An Investigation Into the Cardiovascular Risk and Aetiology of CKDu in Sri Lanka

NCT02226055 | Completed

• 1 other identifier: UoECKDu1
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

1. 1.We hypothesise that CKDu patients will have increased arterial stiffness and thus increased all-cause and cardiovascular mortality. The first objective of this study is to recruit a cohort of \~ 50 CKDu patients who attend the CKDu clinic in Anuradhapura, and measure their arterial stiffness using the TensioMed® Arteriograph™ (details below). We will recruit an age, sex and blood pressure matched control group of healthy Sri Lankans (consenting visitors with patients both to clinic and as inpatients), and if possible, a second control group, similarly age, sex and blood pressure matched, who have CKD of known causes and attend general renal clinic in Anuradhapura.
2. 2.We hypothesise that detailed renal analysis will give insight into the aetiology of CKDu in the North Central Province of Sri Lanka. The second objective of the study is to recruit up to 250 CKDu patients and to characterize their disease profile using analysis serum and urine renal biomarkers, exosomes, proteomics and DNA adducts.

Conditions

CKDu; Arterial Stiffness; Proteinuria; Serum Creatinine; Urinary Biomarkers; DNA Adducts

Keywords

Chronic kidney disease of unknown origin; Chronic kidney disease of unknown aetiology; Sri Lanka; CKDu; Arterial stiffness; Cardiovascular risk; North Central Province

Outcome Measures

Primary Outcomes (1)

• Arterial stiffness

  Arterial stiffness will be measured using the TensioMed® Arteriograph™. Damage to large arteries contributes to increased cardiovascular risk in CKD. Atherosclerosis is the most frequent cause of arterial damage but medial calcification seen in CKD also leads to arterial stiffening. This stiffening causes elevated systolic blood pressure, increased left ventricular workload and the gradual development of LVH, and also a fall in diastolic blood pressure impairing coronary blood flow. Arterial calcification and stiffness are independent predictors of all-cause and cardiovascular mortality in CKD patients. It is unclear whether the CVD risk associated with CKDu is the same as it is for CKD of known cause. We plan to measure arterial stiffness in both CKD and CKDu patients. We will compare stiffness measurements in CKD of unknown cause with those of a well characterised cohort of CKD patients in Edinburgh. Healthy Sri Lankan volunteers will give an assessment of 'background stiffness'.

  3 months

Secondary Outcomes (1)

• Biomarkers of renal disease and DNA adducts

  3 months

Study Arms (4)

Arterial stiffness: CKDu patients

Cohort of 50 patients with CKD of unknown aetiology Inclusion and exclusion criteria below Measure of arterial stiffness using pulse wave velocity technology Assessment of BMI, central and brachial blood pressure, arterial stiffness and 'arterial age' will be made and fed back to the patient. this information will be given in a 'results sheet' that the participant will be encouraged to give to their Gp for further treatments required.

Device: Arterial Stiffness Assessment

Arterial stiffness: CKD known cause

Cohort of 50 patients with CKD of known cause Inclusion and exclusion criteria below Measure of arterial stiffness using pulse wave velocity technology Assessment of BMI, central and brachial blood pressure, arterial stiffness and 'arterial age' will be made and fed back to the patient. this information will be given in a 'results sheet' that the participant will be encouraged to give to their Gp for further treatments required.

Device: Arterial Stiffness Assessment

Arterial Stiffness: Healthy Sri Lankan volunteers

Cohort of 50 participants who are healthy Sri Lankan volunteers Inclusion and exclusion criteria below Measure of arterial stiffness using pulse wave velocity technology Assessment of BMI, central and brachial blood pressure, arterial stiffness and 'arterial age' will be made and fed back to the patient. this information will be given in a 'results sheet' that the participant will be encouraged to give to their Gp for further treatments required.

Device: Arterial Stiffness Assessment

2nd aim: 250 CKDu patients for investigation of aetiology

To recruit a cohort of up to 250 CKDu patients from specific CKDu clinics in Anuradhapura and Padavi-Sri Pura for detailed history, basic anthropometric tests, and further analysis of serum, and urine. Analysis for biomarkers of kidney damage, proteomics, exosomes, and DNA adducts will be used to seek information that may complement already collected data and help refine aetiological hypotheses. Inclusion and Exclusion criteria as per CKDu cases in cohort 1

Interventions

Arterial Stiffness Assessment DEVICE

The following will be measured: brachial systolic and diastolic bp, heart rate, mean arterial bp, pulse pressure, brachial augmentation index (difference between the amplitudes of the late (backward) systolic wave (P2) and the early (forward) systolic wave (P1) over the pulse pressure x 100), central augmentation, ejection duration of the left ventricle, return time (time of the pulse wave travelling from aortic root to the bifurcation and back), aortic pulse wave velocity ( velocity of the pulse wave in the aorta), central systolic bp, central pulse pressure and diastolic reflection area (provides information about the quality of diastolic filling in the coronary arteries). We will perform an arterial age assessment. Patients are given a feedback form with their results to give to their general. Those with increased arterial stiffness will be tested for serum calcium and phosphate levels, and audited to ensure that a statin is commenced if not contraindicated.

Also known as: TensioMed® Arteriograph™, Pulse wave velocity, Arterial Stiffness Monitor

Arterial Stiffness: Healthy Sri Lankan volunteers; Arterial stiffness: CKD known cause; Arterial stiffness: CKDu patients

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients attending clinics or admitted to hospital during Aug 2014 to Oct 2014 with CKDu (Chronic kidney disease of unknown origin). Subjects must be aged 18 to 85 with evidence of renal dysfunction and no other obvious cause noted (see inclusion/exclusion criteria above). Control groups will be sought for the measure of arterial stiffness: Sri Lankan CKD of known cause, Sri Lankan healthy volunteers. Our controls will be age, sex and blood pressure matched to the cases.

You may qualify if:

• Age 18- 85 years
• Attend CKDu clinic in Anuradhapura or Padavi-Sri Pura
• Evidence of renal dysfunction: proteinuria, raised serum creatinine
• Able to understand information given and happy to give consent

You may not qualify if:

• Subjects who are on dialysis
• History of diabetes
• History of major cardiac (including MI), respiratory (including asthma \& COPD) or neurological disease
• Pregnant
• History of significant hypertension (\>140/90mmHg despite anti-hypertensives or \>160/100mmHg untreated)
• History of glomerulonephritis or other known cause of renal disease
• Age 18- 85 years
• Present in Anuradhapura teaching hospital as a visitor/carer of patient in ward or at outpatient clinic at either site
• Able to understand information given and happy to give consent
• Age \< 18 or \>85 years
• Evidence of renal dysfunction: proteinuria, raised serum creatinine
• Evidence of diabetes mellitus, significant hypertension (defined above), glomerulonephritis or other known cause of renal disease.
• Age 18- 85 years
• Attend general renal clinic in Anuradhapura or Padavi-Sri Pura
• Evidence of renal dysfunction: proteinuria, raised serum creatinine

Sponsors & Collaborators

• University of Edinburgh: lead
• Rajarata University, Sri Lanka: collaborator

Study Sites (1)

Teaching Hospital Anuradhapura

Anuradhapura, North Central Province, A13, Sri Lanka

Location

Related Links

• WHO + Sri Lankan Ministry of Health collaborative study
• Oliver JJ, Webb DJ. Noninvasive assessment of arterial stiffness and risk of atherosclerotic events. Arterioscler Thromb Vasc Biol. Apr 1 2003;23(4):554-566
• Sarnak MJ, Levey AS et al. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research,

Biospecimen

Retention: SAMPLES WITH DNA

Urine samples: up to 30ml Blood samples: up to 40ml - 2 x EDTA blood bottles + 2 x serum gel Z bottles

MeSH Terms

Conditions

Proteinuria

Interventions

Pulse Wave Analysis

Condition Hierarchy (Ancestors)

Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Michael Eddleston, MA PhD FRCPEdin

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

• Neeraj Dhaun, PhD MRCP

  University of Edinburgh

  STUDY DIRECTOR

• Sisira Siribaddana, MD FCCP

  Rajarata University, Sri Lanka

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2014
• First Posted: August 26, 2014
• Study Start: September 1, 2014
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: November 1, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

SR (1)