Protein-Bound Uremic Retention Solutes in Long Nocturnal Hemodialysis

A Multicentric Observational Study on the Removal of Protein-Bound Uremic Retention Solutes in Nocturnal Hemodialysis: A Cross-Sectional Analysis

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. But 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 - hemodialysis, peritoneal dialysis (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 Overview

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

• Study Type: Observational
• Enrollment (Actual): 120

Contacts and Locations

Study Locations

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

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 hemodialysis patients

Description

Inclusion Criteria:

• Age > 18 years
• Maintenance hemodialysis (> 3 months duration)
• Informed consent

Exclusion Criteria:

• No consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
1; hemodialysis twice weekly 4 hours	Procedure: hemodialysis; group 1: twice weekly, four hours; Procedure: hemodialysis; group 2: twice weekly, eight hours; Procedure: hemodialysis; group 3: every other day, eight hours; Procedure: hemodialysis; group 4: six days a week, eight hours
2; nocturnal dialysis twice weekly 8 hours	Procedure: hemodialysis; group 1: twice weekly, four hours; Procedure: hemodialysis; group 2: twice weekly, eight hours; Procedure: hemodialysis; group 3: every other day, eight hours; Procedure: hemodialysis; group 4: six days a week, eight hours
3; nocturnal hemodialysis, 8 hours every other night	Procedure: hemodialysis; group 1: twice weekly, four hours; Procedure: hemodialysis; group 2: twice weekly, eight hours; Procedure: hemodialysis; group 3: every other day, eight hours; Procedure: hemodialysis; group 4: six days a week, eight hours
4; nocturnal hemodialysis, 8 hours, six times per week	Procedure: hemodialysis; group 1: twice weekly, four hours; Procedure: hemodialysis; group 2: twice weekly, eight hours; Procedure: hemodialysis; group 3: every other day, eight hours; Procedure: hemodialysis; group 4: six days a week, eight hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
removal of protein-bound retention solutes	1 dialysis session

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, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: December 28, 2006
• First Submitted That Met QC Criteria: December 28, 2006
• First Posted (Estimate): December 29, 2006

Study Record Updates

• Last Update Posted (Estimate): March 5, 2009
• Last Update Submitted That Met QC Criteria: March 4, 2009
• Last Verified: March 1, 2009

More Information

Terms related to this study

• Keywords: chronic kidney disease; hemodialysis; dialysis adequacy
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: NHD001