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      Association of retinal venular tortuosity with impaired renal function in the Northern Ireland Cohort for the Longitudinal Study of Ageing

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          Abstract

          Background

          Previous studies have identified retinal microvascular features associated with renal dysfunction. Biopsies are necessary to confirm kidney microvascular damage and retinal imaging may enable evaluation of microangiopathic characteristics reflecting renal changes associated with chronic kidney disease (CKD). We evaluated retinal microvascular parameters (RMPs) for associations with renal function in a cross-sectional analysis of the Northern Ireland Cohort for the Longitudinal Study of Ageing.

          Methods

          RMPs (central retinal arteriolar/ venular equivalents [CRAE/CRVE], arteriolar to venular ratio [AVR], fractal dimension and tortuosity) were measured from optic disc centred fundus images using semi-automated software. Associations were assessed with multivariable regression analyses between RMPs and estimated glomerular filtration rate (eGFR) defined by serum creatinine (eGFRscr) and cystatin C (eGFRcys) and also CKD status characterised by eGFR < 60 mL/min/1.73m 2. Regression models were adjusted for potential confounders including age, sex, diabetes, smoking status, educational attainment, cardiovascular disease, body mass index, antihypertensive medication, systolic blood pressure, triglycerides, high- and low-density lipoprotein levels.

          Results

          Data were included for 1860 participants that had measures of renal function and retinal fundus images of sufficient quality for analysis. Participants had a mean age of 62.0 ± 8.5 yrs. and 53% were female. The mean eGFR for scr and cys were 82.2 ± 14.9 mL/min/1.73m 2 and 70.7 ± 18.6 mL/min/1.73m 2 respectively. eGFRcys provided lower estimates than eGFRscr resulting in a greater proportion of participants categorised as having CKD stages 3–5 (eGFRcys 26.8%; eGFRscr 7.9%). Multivariable regression analyses showed that increased venular tortuosity (OR = 1.30; 95%CI: 1.10, 1.54; P < 0.01) was associated with CKD stages 3–5 characterised by eGFRscr < 60 mL/min/1.73 m 2. No additional associations between CKD status characterised by eGFRscr or with eGFRcys, were detected ( P > 0.05). Multivariable regression failed to detect associations between CRAE, CRVE, AVR, fractal dimension or tortuosity and eGFRscr or eGFRcys ( P > 0.05).

          Conclusion

          Increased retinal venular tortuosity was associated with CKD stages 3–5 defined by eGFRscr < 60 mL/min/1.73 m 2, in an older population independent of potential confounding factors. These retinal measures may provide non-invasive microvascular assessment of associations with CKD.

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          Most cited references42

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          Leptin and renal disease.

          Leptin is a small peptide hormone that is mainly, but not exclusively, produced in adipose tissue. The circulating leptin concentration therefore directly reflects the amount of body fat. Leptin was identified through positional cloning of the obese (ob) gene, which is mutated in the massively obese ob/ob mouse, and it has a pivotal role in regulating food intake and energy expenditure. It binds to the so-called long receptor (Ob-Rb) in the hypothalamus and regulates food intake through the release of other neurotransmitters. Moreover, leptin exerts several other important metabolic effects on peripheral tissue, including modification of insulin action, induction of angiogenesis, and modulation of the immune system. As a small peptide, leptin is cleared principally by the kidney. Not surprisingly, serum leptin concentrations are increased in patients with chronic renal failure and those undergoing maintenance dialysis. Whether the hyperleptinemia of chronic renal failure contributes to some uremic manifestations, such as anorexia and weight loss, requires additional investigation. The kidney expresses abundant concentrations of the truncated isoform of the leptin receptor Ob-Ra, but only a small amount of the full-length receptor Ob-Rb. We recently discovered that leptin has direct effects on renal pathophysiological characteristics. Both cultured glomerular endothelial cells and mesangial cells obtained from the diabetic db/db mouse possess the Ob-Ra receptor, but whether biological effects of leptin are transduced through this receptor remains unknown. In glomerular endothelial cells, leptin stimulates cellular proliferation, transforming growth factor-beta1 (TGF-beta1) synthesis, and type IV collagen production. Conversely, in mesangial cells, leptin upregulates synthesis of the TGF-beta type II receptor, but not TGF-beta1, and stimulates glucose transport and type I collagen production through signal transduction pathways involving phosphatidylinositol-3-kinase. These data suggest that leptin triggers a paracrine interaction in which glomerular endothelial cells secrete TGF-beta, to which sensitized mesangial cells may respond. Both cell types increase their expression of extracellular matrix in response to leptin. Infusion of leptin into normal rats for 3 weeks fosters the development of focal glomerulosclerosis and proteinuria. Additional previously described direct and indirect effects of leptin on the kidney include natriuresis, increased sympathetic nervous activity, and stimulation of reactive oxygen species. These findings collectively suggest that the kidney is not only a site of leptin metabolism, but also a target organ for leptin action in pathophysiological states. Copyright 2002 by the National Kidney Foundation, Inc.
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            Twisted Blood Vessels: Symptoms, Etiology and Biomechanical Mechanisms

            Tortuous arteries and veins are commonly observed in humans and animals. While mild tortuosity is asymptomatic, severe tortuosity can lead to ischemic attack in distal organs. Clinical observations have linked tortuous arteries and veins with aging, atherosclerosis, hypertension, genetic defects and diabetes mellitus. However, the mechanisms of their formation and development are poorly understood. This review summarizes the current clinical and biomechanical studies on the initiation, development and treatment of tortuous blood vessels. We submit a new hypothesis that mechanical instability and remodeling could be mechanisms for the initiation and development of these tortuous vessels.
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              The aging kidney.

              Renal aging, by itself, is associated with alterations in renal morphology and a decline in renal function, which is accelerated and/or accentuated by diseases such as diabetes mellitus and hypertension. The aging-related renal insufficiency has important implications with regards to body homeostasis, drug toxicity, and renal transplantation. An understanding of renal aging and its distinction from renal insufficiency secondary to diseases is essential for individualized care of the elderly. Toward this end, investigations are underway to elucidate the molecular mechanisms of renal aging. This review summarizes the structural and functional changes of the aging kidney and highlights the advances made in our understanding of the renal aging process.
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                Author and article information

                Contributors
                g.j.mckay@qub.ac.uk
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                3 September 2020
                3 September 2020
                2020
                : 21
                : 382
                Affiliations
                GRID grid.4777.3, ISNI 0000 0004 0374 7521, Centre for Public Health, , Queens University Belfast, ; Belfast, UK
                Article
                2031
                10.1186/s12882-020-02031-0
                7469276
                32883218
                0199c843-26b6-4e1d-b695-73ff6b9cdd9b
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 19 December 2019
                : 20 August 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100008304, Department of Education, Northern Ireland;
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Nephrology
                retinal microvascular parameters,renal function,chronic kidney disease,estimated glomerular filtration rate

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