Non-Thyroidal Illness in Chronic Renal Failure: Triiodothyronine Levels and Modulation of Extra-Cellular Superoxide Dismutase (ec-SOD)

Oxidative stress (OS) is implicated in several chronic diseases. Extra-cellular superoxide dismutase (ec-SOD) catalyses the dismutation of superoxide anions with a protective role in endothelial cells. In chronic kidney disease (CKD), OS and thyroid dysfunction (low fT3 syndrome) are frequently present, but their relationship has not yet been investigated. This cohort study evaluated ec-SOD activity in CKD patients during haemodialysis, divided into "acute haemodialytic patients" (AH, 1-3 months of treatment) and "chronic haemodialytic patients" (CH, treated for a longer period). We also evaluated plasmatic total antioxidant capacity (TAC) and its relationships with thyroid hormones. Two basal samples ("basal 1", obtained 3 days after the last dialysis; and "basal 2", obtained 2 days after the last dialysis) were collected. On the same day of basal 2, a sample was collected 5 and 10 min after the standard heparin dose and at the end of the procedure. The ec-SOD values were significantly higher in CH vs. AH in all determinations. Moreover, the same patients had lower TAC values. When the CH patients were divided into two subgroups according to fT3 levels (normal or low), we found significantly lower ec-SOD values in the group with low fT3 in the basal, 5, and 10 min samples. A significant correlation was also observed between fT3 and ec-SOD in the basal 1 samples. These data, confirming OS and low fT3 syndrome in patients with CKD, suggest that low fT3 concentrations can influence ec-SOD activity and could therefore potentially contribute to endothelial oxidative damage in these patients

Preventive Newborn Male Circumcision: What Is the Child's Best Interest?

Preventive newborn male circumcision has been at the center of scientific debate for many years. The reason for promoting preventive newborn male circumcision, is the reduction of the incidence of UTIs (in the first six months of life), penile cancer, transmission of STDs/HIV infection/AIDS. However preventive interventions in the newborn involving violations of bodily integrity elicit several ethical questions. In this article, we reviewed the literature regarding circumcision, the prevention of UTIs, penile cancer, transmission of STDs/HIV infection/AIDS and complications of this practice in the neonatal period. The very limited reduction of incidence of UTIs and the uncertain preventive role of newborn male circumcision towards penile cancer, STDs/HIV infection and AIDS, makes it difficult to justify male circumcision in newborns. Moreover, the challenge in obtaining a unanimous opinion on newborn male circumcision derives from the fact that, as a preventive intervention, it requires evaluation criteria that are not comparable to those of therapeutic treatments. Since preventive male circumcision determines permanent alteration of the body, some authors believe that it can be used only in subjects that are capable of giving their valid consent. In the case of a newborn, the ″child's best interest″ should be used as a standard, but preventive newborn male circumcision does not satisfy it

New intravenous calcimimetic agents: New options, new problems. an example on how clinical, economical and ethical considerations affect choice of treatment

Background. Dialysis treatment is improving, but several long-term problems remain unsolved, including metabolic bone disease linked to chronic kidney disease (CKD-MBD). The availability of new, efficacious but expensive drugs (intravenous calcimimetic agents) poses ethical problems, especially in the setting of budget limitations. Methods. Reasons of choice, side effects, biochemical trends were discussed in a cohort of 15 patients (13% of the dialysis population) who stared treatment with intravenous calcimimetics in a single center. All patients had previously been treated with oral calcimimetic agents; dialysis efficacy was at target in 14/15; hemodiafiltration was employed in 10/15. Median Charlson Comorbidity Index was 8. The indications were discussed according to the principlist ethics (beneficience, non maleficience, justice and autonomy). Biochemical results were analyzed to support the clinical-ethical choices. Results. In the context of a strict clinical and biochemical surveillance, the lack of side effects ensured “non-maleficence”; efficacy was at least similar to oral calcimimetic agents, but tolerance was better. Autonomy was respected through a shared decision-making model; all patients appreciated the reduction of the drug burden, and most acknowledged better control of their biochemical data. The ethical conflict resides in the balance between the clinical “beneficience, non-maleficience” advantage and “justice” (economic impact of treatment, potentially in attrition with other resources, since the drug is expensive and included in the dialysis bundle). The dilemma is more relevant when a patient’s life expectancy is short (economic impact without clear clinical advantages), or when non-compliance is an issue (unclear advantage if the whole treatment is not correctly taken). Conclusions. In a context of person-centered medicine, autonomy, beneficence and non-maleficence should weight more than economic justice. While ethical discussions are not aimed at finding “the right answer” but asking “the right questions”, this example can raise awareness of the importance of including an ethical analysis in the choice of “economically relevant” drugs

Conservative (non dialytic) management of end-stage renal disease and withdrawal of dialysis

Several key questions help to clarify the evolving debate concerning management of end-stage renal disease and withdrawal of dialysis. First, what is the evidence about survival, quality of life, and course of illness, following conservative management or dialysis withdrawal? Second, what criteria are used for deciding on conservative management or withdrawing dialysis, and how are these criteria justified? Third, who should make the decision and how should it be reached, particularly when there is cognitive impairment and the patient cannot make the decision for themselves? Decision criteria, the evidence, and who decides are each considered in this review

Gonadal function and immunosuppressive therapy after renal transplantation

End-stage renal disease is associated with disorders in hypothalamic-pituitary-gonadal function. Immunosuppressive therapies may influence the restoration of normal levels of gonadal hormones after renal transplantation. The aim of the present study was to evaluate the hormonal status of successful renal transplant recipients who were treated with different immunosuppressive agents. Testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured in 59 male renal transplant recipients with stable graft function with serum creatinine <2.5 mg/dL. Patients were treated with three different immunosuppressive regimens: group I, calcineurin inhibitors (CI; n = 15), group II, sirolimus without calcineurin inhibitors (SRL; n = 15), group III, sirolimus in combination with calcineurin inhibitors (SRL * (*) CI; n = 29). Testosterone was significantly lower in group II versus group I (3.12 \ub1 1.23 versus 4.39 \ub1 1.53 ng/mL; P <. 0197). Group III had higher testosterone values than group II, but lower than group I. FSH and LH were also higher in the SRL group, but the differences were not statistically significant, perhaps because of the small number of patients. No relationship was found between testosterone blood levels and age, posttransplant follow-up, renal function, time on dialysis, body mass index, steroid use, or posttransplant diabetes. Sirolimus seems to impair the improvement of gonadal function after renal transplantation. Further prospective studies are needed to confirm these data before patients are advised of this potential side effect

Non-thyroidal illness syndrome in chronic diseases: role of irisin as modulator of antioxidants

OBJECTIVE: Non-thyroidal-illness syndrome (NTIS) refers to condition found in chronic diseases that is an adaptive mechanism. However, oxidative stress is related to NTIS in a vicious circle, due to deiodinases alteration and negative effects of low T3 on antioxidant levels or activity. Muscle is one of the main targets of thyroid hormones and it can secrete a myokine named irisin, which is able to induce the browning of white adipose tissue, energy expenditure and protect against insulin resistance. Inconclusive data have been reported about irisin role in chronic diseases. Moreover, no correlation with antioxidants has been investigated. Therefore, we performed a case-control study with the primary endpoint to evaluate irisin levels in two models of NTIS, such as chronic heart failure (CHF) and chronic kidney disease (CKD) during haemodialytic treatment. The secondary endpoint was the correlation with total antioxidant capacity (TAC) to establish a possible role of irisin in the modulation of antioxidant systems. PATIENTS AND METHODS: Three groups of subjects were enrolled. Group A included CHF patients (n=18; aged 70.22 ± 2.78 ys; BMI ± 27.75 ± 1.28 kg/m2); Group B included CKD patients (n=29; aged 67.03 ± 2.64; BMI 24.53 ± 1.01); finally, 11 normal subjects (Group C) have been enrolled as controls. Irisin has been evaluated by ELISA method and Total Antioxidant Capacity (TAC) by spectrophotometric method. RESULTS: Irisin was significantly higher in Group B vs. A and C groups (Mean ± SEM: 20.18 ± 0.61 ng/ml vs. 2.77 ± 0.77 and 13.06 ± 0.56, respectively; p<0.05); a significant correlation between irisin and TAC was observed in group B. CONCLUSIONS: These preliminary data suggest a possible role of irisin in the modulation of antioxidants in two chronic syndromes with low T3 (i.e., CHF and CKD) with differential pattern in these two models studied. Further insights are needed to confirm this pilot study, which could be the basis for a longitudinal investigation, to assess a prognostic role of irisin with possible therapeutic implications

Anorexia and serum leptin in chronic hemodialysis patients

Background. Hyperleptinemia is a common feature in hemodialysis (HD) patients. The role of increased serum leptin levels in the pathogenesis of HD-related anorexia is, however, still controversial. The purpose of the present prospective study was to ascertain whether hyperleptinemia is casually implicated in the pathogenesis of HD-related anorexia. Methods. We measured serum leptin levels and the serum leptin/Body Mass Index (BMI) ratio in 24 healthy subjects and in 49 end-stage renal disease patients on maintenance HD. Results. HD patients were subdivided into anorexic (A) (14/49, 28.5%) and non-anorexic (NA) (35/49, 71.5%) according to a questionnaire discriminating for the presence of anorexia-related symptoms. Calorie (Kcal/kg/day) and protein (grams/kg/day) intakes were significantly lower in A than in NA patients (20.1±1.1 vs. 27.9±1.3, p=0.004 and 0.82±0.05 vs. 1.19±0.05, p=0.001, respectively). Accordingly, serum albumin, total lymphocytes count, mid arm muscle circumference, and the protein equivalence of nitrogen appearance (PNA) were significantly lower in A patients. Serum leptin concentration (ng/mL) was significantly higher in HD patients than in controls, both in males (15.33±3.4 vs. 3.7±0.3, p=0.003) and in females (42.31±7.2 vs. 10.5±1.3, p=0.03). Similarly, the serum leptin/BMI ratio was significantly higher in HD patients than in controls, both in males (0.56±0.1 vs. 0.16±0.02, p=0.0028) and in females (1.82±0.2 vs. 0.47±0.04, p<0.0001). However, serum leptin levels were similar in A and NA patients, whether male (15.3±5.6 vs. 16.9±4.2, p=0.85) or female (46.6±12.9 vs. 47.4±9.4, p=0.96). No differences were also observed between the two groups in the serum leptin/BMI ratio, either in males (0.59±0.2 vs. 0.58±0.14, p=0.92) or in females (1.58±0.4 vs. 1.83±0.3, p=0.94). No significant correlations were found between serum leptin levels and PNA, albumin, cholesterol, total lymphocytes number, weight change, C-reactive protein, fibrinogen, ferritin, and complement. Conclusions. The present results would indicate that mechanisms other than increases in serum leptin levels might be involved in the pathogenesis of HD-related anorexia

Evidence-based criteria for the choice and the clinical use of the most appropriate lock solutions for central venous catheters (excluding dialysis catheters): a GAVeCeLT consensus

BACKGROUND:The most appropriate lock solution for central venous access devices is still to be defined. GAVeCeLT - the Italian group for venous access devices - has developed a consensus on the evidence-based criteria for the choice and the clinical use of the most appropriate lock solution for central venous catheters (excluding dialysis catheters). METHOD:After the constitution of a panel of experts, a systematic collection and review of the literature has been performed, focusing on clinical studies dealing with lock solutions used for prevention of occlusion (heparin, citrate, urokinase, recombinant tissue plasminogen activator [r-TPA], normal saline) or for prevention of infection (citrate, ethanol, taurolidine, ethylene-diamine-tetra-acetic acid [EDTA], vancomycin, linezolid and other antibiotics), in both adults and in pediatric patients. Studies on central lines used for dialysis or pheresis, on peripheral venous lines and on arterial lines were excluded from this analysis. Studies on lock solutions used for treatment of obstruction or infection were not considered. The consensus has been carried out according to the Delphi method. RESULTS:The panel has concluded that: (a) there is no evidence supporting the heparin lock; (b) the prevention of occlusion is based on the proper flushing and locking technique with normal saline; (c) the most appropriate lock solution for infection prevention should include citrate and/or taurolidine, which have both anti-bacterial and anti-biofilm activity, with negligible undesired effects if compared to antibiotics; (d) the patient populations most likely to benefit from citrate/taurolidine lock are yet to be defined. CONCLUSIONS:The actual value of heparinization for non-dialysis catheters should be reconsidered. Also, the use of lock with substances with anti-bacterial and anti-biofilm activity (such as citrate or taurolidine) should be taken into consideration in selected populations of patients