Changes in plasma sclerostin level associated with use of a medium cut-off dialyzer in end-stage renal disease

Abstract

Background: Larger middle molecules are important substances associated with cardiovascular complications in end- stage renal disease. Unfortunately, larger middle molecules are not reliably removed by a high-flux dialyzer. A medium cut-off (MCO) membrane could effectively remove larger middle molecules. This study aimed to identify the long -term effect of the MCO membrane for changes of larger middle molecules.

Methods: Thirty-four patients were prospectively analyzed for 12 months. The enrolled patients were divided into control and MCO groups. We measured the plasma levels of growth differentiation factor 15, sclerostin, and fibroblast growth factor 23 in larger middle molecules and those of biomarkers including small solutes. Single-pool Kt/V (spKt/V) and reduction ratios also were evaluated.

Results: Plasma sclerostin did not increase significantly in patients using the MCO dialyzer (135.3 [-637.7 to 908.3], p = 0.715). And there was a significant difference in change of plasma sclerostin level between the two groups (-1,646.9 [-3,015.2 to -278.7], p = 0.033). Furthermore, a negative association between calcium and sclerostin was not observed in the MCO group (r = -0.142, p = 0.587). Solute clearance of larger middle molecules in the MCO group was significantly higher. Moreover, spKt/V values for patients in the MCO group were significantly increased without albumin loss. Values are presented as mean (95% confidence interval [CI]) or adjusted mean (95% CI).

Conclusion: The MCO dialyzer can increase dialytic adequacy and suppress the increase in plasma sclerostin level without significant albumin loss in patients with end-stage renal disease.

Keywords: Dialysis; Membranes; Molecular weight; Renal insufficiency.

Figure 1.. The changes of total protein, albumin, and spKt/V over 12 months.

Data are presented as geometric mean, and error bars represent 95% confidence interval. MCO, medium cut-off; spKt/V, single-pool Kt/V. ^*p < 0.05, ^**p < 0.01, *^**p < 0.001.

Figure 2.

The distribution of normalized protein catabolic rates (nPCR) in the groups at 3, 6, 9, and 12 months.

Figure 3.. The changes in predialytic levels of larger middle molecules over 12 months.

Data are presented as geometric mean, and error bars represent 95% confidence interval. Each graph presents growth differentiation factor 15 (GDF15), leptin, sclerostin, fibroblast growth factor 23 (FGF23), beta-2 microglobulin (β2MG), and retinol-binding protein 4 (RBP4), respectively. MCO, medium cut-off. ^*p < 0.05; ^**p < 0.01; ^***p < 0.05 of adjusted mean difference between control and MCO groups. MCO, medium cut-off.

Figure 4.. The reduction ratios (RR) of larger middle molecules per session of hemodialysis at 12 months.

In the box-and-whisker plots, the whiskers represent the range, and boxes represent median 25th and 75th percentile values. Connecting lines represent significant differences between mean values of the control (C) and MCO (T) groups. CRP, C-reactive protein; GDF15, growth differentiation factor 15; FGF23, fibroblast growth factor 23; MCO, medium cut-off; RBP4, retinol-binding protein 4. ^**p < 0.001, ^*p < 0.01.

Figure 5.. The reduction ratios (RR) of small and middle molecules per session of hemodialysis at 12 months.

In the box-and-whisker plots, the whiskers represent the range, and columns represent median 25th and 75th percentile values. Connecting lines represent significant differences between mean values of the control (C) and MCO (T) groups. β2MG, beta-2 microglobulin. MCO, medium cut-off.