A systematic review and participant-level meta-analysis found little association of retinal microvascular caliber with reduced kidney function

Lye, Weng Kit; Paterson, Euan; Patterson, Christopher; Maxwell, Alexander P.; Abdul, Riswana Banu Binte Mohammed; Tai, E Shyong; Cheng, Ching Yu; Kayama, Takamasa; Yamashita, Hidetoshi; Sarnak, Mark J.; Shlipak, Michael G.; Matsushita, Kunihiro; Mutlu, Ünal; Ikram, M. Arfan; Klaver, Caroline C W; Kifley, Annette; Mitchell, Paul; Myers, Chelsea E.; Klein, Barbara E.K.; Klein, Ronald; Wong, Tien Yin; Sabanayagam, Charumathi; McKay, Gareth J.

doi:10.1016/j.kint.2020.06.033

Cited by 10 publications

(7 citation statements)

References 64 publications

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“…Remarkably, the findings are to some extent surprising, as DR and DKD are considered to be highly correlated and, in the case of DKD, can be very efficiently assessed via the urinary proteome 4 . As such, our data suggest that, on a molecular level, DR and DKD might not be interconnected, which is supported by recent findings 32 . However, this assumption requires more detailed investigation across different biological samples and patient cohorts.…”

Section: Discussionsupporting

confidence: 77%

Urinary peptidome and diabetic retinopathy in the DIRECT‐Protect 1 and 2 trials

Curovic

Magalhães

et al. 2021

Diabet Med

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Background Given the association of diabetic retinopathy (DR) and kidney disease, we investigated the urinary peptidome to presence and deterioration of DR in a post hoc analysis of trials investigating the effect of candesartan on progression of DR in type 1 and type 2 diabetes, respectively. Methods Baseline urinary peptidomic analysis was performed on a random selection of 783 and 792 subjects in two randomized controlled trials, DIRECT‐Protect 1 and 2, respectively. End points were two‐step (RET2) and three‐step (RET3) change in Early Treatment of Diabetic Retinopathy Study protocol (ETDRS) defined level. Peptide levels were correlated to baseline EDTRS level in a discovery set of 2/3 of the participants from DIRECT‐Protect 1. The identified peptides were then validated cross‐sectionally in the remaining 1/3 from DIRECT‐Protect 1. Thereafter, peptides identified in the discovery set were assessed in the entire DIRECT‐Protect 1 and 2 cohorts and significant peptides were tested longitudinally. Results Follow‐up ranged 4.0–4.7 years. 24 peptides were associated with baseline DR in the discovery set. COL3A1 (seq: NTG~) and COL4A1 (seq: DGA~) were associated with baseline DR in the validation set (Rho: −.223, p < 0.001 and Rho: −.141, p = 0.024). Neither was significantly associated with end points. Assessing the 24 identified peptides in the entire cohorts, several collagen peptides were associated with baseline DR and end points; however, there was no overlap across diabetes types. Conclusions We identified several urinary peptides (mainly collagen) associated with the presence of DR, however they could not be conclusively associated with worsening of DR.

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Section: Discussionsupporting

confidence: 77%

Urinary peptidome and diabetic retinopathy in the DIRECT‐Protect 1 and 2 trials

Curovic

Magalhães

et al. 2021

Diabet Med

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“…This has been suggested before, as it has been shown that more than 30% of people with type 2 diabetes and eGFR < 60 mL/min/1.73m 2 had non-albuminuric CKD (16,17). On a molecular level, recent studies have supported the distinction between DR and CKD (10,11). A study by Hong et al, which investigated the relationship between baseline DR and development of kidney impairment or cardiovascular disease over 14 years, found a signi cantly higher risk of cardiovascular disease compared to CKD (18), suggesting that DR may be primarly associated with cardiovascular disease, rather than kidney disease.…”

Section: Discussionmentioning

confidence: 68%

“…Recent studies have suggested that DR and CKD in diabetes might lack a common molecular interplay and physiology (10,11). Therefore, we have investigated their relationship, utilizing data from the PRIORITY study; a prospective multi-center observational study with an embedded randomized clinical trial, including 1775 individuals with type 2 diabetes and normoalbuminuria.…”

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confidence: 99%

Presence of retinopathy and incident kidney and cardiovascular events in type 2 diabetes with normoalbuminuria – A post-hoc analysis of the PRIORITY randomized clinical trial

Curovic

Tofte

Lindhardt

et al. 2023

Journal of Diabetes and its Complications

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“…Cross-sectional regression studies have evaluated retinal vascular findings with respect to kidney disease specifically in diabetic patients as well as more generally. O'Neill et al [20] found an association between retinal vascular tortuosity and chronic kidney disease (CKD) stages 3-5, while the metaanalysis by Lye et al [21] found no significant association between retinal vascular calibre and CKD, all in fundus photographs. Paterson et al [22] found an independent association between albuminuria and retinal microvascular fractal dimension in fundus photographs.…”

Section: Kidney Disease Biomarkers Identified Without Deep Learningmentioning

confidence: 99%

Systemic retinal biomarkers

Ranchod¹

2021

Current Opinion in Ophthalmology

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Purpose of review Systemic retinal biomarkers are biomarkers identified in the retina and related to evaluation and management of systemic disease. This review summarizes the background, categories and key findings from this body of research as well as potential applications to clinical care. Recent findingsPotential systemic retinal biomarkers for cardiovascular disease, kidney disease and neurodegenerative disease were identified using regression analysis as well as more sophisticated image processing techniques. Deep learning techniques were used in a number of studies predicting diseases including anaemia and chronic kidney disease. A virtual coronary artery calcium score performed well against other competing traditional models of event prediction. SummarySystemic retinal biomarker research has progressed rapidly using regression studies with clearly identified biomarkers such as retinal microvascular patterns, as well as using deep learning models. Future systemic retinal biomarker research may be able to boost performance using larger data sets, the addition of metadata and higher resolution image inputs.

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A systematic review and participant-level meta-analysis found little association of retinal microvascular caliber with reduced kidney function

Abstract: A systematic review and participant-level meta-analysis found little association of retinal microvascular caliber and reduced kidney function.

Cited by 10 publications

References 64 publications

Urinary peptidome and diabetic retinopathy in the DIRECT‐Protect 1 and 2 trials

Urinary peptidome and diabetic retinopathy in the DIRECT‐Protect 1 and 2 trials

Presence of retinopathy and incident kidney and cardiovascular events in type 2 diabetes with normoalbuminuria – A post-hoc analysis of the PRIORITY randomized clinical trial

Systemic retinal biomarkers

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