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).

Relationship Between Angiographic Coronary Slow Flow Phenomenon and Subfoveal Choroidal Thickness: What is The Effect of Atorvastatin Therapy?

“…It has been shown in animal models that arteriosclerotic changes occur in retina and choroid [22]. Recent studies related with microcirculation abnormality showed the thinning of SCFT in patients with retinitis pigmentosa [11][12][13] and chronic kidney disease [10] by using SD-OCT measurements. The seemingly obvious connection between the vascular components of the choroid and other vascular beds of the body has produced a number of studies on the relationship between SFCT and various cardiovascular diseases.…”

“…It has been shown that many pathogenic stimuli such as diabetes and oxidative stress induce vascular dysfunction, leading to atherosclerosis, ischemia, inflammation and thrombosis may alter the regulation of retinal and choroidal blood flow [10]. According to recent studies, alteration in SFCT might be related with microvascular dysregulation entities [11][12][13][14]. OCT is a noninvasive and rapid method for multi-modal imaging the retina and choroid.…”

The eye, the kidney, and cardiovascular disease: old concepts, better tools, and new horizons

“…We have used OCT to prospectively examine chorioretinal thickness in patients with established hypertension and age-and sex-matched healthy subjects. 96 We excluded patients with a history of eye disease, diabetes, or overt CVD. We found no differences in OCT metrics between these carefully matched groups.…”

“…We have used OCT to explore the links between the eye and the kidney and shown that mice with hypertension alone had no choroidal thinning whereas mice with matched hypertension but with coexisting renal injury developed significant thinning. 96 This technology is being refined but has been used to perform detailed structural, functional, and biochemical assessments in various models of retinopathy. 150…”

Choroidal thickness is associated with renal hemodynamics in essential hypertension

“…Oxidative stress and endothelial dysfunction, both typical of the early stages of hypertension, have proven to play a key role in determining structural changes of choroidal layer, as previously demonstrated with regard to renal resistive index by Raff et al In a population of 150 patients (50 with hypertension, 50 with CKD and 50 healthy controls), Balmforth et al observed that a thinner choroid was associated with increased circulating C‐reactive protein, IL‐6, asymmetric dimethylarginine, and endothelin‐1: Due to endothelial dysfunction, powerful vasoconstrictors could easily pass from the fenestrated choriocapillaris to the interstitial area, trigger severe vasoconstriction, and produce tissue ischemia.…”