Serum Uremic Toxins and Histological Findings of the Blood Vessels in Dialysis Patients

This study has been completed.
Sponsor:
Collaborator:
Ministry of Science and Education, R. Macedonia
Information provided by:
University of Skopje
ClinicalTrials.gov Identifier:
NCT00412139
First received: December 12, 2006
Last updated: February 8, 2010
Last verified: December 2008
  Purpose

Patients treated by chronic renal replacement therapy are exposed to cardiovascular problems and suffer from an accelerated and sever atherosclerosis. Classical risk factors for atherosclerosis and cardiovascular diseases (CVD) do not explain the full risk of CVD in the dialysis patients. Additional risk factors are therefore likely to exist. The uremic syndrome is attributed to the progressive retention of a large number of compounds, which under normal conditions are excreted by the healthy kidneys. Uremic toxins such are parathormone (PTH), vitamin D and phosphates, cause development of renal osteodystrophy (ROD), i.e. disordered calcium and phosphate metabolism. Both conditions of hyperparathyroid and adynamic bone disease (ABD) lead to an elevated calcium x phosphate product and increased vascular calcification, which might occur in intimal and medial layer of the vessel wall. It is important to consider these processes separately, as the vascular consequences (occlusion with atheromatosis and vascular stiffening through medial calcification) are different. Moreover, the difference between uremic and non-uremic intimal plaque is not the size but its composition, with markedly increased calcium content. Hence, these observations have an important socio-economic impact because of the increased cardiovascular morbidity and mortality.

The investigators hypothesized that uremic toxins in dialysis patients influence directly and/or indirectly the development of atherosclerosis, vascular calcifications and CVD.


Condition
Chronic Renal Failure

Study Type: Observational
Study Design: Observational Model: Case-Crossover
Time Perspective: Prospective
Official Title: A Correlation Between Histological Findings of the Blood Vessels in Patients With Chronic Renal Failure and Serum Uremic Toxins and Its Diagnostic Performance in the Assessment of the Cardiovascular Morbidity and Mortality

Resource links provided by NLM:


Further study details as provided by University of Skopje:

Biospecimen Retention:   None Retained

3 aliquots of 2-3 ml sera are retained for various uremic markers determination


Enrollment: 100
Study Start Date: December 2006
Study Completion Date: January 2010
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Detailed Description:

Rationale: Patients treated by chronic renal replacement therapy are exposed to cardiovascular problems and suffer from an accelerated and sever atherosclerosis. Classical risk factors for atherosclerosis and cardiovascular diseases (CVD) do not explain the full risk of CVD in the dialysis patients. Additional risk factors are therefore likely to exist. The uremic syndrome is attributed to the progressive retention of a large number of compounds, which under normal conditions are excreted by the healthy kidneys. Uremic toxins such are parathormone (PTH), vitamin D and phosphates, cause development of renal osteodystrophy (ROD), i.e. disordered calcium and phosphate metabolism. Both conditions of hyperparathyroid and adynamic bone disease (ABD) lead to an elevated calcium x phosphate product and increased vascular calcification, which might occur in intimal and medial layer of the vessel wall. It is important to consider these processes separately, as the vascular consequences (occlusion with atheromatosis and vascular stiffening through medial calcification) are different. Moreover, the difference between uremic and non-uremic intimal plaque is not the size but its composition, with markedly increased calcium content. Hence, these observations have an important socio-economic impact because of the increased cardiovascular morbidity and mortality.

Hypothesis: We hypothesized that uremic toxins in dialysis patients influence directly and/or indirectly the development of atherosclerosis, vascular calcifications and CVD.

Objectives:

To asses the histology of arterial vessels in patients with end-stage renal failure and to evaluate its relationship with serum uremic toxins.

To determine the biochemical and clinical risk factors that might influence the development of vascular calcifications and their diagnostic performance in the assessment of CVD morbidity and mortality.

Methods: A cross-sectional study will be conducted at the Department of Nephrology Skopje. After the initial assessment patients will be followed for 2 years as the prospective part of the study.

Seventy-five to ninety patients will be included, during one-year period or until proposed number of patients is recruited. The study cohort will be divided to 3 subgroups: 1) patients at the initiation of dialysis therapy, 2) patients on regular dialysis treatment for a few years and 3) patients undergoing renal transplantation. During the follow-up period cardiovascular and cerebrovascular events and the moment of their occurrence will be recorded, as well as the peripheral vascular diseases. Moreover, clinical, laboratory data and arterial vessel samples for histology will be collected at the moment of inclusion.

Expected outcomes: We expect the determination of high correlation coefficient between histological parameters and various uremic toxins, which are responsible for development atherosclerosis and vascular calcifications, leading to an accelerated progression of CVD in dialysis patients. This determination could help to design new preventive therapeutic tools in these patients. The result of this work will impose a positive impact on quality of life and therapeutic costs related to atherosclerosis not only in the dialysis populations but also in the pre-dialysis chronic renal failure populations and kidney transplant recipients.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

CKD patients with a need for dialysis within a few months CKD patients on dialysis with thormbosis of AV fistula CKD patients on dialysis scheduled for kidney transplantation

Criteria

Inclusion Criteria:

  • Chronic renal failure patients with a need for creation of AV fistula
  • Dialysis patients with a need of reanastomosing of the AV fistula (thrombosis or insufficient blood flow)

Exclusion Criteria:

  • Diabetes
  • Malignant disease
  • Prior treatment with corticosteroids
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00412139

Locations
Macedonia, The Former Yugoslav Republic of
Department of Nephrology, University Clinical Center
Skopje, Macedonia, The Former Yugoslav Republic of, 1000
Sponsors and Collaborators
University of Skopje
Ministry of Science and Education, R. Macedonia
Investigators
Principal Investigator: Goce Spasovski, MD, PhD Department of Nephrology, University Clinical Center, Vodnjanska 17, 1000 Skopje, R. Macedonia
Study Chair: Momir Polenakovic, MD, PhD Macedonian Academy of Science and Arts
  More Information

No publications provided

Responsible Party: Goce Spasovski, PI, Department of Nephrology, University Clinical Center
ClinicalTrials.gov Identifier: NCT00412139     History of Changes
Other Study ID Numbers: 13-1001/2-05
Study First Received: December 12, 2006
Last Updated: February 8, 2010
Health Authority: Macedonia: Ethics Committee

Keywords provided by University of Skopje:
vascular calcifications
uremic toxins
renal osteodystrophy
Dialysis

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency
Renal Insufficiency, Chronic
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on July 24, 2014