Serum Uremic Toxins and Histological Findings of the Blood Vessels in Dialysis Patients
Summary
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.
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.
Study Design
Observational Model: Case-Crossover, Time Perspective: Prospective
Conditions
Chronic Renal Failure
Location
Department of Nephrology, University Clinical Center
Skopje
Macedonia, The Former Yugoslav Republic of
1000
Status
Completed
Source
University of Skopje
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00412139
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Kidney Failure
A severe irreversible decline in the ability of kidneys to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal failure, either acute (KIDNEY FAILURE, ACUTE) or chronic (KIDNEY FAILURE, CHRONIC), requires HEMODIALYSIS.
Renal Insufficiency, Chronic
Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002)
Renal Insufficiency
Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE. The most severe form is KIDNEY FAILURE. Renal function may deteriorate slowly (RENAL INSUFFICIENCY, CHRONIC) or precipitously (RENAL INSUFFICIENCY, ACUTE).
Kidney Failure, Chronic
The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.
Metolazone
A quinazoline-sulfonamide that is considered a thiazide-like diuretic which is long-acting so useful in chronic RENAL FAILURE. It also tends to lower BLOOD PRESSURE and increase POTASSIUM loss.
Clinical Trials
The purpose of the study is to determine if low doses of BNP can improve renal function in people with chronic heart failure with renal dysfunction, also to determine whether Sildenafil as...
The purpose of this study is to evaluate the safety and efficacy of an experimental drug for the treatment of anemia in patients with Chronic Renal Failure (CRF), who is not on dialysis an...
In children with chronic kidney disease, progression to end-stage renal failure is associated with high patient morbidity and poor quality of life. In adults, inhibition of the renin angio...
Influence of Amlodipine on the Mortality of Patients With End-Stage Renal Failure
Patients with end-stage renal failure have a markedly higher mortality because of cardiovascular events in comparison with the normal population. Disorders in the calcium metabolism, such...
Intensive care patients with multiple organ dysfunction syndrome often show renal failure with the need for hemofiltration. Resolving renal failure after cessation of hemofiltration may or...
PubMed Articles
Continued progression of renal failure will lead to renal function too low to sustain healthy life. In developed countries, such people will be offered renal replacement therapy in the form of dialysi...
ABSTRACT: OBJECTIVE: To investigate the effects of hemodialysis (HD) and periotoneal dialysis (PD) on oxidative stress in chronic renal failure patients (CRF). Methods: 20 HD patients and 20 PD patien...
Background: The aim of this cross-sectional study was to evaluate multiple myeloma patients presenting with renal failure in a University hospital. Methods: The records of all the patients diagnosed w...
Hyperprolactinemia as a Rare Cause of Hypertension in Chronic Renal Failure.
Chronic renal failure (CRF) is associated with a high risk for hypertension. An individualized treatment should be initiated after the diagnosis of hypertension and underlying etiology. Many metabolic...
Safety of Older Generations of Gadolinium in Mild-to-Moderate Renal Failure.
Nephrogenic systemic fibrosis (NSF) is a rare disease that is mostly reported in patients with chronic kidney disease (CKD) who have received gadolinium as a contrast in imaging techniques. The exact...
