Protein-bound Uremic Retention Solutes and Long Nocturnal Hemodialysis: a Longitudinal Analysis

A Multicentric Observational Trial on Protein Bound Uremic Toxins in Nocturnal Hemodialysis

Study on intradialytic kinetics of protein-bound uremic retention solutes during long nocturnal hemodialysis

Study Overview

• Status: Completed
• Conditions: End Stage Kidney Disease
• Intervention / Treatment: Procedure: hemodialysis

Detailed Description

Although remarkable progress has been made, chronic kidney disease still poses a major burden on both individual patients, as well as on society as a whole. There is a strong inverse relationship between decreasing renal function, as estimated by glomerular filtration rate, and mortality rate, especially death due to cardiovascular disease. The exact cause(s) remain to be elucidated. Uremic toxins might play an important role.

In the course of decreasing renal function the concentration of numerous intracellular and extracellular compounds vary from the non-uremic state. A still increasing number of uremic retention solutes are being identified. Renal replacement strategies aim to remove potentially harmful substances from the body. Traditionally much attention has been paid to small water-soluble molecules such as urea nitrogen and creatinine. Based on the results of the recent HEMO and ADEMEX studies, increases of small water-soluble solute removal above the level reached with modern dialysis techniques (HD, PD) seem not to be advantageous with regard to patient outcome. These findings may point to the importance of other distinct groups of uremic retention solutes. In view of the data described above, protein-bound solutes might be good candidates.

Several advantages of long duration hemodialysis have been observed, including a better control of blood pressure by decreasing extracellular fluid volume, lowering peripheral vascular resistance and improving endothelium-dependent and -independent vasodilation. A normalization of heart rate variability and improvement of left-ventricular function was noted as well. Furthermore, anemia control has been shown to be easier and several nutritional parameters improved in patients treated with long duration HD. The therapy results in higher small water-soluble solute removal, phosphate removal and greater elimination of larger molecules (e.g. β2-microglobulin).

It seems an appealing question whether a better control of the serum levels of protein-bound solutes can be achieved by long duration (nocturnal) hemodialysis. This might be another advantage of this therapeutic modality, or may even in part explain the better outcome of patients treated this way.

The study compares intermittent hemodialysis with long nocturnal hemodialysis with respect to serum concentrations of several protein bound uremic toxins, as well as solute removal.

• Study Type: Observational
• Enrollment (Actual): 38

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
    • Geelong, Victoria, Australia, 3220
      • Geelong Hospital
• Belgium
  • Brabant
    • Leuven, Brabant, Belgium, 3000
      • Universitaire Ziekenhuizen Leuven
  • Limburg
    • Hasselt, Limburg, Belgium, 3500
      • Virga Jesseziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

maintenance dialysis patients

Description

Inclusion Criteria:

• Start hemodialysis during 2007
• Age over 18 years
• Informed consent

Exclusion Criteria:

• Non consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
hemodialysis, 4h, twice weekly; hemodialysis, four hours, twice weekly	Procedure: hemodialysis; individualised
hemodialysis, 8h, twice weekly; hemodialysis, eight hours, twice weekly	Procedure: hemodialysis; individualised
hemodialysis, 8h, every other day; hemodialysis, eight hours, every other day	Procedure: hemodialysis; individualised
hemodialysis, 8h, six days per week; hemodialysis, eight hours, six days per week	Procedure: hemodialysis; individualised

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Investigators: Principal Investigator: Tom Dejagere, MD, Virga Jesse Ziekenhuis; Principal Investigator: Nigel Toussaint, MD, Geelong Hospital

Publications and helpful links

General Publications

• Bammens B, Evenepoel P, Keuleers H, Verbeke K, Vanrenterghem Y. Free serum concentrations of the protein-bound retention solute p-cresol predict mortality in hemodialysis patients. Kidney Int. 2006 Mar;69(6):1081-7. doi: 10.1038/sj.ki.5000115.
• Fagugli RM, De Smet R, Buoncristiani U, Lameire N, Vanholder R. Behavior of non-protein-bound and protein-bound uremic solutes during daily hemodialysis. Am J Kidney Dis. 2002 Aug;40(2):339-47. doi: 10.1053/ajkd.2002.34518.
• Pierratos A. Daily nocturnal home hemodialysis. Kidney Int. 2004 May;65(5):1975-86. doi: 10.1111/j.1523-1755.2004.00603.x. No abstract available.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: December 28, 2006
• First Submitted That Met QC Criteria: December 28, 2006
• First Posted (Estimate): January 1, 2007

Study Record Updates

• Last Update Posted (Estimate): May 13, 2016
• Last Update Submitted That Met QC Criteria: May 12, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: hemodialysis; dialysis adequacy; uremic retention solute
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: NHD002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No