Leypoldt John K, Meijers Björn K I
Renal Therapeutic Area and Medical Affairs, Baxter Healthcare Corporation, Deerfield, Illinois.
Division of Nephrology, Department of Microbiology and Immunology, University Hospitals Leuven, Leuven, Belgium.
Semin Dial. 2016 Nov;29(6):463-470. doi: 10.1111/sdi.12531. Epub 2016 Aug 31.
The kinetics of uremic solute clearances are discussed based on two categories of uremic solutes, namely those that are and those that are not derived directly from nutrient intake, particularly dietary protein intake. This review highlights dialysis treatments that are more frequent and longer (high-dose hemodialysis) than conventional thrice weekly therapy. It is proposed that the dialysis dose measures based on urea as a marker uremic solute, such as Kt/V and stdKt/V, be referred to as measures of dialysis inadequacy, not dialysis adequacy. For uremic solutes derived directly from nutrient intake, it is suggested that inorganic phosphorus and protein-bound uremic solutes be considered as markers in the development of alternative measures of dialysis dose for high-dose hemodialysis prescriptions. As the current gap in understanding the detailed kinetics of protein-bound uremic solutes, it is proposed that normalization of serum phosphorus concentration with a minimum (or preferably without a) need for oral-phosphorus binders be targeted as a measure of dialysis adequacy in high-dose hemodialysis. For large uremic solutes not derived directly from nutrient intake (middle molecules), use of extracorporeal clearances for β -microglobulin that are higher than currently available during thrice weekly therapy is unlikely to reduce predialysis serum β -microglobulin concentrations. High-dose hemodialysis prescriptions will lead to reductions in predialysis serum β -microglobulin concentrations, but such reductions are also limited by significant residual kidney clearance. Kinetic data regarding middle molecules larger than β -microglobulin are scarce; additional studies on such uremic solutes are of high interest to better understand improved methods for prescribing high-dose hemodialysis prescriptions to improve patient outcomes.
基于两类尿毒症溶质,即直接来源于营养摄入(特别是膳食蛋白质摄入)的溶质和非直接来源于营养摄入的溶质,讨论了尿毒症溶质清除的动力学。本综述重点介绍了比传统每周三次治疗更频繁、时间更长的透析治疗(高剂量血液透析)。有人提出,以尿素作为尿毒症溶质标志物的透析剂量测量指标,如Kt/V和stdKt/V,应被视为透析不充分的指标,而非透析充分的指标。对于直接来源于营养摄入的尿毒症溶质,建议在制定高剂量血液透析处方的替代透析剂量测量指标时,将无机磷和与蛋白质结合的尿毒症溶质视为标志物。由于目前在理解与蛋白质结合的尿毒症溶质详细动力学方面存在差距,建议将血清磷浓度正常化且口服磷结合剂需求最小(或最好无需口服磷结合剂)作为高剂量血液透析中透析充分性的一项指标。对于并非直接来源于营养摄入的大分子尿毒症溶质(中分子物质),使用比每周三次治疗期间现有水平更高的体外β-微球蛋白清除率不太可能降低透析前血清β-微球蛋白浓度。高剂量血液透析处方会导致透析前血清β-微球蛋白浓度降低,但这种降低也受到显著残余肾清除率的限制。关于大于β-微球蛋白的中分子物质的动力学数据稀缺;对这类尿毒症溶质进行更多研究对于更好地理解改进高剂量血液透析处方的方法以改善患者预后具有重要意义。