The Medium Cut-Off Membrane Does Not Lower Protein-Bound Uremic Toxins
Abstract
1. Introduction
2. Results
2.1. Patients and Dialysis Characteristics
2.2. The Clearance of Small and Middle Molecular Weight Toxins
2.3. Dialysate Albumin Removal
2.4. The Clearance of Protein-Bound Uremic Toxins
3. Discussion
4. Conclusions
5. Materials and Methods
5.1. Study Designs and Patient Selection
5.2. Treatment Protocols
5.3. Measurement Methods
5.4. Calculation
5.5. Statistics
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
- Aronov, P.A.; Luo, F.J.; Plummer, N.S.; Quan, Z.; Holmes, S.; Hostetter, T.H.; Meyer, T.W. Colonic contribution to uremic solutes. J. Am. Soc. Nephrol. 2011, 22, 1769–1776. [Google Scholar] [CrossRef] [PubMed]
- Vaziri, N.D.; Wong, J.; Pahl, M.; Piceno, Y.M.; Yuan, J.; DeSantis, T.Z.; Ni, Z.; Nguyen, T.H.; Andersen, G.L. Chronic kidney disease alters intestinal microbial flora. Kidney Int. 2013, 83, 308–315. [Google Scholar] [CrossRef] [PubMed]
- Wong, J.; Piceno, Y.M.; DeSantis, T.Z.; Pahl, M.; Andersen, G.L.; Vaziri, N.D. Expansion of urease- and uricase-containing, indole- and p-cresol-forming and contraction of short-chain fatty acid-producing intestinal microbiota in ESRD. Am. J. Nephrol. 2014, 39, 230–237. [Google Scholar] [CrossRef] [PubMed]
- Gryp, T.; Vanholder, R.; Vaneechoutte, M.; Glorieux, G. p-Cresyl Sulfate. Toxins 2017, 9, 52. [Google Scholar] [CrossRef]
- Mair, R.D.; Sirich, T.L.; Plummer, N.S.; Meyer, T.W. Characteristics of Colon-Derived Uremic Solutes. Clin. J. Am. Soc. Nephrol. 2018, 13, 1398–1404. [Google Scholar] [CrossRef]
- Meijers, B.K.; Claes, K.; Bammens, B.; de Loor, H.; Viaene, L.; Verbeke, K.; Kuypers, D.; Vanrenterghem, Y.; Evenepoel, P. p-Cresol and cardiovascular risk in mild-to-moderate kidney disease. Clin. J. Am. Soc. Nephrol. 2010, 5, 1182–1189. [Google Scholar] [CrossRef]
- Lin, C.J.; Wu, C.J.; Pan, C.F.; Chen, Y.C.; Sun, F.J.; Chen, H.H. Serum protein-bound uraemic toxins and clinical outcomes in haemodialysis patients. Nephrol. Dial. Transplant. 2010, 25, 3693–3700. [Google Scholar] [CrossRef]
- Banoglu, E.; Jha, G.G.; King, R.S. Hepatic microsomal metabolism of indole to indoxyl, a precursor of indoxyl sulfate. Eur. J. Drug Metab. Pharm. 2001, 26, 235–240. [Google Scholar] [CrossRef]
- Aklujkar, M.; Risso, C.; Smith, J.; Beaulieu, D.; Dubay, R.; Giloteaux, L.; DiBurro, K.; Holmes, D. Anaerobic degradation of aromatic amino acids by the hyperthermophilic archaeon Ferroglobus placidus. Microbiology 2014, 160, 2694–2709. [Google Scholar] [CrossRef]
- Viaene, L.; Annaert, P.; de Loor, H.; Poesen, R.; Evenepoel, P.; Meijers, B. Albumin is the main plasma binding protein for indoxyl sulfate and p-cresyl sulfate. Biopharm. Drug Dispos. 2013, 34, 165–175. [Google Scholar] [CrossRef]
- Deltombe, O.; Van Biesen, W.; Glorieux, G.; Massy, Z.; Dhondt, A.; Eloot, S. Exploring Protein Binding of Uremic Toxins in Patients with Different Stages of Chronic Kidney Disease and during Hemodialysis. Toxins 2015, 7, 3933–3946. [Google Scholar] [CrossRef] [PubMed]
- Vanholder, R.; Schepers, E.; Pletinck, A.; Nagler, E.V.; Glorieux, G. The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: A systematic review. J. Am. Soc. Nephrol. 2014, 25, 1897–1907. [Google Scholar] [CrossRef] [PubMed]
- Gryp, T.; De Paepe, K.; Vanholder, R.; Kerckhof, F.M.; Van Biesen, W.; Van de Wiele, T.; Verbeke, F.; Speeckaert, M.; Joossens, M.; Couttenye, M.M.; et al. Gut microbiota generation of protein-bound uremic toxins and related metabolites is not altered at different stages of chronic kidney disease. Kidney Int. 2020, 97, 1230–1242. [Google Scholar] [CrossRef] [PubMed]
- Masereeuw, R.; Mutsaers, H.A.; Toyohara, T.; Abe, T.; Jhawar, S.; Sweet, D.H.; Lowenstein, J. The kidney and uremic toxin removal: Glomerulus or tubule? Semin. Nephrol. 2014, 34, 191–208. [Google Scholar] [CrossRef]
- van Gelder, M.K.; Mihaila, S.M.; Jansen, J.; Wester, M.; Verhaar, M.C.; Joles, J.A.; Stamatialis, D.; Masereeuw, R.; Gerritsen, K.G.F. From portable dialysis to a bioengineered kidney. Expert Rev. Med. Devices 2018, 15, 323–336. [Google Scholar] [CrossRef]
- Sirich, T.L.; Funk, B.A.; Plummer, N.S.; Hostetter, T.H.; Meyer, T.W. Prominent accumulation in hemodialysis patients of solutes normally cleared by tubular secretion. J. Am. Soc. Nephrol. 2014, 25, 615–622. [Google Scholar] [CrossRef]
- Cornelis, T.; Eloot, S.; Vanholder, R.; Glorieux, G.; van der Sande, F.M.; Scheijen, J.L.; Leunissen, K.M.; Kooman, J.P.; Schalkwijk, C.G. Protein-bound uraemic toxins, dicarbonyl stress and advanced glycation end products in conventional and extended haemodialysis and haemodiafiltration. Nephrol. Dial. Transplant. 2015, 30, 1395–1402. [Google Scholar] [CrossRef]
- Ok, E.; Asci, G.; Toz, H.; Ok, E.S.; Kircelli, F.; Yilmaz, M.; Hur, E.; Demirci, M.S.; Demirci, C.; Duman, S.; et al. Mortality and cardiovascular events in online haemodiafiltration (OL-HDF) compared with high-flux dialysis: Results from the Turkish OL-HDF Study. Nephrol. Dial. Transplant. 2013, 28, 192–202. [Google Scholar] [CrossRef]
- Krieter, D.H.; Kerwagen, S.; Ruth, M.; Lemke, H.D.; Wanner, C. Differences in Dialysis Efficacy Have Limited Effects on Protein-Bound Uremic Toxins Plasma Levels over Time. Toxins 2019, 11, 47. [Google Scholar] [CrossRef]
- Bammens, B.; Evenepoel, P.; Verbeke, K.; Vanrenterghem, Y. Removal of the protein-bound solute p-cresol by convective transport: A randomized crossover study. Am. J. Kidney Dis. 2004, 44, 278–285. [Google Scholar] [CrossRef]
- Meert, N.; Waterloos, M.A.; Van Landschoot, M.; Dhondt, A.; Ledebo, I.; Glorieux, G.; Goeman, J.; Van der Eycken, J.; Vanholder, R. Prospective evaluation of the change of predialysis protein-bound uremic solute concentration with postdilution online hemodiafiltration. Artif. Organs 2010, 34, 580–585. [Google Scholar] [CrossRef] [PubMed]
- Meert, N.; Eloot, S.; Schepers, E.; Lemke, H.D.; Dhondt, A.; Glorieux, G.; Van Landschoot, M.; Waterloos, M.A.; Vanholder, R. Comparison of removal capacity of two consecutive generations of high-flux dialysers during different treatment modalities. Nephrol. Dial. Transplant. 2011, 26, 2624–2630. [Google Scholar] [CrossRef] [PubMed]
- Cha, R.H.; Kang, S.W.; Park, C.W.; Cha, D.R.; Na, K.Y.; Kim, S.G.; Yoon, S.A.; Kim, S.; Han, S.Y.; Park, J.H.; et al. Sustained uremic toxin control improves renal and cardiovascular outcomes in patients with advanced renal dysfunction: Post-hoc analysis of the Kremezin Study against renal disease progression in Korea. Kidney Res. Clin. Pract. 2017, 36, 68–78. [Google Scholar] [CrossRef] [PubMed]
- Sumida, K.; Kovesdy, C.P. The gut-kidney-heart axis in chronic kidney disease. Physiol. Int. 2019, 106, 195–206. [Google Scholar] [CrossRef] [PubMed]
- Rossi, M.; Johnson, D.W.; Xu, H.; Carrero, J.J.; Pascoe, E.; French, C.; Campbell, K.L. Dietary protein-fiber ratio associates with circulating levels of indoxyl sulfate and p-cresyl sulfate in chronic kidney disease patients. Nutr. Metab. Cardiovasc. Dis. 2015, 25, 860–865. [Google Scholar] [CrossRef]
- Natarajan, R.; Pechenyak, B.; Vyas, U.; Ranganathan, P.; Weinberg, A.; Liang, P.; Mallappallil, M.C.; Norin, A.J.; Friedman, E.A.; Saggi, S.J. Randomized controlled trial of strain-specific probiotic formulation (Renadyl) in dialysis patients. Biomed. Res. Int. 2014, 2014, 568571. [Google Scholar] [CrossRef]
- Lim, P.S.; Wang, H.F.; Lee, M.C.; Chiu, L.S.; Wu, M.Y.; Chang, W.C.; Wu, T.K. The Efficacy of Lactobacillus-Containing Probiotic Supplementation in Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial. J. Ren. Nutr. 2021, 31, 189–198. [Google Scholar] [CrossRef]
- Madero, M.; Cano, K.B.; Campos, I.; Tao, X.; Maheshwari, V.; Brown, J.; Cornejo, B.; Handelman, G.; Thijssen, S.; Kotanko, P. Removal of Protein-Bound Uremic Toxins during Hemodialysis Using a Binding Competitor. Clin. J. Am. Soc. Nephrol. 2019, 14, 394–402. [Google Scholar] [CrossRef]
- Kim, T.H.; Kim, S.H.; Kim, T.Y.; Park, H.Y.; Jung, K.S.; Lee, M.H.; Jhee, J.H.; Lee, J.E.; Choi, H.Y.; Park, H.C. Removal of large middle molecules via haemodialysis with medium cut-off membranes at lower blood flow rates: An observational prospective study. BMC Nephrol. 2019, 21, 2. [Google Scholar] [CrossRef]
- Kirsch, A.H.; Rosenkranz, A.R.; Lyko, R.; Krieter, D.H. Effects of Hemodialysis Therapy Using Dialyzers with Medium Cut-Off Membranes on Middle Molecules. Contrib. Nephrol. 2017, 191, 158–167. [Google Scholar] [CrossRef]
- Ronco, C.; Marchionna, N.; Brendolan, A.; Neri, M.; Lorenzin, A.; Martinez Rueda, A.J. Expanded haemodialysis: From operational mechanism to clinical results. Nephrol. Dial. Transplant. 2018, 33, iii41–iii47. [Google Scholar] [CrossRef] [PubMed]
- Maduell, F.; Rodas, L.; Broseta, J.J.; Gomez, M.; Xipell, M.; Guillen, E.; Montagud-Marrahi, E.; Arias-Guillen, M.; Fontsere, N.; Vera, M.; et al. Medium Cut-Off Dialyzer versus Eight Hemodiafiltration Dialyzers: Comparison Using a Global Removal Score. Blood Purif. 2019, 48, 167–174. [Google Scholar] [CrossRef] [PubMed]
- Sakurai, K. Biomarkers for evaluation of clinical outcomes of hemodiafiltration. Blood Purif. 2013, 35 (Suppl. S1), 64–68. [Google Scholar] [CrossRef] [PubMed]
- Nagai, K.; Tsuchida, K.; Ishihara, N.; Minagawa, N.; Ichien, G.; Yamada, S.; Hirose, D.; Michiwaki, H.; Kanayama, H.O.; Doi, T.; et al. Implications of Albumin Leakage for Survival in Maintenance Hemodialysis Patients: A 7-year Observational Study. Ther. Apher. Dial. 2017, 21, 378–386. [Google Scholar] [CrossRef]
- Potier, J.; Queffeulou, G.; Bouet, J. Are all dialyzers compatible with the convective volumes suggested for postdilution online hemodiafiltration? Int. J. Artif. Organs 2016, 39, 460–470. [Google Scholar] [CrossRef]
- Fabresse, N.; Uteem, I.; Lamy, E.; Massy, Z.; Larabi, I.A.; Alvarez, J.C. Quantification of free and protein bound uremic toxins in human serum by LC-MS/MS: Comparison of rapid equilibrium dialysis and ultrafiltration. Clin. Chim. Acta 2020, 507, 228–235. [Google Scholar] [CrossRef]
- Kikuchi, K.; Itoh, Y.; Tateoka, R.; Ezawa, A.; Murakami, K.; Niwa, T. Metabolomic analysis of uremic toxins by liquid chromatography/electrospray ionization-tandem mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2010, 878, 1662–1668. [Google Scholar] [CrossRef]
- Kim, H.Y.; Yoo, T.H.; Hwang, Y.; Lee, G.H.; Kim, B.; Jang, J.; Yu, H.T.; Kim, M.C.; Cho, J.Y.; Lee, C.J.; et al. Indoxyl sulfate (IS)-mediated immune dysfunction provokes endothelial damage in patients with end-stage renal disease (ESRD). Sci. Rep. 2017, 7, 3057. [Google Scholar] [CrossRef]
- Lin, C.N.; Wu, I.W.; Huang, Y.F.; Peng, S.Y.; Huang, Y.C.; Ning, H.C. Measuring serum total and free indoxyl sulfate and p-cresyl sulfate in chronic kidney disease using UPLC-MS/MS. J. Food Drug Anal. 2019, 27, 502–509. [Google Scholar] [CrossRef]
- Bergstrom, J.; Wehle, B. No change in corrected beta 2-microglobulin concentration after cuprophane haemodialysis. Lancet 1987, 1, 628–629. [Google Scholar] [CrossRef]
- Hemodialysis Adequacy Work, G. Clinical practice guidelines for hemodialysis adequacy, update 2006. Am. J. Kidney Dis. 2006, 48 (Suppl. S1), S2–S90. [Google Scholar] [CrossRef]
Variable | Results |
---|---|
Age | 62.2 ± 11.4 |
Sex (M:F) | 11:11 |
BMI | 23.0 ± 2.7 |
Dialysis vintage (months) | 67.1 ± 41.3 |
Causative disease of ESRD (number,%) | |
Diabetes | 10, 45.5 |
Hypertension | 9, 40.9 |
Glomerulonephritis | 1, 4.5 |
Polycystic kidney | 2, 9.1 |
Dry weight (kg) | 59.5 ± 7.5 |
Blood flow (mL/min) | 302.7 ± 6.9 |
Pre-dialysis SBP (mmHg) | 138.7 ± 22.2 |
Pre-dialysis DBP (mmHg) | 65.5 ± 8.5 |
Hb (mg/dL) | 11.1 ± 1.2 |
Albumin (g/dL) | 4.0 ± 0.2 |
BUN (mg/dL) | 51.2 ± 15.2 |
Cr (mg/dL) | 7.6 ± 2.0 |
HF-HD | Post-OL-HDF | MCO-HD | |
---|---|---|---|
Dialyser | Fx CorDiax 80 | Fx CorDiax 800 | Theranova 400 |
Inner diameter (μm) | 185 | 210 | 180 |
Wall thickness (μm) | 35 | 35 | 35 |
Membrane polymer | polysulphone-PVP blend | polysulphone-PVP blend | polyarylethersulphone-PVP blend |
Effective surface area (m2) | 1.8 | 2.0 | 1.7 |
Sieving coefficients of albumin | <0.001 | <0.001 | 0.008 |
Clearance of inulin | 135 | 178 | 183 |
UF coefficient (mL/h/mmHg) | 64 | 62 | 48 |
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Kim, Y.G.; Lee, S.H.; Jung, S.W.; Jung, G.T.; Lim, H.J.; Kim, K.P.; Jo, Y.-I.; Jin, K.; Moon, J.Y. The Medium Cut-Off Membrane Does Not Lower Protein-Bound Uremic Toxins. Toxins 2022, 14, 779. https://doi.org/10.3390/toxins14110779
Kim YG, Lee SH, Jung SW, Jung GT, Lim HJ, Kim KP, Jo Y-I, Jin K, Moon JY. The Medium Cut-Off Membrane Does Not Lower Protein-Bound Uremic Toxins. Toxins. 2022; 14(11):779. https://doi.org/10.3390/toxins14110779
Chicago/Turabian StyleKim, Yang Gyun, Sang Ho Lee, Su Woong Jung, Gun Tae Jung, Hyun Ji Lim, Kwang Pyo Kim, Young-Il Jo, KyuBok Jin, and Ju Young Moon. 2022. "The Medium Cut-Off Membrane Does Not Lower Protein-Bound Uremic Toxins" Toxins 14, no. 11: 779. https://doi.org/10.3390/toxins14110779
APA StyleKim, Y. G., Lee, S. H., Jung, S. W., Jung, G. T., Lim, H. J., Kim, K. P., Jo, Y.-I., Jin, K., & Moon, J. Y. (2022). The Medium Cut-Off Membrane Does Not Lower Protein-Bound Uremic Toxins. Toxins, 14(11), 779. https://doi.org/10.3390/toxins14110779