Clinical trial NCT02684656: Reduction of Oxalate and Inflammation by Hemodiafiltration vs. Hemodialysis
Official title: Pilot Study of Lowering Plasma Oxalate With Hemodiafiltration to Reduce Systemic Inflammation in Patients With End-Stage Renal Disease (ESRD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Kidney Disease Requiring Chronic Dialysis
Keywords: Oxalate
Inflammation
Hemodiafiltration
Hemodialysis
Oxalate Blood Sample
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
Collaborators: name: Renal Research Institute
First posted: 2016-02-18
Enrollment: 14
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Plasma oxalate
timeFrame: 6 months
Secondary outcomes:
measure: Cytokines measured by multiplex analysis
timeFrame: 6 months
Other outcomes:
Locations:
city: Erlangen
country: Germany
facility: Nephrology Department, University Hospital Erlangen
state: Bavaria
Study officials:
affiliation: University Erlangen-Nuremberg, Germany
name: Felix Knauf, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Erlangen-Nuremberg, Germany
name: Kai-Uwe Eckardt, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical Director of New Haven Home Dialysis
name: Fred Finkelstein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University New Haven, USA
name: Peter S Aronson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University New Haven
name: Chirag Parikh, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University New Haven
name: Mark A Perazella, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.