The Immune System in End Stage CKD Patients - Comparison Among Different Modalities of RRT

NCT04286477 | Unknown

• 1 other identifier: RESCOMUOI82758
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The evaluation and assessment of the influence of the different modalities of renal replacement therapy (RRT), including peritoneal dialysis (PD), conventional hemodialysis with high flux dialyzers, hemodiafiltration (HDF) and expanded hemodialysis (HDx) with Medium Cut Off (MCO) dialyzers on the levels of the cell subsets of the innate and acquired immune system as well as the investigation of the possible role of these cells as prognostic indices of morbidity and mortality in patients with end-stage Chronic Kidney Disease (CKD) undergoing different modalities of RRT.

Conditions

End Stage Renal Disease on Dialysis

Keywords

Peritoneal Dialysis; Hemodiafiltration; Expanded Hemodialysis; Monocytes subpopulations; Regulatory T cells; Natural Killer cells; Lymphocytes

Outcome Measures

Primary Outcomes (3)

• Change in the peripheral blood levels of the cell subsets of the innate and acquired immune system in patients with end-stage CKD transitioning from hemodialysis to hemodiafiltration or expanded hemodialysis.

  Immune cell subtypes (CD14++CD16- monocytes, CD14++CD16+ monocytes, CD 14+CD16+ monocytes, NK cells, CD4+ lymphocytes, CD8+ lymphocytes and Tregs) will be measured by flow cytometry at baseline in patients undergoing hemodialysis in the midweek dialysis session. 15 of patients undergoing conventional hemodialysis will be allocated to online-HDF with the same dialyzer and 15 conventional hemodialysis patients will be allocated to HDx with an MCO dialyzer (THERANOVA dialyzer, Baxter International Inc. (NYSE: BAX)), for 12 weeks. Immune cell subtypes will be measured in the 12th week.

  1st-12th week

• Comparison of the peripheral blood levels of the cell subsets of the innate and acquired immune system in patients with end-stage CKD undergoing hemodiafiltration versus expanded hemodialysis.

  Patients allocated to online-HDF and patients allocated to HDx with an MCO dialyzer (THERANOVA dialyzer, Baxter International Inc. (NYSE: BAX)), will be allocated to conventional hemodialysis for 4 weeks as a wash-out phase and then they will be crossed over to online-HDF and HDx with THERANOVA dialyzer for 12 weeks. Immune cell subtypes (CD14++CD16- monocytes, CD14++CD16+ monocytes, CD 14+CD16+ monocytes, NK cells, CD4+ lymphocytes, CD8+ lymphocytes and Tregs)will be measured by flow cytometry in the 28th week.

  12th-28th

• Comparison between the peripheral blood levels of the cell subsets of the innate and acquired immune system in patients with end-stage CKD undergoing hemodialysis, hemodiafiltration, expanded hemodialysis and peritoneal dialysis.

  Immune cell subtypes (CD14++CD16- monocytes, CD14++CD16+ monocytes, CD 14+CD16+ monocytes, NK cells, CD4+ lymphocytes, CD8+ lymphocytes and Tregs)will be measured in 15 PD patients during a programmed visit at the PD unit.

  12-28th

Secondary Outcomes (3)

• Correlation between peripheral blood levels of the cell subsets of the innate and acquired immune system with dialysis adequacy, adequacy of fluid control, nutritional indices, and inflammatory markers.

  1st - 48th week

• Correlation between peripheral blood levels of the cell subsets of the innate and acquired immune system with established cardiovascular disease, atherosclerosis markers, indicesof systolic and diastolic cardiac function and occurrence of infections.

  1st - 48th week

• Prognostic indices of morbidity (hospitalizations, cardiovascular events, infections) and mortality (due to any cause or cardiovascular mortality).

  24 months

Study Arms (4)

15 conventional hemodialysis patients

15 patients undergoing hemodialysis with high-flux dialyzer

15 patients undergoing online-hemodiafiltration

15 patients undergoing conventional hemodialysis with high-flux dialyzer will be allocated to online-hemodiafiltration with the same dialyzer

15 patients undergoing expanded hemodialysis with MCO dialyzer

15 hemodialysis patients undergoing hemodialysis with a high-flux dialyzer will be allocated to HDx with an MCO dialyzers (THERANOVA dialyzer, Baxter International Inc. (NYSE: BAX))

15 patients undergoing peritoneal dialysis

15 patients undergoing peritoneal dialysis

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will include patients undergoing RRT in the Hemodialysis and PD Unit of the Nephrology Department of the University Hospital of Ioannina. Patients will be informed with regard to the study and they will provide written informed consent before enrollment. The study will be approved by the Ethics Committee of the University Hospital of Ioannina. Accordingly, adult patients between 18 and 90 years and CKD G5 (GFR \< 15ml/min/ 1.73m2) requiring conventional hemodialysis treatment thrice weekly, since at least three months via a permanent vascular access (fistula, graft or a tunneled central venous catheter) and patients undergoing PD (continuous ambulatory peritoneal dialysis (CAPD) or Automated peritoneal dialysis (APD)) for at least three months.

You may qualify if:

• adult patients between 18 and \<90 years
• CKD G5 (glomerular filtration rate (GFR) \<15 ml/min/1.73m2)
• conventional hemodialysis treatment thrice weekly for at least three months via permanent vascular access
• patients undergoing PD for at least three months.

You may not qualify if:

• presence of infection
• active malignancy
• liver cirrhosis
• inflammatory bowel disease
• active autoimmune disease
• decompensated heart failure (New York Heart Association (NYHA) IV
• occurence of a major cardiovascular event within less that three months

Sponsors & Collaborators

• University of Ioannina: lead
• Baxter Healthcare Corporation: collaborator

Study Sites (1)

University Hospital of Ioannina

Ioannina, 45110, Greece

RECRUITING

Related Publications (5)

• Heine GH, Ulrich C, Seibert E, Seiler S, Marell J, Reichart B, Krause M, Schlitt A, Kohler H, Girndt M. CD14(++)CD16+ monocytes but not total monocyte numbers predict cardiovascular events in dialysis patients. Kidney Int. 2008 Mar;73(5):622-9. doi: 10.1038/sj.ki.5002744. Epub 2007 Dec 26.

  PMID: 18160960 BACKGROUND

• Vacher-Coponat H, Brunet C, Lyonnet L, Bonnet E, Loundou A, Sampol J, Moal V, Dussol B, Brunet P, Berland Y, Dignat-George F, Paul P. Natural killer cell alterations correlate with loss of renal function and dialysis duration in uraemic patients. Nephrol Dial Transplant. 2008 Apr;23(4):1406-14. doi: 10.1093/ndt/gfm596. Epub 2007 Nov 20.

  PMID: 18029366 BACKGROUND

• Caprara C, Kinsey GR, Corradi V, Xin W, Ma JZ, Scalzotto E, Martino FK, Okusa MD, Nalesso F, Ferrari F, Rosner M, Ronco C. The Influence of Hemodialysis on T Regulatory Cells: A Meta-Analysis and Systematic Review. Blood Purif. 2016;42(4):307-313. doi: 10.1159/000449242. Epub 2016 Oct 1.

  PMID: 27694753 BACKGROUND

• Kim HW, Yang HN, Kim MG, Choi HM, Jo SK, Cho WY, Kim HK. Microinflammation in hemodialysis patients is associated with increased CD14CD16(+) pro-inflammatory monocytes: possible modification by on-line hemodiafiltration. Blood Purif. 2011;31(4):281-8. doi: 10.1159/000321889. Epub 2011 Jan 14.

  PMID: 21242682 BACKGROUND

• Wolley M, Jardine M, Hutchison CA. Exploring the Clinical Relevance of Providing Increased Removal of Large Middle Molecules. Clin J Am Soc Nephrol. 2018 May 7;13(5):805-814. doi: 10.2215/CJN.10110917. Epub 2018 Mar 5.

  PMID: 29507008 BACKGROUND

Central Study Contacts

Evangelia Ntounousi, PHD

CONTACT

+302651099653; edounous@uoi.gr

Study Design

• Study Type: observational
• Observational Model: CASE CROSSOVER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 13, 2020
• First Posted: February 27, 2020
• Study Start: November 7, 2018
• Primary Completion: March 1, 2022
• Study Completion: December 31, 2022
• Last Updated: November 13, 2020

Record last verified: 2020-11

Locations

GR (1)