Chorioretinal thinning in chronic kidney disease links to inflammation and endothelial dysfunction
Craig Balmforth, … , David J. Webb, Neeraj Dhaun
Craig Balmforth, … , David J. Webb, Neeraj Dhaun
Published December 8, 2016
Citation Information: JCI Insight. 2016;1(20):e89173. https://doi.org/10.1172/jci.insight.89173.
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Clinical Medicine Clinical trials Nephrology

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 volume P < 0.0001 for CKD vs. healthy and for CKD vs. hypertensive subjects; for choroidal thickness P < 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

Craig Balmforth, Job J.M.H. van Bragt, Titia Ruijs, James R. Cameron, Robert Kimmitt, Rebecca Moorhouse, Alicja Czopek, May Khei Hu, Peter J. Gallacher, James W. Dear, Shyamanga Borooah, Iain M. MacIntyre, Tom M.C. Pearson, Laura Willox, Dinesh Talwar, Muriel Tafflet, Christophe Roubeix, Florian Sennlaub, Siddharthan Chandran, Baljean Dhillon, David J. Webb, Neeraj Dhaun

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Figure 2

Retinal thickness as a function of macular location.

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Retinal thickness as a function of macular location. Box-and-whisker plo...
Box-and-whisker plots showing retinal thickness in subjects with hypertension (HT), chronic kidney disease (CKD), and healthy volunteers (HV) across different areas of the macula (see Figure 1A): ON, outer nasal; OS, outer superior; OT, outer temporal; OI, outer inferior; IN, inner nasal; IS, inner superior; IT, inner temporal; II, inner inferior; IC, inner circle. At each of the 4 locations ON, OS, OT, and OI, ****P < 0.0001 for CKD vs. healthy and for CKD vs. hypertensive subjects. At each of the 5 locations IN, IS, IT, II, IC, *P < 0.05 for CKD vs. healthy and for CKD vs. hypertensive subjects. The box-and-whisker plots display the first and third quartiles, with the line within the box representing the median value. The whiskers denote the minimum and maximum values. Thicknesses were examined by 2-way ANOVA, comparing thicknesses between all 3 patient groups at each macular location using Tukey correction for multiple comparisons. n = 50 subjects per group.