Reduction of Oxalate and Inflammation by Hemodiafiltration vs. Hemodialysis

NCT02684656 | Completed

• 1 other identifier: UErlangen-Nurnberg
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The health care burden of CKD is substantial and growing with 10-15% of the population affected in both developed and developing countries. It is well established that CKD is associated with systemic inflammation, which promotes cardiovascular disease and body wasting. However, causal therapies to treat systemic inflammation, and treat its adverse consequences remain sparse. As kidney function declines in all forms of CKD, oxalate levels increase in the plasma, leading to increased systemic exposure to oxalate and consequent tissue injury. Work from the investigators has shown that elevated plasma oxalate levels activate the NLRP3 inflammasome which in turn leads to the processing and release of cytokines. The investigators seek to test the hypothesis that oxalate contributes to the systemic inflammation observed in patients with end-stage renal disease (ESRD). The investigators plan to define the association between plasma oxalate levels and signs of systemic inflammation in patients on hemodialysis. In a second step the investigators will examine whether hemodiafiltration lowers plasma oxalate more efficiently than hemodialysis and reduces signs of systemic inflammation. Confirmation of the hypothesis may lead to the identification of oxalate as a novel therapeutic target for interventional trials aimed at reducing plasma oxalate in patients with ESRD.

Conditions

Chronic Kidney Disease Requiring Chronic Dialysis

Keywords

Oxalate; Inflammation; Hemodiafiltration; Hemodialysis; Oxalate Blood Sample

Outcome Measures

Primary Outcomes (1)

• Plasma oxalate

  6 months

Secondary Outcomes (1)

• Cytokines measured by multiplex analysis

  6 months

Study Arms (2)

Hemodialysis

ACTIVE COMPARATOR

Intervention: Patients will be switch to hemodialysis and basal plasma oxalate levels as well as oxalate removal by hemodialysis will be determined after two weeks of treatment.

Procedure: Hemodialysis

Hemodiafiltration

ACTIVE COMPARATOR

Intervention: Patients will be switch back to hemodiafiltration and basal plasma oxalate levels as well as oxalate removal by hemodiafiltration will be determined after two weeks of treatment.

Procedure: Hemodiafiltration

Interventions

Hemodialysis PROCEDURE

Hemodialysis \>/=4h

Hemodialysis

Hemodiafiltration PROCEDURE

Hemodiafiltration \>/=4h, \> 20l convection

Hemodiafiltration

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Blood Flow ≥ 250 ml/min
• Dialysate Flow ≥ 500 ml/min
• Urinary Excretion \< 400 ml/24h
• Duration of Dialysis ≥ 4h
• On HDF/HD treatment for ≥ 4 weeks
• Extended HDF/HD for ≥ 4 weeks

You may not qualify if:

• Recirculation (online measurement) \> 15%
• Single needle dialysis or single lumen catheter
• Substitution volume of \< 20l on HDF

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead
• Renal Research Institute: collaborator

Study Sites (1)

Nephrology Department, University Hospital Erlangen

Erlangen, Bavaria, 91054, Germany

Location

Related Publications (2)

• Hoppe B, Kemper MJ, Bokenkamp A, Portale AA, Cohn RA, Langman CB. Plasma calcium oxalate supersaturation in children with primary hyperoxaluria and end-stage renal failure. Kidney Int. 1999 Jul;56(1):268-74. doi: 10.1046/j.1523-1755.1999.00546.x.

  PMID: 10411702 BACKGROUND

• Knauf F, Asplin JR, Granja I, Schmidt IM, Moeckel GW, David RJ, Flavell RA, Aronson PS. NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy. Kidney Int. 2013 Nov;84(5):895-901. doi: 10.1038/ki.2013.207. Epub 2013 Jun 5.

  PMID: 23739234 BACKGROUND

MeSH Terms

Conditions

Inflammation

Interventions

Renal Dialysis; Hemodiafiltration

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Renal Replacement Therapy; Therapeutics; Sorption Detoxification; Hemofiltration; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Felix Knauf, MD

  University Erlangen-Nuremberg, Germany

  PRINCIPAL INVESTIGATOR

• Kai-Uwe Eckardt, MD

  University Erlangen-Nuremberg, Germany

  PRINCIPAL INVESTIGATOR

• Fred Finkelstein, MD

  Medical Director of New Haven Home Dialysis

  PRINCIPAL INVESTIGATOR

• Peter S Aronson, MD

  Yale University New Haven, USA

  PRINCIPAL INVESTIGATOR

• Chirag Parikh, MD

  Yale University New Haven

  PRINCIPAL INVESTIGATOR

• Mark A Perazella, MD

  Yale University New Haven

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2016
• First Posted: February 18, 2016
• Study Start: February 1, 2016
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: December 24, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)