Catheter lock solutions: it's time for a change.

In recent years, the number of patients on hemodialysis (HD) with central vascular catheters (CVCs) has grown. However, CVC use is often associated with an important risk for catheter related bloodstream infections (CR-BI) and inadequate dialysis due to flow problems. In this study, we reviewed alternative solutions to heparin for locking HD CVCs. Several experiences have demonstrated that trisodium citrate (TSC) (30-47%), citrate (4%) and taurolidine (1.35%) solutions are effective and safe for the prevention of CRBI, while heparin stimulates biofilm formation. High citrate (47%) concentrations can also provide significant advantages in reducing catheter clotting, but controlled studies with larger populations are necessary to confirm and to extend the use of such solutions in clinical practice. Side effects with high sodium citrate concentrations have been reported only immediately after locking, the symptoms are probably caused by a temporary drop in ionized calcium and magnesium, but it is evident that these solutions should only be used by skilled and authorized personnel, with a rigorous protocol.

How to improve dialysis adequacy in patients with vascular access problems.

Blood flow rate is a critical factor in the achievement of an adequate dialysis dose. The aim of this review is to evaluate the possibility of optimizing dialysis dose in terms of Kt/V in patients with reduced vascular access (VA) flow rate, considering effective blood flow (Qb eff), recirculation, access flow and hemodialyzer. In patients where the achievement of adequate blood flow rates are difficult to obtain and no surgical revision is necessary, to avoid under dialysis the increase in the treatment time should be the first choice solution. If such a solution is difficult for various reasons, a forced partial blood flow recirculation, especially in central venous catheters (CVCs) with reversed lines can be useful, on condition that the dialysis session is prolonged. The possibility of increasing the efficiency of dialysis through an increase in filter clearance has to be considered. Monitoring arterial pre-pump pressure (P asp) and optimizing ratio P asp/Qb eff during hemodialysis (HD) is one possible solution to improve blood flow rates, but it is necessary to educate and involve the staff. Recent developments in a new class of highly effective hemodialyzer due to dialysate distribution, has opened up interesting opportunities in terms of dialysis adequacy in patients with reduced VA flow rate.

Leptin and beta2-microglobulin kinetics with three different dialysis modalities.

BACKGROUND: Leptin is a protein produced by fat cells and involved in body weight regulation. In patients with normal kidney function, leptin has been considered an independent predictor of cardiovascular events. In uremic patients, leptin in plasma serum was assumed to be associated with malnutrition, inflammation and atherosclerosis. Because of its molecular weight and characteristics, leptin can be considered as a protein-bound uremic retention solute. Some authors have reported the possibility of decreasing the serum leptin concentration with high flux membranes, but limited data are available on the elimination with medium-flux membranes or alternative dialysis strategies such as hemodiafiltration. METHODS: We evaluated the kinetics of leptin and beta2m in a study of 18 chronic hemodialysis patients using low-flux, medium-flux and high-flux biocompatible membranes, the last one used in hemodiafiltration (HDF). Blood samples for leptin and beta2m were collected pre- and post-treatment and 30 minutes after the end of treatment, over a 1-week period that included 3 dialysis sessions. Clearances of leptin and beta2m across the dialyzer were also determined directly from the arterial and venous blood concentrations 60 and 210 minutes after starting dialysis. RESULTS: At baseline, all groups showed similar leptin (18.8+/-4.4 ng/mL) and beta2m concentrations (29.2+/-7.1 ng/mL). After a single dialysis session, a reduction of both solutes was observed with HDF (39.8+/-1.9%, 78.1+/-4.9) and medium flux membranes (18.2+/-0.9%, 52.2+/-1.7%), whereas the concentrations remained unchanged with the low-flux membranes. After one-week period, a trend of reduction of plasma pre dialysis leptin and beta2m were observed with HDF and medium flux membranes. At 60 minutes, HDF showed the best instantaneous clearance across the filter for leptin (56.2+/-10.1 ml/min) and beta2m (75.3+/-4.4 ml/min). The magnitude of post dialysis rebound of leptin at 30 min was variable and strongly correlated with the instantaneous clearance of the solute (r2= 0.88). CONCLUSIONS: Leptin serum concentration can be influenced by dialysis modalities and membrane permeability; data on rebound suggest a multicompartimental kinetic of leptin similar to beta2m. Leptin removal, as measured by the reduction rate, can be considered as an index of dialysis efficiency for protein-bound uremic retention solutes.

[Acute renal failure and thrombotic microangiopathy (TM)]. / Insufficienza renale acuta e microangiopatia trombotica.

BACKGROUND: Thrombotic microangiopathy (TM) is a disorder characterized by fibrin formation and platelet aggregation in the small arteries and capillaries. Two main clinical settings are reported in association with this disorder: hemolitic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Both conditions share common findings such as microangiopathic anemia and thrombocytopenia. HUS is more frequent in children and is mainly characterized by renal symptoms, whereas PTT is dominated by neurologic abnormalities. However, in many patients, the clinical distinction between HUS and PTT is not clear; therefore, some authors consider the two syndromes as manifestations of the same entity. In children, the most common cause of HUS is an enteric infection caused by cytotoxin-producing bacteria (mainly Escherichia coli with serotype O157:H7). This toxin--the Shiga toxin--can bind to glomerular endothelial cells and stimulate the production of cytokines and the secretion of von Willebrand factor (vWf). TM may be caused by drugs such as cyclosporin, tacrolimus, mytomicin C, ticlopidine, quinine, and oral contraceptives. It may be associated with disorders of pregnancy (severe pre-eclampsia and postpartum HUS) or with systemic disorders such as systemic lupus erythematosus (SLE), antiphospholipid syndrome, systemic sclerosis, and human immunodeficiency virus (HIV) infection. Abnormalities of the gene of complement factor H have been found in familial HUS and in some sporadic cases of HUS not associated with diarrhea. Factor H abnormalities induce an uncontrolled complement activation that can activate the coagulation cascade. In familial PTT, genetic abnormalities of the cleaving metalloproteinase of fWf ADAMTS 13 have been identified. In other patients with TTP, antibodies inhibiting this enzyme have been found. As a consequence of plasma ADAMTS 13 deficiency, unusually large vWf multimers are produced. This abnormality, in the presence of an increased shear stress, stimulates platelet adhesion and aggregation. CONCLUSIONS: Knowledge of the type of causative abnormality is relevant to a therapeutic approach. Children with diarrheal HUS usually do not benefit from plasma infusion or exchange, whereas in patients with factor H or ADAMTS 13 deficiency procedures that include the administration of the lacking product and removal of the inhibiting or toxic factors, such as ultralarge vWfs, are mandatory. Potentially renal transplantation candidates should be screened for genetic defects to avoid the recurrence of TM in the graft.

[Pharmacoeconomics in hemodialysis. Role of iron in the treatment with erythropoietin]. / Farmacoeconomia in emodialisi. Il ruolo del ferro nel trattamento con eritropoietina.

BACKGROUND: Although its efficacy is well known, the high economic cost of erythropoietin (EPO) raises the question of pharmacoeconomics in HD. An optimal Hb level with the lowest dosage of EPO seams to be correlated to the way of administration and an adequate iron supplementation. METHODS: The study evaluates the influence of iron supplementation on the control of EPO-related expenses. RESULTS: A serum ferritin level higher than 50 pg/ml in hemodialysis patients on chronic EPO therapy turned out to be adequate to keep an optimal Hb level. Our data show that this value, as far as pharmacoeconomic is concerned, is highly underestimated. CONCLUSIONS: A higher i.v. iron supplementation correlates with a significant raise of serum ferritin level and saves on EPO-related expenses up to 1 million/per patient/per year.