REmoval of Free Light Chains. A COmpaRison of Three Different dialyzERs

NCT02950389 | Completed

• 1 other identifier: 2016/GD/2
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Immunoglobulin light chains are classified as middle molecule uremic toxins able to interact with B lymphocyte membranes leading to the activation of transmembrane signaling. The ensuing impairment of neutrophil function can contribute to the chronic inflammation state of uremic patients, and the increased risk of bacterial infections or vascular calcifications. The aim of this crossover observational study was to assess the difference in free light chain removal by three different hemodialysis filters in patients not affected by multiple myeloma. Free light chain removal was compared in the polymethylmethacrylate (PMMA) membrane Filtryzer BK-F, the polyphenylene HFR17 filter and the conventional polysulfone filter F7 High Performance dialysers (HPS). Twenty chronic hemodialysis patients were enrolled. The patients were randomized into two groups of treatment lasting six weeks each. The dialysis sessions checked were the midweek sessions and the blood was drawn at times 0, 120' and 240'. Kappa (k) and lambda (l) light chain levels, beta2microglobulin (β2M), C reactive protein (CRP) and albumin were checked.

Conditions

Complication of Hemodialysis

Keywords

PMMA; on-line HFR; free light chains; toxins; removal; hemodialysis

Outcome Measures

Primary Outcomes (1)

• Compare free light chain removal by three different hemodialysis filters in a cohort of chronic dialysis patients not affected by multiple myeloma

  45 days

Secondary Outcomes (1)

• Compare beta 2 microglobulin removal by three different hemodialysis filters

  45 days

Study Arms (2)

Group A

EXPERIMENTAL

Six bicarbonate dialysis session with PMMA dialysis filter for 2 weeks, followed by 2 weeks of 6 on-line HFR session with HFR17 dialysis filter, than 6 bicarbonate dialysis session for 2 weeks with F7 dialysis filter.

Device: PMMA filter; Device: HFR17 filter; Device: F7 filter

Group B

EXPERIMENTAL

Six on-line HFR session with HFR17 dialysis filter for 2 weeks, followed by 2 weeks of 6 o bicarbonate dialysis session with PMMA dialysis filter for 2 weeks, than 6 bicarbonate dialysis session for 2 weeks with F7 dialysis filter.

Device: PMMA filter; Device: HFR17 filter; Device: F7 filter

Interventions

PMMA filter DEVICE

Group A; Group B

HFR17 filter DEVICE

Group A; Group B

F7 filter DEVICE

Group A; Group B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• chronic hemodialysis patients
• free light chain values \>100 mg/L for k chains or \>50 mg/L for lambda chains.
• absence or \<200 ml/die residual diuresis
• fistula or central venous catheter with blood flow \>250 ml/min.

You may not qualify if:

• intradialytic hypotension
• multiple myeloma
• poly-allergy
• HIV positivity

Sponsors & Collaborators

• IRCCS Azienda Ospedaliero-Universitaria di Bologna: lead

Study Sites (1)

Nephrology Dialysis and Renal Transplantation Unit, S.Orsola University Hospital

Bologna, Italy

Location

Related Publications (23)

• Vanholder R, De Smet R, Glorieux G, Argiles A, Baurmeister U, Brunet P, Clark W, Cohen G, De Deyn PP, Deppisch R, Descamps-Latscha B, Henle T, Jorres A, Lemke HD, Massy ZA, Passlick-Deetjen J, Rodriguez M, Stegmayr B, Stenvinkel P, Tetta C, Wanner C, Zidek W; European Uremic Toxin Work Group (EUTox). Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int. 2003 May;63(5):1934-43. doi: 10.1046/j.1523-1755.2003.00924.x.

  PMID: 12675874 BACKGROUND

• Cohen G. Immunoglobulin light chains in uremia. Kidney Int Suppl. 2003 May;(84):S15-8. doi: 10.1046/j.1523-1755.63.s84.8.x.

  PMID: 12694299 BACKGROUND

• Desjardins L, Liabeuf S, Lenglet A, Lemke HD, Vanholder R, Choukroun G, Massy ZA; European Uremic Toxin (EUTox) Work Group. Association between free light chain levels, and disease progression and mortality in chronic kidney disease. Toxins (Basel). 2013 Nov 8;5(11):2058-73. doi: 10.3390/toxins5112058.

  PMID: 24217396 BACKGROUND

• Haynes R, Hutchison CA, Emberson J, Dasgupta T, Wheeler DC, Townend JN, Landray MJ, Cockwell P. Serum free light chains and the risk of ESRD and death in CKD. Clin J Am Soc Nephrol. 2011 Dec;6(12):2829-37. doi: 10.2215/CJN.03350411. Epub 2011 Oct 27.

  PMID: 22034503 BACKGROUND

• Aoike I. Clinical significance of protein adsorbable membranes--long-term clinical effects and analysis using a proteomic technique. Nephrol Dial Transplant. 2007 Jul;22 Suppl 5:v13-9. doi: 10.1093/ndt/gfm295.

  PMID: 17586841 BACKGROUND

• Hutchison CA, Blade J, Cockwell P, Cook M, Drayson M, Fermand JP, Kastritis E, Kyle R, Leung N, Pasquali S, Winearls C; International Kidney and Monoclonal Gammopathy Research Group. Novel approaches for reducing free light chains in patients with myeloma kidney. Nat Rev Nephrol. 2012 Feb 21;8(4):234-43. doi: 10.1038/nrneph.2012.14.

  PMID: 22349488 BACKGROUND

• Testa A, Dejoie T, Lecarrer D, Wratten M, Sereni L, Renaux JL. Reduction of free immunoglobulin light chains using adsorption properties of hemodiafiltration with endogenous reinfusion. Blood Purif. 2010;30(1):34-6. doi: 10.1159/000316684. Epub 2010 Jun 24.

  PMID: 20588010 BACKGROUND

• Borrelli S, Minutolo R, De Nicola L, De Simone E, De Simone W, Zito B, Guastaferro P, Nigro F, Iulianiello G, Credendino O, Bassi A, Leone L, Capuano M, Auricchio MR, Conte G. Effect of hemodiafiltration with endogenous reinfusion on overt idiopathic chronic inflammation in maintenance hemodialysis patients: a multicenter longitudinal study. Hemodial Int. 2014 Oct;18(4):758-66. doi: 10.1111/hdi.12178. Epub 2014 May 28.

  PMID: 24865622 BACKGROUND

• Bourguignon C, Chenine L, Bargnoux AS, Leray-Moragues H, Canaud B, Cristol JP, Morena M. Hemodiafiltration improves free light chain removal and normalizes kappa/lambda ratio in hemodialysis patients. J Nephrol. 2016 Apr;29(2):251-257. doi: 10.1007/s40620-015-0207-z. Epub 2015 May 29.

  PMID: 26022721 BACKGROUND

• Donati G, La Manna G, Cianciolo G, Grandinetti V, Carretta E, Cappuccilli M, Panicali L, Iorio M, Piscaglia F, Bolondi L, Coli L, Stefoni S. Extracorporeal detoxification for hepatic failure using molecular adsorbent recirculating system: depurative efficiency and clinical results in a long-term follow-up. Artif Organs. 2014 Feb;38(2):125-34. doi: 10.1111/aor.12106. Epub 2013 Jul 3.

  PMID: 23834711 BACKGROUND

• Bergstrom J, Wehle B. No change in corrected beta 2-microglobulin concentration after cuprophane haemodialysis. Lancet. 1987 Mar 14;1(8533):628-9. doi: 10.1016/s0140-6736(87)90266-2. No abstract available.

  PMID: 2881162 BACKGROUND

• Harding S, Provot F, Beuscart JB, Cook M, Bradwell AR, Stringer S, White D, Cockwell P, Hutchison CA. Aggregated serum free light chains may prevent adequate removal by high cut-off haemodialysis. Nephrol Dial Transplant. 2011 Apr;26(4):1438. doi: 10.1093/ndt/gfr019. Epub 2011 Mar 15.

  PMID: 21406545 BACKGROUND

• Cohen G, Rudnicki M, Schmaldienst S, Horl WH. Effect of dialysis on serum/plasma levels of free immunoglobulin light chains in end-stage renal disease patients. Nephrol Dial Transplant. 2002 May;17(5):879-83. doi: 10.1093/ndt/17.5.879.

  PMID: 11981077 BACKGROUND

• Fabbrini P, Sirtori S, Casiraghi E, Pieruzzi F, Genovesi S, Corti D, Brivio R, Gregorini G, Como G, Carati ML, Vigano MR, Stella A. Polymethylmethacrylate membrane and serum free light chain removal: enhancing adsorption properties. Blood Purif. 2013;35 Suppl 2:52-8. doi: 10.1159/000350849. Epub 2013 May 3.

  PMID: 23676837 BACKGROUND

• Birk HW, Kistner A, Wizemann V, Schutterle G. Protein adsorption by artificial membrane materials under filtration conditions. Artif Organs. 1995 May;19(5):411-5. doi: 10.1111/j.1525-1594.1995.tb02351.x.

  PMID: 7625919 BACKGROUND

• Lamy T, Henri P, Lobbedez T, Comby E, Ryckelynck JP, Ficheux M. Comparison between on-line high-efficiency hemodiafiltration and conventional high-flux hemodialysis for polyclonal free light chain removal. Blood Purif. 2014;37(2):93-8. doi: 10.1159/000357968. Epub 2014 Mar 1.

  PMID: 24603634 BACKGROUND

• Stefoni S, Coli L, Cianciolo G, Donati G, Ruggeri G, Ramazzotti E, Pohlmeier R, Lang D. Inflammatory response of a new synthetic dialyzer membrane. A randomised cross-over comparison between polysulfone and helixone. Int J Artif Organs. 2003 Jan;26(1):26-32. doi: 10.1177/039139880302600105.

  PMID: 12602466 BACKGROUND

• Rousseau-Gagnon M, Agharazii M, De Serres SA, Desmeules S. Effectiveness of Haemodiafiltration with Heat Sterilized High-Flux Polyphenylene HF Dialyzer in Reducing Free Light Chains in Patients with Myeloma Cast Nephropathy. PLoS One. 2015 Oct 14;10(10):e0140463. doi: 10.1371/journal.pone.0140463. eCollection 2015.

  PMID: 26466100 BACKGROUND

• Cianciolo G, Coli L, La Manna G, Donati G, D'Addio F, Comai G, Ricci D, Dormi A, Wratten M, Feliciangeli G, Stefoni S. Is beta2-microglobulin-related amyloidosis of hemodialysis patients a multifactorial disease? A new pathogenetic approach. Int J Artif Organs. 2007 Oct;30(10):864-78. doi: 10.1177/039139880703001003.

  PMID: 17992647 BACKGROUND

• Santoro A, Grazia M, Mancini E. The double polymethylmethacrylate filter (DELETE system) in the removal of light chains in chronic dialysis patients with multiple myeloma. Blood Purif. 2013;35 Suppl 2:5-13. doi: 10.1159/000350837. Epub 2013 May 3.

  PMID: 23676829 BACKGROUND

• Pasquali S, Iannuzzella F, Corradini M, Mattei S, Bovino A, Stefani A, Palladino G, Caiazzo M. A novel option for reducing free light chains in myeloma kidney: supra-hemodiafiltration with endogenous reinfusion (HFR). J Nephrol. 2015 Apr;28(2):251-4. doi: 10.1007/s40620-014-0130-8. Epub 2014 Aug 23.

  PMID: 25149172 BACKGROUND

• Machiguchi T, Tamura T, Yoshida H. Efficacy of haemodiafiltration treatment with PEPA dialysis membranes in plasma free light chain removal in a patient with primary amyloidosis. Nephrol Dial Transplant. 2002 Sep;17(9):1689-91. doi: 10.1093/ndt/17.9.1689. No abstract available.

  PMID: 12198225 BACKGROUND

• Donati G, Moretti MI, Baraldi O, Spazzoli A, Capelli I, Comai G, Marchetti A, Sarma M, Mancini R, La Manna G. Removal of free light chains in hemodialysis patients without multiple myeloma: a crossover comparison of three different dialyzers. BMC Nephrol. 2016 Nov 25;17(1):193. doi: 10.1186/s12882-016-0405-5.

  PMID: 27884120 DERIVED

Study Officials

• Gabriele Donati, MD, PhD

  S.Orsola University Hospital, Nephrology Dialysis and Renal Transplantation Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SCREENING
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D. Ph.D.

Study Record Dates

• First Submitted: October 28, 2016
• First Posted: November 1, 2016
• Study Start: January 1, 2016
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: March 18, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)