title: Chorioretinal thinning in chronic kidney disease links to inflammation and endothelial dysfunction.
abstract: BACKGROUND.Chronic kidney disease (CKD) is strongly associated with cardiovascular disease and there is an established association between vasculopathy affecting the kidney and eye. Optical coherence tomography (OCT) is a novel, rapid method for high-definition imaging of the retina and choroid. Its use in patients at high cardiovascular disease risk remains unexplored.METHODS.We used the new SPECTRALIS OCT machine to examine retinal and retinal nerve fiber layer (RNFL) thickness, macular volume, and choroidal thickness in a prospective cross-sectional study in 150 subjects: 50 patients with hypertension (defined as a documented clinic BP greater than or equal to 140/90 mmHg (prior to starting any treatment) with no underlying cause identified); 50 with CKD (estimated glomerular filtration rate (eGFR) 8-125 ml/min/1.73 m2); and 50 matched healthy controls. We excluded those with diabetes. The same, masked ophthalmologist carried out each study. Plasma IL-6, TNF-α , asymmetric dimethylarginine (ADMA), and endothelin-1 (ET-1), as measures of inflammation and endothelial function, were also assessed.RESULTS.Retinal thickness, macular volume, and choroidal thickness were all reduced in CKD compared with hypertensive and healthy subjects (for retinal thickness and macular volumeP< 0.0001 for CKD vs. healthy and for CKD vs. hypertensive subjects; for choroidal thicknessP< 0.001 for CKD vs. healthy and for CKD vs. hypertensive subjects). RNFL thickness did not differ between groups. Interestingly, a thinner choroid was associated with a lower eGFR (r= 0.35,P<0.0001) and, in CKD, with proteinuria (r= -0.58,P< 0.001) as well as increased circulating C-reactive protein (r= -0.57,P= 0.0002), IL-6 (r= -0.40,P< 0.01), ADMA (r= -0.37,P= 0.02), and ET-1 (r= -0.44,P< 0.01). Finally, choroidal thinning was associated with renal histological inflammation and arterial stiffness. In a model of hypertension, choroidal thinning was seen only in the presence of renal injury.CONCLUSIONS.Chorioretinal thinning in CKD is associated with lower eGFR and greater proteinuria, but not BP. Larger studies, in more targeted groups of patients, are now needed to clarify whether these eye changes reflect the natural history of CKD. Similarly, the associations with arterial stiffness, inflammation, and endothelial dysfunction warrant further examination.TRIAL REGISTRATION.Registration number at www.clinicalTrials.gov: NCT02132741.SOURCE OF FUNDING.TR was supported by a bursary from the Erasmus Medical Centre, Rotterdam. JJMHvB was supported by a bursary from the Utrecht University. JRC is supported by a Rowling Scholarship. SB was supported by a Wellcome Trust funded clinical research fellowship from the Scottish Translational Medicine and Therapeutics Initiative, and by a Rowling Scholarship, at the time of this work. ND is supported by a British Heart Foundation Intermediate Clinical Research Fellowship (FS/13/30/29994).
authors.affiliation: BHF Centre of Research Excellence, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh.
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authors.lastname: Balmforth
authors.affiliation: BHF Centre of Research Excellence, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh.
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authors.affiliation: BHF Centre of Research Excellence, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh.
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authors.affiliation: Anne Rowling Regenerative Neurology Clinic, Centre for Clinical Brain Sciences, University of Edinburgh.
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authors.affiliation: BHF Centre of Research Excellence, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh.
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authors.affiliation: BHF Centre of Research Excellence, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh.
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authors.affiliation: BHF Centre of Research Excellence, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh.
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authors.affiliation: BHF Centre of Research Excellence, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh.
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authors.affiliation: BHF Centre of Research Excellence, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh.
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authors.affiliation: BHF Centre of Research Excellence, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh.
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authors.affiliation: Anne Rowling Regenerative Neurology Clinic, Centre for Clinical Brain Sciences, University of Edinburgh.|Princess Alexandra Eye Pavilion, Edinburgh, United Kingdom.
authors.forename: Shyamanga
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authors.lastname: Borooah
authors.affiliation: BHF Centre of Research Excellence, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh.
authors.forename: Iain M
authors.initials: IM
authors.lastname: MacIntyre
authors.affiliation: Anne Rowling Regenerative Neurology Clinic, Centre for Clinical Brain Sciences, University of Edinburgh.
authors.forename: Tom Mc
authors.initials: TM
authors.lastname: Pearson
authors.affiliation: Department of Clinical Biochemistry and Metabolic Medicine, Royal Infirmary of Glasgow, United Kingdom.
authors.forename: Laura
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authors.lastname: Willox
authors.affiliation: Department of Clinical Biochemistry and Metabolic Medicine, Royal Infirmary of Glasgow, United Kingdom.
authors.forename: Dinesh
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authors.affiliation: INSERM Unit 970, Paris Cardiovascular Research Center - PARCC and Descartes University, Paris, France.
authors.forename: Muriel
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authors.lastname: Tafflet
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Institut de la Vision, Paris, France.
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authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Institut de la Vision, Paris, France.
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authors.lastname: Sennlaub
authors.affiliation: Anne Rowling Regenerative Neurology Clinic, Centre for Clinical Brain Sciences, University of Edinburgh.
authors.forename: Siddharthan
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authors.lastname: Chandran
authors.affiliation: Anne Rowling Regenerative Neurology Clinic, Centre for Clinical Brain Sciences, University of Edinburgh.|Princess Alexandra Eye Pavilion, Edinburgh, United Kingdom.
authors.forename: Baljean
authors.initials: B
authors.lastname: Dhillon
authors.affiliation: BHF Centre of Research Excellence, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh.
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authors.affiliation: BHF Centre of Research Excellence, University of Edinburgh, The Queen's Medical Research Institute, Edinburgh.
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mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D002829:Choroid / Q000473:pathology*; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000473:pathology; D007249:Inflammation / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000150:complications*