recipients were studied. There was a significant difference in Troponins T and I levels were significantly higher in the CKD group than in the transplant recipients. In the CKD group, 14 patients (17.5%) had an elevated troponin T level and 8 (10.0%) had an elevated troponin I, all of whom were in stage 4 of CKD. None of the kidney transplant patients had a positive troponin. Among CKD patients, decreased glomerular filtration rate was associated with elevated troponin I level. Elevated troponin T level was significantly associated with age and decreased glomerular filtration rate. In multivariable analysis, significant associations were found between troponin T level and age, serum creatinine, and glomerular filtration rate. A significant relationship was also found between troponin I and cholesterol and glomerular filtration rate. CONCLUSIONS: The assessment of troponin T and I in CKD and kidney transplant patients shows that in patients with CKD and without any symptoms of acute coronary syndrome, serum level of cardiac troponins increase and it is linked to serum creatinine and GFR.

Health-related quality of life in hemodialysis patients: an Iranian multi-center study.

BACKGROUND: The effectiveness of health care and health policy developments are often determined by health-related quality of life (HRQOL) assessment. OBJECTIVES: The objective of this study was to explore the potential corresponding factors and traditional biomarkers of HRQOL in a large number of Iranian hemodialysis patients. PATIENTS AND METHODS: A total of 6,930 chronic hemodialysis (HD) patients enrolled. KDCS-SF version 1.3 questionnaire was used to assess the health related quality of life (HRQOL). We pooled PCS, MCS and KDCS scores with random effect model from 19 similar studies performed between 1996 and 2010. RESULTS: The mean age was 54.4 ± 17.1 years. Mean PCS, MCS and KDCS scores obtained for the study cohort were 40.79 ± 20.10, 47.79 ± 18.31 and 57.97 ± 11.70, respectively; the total score of SF-36 plus KDCS was 51.12 ± 13.41 as well. The most common primary known disease was hypertension (31.9%) and the second etiology was diabetes (25.5%). In multilevel logistic regression, Kt/V between 1 and 1.2 and PCS, KDCS more than 50 were considered as a significant reduction in the risk of hospitalization. CONCLUSIONS: This study showed that PCS and MCS score were slightly more than overall results while KDCS was slightly less than overall results. In addition, dialysis adequacy with Kt/V between 1 and 1.2 is associated with lower rate of hospitalization.

Statins against drug-induced nephrotoxicity.

Drug-induced nephrotoxicity (DIN) accounts for up to 60% of hospital acquired acute kidney injury with considerable morbidity and mortality. Several efforts have been made to reduce drug-induced nephrotoxicity; however, DIN remains a matter of concern. Statins with their antioxidant, anti-inflammatory and anti-apoptotic effects may have the potential to protect kidney against DIN. The present review evaluated all of the available in vitro and in vivo studies that examined the use of statins as renoprotective agents against nephrotoxic drugs. Materials for this review were obtained by searching Medline, PubMed, Scopus, Cochrane central register of controlled trials, and Cochrane database of systematic reviews. Key words used as search terms included "statin", "3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, "HMG-CoA reductase inhibitors", "nephroprotective", "renoprotective", "drug-induced renal diseases", "drug-induced nephrotoxicity", "drug-induced renal toxicity", "drug-induced nephropathy", "drug-induced renal side effects", and "contrast-induced nephropathy". This search was performed without time limitation. Only English language articles were included in this review. This review concluded that chronic statin user may be less prone to contrast-induced nephropathy (CIN) compared with statin non-users. Short-term high dose statin administration may also reduce the incidence of CIN in statin naïve patients. This renoprotective effect of statins against CIN is seen in low risk patients with normal kidney function or mild kidney dysfunction, but probably not in patients with moderate to severe renal dysfunction. Based on available animal data, statins may protect kidney against gentamicin-, cisplatin- and cyclosporine-induced nephrotoxicity, however, theses animal results have not yet been confirmed by human data. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Impact of UGT1A9 Polymorphism on Mycophenolic Acid Pharmacokinetic Parameters in Stable Renal Transplant Patients.

There are wide individual differences in pharmacokinetic parameters of mycophenolate mofetil (MMF) among transplanted patients. Some studies have shown that single nucleotide polymorphisms (SNPs) of the Uridine Diphosphate Glucuronosyl Transferase1A9 (UGT1A9) are responsible for these differences in early days after transplantation. Therefore it was decided to evaluate the influence of UGT polymorphism on MMF pharmacokinetics among stable Iranian transplant patients. This was a cross sectional study from March 2008 through December 2008 in Imam Khomeini Hospital affiliated to the Tehran University of Medical Sciences in Iran. Blood samples were taken from 40 de novo stable Iranian renal transplant patients taking 2 g MMF daily with SrCr≤1.4 mg/dL with at least 3 months history of transplantation. Appropriate PCR and HPLC methods were used for the determination of SNPs and their impact on MPA pharmacokinetics. T-275A polymorphism occurred in 15% of patients, UGT1A9*3 occurred in 2.5% of patients. Carriers of T-275A polymorphism had significant lower MPA AUC 0-12 in comparison with non-carriers or wild type (73.3±17.8 g/h/mL vs. 110.8±31.1 µg/h/mL, p = 0.006). There was no significant difference in AUC 6-12 between the two groups although carriers of T-275A SNP had lower MPA AUC 6-12 (22.4±4.5 µg/h/mL vs. 26.8±10.2 µg/h/mL, p = 0.24). Cmax was lower in the carriers of (20.2±9.0 µg/mL vs. 37.2±12.5 µg/mL, p=0.004). There was no significant difference in C0 between two groups. (3.0±1.2 µg/mL vs. 3.9±1.6 µg/mL, p = 0.1). This study in Iranian stable transplanted patients shows that carriers of T-275A polymorphism had significantly lower MPA exposure compared to non-carriers.

Health related quality of life in Iranian hemodialysis patients with viral hepatitis: changing epidemiology.

BACKGROUND: There are surprisingly a few studies that evaluate the impact of chronic viral hepatitis, which is common in HD (hemodialysis) patients, on HRQOL (health related quality of life). OBJECTIVES: We conducted a study to evaluate the impact of chronic viral hepatitis on HRQOL and to compare their HRQOL with non-infected HD patients via a HRQOL questionnaire. PATIENTS AND METHODS: The Iranian adapted version of the Kidney Disease Quality of Life Short Form (KDQOL-SF) version 1.3 questionnaires were filled out by the HD patients. In all HD patients, serum HBsAg, HBS Abs, and HCV Abs [enzyme-linked immunosorbant assay (ELISA)] were routinely checked every six months. Patients were considered to have chronic HBV infection if HBsAg was positive for more than six months. In all HD patients, third generation assay was used to detect HCV infection. Furthermore, serum HCV-RNA (PCR) was examined in anti-HCV-positive patients for confirmation of HCV infection. RESULTS: in this cross sectional study 4101 patients from 103 dialysis units in Iran between October 2010 and August 2011 were included. Prevalence of hepatitis B and hepatitis C infection was 2.1% and 1.3% respectively. Almost all KDQOL items for viral hepatitis patients had equivalent or better scores than those without viral hepatitis. In the logistic regression after adjustment for age, sex, educational level, marital status, dialysis vintage, HBs Ag positivity and HCV Ab positivity, only age (P < 0.001) and educational level (P = 0.015) had negative impact on quality of life. CONCLUSIONS: Our data show that not only general health and physical activity were preserved but also health perception may be better among HD patients with viral hepatitis.

Uremic pruritus and serum phosphorus level.

Pruritus is a common and bothersome problem among uremic patients which negatively affects life quality and prognosis of the patient. Various factors are known to be involved in the development of pruritus. The aim of this study was to assess the frequency and the factors which may have relationship with uremic pruritus, especially bone mineral metabolism indicators. Current cross-sectional study was done on 99 hemodialysis patients. Having pruritus, its duration, severity and correlation with patient's laboratory data was evaluated. For each patient a questionnaire was filled. The mean age of patients was 55.9±15.4 (23-87) years and 35.7% were female. They were on hemodialysis for 74.79±75.04 months. Frequency of pruritus was 58.6% (58 patients). Considering the severity, 16.2% suffered from severe pruritus, measured by visual analogue scale (VAS). Pruritus was more common in those on dialysis for more than 2 years (0.014). 82.8% of those with VAS of less than 3, in comparison with 37.5% of those with VAS of greater than 7, had no complaint of awakening due to pruritus. The frequency of pruritus and its severity was more in patients with higher serum phosphorus level (P=0.048). It seems that phosphate control which is not mainly attributed to dialysis adequacy and efficiency, needs more attention not only by medical team but also by patient. Decreasing the phosphate content of regimen may be cheap and helpful modality in pruritus management.

Potential nephroprotective effects of l-carnitine against drug-induced nephropathy: a review of literature.

INTRODUCTION: Drug-induced nephrotoxicity (DIN) has been reported with a great number of medications and contributes to ∼ 20% of hospital admissions. l-carnitine owing to its antioxidant, anti-inflammatory and antiapoptotic properties has been proposed as a candidate for nephroprotection against DIN. Increasing need to use nephrotoxic therapeutic agents necessitated this review. AREAS COVERED: The present review covers all published clinical and animal researches on nephroprotective effects of l-carnitine against DIN. l-carnitine significantly ameliorates DIN in animal studies especially against cisplatin-induced renal damage. Inhibition of reactive oxygen species generation, lipid peroxidation, matrix remodeling and apoptosis, anti-inflammatory properties and improvement in carnitine deficiency has been suggested as probable nephroprotective mechanisms of l-carnitine. EXPERT OPINION: In spite of the evidences that support the nephroprotective effect of l-carnitine, the main problems in this area are inadequacy of reliable studies in humans and difficulty of translating the experimental results into clinical practice. In most of the described studies, l-carnitine treatment is prophylactically given. Use of l-carnitine as a prophylactic agent in clinical situations with an indication for nephrotoxic therapies is rarely possible except for contrast-induced nephrotoxicity. Development of validated early biomarkers to detect DIN may provide the opportunity to use prophylactic nephroprotective agents at golden time.

A review of the potential protective effects of pentoxifylline against drug-induced nephrotoxicity.

PURPOSE: Drug-induced nephrotoxicity is one of the most common side effects of medications and accounts for about 20 % of hospital admissions for acute kidney injury (AKI). Some possible pharmacologic mechanisms of pentoxifylline (PTX) that suggest it as a candidate to ameliorate AKI include interaction at the level of the adenosine receptors, increase in erythrocyte deformability, stimulation of vasodilatory prostaglandins production and prevention of vascular congestion, and suppression of tumor necrosis factor alpha (TNF-α) and apoptosis. This manuscript reviews all clinical and animal studies on the use of PTX as a renoprotective agent against a number of nephrotoxic drugs. METHODS: Data were collected by searching MEDLINE, PubMed, Scopus, Cochrane central register of controlled trials, and Cochrane database systematic reviews. Key words used as search terms were pentoxifylline, nephroprotective, renoprotective, drug-induced renal diseases, drug-induced nephrotoxicity, drug-induced renal toxicity, and drug-induced nephropathy. This search was performed without time limitation. RESULTS AND CONCLUSION: Most greatest number of studies and human clinical trials on the renoprotective effect of PTX against drug-induced nephrotoxicity involves cyclosporine (Cyc). It seems that despite encouraging results from animal studies, there is insufficient evidence to support the renoprotective effect of PTX against Cyc-induced nephrotoxicity in humans. Although some available animal studies show protective effects of PTX against renal toxicity of some antimicrobial and cytotoxic agents, designing clinical trials to approve these nephroprotective effects requires prior confirmation of no reducing antimicrobial or antitumor action of these medications by PTX.