Current Evidence in Haemodiafiltration.

BACKGROUND: Standard low-flux haemodialysis (HD) is not very efficacious, and patient morbidity and mortality rates are still very high. According to the initial study design, the MPO study reported that high-flux HD (hf-HD) showed a significant 37% relative risk reduction of mortality in patients with serum albumin ≤4 g/dl; online haemodiafiltration (HDF) is considered the most efficient technique of using high-flux membranes, as clearances of small solutes, like urea, are higher than in haemofiltration and clearances of middle solutes, like ß2-microglobulin, are higher than in hf-HD. SUMMARY: Three randomized trials have recently been published analysing the effect of online HDF on mortality. Two trials were unable to demonstrate a positive effect of HDF on survival, while 1 showed a significantly better survival in patients randomized to HDF in comparison to those randomized to hf-HD. It is intriguing that post hoc analyses of these 3 studies showed that the patients randomized to online HDF who received the highest convection volumes had a lower risk of mortality and cardiovascular events than those randomized to HD. Four very recently published meta-analyses have shown inconsistent results concerning the effect of convective treatments in improving patient general and cardiovascular survival, while they have consistently shown a significant reduction of the intradialytic symptomatic hypotension in patients treated with convective techniques in comparison with those treated with prevalent diffusive ones. Key Messages: The results of the randomized trials on the effect of HDF in improving patient survival are inconclusive. Moreover, trials specifically designed for testing the effect of increased convection of online HDF on patient survival and morbidity in comparison to patients treated with hf-HD are still awaited.

Optimizing haemodialysate composition.

Survival and quality of life of dialysis patients are strictly dependent on the quality of the haemodialysis (HD) treatment. In this respect, dialysate composition, including water purity, plays a crucial role. A major aim of HD is to normalize predialysis plasma electrolyte and mineral concentrations, while minimizing wide swings in the patient's intradialytic plasma concentrations. Adequate sodium (Na) and water removal is critical for preventing intra- and interdialytic hypotension and pulmonary edema. Avoiding both hyper- and hypokalaemia prevents life-threatening cardiac arrhythmias. Optimal calcium (Ca) and magnesium (Mg) dialysate concentrations may protect the cardiovascular system and the bones, preventing extraskeletal calcifications, severe secondary hyperparathyroidism and adynamic bone disease. Adequate bicarbonate concentration [HCO3 (-)] maintains a stable pH in the body fluids for appropriate protein and membrane functioning and also protects the bones. An adequate dialysate glucose concentration prevents severe hyperglycaemia and life-threating hypoglycaemia, which can lead to severe cardiovascular complications and a worsening of diabetic comorbidities.

Phosphate binders for the treatment of hyperphosphatemia in chronic kidney disease patients on dialysis: a comparison of safety profiles.

INTRODUCTION: Hyperphosphatemia is common in the late stages of chronic kidney disease (CKD) and is associated with elevated parathormone levels, abnormal bone mineralization, extraosseous calcification and increased risk of cardiovascular events and death. Several classes of oral phosphate binders are available to help control phosphorus levels. Although effective at lowering serum phosphorus, they all have safety issues that need to be considered when selecting which one to use. AREAS COVERED: This paper reviews the use of phosphate binders in patients with CKD on dialysis, with a focus on safety and tolerability. In addition to the more established agents, a new resin-based phosphate binder, colestilan, is discussed. EXPERT OPINION: Optimal phosphate control is still an unmet need in CKD. Nonetheless, we now have an extending range of phosphate binders available. Aluminium has potentially serious toxic risks. Calcium-based binders are still very useful but can lead to hypercalcemia and/or positive calcium balance and cardiovascular calcification. No long-term data are available for the new calcium acetate/magnesium combination product. Lanthanum is an effective phosphate binder, but there is insufficient evidence about possible long-term effects of tissue deposition. The resin-based binders, colestilan and sevelamer, appear to have profiles that would lead to less vascular calcification, and the main adverse events seen with these agents are gastrointestinal effects.

Renal sympathetic nerve ablation for the treatment of difficult-to-control or refractory hypertension in a haemodialysis patient.

Haemodialysis patients show sympathetic hyperactivity. Hyperactivation of the sympathetic nervous system aggravates hypertension and it is related to left ventricular hypertrophy, heart failure, arrhythmias and atherogenesis. We report the first use of renal sympathetic nerve ablation for correction of uncontrolled hypertension in an end-stage renal disease patient on maintenance dialysis. We observed a progressive and sustained reduction of systemic blood pressure. Our case demonstrates the safety, the feasibility and the efficacy of this procedure. These findings suggest, however, that further clinical trials are needed into renal nerve radiofrequency ablation therapy for the treatment of hypertension and for the improvement of cardiovascular prognosis in this high-risk patient group.

Palifermin in the management of mucositis in hematological malignancies: current evidences and future perspectives.

BACKGROUND: In the management of hematological malignancies, chemotherapy-induced mucositis is an increasingly recognized problem, leading to potentially severe clinical complications, treatment delays, increased costs and impairment of patient's quality of life. Many forms of cytotoxic treatments given in this setting may induce several degrees of mucositis. In particular, conditioning therapy with hematopoietic stem cell transplantation (HSCT) induces a disruption of the mucosal barrier function throughout the entire gastrointestinal tract facilitating the spreading of bacteria and endotoxin with subsequent increased risk of septicemia and, in the allogeneic setting, a worsening of Graft Versus Host Disease (GVHD). OBJECTIVES: To review the role of palifermin and of other existing and potential treatments for chemotherapy-induced mucositis in the context of current knowledge of pathobiology in the setting of hematological malignancies. METHODS: We searched for palifermin and mucositis of any region of the gastrointestinal tract using Medline; the abstract books of the most important hematological and oncological meetings were also reviewed. RESULTS/CONCLUSIONS: The pathobiology of mucositis is complex, and agents that target mechanisms to prevent mucositis or accelerate healing are highly required. In this regard, palifermin (recombinant human keratinocyte growth factor) has been demonstrated to reduce the severity and the duration of oral mucositis and to significantly improve several treatment outcomes in patients submitted to autologous HSCT; data are insufficient to recommend its use in the non-autologous HSCT settings, although interesting properties of this agent deserves other investigations in order to explore other possible indications.