Inflammation and premature aging in advanced chronic kidney disease

Jeroen P. Kooman*, Marijke J. Dekker, Len A. Usvyat, Peter Kotanko, Frank M. van der Sande, Casper G. Schalkwijk, Paul G. Shiels, Peter Stenvinkel

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

121 Citations (Web of Science)

Abstract

Systemic inflammation in end-stage renal disease 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 a 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 patterns, as well as the senescence-associated secretory phenotype. 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 reserves, 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 relationship between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences, are discussed.

Original languageEnglish
Pages (from-to)F938-F950
Number of pages13
JournalAmerican Journal of Physiology-Renal Physiology
Volume313
Issue number4
DOIs
Publication statusPublished - Oct 2017

Keywords

  • aging
  • end stage renal disease
  • inflammation
  • STAGE RENAL-DISEASE
  • PERITONEAL-DIALYSIS PATIENTS
  • NF-KAPPA-B
  • ENDOPLASMIC-RETICULUM STRESS
  • GLYCATION END-PRODUCTS
  • SMOOTH-MUSCLE-CELLS
  • FETUIN-A LEVELS
  • AGE-RELATED DISEASES
  • BLOOD-BRAIN-BARRIER
  • HEMODIALYSIS-PATIENTS

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