Uremic Toxins Affecting Cardiovascular Calcification: A Systematic Review

Jana Holmar, Sofia de la Puente-secades, Jurgen Floege, Heidi Noels, Joachim Jankowski*, Setareh Orth-Alampour

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

5 Citations (Web of Science)

Abstract

Cardiovascular calcification is highly prevalent and associated with increased morbidity in chronic kidney disease (CKD). This review examines the impact of uremic toxins, which accumulate in CKD due to a failing kidney function, on cardiovascular calcification. A systematic literature search identified 41 uremic toxins that have been studied in relation to cardiovascular calcification. For 29 substances, a potentially causal role in cardiovascular calcification was addressed in in vitro or animal studies. A calcification-inducing effect was revealed for 16 substances, whereas for three uremic toxins, namely the guanidino compounds asymmetric and symmetric dimethylarginine, as well as guanidinosuccinic acid, a calcification inhibitory effect was identified in vitro. At a mechanistic level, effects of uremic toxins on calcification could be linked to the induction of inflammation or oxidative stress, smooth muscle cell osteogenic transdifferentiation and/or apoptosis, or alkaline phosphatase activity. For all middle molecular weight and protein-bound uremic toxins that were found to affect cardiovascular calcification, an increasing effect on calcification was revealed, supporting the need to focus on an increased removal efficiency of these uremic toxin classes in dialysis. In conclusion, of all uremic toxins studied with respect to calcification regulatory effects to date, more uremic toxins promote rather than reduce cardiovascular calcification processes. Additionally, it highlights that only a relatively small part of uremic toxins has been screened for effects on calcification, supporting further investigation of uremic toxins, as well as of associated post-translational modifications, on cardiovascular calcification processes.

Original languageEnglish
Article number2428
Number of pages22
JournalCells
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 2020

Keywords

  • cardiovascular calcification
  • uremic toxins
  • chronic kidney disease
  • cardiovascular disease
  • CHRONIC KIDNEY-DISEASE
  • STAGE RENAL-DISEASE
  • CHRONIC-HEMODIALYSIS PATIENTS
  • BONE MORPHOGENETIC PROTEIN-2
  • VASCULAR CALCIFICATION
  • IN-VITRO
  • AORTIC CALCIFICATION
  • DIALYSIS PATIENTS
  • MORTALITY RISK
  • SERUM-CALCIUM

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