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Extended hemodialysis using a high cut-off dialyzer (HCO-HD) removes large quantities of free light chains in patients with multiple myeloma. However, the clinical utility of this method is uncertain. This study assessed the combination of chemotherapy and HCO-HD on serum free light chain concentrations and renal recovery in patients with myeloma kidney (cast nephropathy) and dialysis-dependent acute renal failure. An open-label study of the relationship between free light chain levels and clinical outcomes in 19 patients treated with standard chemotherapy regimens and HCO-HD. There were sustained early reductions in serum free light chain concentrations (median 85% [range 50 to 97]) in 13 patients. These 13 patients became dialysis independent at a median of 27 d (range 13 to 120). Six patients had chemotherapy interrupted because of early infections and did not achieve sustained early free light chain reductions; one of these patients recovered renal function (at 105 d) the remaining 5 patients did not recover renal function. Patients who recovered renal function had a significantly improved survival (P < 0.012). In dialysis-dependent acute renal failure secondary to myeloma kidney, patients who received uninterrupted chemotherapy and extended HCO-HD had sustained reductions in serum free light chain concentrations and recovered independent renal function.
Reviewing the current picture of uremic toxicity reveals its complexity. Focusing on cardiovascular damage as a model of uremic effects resulting in substantial morbidity and mortality, most molecules with potential to affect the function of a variety of cell types within the vascular system are difficult to remove by dialysis. Examples are the larger middle molecular weight molecules and protein-bound molecules. Recent clinical studies suggest that enhancing the removal of these compounds is beneficial for survival. Future therapeutic options are discussed, including improved removal of toxins and the search for pharmacologic strategies blocking responsible pathophysiologic pathways.
Introduction. From the beginning of the dialysis era, the most appropriate composition of the dialysate has been one of the central topics in the delivery of dialysis treatment. A discussion is employed to achieve a consensus on key points relating to the composition of the dialysate, focusing on the relationships with blood pressure behaviour. Sodium balance is the cornerstone of intra-dialysis cardiovascular stability and good inter-dialysis blood pressure control. Hypernatric dialysis carries the risk of positive sodium balance, with the consequent possibility of the worsening sense of thirst and hypertension. Conversely, hyponatric dialysis may lead to negative sodium balance, with the possibility of intra-dialysis cardiovascular instability and 'disequilibrium' symptoms including fatigue, muscle cramps and headache. The goal is to remove with dialysis the exact amount of sodium that has accumulated in the inter-dialysis interval. The conductivity kinetic model is applicable on-line at each dialysis session and has been proved to be able to improve intra-dialytic cardiovascular stability in hypotension-prone patients. Therefore, it should be regarded as a promising tool to be implemented in everyday clinical practice. Serum potassium concentration and variations during dialysis treatment certainly play a role in the genesis of cardiac arrhythmia. Potassium profiling, with a constant gradient between plasma and dialysate, should be implemented in clinical practice to minimize the arrhythmogenic potential of dialysis. Calcium plays a role both in myocardial contractility and in peripheral vascular resistance. Therefore, an increase in dialysate calcium concentration may be useful in cardiac compromised hypotension-prone patients. Acid-buffering by means of base supplementation is one of the major roles of dialysis. Bicarbonate concentration in the dialysate should be personalized in order to reach a midweek pre-dialysis serum bicarbonate concentration of 22 mmol/l. The role of convective dialysis techniques in cardiovascular stability is still under debate. It has been demonstrated that dialysate temperature and sodium balance play a role and this should be taken into account. Whether removal of vasoactive, middle-sized compounds by convection plays an independent role in improving cardiovascular stability is still uncertain. The prescription of dialysis fluid is moving from a pre-fixed, standard dialysate solution to individualization of electrolyte and buffer composition, not only during the dialysis session, but also within the same session (profiling) in order to provide patients with an optimal blood purification coupled with a high degree of tolerability.
