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- Mccafferty, Kieran, et al.
(författare)
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HEROIC: a 5-year observational cohort study aimed at identifying novel factors that drive diabetic kidney disease: rationale and study protocol
- 2020
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Ingår i: BMJ Open. - : BMJ. - 2044-6055 .- 2044-6055. ; 10:9, s. e033923-
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Tidskriftsartikel (refereegranskat)abstract
- Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. INTRODUCTION: Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease worldwide and a major cause of premature mortality in diabetes mellitus (DM). While improvements in care have reduced the incidence of kidney disease among those with DM, the increasing prevalence of DM means that the number of patients worldwide with DKD is increasing. Improved understanding of the biology of DKD and identification of novel therapeutic targets may lead to new treatments. A major challenge to progress has been the heterogeneity of the DKD phenotype and renal progression. To investigate the heterogeneity of DKD we have set up The East and North London Diabetes Cohort (HEROIC) Study, a secondary care-based, multiethnic observational study of patients with biopsy-proven DKD. Our primary objective is to identify histological features of DKD associated with kidney endpoints in a cohort of patients diagnosed with type 1 and type 2 DM, proteinuria and kidney impairment. METHODS AND ANALYSIS: HEROIC is a longitudinal observational study that aims to recruit 500 patients with DKD at high-risk of renal and cardiovascular events. Demographic, clinical and laboratory data will be collected and assessed annually for 5 years. Renal biopsy tissue will be collected and archived at recruitment. Blood and urine samples will be collected at baseline and during annual follow-up visits. Measured glomerular filtration rate (GFR), echocardiography, retinal optical coherence tomography angiography and kidney and cardiac MRI will be performed at baseline and twice more during follow-up. The study is 90% powered to detect an association between key histological and imaging parameters and a composite of death, renal replacement therapy or a 30% decline in estimated GFR. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Bloomsbury Research Ethics Committee (REC 18-LO-1921). Any patient identifiable data will be stored on a password-protected National Health Services N3 network with full audit trail. Anonymised imaging data will be stored in a ISO27001-certificated data warehouse.Results will be reported through peer-reviewed manuscripts and conferences and disseminated to participants, patients and the public using web-based and social media engagement tools as well as through public events.
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| 3. |
- O'Callaghan-Gordo, Cristina, et al.
(författare)
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Prevalence of and risk factors for chronic kidney disease of unknown aetiology in India : Secondary data analysis of three population-based cross-sectional studies
- 2019
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To assess whether chronic kidney disease of unknown aetiology (CKDu) is present in India and to identify risk factors for it using population-based data and standardised methods. Design Secondary data analysis of three population-based cross-sectional studies conducted between 2010 and 2014. Setting Urban and rural areas of Northern India (states of Delhi and Haryana) and Southern India (states of Tamil Nadu and Andhra Pradesh). Participants 12 500 individuals without diabetes, hypertension or heavy proteinuria. Outcome measures Mean estimated glomerular filtration rate (eGFR) and prevalence of eGFR below 60 mL/min per 1.73 m 2 (eGFR <60) in individuals without diabetes, hypertension or heavy proteinuria (proxy definition of CKDu). Results The mean eGFR was 105.0±17.8 mL/min per 1.73 m 2. The prevalence of eGFR <60 was 1.6% (95% CI=1.4 to 1.7), but this figure varied markedly between areas, being highest in rural areas of Southern Indian (4.8% (3.8 to 5.8)). In Northern India, older age was the only risk factor associated with lower mean eGFR and eGFR <60 (regression coefficient (95% CI)=a '0.94 (0.97 to 0.91); OR (95% CI)=1.10 (1.08 to 1.11)). In Southern India, risk factors for lower mean eGFR and eGFR <60, respectively, were residence in a rural area (a '7.78 (-8.69 to -6.86); 4.95 (2.61 to 9.39)), older age (a '0.90 (-0.93 to -0.86); 1.06 (1.04 to 1.08)) and less education (a '0.94 (-1.32 to -0.56); 0.67 (0.50 to 0.90) for each 5 years at school). Conclusions CKDu is present in India and is not confined to Central America and Sri Lanka. Identified risk factors are consistent with risk factors previously reported for CKDu in Central America and Sri Lanka.
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| 4. |
- Smpokou, Evangelia Theano, et al.
(författare)
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Environmental exposures in young adults with declining kidney function in a population at risk of Mesoamerican nephropathy
- 2019
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Ingår i: Occupational and environmental medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 76:12, s. 920-926
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Tidskriftsartikel (refereegranskat)abstract
- Objectives There is an epidemic of Mesoamerican nephropathy (MeN) in Central America, where sugarcane production is prominent. Numerous causes are proposed, but to date limited evidence supports any one hypothesis. A nested case-control study using biosamples from a rural, community-based follow-up study of 350 young adults from Northwest Nicaragua at risk of MeN was conducted with the aim of characterising the associations between urinary concentrations of metals, pesticides and mycotoxins from samples collected in the first 6 months and decline in kidney function over 2 years. Methods Urine samples collected at baseline (pre-sugarcane harvest) and the first 6 month follow-up (post-sugarcane harvest) visit were tested. Twelve metals and metalloids (aluminium, total arsenic, cadmium, chromium, cobalt, copper, lead, manganese, mercury, selenium, silicon and strontium) were analysed by inductively coupled plasma-mass spectrometry. Twelve pesticides or their metabolites (2,4-dichlorophenoxyacetic acid, 3-phenoxybenzoic acid, 4-fluoro-3-phenoxybenzoic acid, chloro-3,3,3-trifluoro-1-propen-1-yl-2,2-dimethylcyclopropanecarboxylic acid, cis/trans 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, ethylenethiourea, glyphosate, 4-chloro-2-methylphenoxy acetic acid, 3-hydroxy-pyrimetanil, 5-hydroxytiabendazole, hydroxy-tebuconazole and 3,5,6-trichloro-2-pyridinol) and two mycotoxins (ochratoxin A (OTA) and citrinin (CIT)) were analysed by liquid chromatography coupled-mass spectrometry. Differences in the creatinine-corrected urinary concentrations of the measured exposures between outcome groups (participants with stable vs declining kidney function) were examined. Results Elevated levels of aluminium and total arsenic as well as metabolites of several pesticides were detected across the population. No differences were identified between the declining and stable groups in the levels of metals or pesticides tested. OTA and CIT were below the limit of detection. Conclusions The tested metals, metalloids, pesticides and mycotoxins were not associated with loss of kidney function in participants at-risk of MeN.
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