Effect of Membrane Permeability on Survival of Hemodialysis Patients

Abstract

The effect of high-flux hemodialysis membranes on patient survival has not been unequivocally determined. In this prospective, randomized clinical trial, we enrolled 738 incident hemodialysis patients, stratified them by serum albumin Յ4 and Ͼ4 g/dl, and assigned them to either low-flux or high-flux membranes. We followed patients for 3 to 7.5 yr. Kaplan-Meier survival analysis showed no significant difference between high-flux and low-flux membranes, and a Cox proportional hazards model concurred. Patients with serum albumin Յ4 g/dl had significantly higher survival rates in the high-flux group compared with the low-flux group (P ϭ 0.032). In addition, a secondary analysis revealed that high-flux membranes may significantly improve survival of patients with diabetes. Among those with serum albumin Յ4 g/dl, slightly different effects among patients with and without diabetes suggested a potential interaction between diabetes status and low serum albumin in the reduction of risk conferred by high-flux membranes. In summary, we did not detect a significant survival benefit with either high-flux or low-flux membranes in the population overall, but the use of high-flux membranes conferred a significant survival benefit among patients with serum albumin Յ4 g/dl. The apparent survival benefit among patients who have diabetes and are treated with high-flux membranes requires confirmation given the post hoc nature of our analysis. 20: 645-654, 200920: 645-654, . doi: 10.1681 Patients who have stage 5 chronic kidney disease (CKD) and are on dialysis therapy have a high mortality rate, estimated between 14 and 26% in Europe and at 24% per year in the United States. 1 The accumulation of various retention solutes over a broad range of molecular weights and chemical composition is involved in the complex pathophysiology of uremia and, among other factors, implicated in the high mortality observed in CKD. 2 Because of their higher porosity, high-flux hemodialysis (HD) membranes have the capacity to remove retention solutes of higher molecular weight than do low-flux membranes, 3 which contain smaller pores. Whether this enhanced solute elimination of high-flux membranes translates J Am Soc Nephrol

A Patient with CKD and Poor Nutritional Status

“…Increasing dialysis dose beyond these targets does not further improve the nutritional status. Further, most nutritional measures did not differ among patients exposed to highflux compared with low-flux HD membranes (25). The Frequent Hemodialysis Networks trial found no appreciable difference in nutritional markers between patients randomly assigned to in-center HD six times per week versus standard in-center HD three times per week (26).…”

Role of Residual Kidney Function and Convective Volume on Change in β2-Microglobulin Levels in Hemodiafiltration Patients

“…In contrast, significant removal of ␤2M can be established with high-flux HD, because of convective transport by internal filtration within the dialyzer. The Hemodialysis (HEMO) and the Membrane Permeability Outcome (MPO) study showed lower serum ␤2M levels in high-flux HD as compared with low-flux HD patients (4,9). In addition, it has been shown that removal of ␤2M is further increased with online hemodiafiltration (HDF) by using excess ultrafiltration to provide increased convective transport.…”

Large Middle Molecule and Albumin Removal: Why Should We Not Rest on Our Laurels?

“…Moreover, oxidized forms of albumin can lead to an underestimation of the serum albumin level [30], questioning the rationale of the real significance of low serum albumin levels in CKD patients and in the evaluation of their nutritional status. In MPO study [10] , survival of patients with a low serum albumin level was increased with the use of high-flux membranes, while no effect was found in normo-albuminemic patients. As lower level of albumin raise the question of a possible increase in oxidized forms, the better survival could result from a significant removal of toxic forms of albumin by high-flux membranes.…”

“…However, the amount of albumin leak needs to be questioned in regard to the quality of albumin leaked. Interestingly, in MPO study [10] , the use of high-flux membranes was linked with a better survival in the low serum albumin group despite a higher sieving coefficient leading to an increased albumin leak. These facts raised the question of the merit of the specific removal of toxic and dysfunctional forms of albumin in HD ( Fig.…”

“…Conversely, low-cut off membranes severely limit the toxin removal. The incidence of amyloidosis and dialysis arthropathy significantly decreased with the use of high-flux membranes and HDF techniques due to a better removal of β2-microglobulin [9,10] and with it many toxins from the LMM group. High-flux membranes have a higher sieving (for β2-microglobulin) and ultrafiltration coefficients than low-flux membranes.…”