Reduction of Oxalate and Inflammation by Hemodiafiltration vs. Hemodialysis

Chronic Kidney Disease Requiring Chronic Dialysis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02684656
• Other study ID #: UErlangen-Nurnberg
• Status: Completed
• Phase: N/A
• Start date: February 2016
• Est. completion date: September 2016

Study information

• Verified date: December 2019
• Source: University of Erlangen-Nürnberg Medical School
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Disease Requiring Chronic Dialysis
• Inflammation
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Procedure:
• Hemodialysis
Hemodialysis >/=4h
• Hemodiafiltration
Hemodiafiltration >/=4h, > 20l convection

Locations

Country	Name	City	State
Germany	Nephrology Department, University Hospital Erlangen	Erlangen	Bavaria

Sponsors (2)

Lead Sponsor	Collaborator
University of Erlangen-Nürnberg Medical School	Renal Research Institute

Country where clinical trial is conducted

Germany, 

References & Publications (2)

Hoppe B, Kemper MJ, Bökenkamp 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma oxalate		6 months
Secondary	Cytokines measured by multiplex analysis		6 months