Ignite Creation Date:
2024-05-06 @ 3:10 AM
Last Modification Date:
2024-10-26 @ 11:29 AM
Study NCT ID:
NCT02226055
Status:
COMPLETED
Last Update Posted:
2017-11-01
First Post:
2014-08-25
Brief Title:
An Investigation Into the Cardiovascular Risk and Aetiology of CKDu in Sri Lanka
Sponsor:
University of Edinburgh
Organization:
University of Edinburgh
Study Overview
Official Title:
An Investigation Into the Cardiovascular Risk and Aetiology of CKDu in Sri Lanka
Status:
COMPLETED
Status Verified Date:
2017-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 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
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
Detailed Description:
Chronic kidney disease CKD is one of the leading causes of hospital admission clinic attendance and mortality in some provinces of Sri Lanka In central and southern provinces increased incidence is attributed to type-2 diabetes and hypertension however this is not the case in North Central Province NCP where CKD of unknown aetiology CKDu is the commonest diagnosis A recent World Health Organisation WHO investigation concluded that at least 8000 people have CKDu2
First recognized in the early nineties much work has been done to try to characterise the disease however results are conflicting Most suggest male paddy farmers working in rural areas of the NCP are worst affected presenting in their fifth decade with end stage renal failure However a recent WHO study revealed higher prevalence in females although more severe renal impairment was more common in men
Risk factors include inhabiting NCP five years inhabiting the dry zone reduced BMI lower socio-economic class and exposure to agrochemicals There has been suggestion of a genetic link although positive family history is limited to one generation with no evidence of mendelian progression Epidemiological studies reveal a clustered geographical distribution with areas such as Medawachchiya Padaviya and Girandurukotte most affected High prevalence areas encompass a well-developed irrigation system used for agricultural purposes
Renal biopsies show tubulointerstitial disease with tubular atrophy interstitial mononuclear cell infiltration interstitial fibrosis but no immune-complex deposition on immunofluorescence This supports a toxin-mediated process
Many aetiologies have been considered including exposure to heavy metals cadmium arsenic and their chelation by herbicides fluro-aluminium complexes agricultural pesticides mycotoxins and herbal medicines Selenium deficiency and genetic susceptibility may be predisposing factors The true aetiology is likely multifactorial
The multi-system impact of CKDu has yet to be fully realised Epidemiological and clinical data show that damage to large arteries contributes to the increased cardiovascular risk observed in CKD Atherosclerosis is the most frequent cause of arterial damage but the medial calcification seen in CKD also leads to arterial stiffening This stiffening causes elevation in systolic blood pressure increasing left ventricular workload with 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 patients with CKD Arterial stiffness will be compared in CKDu patients healthy Sri Lankan controls and CKD patients both in Sri Lanka and Scotland
We will perform a prospective observational study of up to 250 patients with CKDu presenting to renal clinics in Teaching Hospital Anuradhapura Patient history basic anthropometric measurements and simple non-invasive tests eg blood pressure and arterial stiffness will be performed Urine serum and plasma samples will be collected for quantitative PCR and further analysis for biomarkers of renal injury exosomes proteomics and any DNA-adducts Patients will be graded using the WHO CKDu grading system When a renal biopsy is performed a copy of the light microscopy findings will be obtained Comparisons of interest will be tested via paired t-tests with statistical significance taken at 5
First recognized in the early nineties much work has been done to try to characterise the disease however results are conflicting Most suggest male paddy farmers working in rural areas of the NCP are worst affected presenting in their fifth decade with end stage renal failure However a recent WHO study revealed higher prevalence in females although more severe renal impairment was more common in men
Risk factors include inhabiting NCP five years inhabiting the dry zone reduced BMI lower socio-economic class and exposure to agrochemicals There has been suggestion of a genetic link although positive family history is limited to one generation with no evidence of mendelian progression Epidemiological studies reveal a clustered geographical distribution with areas such as Medawachchiya Padaviya and Girandurukotte most affected High prevalence areas encompass a well-developed irrigation system used for agricultural purposes
Renal biopsies show tubulointerstitial disease with tubular atrophy interstitial mononuclear cell infiltration interstitial fibrosis but no immune-complex deposition on immunofluorescence This supports a toxin-mediated process
Many aetiologies have been considered including exposure to heavy metals cadmium arsenic and their chelation by herbicides fluro-aluminium complexes agricultural pesticides mycotoxins and herbal medicines Selenium deficiency and genetic susceptibility may be predisposing factors The true aetiology is likely multifactorial
The multi-system impact of CKDu has yet to be fully realised Epidemiological and clinical data show that damage to large arteries contributes to the increased cardiovascular risk observed in CKD Atherosclerosis is the most frequent cause of arterial damage but the medial calcification seen in CKD also leads to arterial stiffening This stiffening causes elevation in systolic blood pressure increasing left ventricular workload with 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 patients with CKD Arterial stiffness will be compared in CKDu patients healthy Sri Lankan controls and CKD patients both in Sri Lanka and Scotland
We will perform a prospective observational study of up to 250 patients with CKDu presenting to renal clinics in Teaching Hospital Anuradhapura Patient history basic anthropometric measurements and simple non-invasive tests eg blood pressure and arterial stiffness will be performed Urine serum and plasma samples will be collected for quantitative PCR and further analysis for biomarkers of renal injury exosomes proteomics and any DNA-adducts Patients will be graded using the WHO CKDu grading system When a renal biopsy is performed a copy of the light microscopy findings will be obtained Comparisons of interest will be tested via paired t-tests with statistical significance taken at 5
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None