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01-08-2017 | Original Article

Long term variation of serum levels of uremic toxins in patients treated by post-dilution high volume on-line hemodiafiltration in comparison to standard low-flux bicarbonate dialysis: results from the REDERT study

Authors: Vincenzo Panichi, Maria Teresa Rocchetti, Alessia Scatena, Alberto Rosati, Massimiliano Migliori, Francesco Pizzarelli, Loreto Gesualdo, REDERT Study group

Published in: Journal of Nephrology | Issue 4/2017

Abstract

Purpose of the study

Little information have been provided till now regarding the effect of high volume HDF (hv-OL-HDF) in respect to standard bicarbonate dialysis (BHD) in medium-long term protein-bound toxins removal.

Procedures

A randomised cross-over multicentre study (REDERT study) was designed to compare the effects of hv-OL-HDF and low-flux BHD on uremic toxins serum levels in 36 chronic dialysis patients followed for 13 months. Group 1 patients were treated with BHD (Treatment A) for 6 months, and afterwards, they were transferred to hv-OL-HDF for a further 6 months (Treatment B). Group 2 patients were treated with Treatment B for 6 months, and afterwards, they were transferred to Treatment A for a further 6 months. Total and free pre-dialysis indoxyl-sulfate (IS) and p-cresyl-sulfate (pCS) were determined starting a midweek dialysis session at baseline and after six months of hv-OL-HDF or BHD. IS and pCS, were simultaneously measured, by liquid chromatography/electrospray ionization-tandem mass spectrometry, Kt/v and pre and post-dialysis b-2microglobulin (b2MG) levels were measured every three months.

Results

Kt/V was significantly increased in hv-OL-HDF (from 1.47 ± 0.24 to 1.49 ± 0.16; p < 0.01) and was reduced in BHD (from 1.51 ± 0.2 to 1.36 ± 0.21; p < 0.001). The mean infusion volume in HDF was 20.9 ± 2.1 L with a mean total convective volume of 23.8 ± 2.3 L and a significant removal of b2MG was obtained in hv-OL-HDF at month 3 and month 6. Both free and total levels of IS and pCS were significantly reduced in hv-OL-HDF at month 6 in respect to BHD.

Conclusions

In the present study we confirm the assumption that post-HDF is an effective technique in small and protein-bound uremic toxins removal.Introduction

Vanholder R, de Smet R, Glorieux G, Argiles A, Baurmeister U, Brunet P, Clarck W, Cohen G, de Deyn PP, Deppisch R et al (2003) Review on uremic toxins: classification, concentration and interindividual variability. Am J Soc Nephrol 63:1934–1943

Duranton F, Cohen G, de Smet R, Rodriguez M, Jankowski J, Vanholder R, Argiles A (2012) Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol 23:1258–1270CrossRefPubMedPubMedCentral

Rroji M, Eloot S, Dhondt A, Van Biesen W, Glorieux G, Neirynck N, Vandennoortgate N, Liabeuf S, Massy Z, Vanholder R (2016) Association of advanced age with concentrations of uremic toxins in CKD. J Nephrol 29(1):81–91CrossRefPubMed

Poveda J, Sanchez-Ni ~ no MD, Glorieux G, Sanz AB, Egido J, Vanholder R, Ortiz A (2014) p-cresyl sulphate has pro-inflammatory and cytotoxic actions on human proximal tubular epithelial cells. Nephrol Dial Transplant 29:56–64CrossRefPubMed

Dou L, Bertrand E, Cerini C, Faure V, Sampol J, Vanholder R, Berland Y, Brunet P (2004) The uremic solutes p-cresol and indoxyl sulfate inhibit endothelial proliferation and wound repair. Kidney Int 65:442–451CrossRefPubMed

Yamamoto H, Tsuruoka S, Ioka T, AndoH, Ito C, Akimoto T, Fujimura A, Asano Y, Kusano E (2006) Indoxyl sulfate stimulates proliferation of rat vascular smooth muscle cells. Kidney Int 69:1780–1785CrossRefPubMed

Vanholder R, Schepers E, Pletinck A, Nagler EV, Glorieux G (2014) The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: a systematic review. J Am Soc Nephrol 25(9):1897–1907CrossRefPubMedPubMedCentral

Bammens B, Evenepoel P, Keuleers H, Verbeke K, Vanrenterghem Y (2006) Free serum concentrations of the protein-bound retention solute p-cresol predict mortality in hemodialysis patients. Kidney Int 69:1081–1087CrossRefPubMed

Liabeuf S, Barreto DV, Barreto FC, Meert N, Glorieux G, Schepers E et al (2010) (EUTox) EUTWG. Free p-cresyl sulphate is a predictor of mortality in patients at different stages of chronic kidney disease. Nephrol Dial Transplant 25:1183–1191CrossRefPubMed

10.

Wu IW, Hsu KH, Hsu HJ, Lee CC, Sun CY, Tsai CJ (2012) Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortality in elderly hemodialysis patients–a prospective cohort study. Nephrol Dial Transplant 27:1169–1175CrossRefPubMed

11.

Vanholder R, Schepers E, Pletinck A, Neirynck N, Glorieux G (2012) An update on protein-bound uremic retention solutes. J Ren Nutr 22:90–94CrossRefPubMed

12.

Meijers BK, Claes K, Bammens B, de Loor H, Viaene L, Verbeke K, Kuypers D, Vanrenterghem Y, Evenepoel P (2010) p-Cresol and cardiovascular risk in mild-to-moderate kidney disease. Clin J Am Soc Nephrol 5:1182–1189CrossRefPubMedPubMedCentral

13.

De Smet R, Van Kaer J, Van Vlem B, De Cubber A, Brunet P, Lameire N, Vanholder R (2003) Toxicity of free p-cresol: a prospective and cross-sectional analysis. Clin Chem 49:470–478CrossRefPubMed

14.

Meijers BK, Bammens B, De Moor B, Verbeke K, Vanrenterghem Y, Evenepoel P (2008) Free p-cresol is associated with cardiovascular disease in hemodialysis patients. Kidney Int 73:1174–1180CrossRefPubMed

15.

Lin CJ, Wu CJ, Pan CF, Chen YC, Sun FJ, Chen HH (2010) Serum protein-bound uraemic toxins and clinical outcomes in haemodialysis patients. Nephrol Dial Transplant 25:3693–3700CrossRefPubMed

16.

Wang CP, Lu LF, Yu TH, Hung WC, Chiu CA, Chung FM, Yeh LR, Chen HJ, Lee YJ, Houng JY (2010) Serum levels of total p-cresylsulphate are associated with angiographic coronary atherosclerosis severity in stable angina patients with early stage of renal failure. Atherosclerosis 211:579–583CrossRefPubMed

17.

Wang CP, Lu LF, Yu TH, Hung WC, Chiu CA, Chung FM, Hsu CC, Lu YC, Lee YJ, Houng JY (2013) Associations among chronic kidney disease, high total p-cresylsulfate and major adverse cardiac events. J Nephrol 26:111–118CrossRefPubMed

18.

Wu IW, Hsu KH, Hsu HJ, Lee CC, Sun CY, Tsai CJ, Wu MS (2012) Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortality in elderly hemodialysis patients—a prospective cohort study. Nephrol Dial Transplant 27:1169–1175CrossRefPubMed

19.

Wu IW, Hsu KH, Lee CC, Sun CY, Hsu HJ, Tsai CJ, Tzen CY, Wang YC, Lin CY, Wu MS (2011) p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease. Nephrol Dial Transplant 26:938–947CrossRefPubMed

20.

Chiu CA, Lu LF, Yu TH, Hung WC, Chung FM, Tsai IT, Yang CY, Hsu CC, Lu YC, Wang CP, Lee YJ (2010) Increased levels of total P-Cresylsulphate and indoxyl sulphate are associated with coronary artery disease in patients with diabetic nephropathy. Rev Diabet Stud 7:275–284CrossRefPubMed

21.

Lin CJ, Wu V, Wu PC, Wu CJ (2015) Meta-analysis of the associations of p-cresyl sulfate (PCS) and indoxyl sulfate (IS) with cardiovascular events and all-cause mortality in patients with chronic renal failure. Plos ONE 10(7):e0132589CrossRefPubMedPubMedCentral

22.

Meijers BKI, Evenepoel P (2011) The gut–kidney axis: indoxyl sulfate, p-cresyl sulfate and CKD progression. Nephrol Dial Transplant 26:759–761CrossRefPubMed

23.

Ramezani A, Raj DS (2014) The gut microbiome, kidney disease, and targeted interventions. J Am Soc Nephrol 25(4):657–670CrossRefPubMed

24.

Viaene L, Annaert P, de Loor H, Poesen R, Evenepoel P, Meijers B (2013) Albumin is the main plasma binding protein for indoxyl sulfate and p-cresyl sulfate. Biopharm Drug Dispos 34:165–175CrossRefPubMed

25.

Rossi M, Johnson DW, Morrison M, Pascoe EM, Coombes JS, Forbes JM, Szeto CC, McWhinney BC, Ungerer JP, Campbell KL (2016) Synbiotics easing renal failure by improving gut microbiology (SYNERGY): a randomized trial. Clin J Am Soc Nephrol 11(2):223–231CrossRefPubMedPubMedCentral

26.

Cha RH, Kang SW, Park CW, Cha DR, Na KY, Kim SG, Yoon SA, Han SY, Chang JH, Park SK, Lim CS, Kim YS. A randomized, controlled trial of oral intestinal sorbent AST-120 on renal function deterioration in patients with advanced renal dysfunction. Clin J Am Soc Nephrol. 2016;11(4):559–67)

27.

Deltombe O, Van Biesen W, Glorieux G, Massy Z, Dhondt A, Eloot S (2015) Exploring Protein Binding of Uremic Toxins in Patients with Different Stages of Chronic Kidney Disease and during Hemodialysis. Toxins (Basel) 7(10):3933–3946CrossRefPubMedPubMedCentral

28.

Basile C, Davenport A, Blankestijn PJ (2016) Why choose high volume online post-dilution hemodiafiltration? J Nephrol 30(2):181–186CrossRefPubMed

29.

Panichi V, Scatena A, Rosati A, Giusti R, Ferro G, Malagnino E, Capitanini A, Piluso A, Conti P, Bernabini G, Migliori M, Caiani D, Tetta C, Casani A, Betti G, Pizzarelli F (2015 Apr) High-volume online haemodiafiltration improves erythropoiesis-stimulating agent (ESA) resistance in comparison with low-flux bicarbonate dialysis: results of the REDERT study. Nephrol Dial Transplant 30(4):682–689CrossRefPubMed

30.

Itoh Y, Ezawa A, Kikuchi K, Tsuruta Y, Niwa T (2012) Protein bound uremic toxins in hemodialysis patients measured by liquid chromatography/tandem mass spectrometry and their effects on endothelial ROS production. Anal Bioanal Chem 403:1841–1850CrossRefPubMed

31.

Daugirdas JT, Depner TA, Greene T, Levin NW, Chertow GM, Rocco MV, Frequent Hemodialysis Network Trial Group (2010) Standard Kt/Vurea: a method of calculation that includes effects of fluid removal and residual kidney clearance. Kidney Int 77(7):637–644CrossRefPubMed

32.

Barreto FC, Barreto DV, Liabeuf S, Meert N, Glorieux G, Temmar M, Choukroun G, Vanholder R, Massy ZA, European Uremic Toxin Work Group (EUTox) (2009) Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. Clin J Am Soc Nephrol 4(10):1551–1558CrossRefPubMedPubMedCentral

33.

Krieter DH, Hackl A, Rodriguez A, Chenine L, Moragues HL, Lemke HD, Wanner C, Canaud B (2010) Protein-bound uraemic toxin removal in haemodialysis and post-dilution haemodiafiltration. Nephrol Dial Transplant 25(1):212–218CrossRefPubMed

34.

Meijers BK, Evenepoel P (2011) The gut-kidney axis: indoxyl sulfate, p-cresyl sulfate and CKD progression. Nephrol Dial Transplant 26(3):759–761CrossRefPubMed

35.

Meert N, Eloot S, Waterloos MA, Van Landschoot M, Dhondt A, Glorieux G et al (2009) Effective removal of protein-bound uraemic solutes by different convective strategies: a prospective trial. Nephrol Dial Transplant 24:562–570CrossRefPubMed

36.

Lesaffer G, De Smet R, Lameire N, Dhondt A, Duym P, Vanholder R (2000) Intradialytic removal of protein-bound uraemic toxins: role of solute characteristics and of dialyser membrane. Nephrol Dial Transplant 15(1):50–57CrossRefPubMed

37.

Bammens B, Evenepoel P, Verbeke K et al (2004) Removal of the protein-bound solute p-cresol by convective transport: a randomized crossoverstudy. Am J Kidney Dis 44:278–285CrossRefPubMed

38.

Bammens B, Evenepoel P, Verbeke K et al (2003) Removal of middle molecules and protein-bound solutes by peritoneal dialysis and relation with uremic symptoms. Kidney Int 64:2238–2243CrossRefPubMed

39.

Dhondt AW, Vanholder RC, De Smet RV et al (2003) Studies on dialysate mixing in the Genius single-pass batch system for hemodialysis therapy. Kidney Int 63:1540–1547CrossRefPubMed

40.

Evenepoel P, Bammens B, Verbeke K et al (2006) Superior dialytic clearance of beta(2)-microglobulin and p-cresol by high-flux hemodialysis as compared to peritoneal dialysis. Kidney Int 70:794–799CrossRefPubMed

41.

Evenepoel P, Bammens B, Verbeke K et al (2006) Acarbose treatment lowers generation and serum concentrations of the protein-bound solute p-cresol: a pilot study. Kidney Int 70:192–198CrossRefPubMed

42.

Meert N, Eloot S, Schepers E, Lemke HD, Dhondt A, Glorieux G, Van Landschoot M, Waterloos MA, Vanholder R (2011) Comparison of removal capacity of two consecutive generations of high-flux dialysers during different treatment modalities. Nephrol Dial Transplant 26(8):2624–2630CrossRefPubMed

43.

Penne EL, Blankstijn PJ, Bots ML et al (2005) Effect of increased convective clearance by on-line hemodiafiltration on all cause and cardiovascular mortality in chronic hemodialysis patients—the Dutch CONvective TRAnsport STudy (CONTRAST): rationale and design of a randomised controlled trial. Curr Control Trials Cardiovasc Med 6:8CrossRefPubMedPubMedCentral

44.

Lee CT, Kuo CC, Chen YM, Hsu CY, Lee WC, Tsai YC, Ng HY, Kuo LC, Chiou TT, Yang YK, Cheng BC, Chen JB (2010) Factors associated with blood concentrations of indoxyl sulfate and p-cresol in patients undergoing peritoneal dialysis. Perit Dial Int 30(4):456–463CrossRefPubMed

Title: Long term variation of serum levels of uremic toxins in patients treated by post-dilution high volume on-line hemodiafiltration in comparison to standard low-flux bicarbonate dialysis: results from the REDERT study
Authors: Vincenzo Panichi
Maria Teresa Rocchetti
Alessia Scatena
Alberto Rosati
Massimiliano Migliori
Francesco Pizzarelli
Loreto Gesualdo
REDERT Study group
Publication date: 01-08-2017
Publisher: Springer International Publishing
Published in: Journal of Nephrology / Issue 4/2017
Print ISSN: 1121-8428
Electronic ISSN: 1724-6059
DOI: https://doi.org/10.1007/s40620-017-0381-2

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