Reduction of Oxalate and Inflammation by Hemodiafiltration vs. Hemodialysis

December 20, 2019 updated by: University of Erlangen-Nürnberg Medical School

Pilot Study of Lowering Plasma Oxalate With Hemodiafiltration to Reduce Systemic Inflammation in Patients With End-Stage Renal Disease (ESRD)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The positive interaction between diffusive and convective flux has suggested that hemodiafiltration (HDF) has a higher oxalate extraction rate as compared with hemodialysis (HD). However, it has not been evaluated whether HDF can lower predialysis oxalate levels below the level of supersaturation. By using an intra-individual approach with the inclusion/exclusion criteria listed for the study, we plan to determine plasma oxalate and cytokine levels in 20 patients (10 on regular duration HD, 10 patients on extended duration HD) before dialysis. Subsequently, patients will be switched to HDF and plasma oxalate concentration and cytokines will be analyzed again two weeks following HDF treatment. Plasma oxalate (Pox) will be measured at beginning of treatment, mid, end and 2 hrs post treatment (to determine rebound) in order to provide oxalate kinetics on HD/HDF treatment. Cytokines will only be measured pre HD/HDF treatment to assess steady state inflammation.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • Bavaria
      • Erlangen, Bavaria, Germany, 91054
        • Nephrology Department, University Hospital Erlangen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Hemodialysis
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
Hemodialysis >/=4h
Active Comparator: Hemodiafiltration
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
Hemodiafiltration >/=4h, > 20l convection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Plasma oxalate
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Cytokines measured by multiplex analysis
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Erlangen-Nürnberg Medical School

Collaborators

Renal Research Institute

Investigators

  • Principal Investigator: 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2016

Primary Completion (Actual)

September 1, 2016

Study Completion (Actual)

September 1, 2016

Study Registration Dates

First Submitted

February 9, 2016

First Submitted That Met QC Criteria

February 12, 2016

First Posted (Estimate)

February 18, 2016

Study Record Updates

Last Update Posted (Actual)

December 24, 2019

Last Update Submitted That Met QC Criteria

December 20, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UErlangen-Nurnberg

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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