Inflammation and premature aging in advanced chronic kidney disease

Kooman, J. P., Dekker, M. J., Usvyat, L. A., Kotanko, P., van der Sande, F. M., Schalkwijk, C. G., Shiels, P. G. and Stenvinkel, P. (2017) Inflammation and premature aging in advanced chronic kidney disease. American Journal of Physiology: Renal Physiology, 313(4), F938-F950. (doi: 10.1152/ajprenal.00256.2017) (PMID:28701312)

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Abstract

Systemic inflammation in end-stage renal disease (ESRD) is an established risk factor for mortality and a catalyst for other complications which are related to a premature aging phenotype, including muscle wasting, vascular calcification and other forms of premature vascular disease, depression, osteoporosis and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have direct effect on cellular and tissue function. In addition to uremia-specific causes such as abnormalities in the phosphate- Klotho axis, there are remarkable similarities between the pathophysiology of uremic inflammation and so-called "inflammaging" in the general population. Potentially relevant, but still somewhat unexplored in this respect are abnormal or misplaced protein structures as well as abnormalities in tissue homeostasis, which evoke danger signals through damage associated molecular patters (DAMPS) as well as the senescence associated secretory phenotype (SASP). Systemic inflammation, in combination with the loss of kidney function, can impair the resilience of the body to external and internal stressors by reduced functional and structural tissue reserve, and by impairing normal organ crosstalk, thus providing an explanation for the greatly increased risk of homeostatic breakdown in this population. In this review, the relation between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences are discussed.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Shiels, Professor Paul
Authors: Kooman, J. P., Dekker, M. J., Usvyat, L. A., Kotanko, P., van der Sande, F. M., Schalkwijk, C. G., Shiels, P. G., and Stenvinkel, P.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
Journal Name:American Journal of Physiology: Renal Physiology
Publisher:American Physiological Society
ISSN:1931-857X
ISSN (Online):1522-1466
Published Online:12 July 2017
Copyright Holders:Copyright © 2017 The American Physiological Society
First Published:First published in American Journal of Physiology: Renal Physiology 313(4):F938-F950
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

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