Management of drug-induced neutropenia, thrombocytopenia, and anaemia after solid organ transplantation: A comprehensive review.

WHAT IS KNOWN AND OBJECTIVE: Advances in the development of more effective immunosuppressive drugs have increased graft survival and drug induced adverse effects. Haematological complications including neutropenia, thrombocytopenia, and anaemia are common side effects that affect the grafts' and patients' outcomes. Several studies have stated the important role of various medications in haematological complications after transplantation. They have reported the incidence and different mechanisms of drug induced cytopenia, as well as an overview of possible treatment modalities. However, there is no comprehensive protocol for the management of these complications following transplantation. This narrative review was performed to develop a comprehensive practical approach for management of drug induced haematological complications following solid organ transplantation. METHOD: PubMed, Embase, Cochrane library, Web of Science, and Google scholar databases were searched without time limitations until March, 2021. In addition, some valid drug information data bases (Uptodate and Micromedex) were searched for detailed information until October, 2021. RESULTS AND DISCUSSION: Several immunosuppressive and antimicrobial medications may induce neutropenia, thrombocytopenia or anaemia following transplantation. Most of these agents cause dose-related cytopenia, which resolves with dose reduction or drug withdrawal. However, any change in medications may result in negative consequences such as severe infections, bleeding, cardiovascular complications, acute allograft rejection, and graft or patient loss. Thus, cautious evaluation of the patient's condition and the pharmacological properties of the culprit medication are required. WHAT IS NEW AND CONCLUSION: Three algorithms are presented to guide healthcare providers in the stepwise management of drug-induced neutropenia, thrombocytopenia, and anaemia after solid organ transplantation.

Comparing safety of proton-pump inhibitors versus H2-receptor antagonists in kidney transplant recipients: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Multiple studies have been conducted to compare the safety of proton-pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) as acid-suppressive treatment in kidney transplant recipients with conflicting results. This systematic review and meta-analysis aimed to evaluate the risk of adverse effects in kidney transplant patients receiving PPIs compared to those treated with H2RAs. METHODS: A systematic search was performed on the databases from inception to June 2021. The treatment effects were expressed as odds ratio (OR), weighted mean differences (WMD) and their 95% confidence intervals (CI) and pooled by a random-effects model. RESULTS AND DISCUSSIONS: Eight studies, consisting 4,844 patients, were included. Patients were followed for a mean duration of 23.57 months after transplantation. Compared with H2RAs, PPIs exposure was associated with similar rate of biopsy-proven acute rejection (BPAR) (OR = 1.05, 95% CI 0.83-1.34, p = 0.67), mortality (OR = 1.31, 95% CI 0.56-3.07, p = 0.533), graft loss (OR = 1.06, 95% CI 0.59-1.93, p = 0.842), Clostridioides difficile infection (OR = 1.37, 95% CI 0.49-3.85, p = 0.545) and pneumonia (OR = 1.83, 95% CI 0.95-3.52, p = 0.072). The estimated glomerular filtration rate (eGFR) at 12 months was lower in patients who received PPIs than those treated with H2RAs (WMD = -1.01, 95% CI -1.89 to -0.12 ml/min/1.73m2 , p = 0.02). The PPI-treated kidney transplant patients experienced higher rate of antibody-mediated rejection (AMR) (OR = 1.87, 95% CI 1.03-3.04, p = 0.039) and hypomagnesemia (OR = 2.16, 95% CI 1.46-3.20, p Ë‚ 0.001). WHAT IS NEW AND CONCLUSIONS: Compared with H2RAs, PPIs were not associated with higher risks of BPAR, mortality, graft loss or infection-related outcomes. However, taking PPIs was associated with higher rates of AMR and hypomagnesemia, and lower eGFR at one year after transplantation. Further well-controlled studies are needed to assess the impact of acid-suppressive strategy on long-term outcomes in KTRs.

Clinical characteristics and outcome of COVID-19 pneumonia in kidney transplant recipients in Razi hospital, Rasht, Iran.

BACKGROUND: In late December 2019, a novel coronavirus SARS-CoV-2 started to spread around the world in different populations. Its clinical and laboratory characteristics and outcome in kidney transplant recipients are little known. Therefore, we describe 22 kidney transplant recipients with SARS-CoV-2-induced pneumonia. METHODS: All kidney transplant recipients who referred to the Razi Hospital of Rasht with a diagnosis of SARS-CoV-2 infection from February 20 to 19th of April 2020 have been included in this observational study. RESULTS: We present 22 cases of COVID-19 in kidney transplant recipients (median age 52 years [interquartile range 40.75-62.75 years]) and baseline eGFR 60 (mL/min/1.73 m2 ) (44.75-86.75). Patients complained of cough (72.7%), dyspnea (63.6%), fever (68.2%), and chill (72.7%) with greater prevalence. We decreased the dose of immunosuppression and started stress dose of intravenous hydrocortisone or equivalent oral prednisolone. Each patient received antiviral therapy based on the latest updated version of local protocol at the time of admission. CT scan findings in 90.9% of patients showed bilateral multifocal lesions. Acute kidney injury (AKI) was observed in 12 patients during hospitalization. Six patients died after a median of 12 days from admission (IQR, 1-21). CONCLUSIONS: In this small observational study, we observed high AKI occurrence and mortality rate in kidney transplant recipients with COVID-19.

m-TOR inhibitors and risk of Pneumocystis pneumonia after solid organ transplantation: a systematic review and meta-analysis.

PURPOSE: Although there is controversy, some evidences proposed increased risk of post-transplant Pneumocystis carinii pneumonia (PCP) in patients receiving mammalian target of rapamycin (mTOR) inhibitors. This study aimed to examine the association between m-TOR inhibitors and the risk of developing PCP in solid organ transplant (SOT) recipients. METHODS: A comprehensive search was performed to find the eligible studies that investigated the incidence of PCP in patients treated with mTOR inhibitors after SOT. Random effect model was applied for meta-analysis. RESULTS: Combination of 15 effect sizes showed a significant positive association between mTOR inhibitor administration and the risk of PCP (OR = 1.90, 95%CIs = 1.44, 2.75). There was no heterogeneity between studies (I2 = 3.5%). Subgroup analysis revealed increased risk of PCP after the first year of transplantation (P < 0.001). CONCLUSION: In conclusion, administration of mTOR inhibitors is a potential risk factor for late-onset PCP after SOT. Targeted PCP prophylaxis based on recipients' risk factors rather universal prophylaxis may lessen the risk.

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.

mTOR inhibitors for management of encapsulating peritoneal sclerosis: a review of literatures.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is an infrequent, serious complication of peritoneal dialysis (PD). EPS may develop after kidney transplantation of PD-treated patients possibly due to the fibrotic effect of calcineurin inhibitors (CNIs). Some experimental and clinical studies proposed inhibitors of mammalian target of rapamycin (mTOR) for EPS management due to their anti-fibrotic and anti-angiogenesis effects. This review evaluated the therapeutic role of mTOR inhibitors in the management of EPS. METHOD: Thirteen case reports/series consisted of 20 patients (16 post-transplant and four post-hemodialysis EPS cases) were evaluated. We tried to extract the effect of mTOR inhibitors according to authors' conclusion and the time of improvement of patients' symptoms and each treatment modality such as surgery, parenteral nutrition, tamoxifen and mTOR inhibitors. RESULTS: Of 20 patients, clinical improvement of five patients (25%) is more attributable to mTOR inhibitor therapy. All these five patients were post-kidney transplant EPS cases. Therefore, EPS improvement rate in post-transplant EPS patients was 31.25% (5 of 16 patients). Death after EPS diagnosis occurred in two of seven patients with continued CNIs therapy (28.57%) and 1 of 11 cases (9.09%) who didn't receive CNIs after EPS diagnosis. CONCLUSION: Although the therapeutic effect of mTOR inhibitors against EPS remains unproven, it seems that for patients with post kidney transplant EPS who do not have any contraindication for mTOR inhibitor administration, converting from CNIs to mTOR inhibitors in addition to other EPS treatments may result in improving EPS in approximately one-third of patients and decreasing patients' mortality.

Effect of Silymarin Administration on Cisplatin Nephrotoxicity: Report from A Pilot, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

Despite several introduced preventive modalities, cisplatin nephrotoxicity remains a clinical problem. Some in vitro and in vivo studies have addressed the protective effects of silymarin against cisplatin nephrotoxicity. This study evaluated the effects of silymarin administration on cisplatin nephrotoxicity as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting 24-48 h before the initiation of cisplatin infusion and continuing to the end of three 21-day cisplatin-containing chemotherapy courses on cisplatin-induced renal electrolytes wasting and kidney function were assessed. Cisplatin-associated acute kidney injury (AKI) occurred in 8% of the patients. Urine neutrophil gelatinase-associated lipocalin to urine creatinine ratio (NGAL/Cr) and urinary magnesium and potassium wasting increased significantly after cisplatin infusion in both groups. Significant positive correlation was found between cumulative dose of cisplatin and urine NGAL/Cr after three courses of cisplatin infusion. Incidence of AKI and the magnitude of urinary magnesium and potassium wasting did not differ between silymarin and placebo groups. No adverse reaction was reported by silymarin administration. Prophylactic administration of conventional form of silymarin tablets could not prevent cisplatin-induced urine electrolyte wasting or renal function impairment.

Efficacy of decontamination protocol by antimicrobial treatment in Iranian Tissue Bank (ITB).

Iranian Tissue Bank established in 1994 provides soft tissues for implantation in Iran. This study was designed to evaluate the efficacy of decontamination process of cardiac and soft tissues in Iranian Tissue Bank. In this bank after initial assessments, the tissues were incubated in a 5-antibiotic cocktail at room temperature for 24 h and then at 4 °C for 14 days. Contamination status was compared before and after antibiotic cocktail incubation. Of 3,315 assessed tissues, 1,057 were pericardia, 1,051 were fascia and 1,207 were other soft tissues including tibialis and aorta. The initial contamination rate was 36.86%. Pericardia showed the highest contamination rate. Klebsiella species was the most prevalent organism causing contamination. Decontamination rate after antibiotic incubation was 86.91% with the highest successful decontamination rate for fascia tissue. Klebsiella species was the major source of contamination in tissues that remained contaminated after antibiotic incubation. This may be due to resistance of this organism to applied antibiotics in the decontamination cocktail possibly due to a negative drug interaction between aminoglycoside and penicillin derivatives in this antibiotic cocktail. In conclusion collected data shows comparable efficacy of the decontamination process that is used in ITB compared with homograft banks of other countries.

Effects of omega-3 fatty acids on depression and quality of life in maintenance hemodialysis patients.

Depression and health-related quality of life (HRQoL) are closely interrelated among hemodialysis (HD) patients and associated with negative impacts on patients' clinical outcomes. Considering previous reports on clinical benefits of omega-3 fatty acids in major depression and HRQoL in other patient populations, this study examined effects of omega-3 fatty acids on depression and HRQoL in chronic HD patients. In this randomized placebo-controlled trial, 40 adult patients with a Beck Depression Inventory (BDI) score of ≥16 and HD vintage of at least 3 months were randomized to ingest 6 soft-gel capsules of either omega-3 fatty acids (180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid in each capsule) or corresponding placebo, daily for 4 months. At baseline and after 4 months, 2 questionnaires of BDI and the Medical Outcome Study 36-Item Short-Form Health Survey were completed by each patient. Although baseline BDI score was comparable between the 2 groups, it was significantly lower in the omega-3 group compared with the placebo group at the end of the study (P = 0.008). Except for mental health, social functioning, and general health, other domains of HRQoL showed significant improvement in the omega-3 group compared with the placebo group at month 4 of the study (P < 0.05 for all). Regression analysis revealed that ameliorated BDI score by omega-3 treatment had considerable role in the improvement of overall HRQoL score, physical and mental component dimensions, and score of physical functioning, role-physical, and bodily pain. Supplemental use of omega-3 fatty acids in HD patients with depressive symptoms seems to be efficacious in improving depressive symptoms and HRQoL.

Carnitine for prevention of antituberculosis drug-induced hepatotoxicity: a randomized, clinical trial.

BACKGROUND AND AIM: In the present study, the potential benefits of oral carnitine in preventing antituberculosis drug-induced hepatotoxicity (ATDH) were evaluated. METHODS: Fifty-four patients in the carnitine and 62 patients in the placebo group completed the study. The carnitine group received 1000 mg oral carnitine solution twice daily for 4 weeks. The placebo group received 10 mL of oral placebo solution twice daily for 4 weeks. ATDH was defined as an increase in the serum level of aspartate aminotransferase or alanine aminotransferase greater than three or five times of the upper limit of normal with or without clinical symptoms of hepatotoxicity, respectively. RESULTS: During the study period, 29 (25%) patients experienced ATDH. Among these patients, nine (16.7%) and 20 (32.3%) were in the carnitine and placebo groups, respectively (P = 0.049). Based on multivariate logistic regression model, age over 35 years old (odds ratio [OR] = 7.01, P = 0.002), human immunodeficiency virus infection (OR = 40.4, P < 0.001), diabetes mellitus (OR = 37.6, P = 0.001), and placebo treatment (OR = 0.1, P = 0.01) were identified as predisposing factors for ATDH. CONCLUSION: Results of our preliminary clinical trial suggested that cotreatment with 2000 mg oral L-carnitine solution daily for 4 weeks significantly decreased the rate of ATDH.

Tenofovir-induced nephrotoxicity: incidence, mechanism, risk factors, prognosis and proposed agents for prevention.

OBJECTIVE: In this study, data regarding epidemiology, risk factors, pathogenesis and outcome of tenofovir-induced nephrotoxicity will be reviewed, and current and future approaches for prevention will be discussed. METHOD: The data were collected by searching Scopus, PubMed, Medline, Science direct, Clinical trials and Cochrane database systematic reviews. The keywords used as search terms were "Tenofovir", "TDF", "NRTI", "Nephrotoxicity", "Renal failure", "Kidney damage", "HIV" and "AIDS". RESULTS AND CONCLUSION: Several predisposing factors including elevated baseline SCr, concomitant nephrotoxic medications, low body weight, advanced age, tenofovir disoproxil fumarate (TDF) dose and duration of treatment and lower CD4 cell count were identified as risk factors for development of TDF-induced nephrotoxicity. Cellular accumulation through increased entry from the human organic anion transporters and decreased efflux into tubular lumen is main mechanism of nucleotide analogue antiviral induced nephrotoxicity. Renal function assessment and monitoring at baseline and during TDF treatment are the main approach of prevention of TDF-induced nephrotoxicity. Rosiglitazone may be helpful in patients presenting with TDF-induced nephrotoxicity. Pretreatment with melatonin prevented all known histological changes in proximal tubular mitochondira induced by TDF. Use of antioxidants with mitochondria-targeted properties such as MitoQ or Mito-CP may prevent proximal tubular mitochondrial against TDF damage. Vitamin E, ebselen, lipoic acid, plastoquinone, nitroxides, SOD enzyme mimetics, Szeto-Schiller (SS) peptides, and quercetin are other potential agents for prevention of TDF-induced nephrotoxicity. However, data regarding effectiveness of nephroprotective agents against TDF-induced nephrotoxicity are not conclusive. Before extrapolation of the preclinical evidence to clinical practice, these evidence should be confirmed in future human studies.

N-acetyl cysteine in prevention of amphotericin- induced electrolytes imbalances: a randomized, double-blinded, placebo-controlled, clinical trial.

PURPOSE: The aim of this study was to evaluate the effectiveness of oral n-acetyl cysteine, as a potential nephroprotective agent, in preventing and/or attenuating amphotericin B-induced electrolytes imbalances. METHODS: During a one year period, patients were to receive conventional amphotericin b for any indication for at least one week and were randomly allocated to receive either placebo or 600 mg oral n-acetyl cysteine twice daily during the treatment course of amphotericin b. Demographic and clinical data of the study population were gathered. Different aspects of amphotericin b nephrotoxicity including decrease of glomerular filtration rate, hypokalemia, hypomagnesemia, renal magnesium and potassium wasting were assessed. Each patient was monitored for any adverse reaction to n-acetyl cysteine. Sixteen and 14 patients in the n-acetyl cysteine and placebo groups completed the study, 3incidences of hypokalemia (75 % versus 70 %; P = 0.724) and hypomagnesemia (30 % versus 20 %; P = 0.468) did not differ significantly between placebo and NAC groups, respectively. Although the rate of AmB nephrotoxicity was higher in the placebo than in the NAC group (60 % versus 40 %), this difference was not statistically significant (P = 0.209) even after adjusting for probable associated factors of amphotericin b nephrotoxicity (P = 0.206). The incidence as well as time of onset of electrolyte abnormalities also did not differ significantly between placebo and n-acetyl cysteine groups. About 44 % of n-acetyl cysteine recipients experienced new onset nausea and a mild unpleasant taste during the study. CONCLUSION: Oral n-acetyl cysteine during the amphotericin B treatment course was not significantly effective in preventing or mitigating different features of its nephrotoxicity including decrease of glomerular filtration rate, hypokalemia, hypomagnesemia, and renal potassium as well as magnesium wasting.

The effect of omega-3 fatty acids on depressive symptoms and inflammatory markers in maintenance hemodialysis patients: a randomized, placebo-controlled clinical trial.

PURPOSE: This study was designed to investigate the effects of omega-3 fatty acids on depression and chronic inflammation in hemodialysis patients. METHOD: Fifty-four maintenance hemodialysis patients were randomized to ingest two omega-3 (each containing 180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid) or placebo capsules, three times daily for 4 months. MAIN OUTCOME MEASURES: Beck Depression Inventory (BDI) score and serum levels of C-reactive protein (CRP), interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, ferritin, intact parathyroid hormone (iPTH), and ratios of IL-10 to IL-6 and IL-10 to TNF-α were measured at baseline and at the end of the study. RESULTS: Omega-3 supplement lowered BDI score significantly after 4 months of intervention. Among pro- and anti-inflammatory mediators, only serum ferritin level and IL-10 to IL-6 ratio showed significant changes in favor of omega-3 supplement during the study. In linear regression model adjusted for baseline values, omega-3 treatment was a significant predictor of reduced serum CRP, ferritin, and iPTH levels, and increased IL-10 to IL-6 ratio. No significant association was found between the anti-inflammatory and anti-depressant effects of omega-3 supplement. CONCLUSIONS: Supplemental use of omega-3 fatty acids decreases depressive symptoms in hemodialysis patients apart from their anti-inflammatory effects.

Effects of oral supplementation with omega-3 fatty acids on nutritional state and inflammatory markers in maintenance hemodialysis patients.

OBJECTIVE: The objective was to determine the effects of omega-3 supplementation on nutritional state and inflammatory markers of hemodialysis patients. DESIGN AND METHODS: This was a randomized, placebo-controlled trial. Adult patients undergoing maintenance hemodialysis were included. Patients with malignancy, pregnancy, concurrent inflammatory or infectious diseases, or concomitant use of any medication affecting inflammation status were excluded. The omega-3 group received 6 soft-gel capsules of fish oil (180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid in each) daily for 4 months, and the placebo group received corresponding paraffin oil capsules.Nutrition indices including body mass index; mid-arm muscle circumference; serum concentrations of albumin, prealbumin, and transferrin; and serum levels of inflammatory/anti-inflammatory markers including interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, C-reactive protein, ferritin, parathyroid hormone, and ratios of IL-10 to TNF-α and IL-10 to IL-6 were measured before and after 4 months of intervention. RESULTS: Twenty patients in the placebo and 25 patients in the omega-3 group completed the study. There were no significant changes in nutritional markers between the omega-3 and placebo groups after 4 months of intervention. Regression analysis adjusting post-treatment values of nutrition markers for baseline values, omega-3 treatment, and patients' baseline demographic and clinical data revealed that omega-3 treatment was a significant independent predictor of increased serum prealbumin level (182.53; 95% confidence interval 21.14, 511.18; P = .11). Although slight reduction of inflammatory state was observed in the omega-3 group, no significant differences were evident in the mean changes of inflammatory and anti-inflammatory markers between the 2 groups with the exception of serum ferritin level and the IL-10 to IL-6 ratio, which significantly changed in favor of omega-3 supplementation (P < .001 and P = .003, respectively). CONCLUSIONS: Omega-3 supplementation in hemodialysis patients produced a slight attenuation in systemic inflammation without any remarkable effects on nutritional markers.

Frequency, types, and direct related costs of medication errors in an academic nephrology ward in Iran.

Medication errors are ongoing problems among hospitalized patients especially those with multiple co-morbidities and polypharmacy such as patients with renal diseases. This study evaluated the frequency, types and direct related cost of medication errors in nephrology ward and the role played by clinical pharmacists. During this study, clinical pharmacists detected, managed, and recorded the medication errors. Prescribing errors including inappropriate drug, dose, or treatment durations were gathered. To assess transcription errors, the equivalence of nursery charts and physician's orders were evaluated. Administration errors were assessed by observing drugs' preparation, storage, and administration by nurses. The changes in medications costs after implementing clinical pharmacists' interventions were compared with the calculated medications costs if the medication errors were continued up to patients' discharge time. More than 85% of patients experienced medication error. The rate of medication errors was 3.5 errors per patient and 0.18 errors per ordered medication. More than 95% of medication errors occurred at prescription nodes. Most common prescribing errors were omission (26.9%) or unauthorized drugs (18.3%) and low drug dosage or frequency (17.3%). Most of the medication errors happened on cardiovascular drugs (24%) followed by vitamins and electrolytes (22.1%) and antimicrobials (18.5%). The number of medication errors was correlated with the number of ordered medications and length of hospital stay. Clinical pharmacists' interventions decreased patients' direct medication costs by 4.3%. About 22% of medication errors led to patients' harm. In conclusion, clinical pharmacists' contributions in nephrology wards were of value to prevent medication errors and to reduce medications cost.

Potential effects of omega-3 fatty acids on anemia and inflammatory markers in maintenance hemodialysis patients.

BACKGROUND: Anemia is a common complication among hemodialysis (HD) patients. Although intravenous iron and erythropoiesis-stimulating agents revolutionized anemia treatment, about 10% of HD patients show suboptimal response to these agents. Systemic inflammation and increased serum hepcidin level may contribute to this hyporesponsiveness. Considering the anti-inflammatory properties of omega-3 fatty acids, this study aimed to evaluate potential role of these fatty acids in improving anemia and inflammation of chronic HD patients. METHODS: In this randomized, placebo-controlled trial, 54 adult patients with HD duration of at least 3 months were randomized to ingest 1800 mg of either omega-3 fatty acids or matching placebo per day for 4 months. Anemia parameters including blood hemoglobin, serum iron, transferrin saturation (TSAT), erythropoietin resistance index, and required dose of intravenous iron and erythropoietin, and serum concentrations of inflammatory/anti-inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, C-reactive protein (CRP), hepcidin, ferritin, intact parathyroid hormone (iPTH), and ratios of IL-10 to IL-6 and IL-10 to TNF-α were measured at baseline and after 4 months of the intervention. RESULTS: 45 subjects (25 in the omega-3 and 20 in the placebo group) completed the study. No significant changes were observed in blood hemoglobin, serum iron, TSAT, and required dose of intravenous iron in either within or between group comparisons. Additionally, erythropoietin resistance index as well as required dose of intravenous erythropoietin showed no significant change in the omega-3 group compared to the placebo group. Although a relative alleviation in inflammatory state appeared in the omega-3 group, the mean differences of inflammatory and anti-inflammatory markers between the two groups did not reach statistically significant level except for IL-10-to-IL-6 ratio and serum ferritin level which showed significant changes in favor of omega-3 treatment (P <0.001 and P = 0.003, respectively). CONCLUSION: Omega-3 fatty acids relatively improved systemic inflammation of chronic HD patients without any prominent benefits on anemia. However, future well-designed studies on larger number of patients may determine utility of omega-3 fatty acids in HD patients with respect to inflammation and anemia.

Prevention of vancomycin induced nephrotoxicity: a review of preclinical data.

PURPOSE: Several strategies have been proposed for the prevention of vancomycin-induced nephrotoxicity. Here, we review available evidence supporting the respective strategies. METHOD: Data were collected by searching the Scopus, PubMed, and Medline databases and the Cochrane database of systematic reviews. The key words used as search terms were "vancomycin," "nephrotoxicity", "renal failure," "renal damage," "nephroprotective," "renoprotective", and "prevention." Prospective or retrospective observational animal studies that evaluated the effects of a modality for the prevention of vancomycin-induced nephrotoxicity was included. RESULTS AND CONCLUSION: Animal studies show beneficial effects of various antioxidants, such as erdosteine, vitamin E, vitamin C, N-acetylcysteine, caffeic acid phenethyl ester, and erythropoietin, in the prevention of vancomycin-induced nephrotoxicity. However, before these agents can be used in clinical practice, their potential benefits must be confirmed in future randomized controlled human studies.

A probable clinically significant interaction between warfarin and cloxacillin: three case reports.

CASES: Three patients were admitted to the Imam Hospital, Tehran, Iran with a diagnosis of bacterial endocarditis. The patients had indications for valve replacement surgery and anticoagulant therapy. The administration of cloxacillin reduced the effect of warfarin, and subsequent increases in warfarin doses were unable to overcome this effect. CONCLUSION: A decrease in warfarin anticoagulation effects was detected in our three patients following cloxacillin therapy for infective endocarditis. Penicillinase-resistant penicillins remain essential antibiotics in the treatment of severe infections caused by Staphylococcus aureus due to their bactericidal activity, safety, and cost. Thus, in situations where anticoagulants are indicated in patients with infective endocarditis, it would be better to replace warfarin with low-molecular-weight or unfractionated heparin.

Role of diuretics and lipid formulations in the prevention of amphotericin B-induced nephrotoxicity.

PURPOSE: To collect available clinical data to define the role of diuretics and lipid formulations in the prevention of amphotericin B (AmB)-induced nephrotoxicity (AIN) in human populations. METHOD: A literature search was performed in the following databases: Scopus, Medline, Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. RESULTS AND CONCLUSION: Co-administration of mannitol failed to show any clinically significant benefit in preventing AIN. Potassium-sparing diuretics, such as amiloride and spironolactone, have been shown to have beneficial effects as an alternative or adjunct to oral/parenteral potassium supplements in preventing hypokalemia due to AmB. Lipid-based formulations of AmB are clinically effective and safe in preventing AIN. However, due to their high cost and limited accessibility, these formulations are generally used as second-line antifungal therapy in cases of conventional AmB refractoriness and/or intolerance or pre-existing renal dysfunction. The potential effects of other nephroprotective agents, such as N-acetylcysteine, AIN merit further considerations and investigations.

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.