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Review

Uremic Toxins Affecting Cardiovascular Calcification: A Systematic Review

1
Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, University Hospital Aachen, 52074 Aachen, Germany
2
Division of Nephrology, RWTH Aachen University, University Hospital Aachen, 52074 Aachen, Germany
3
Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6229 ER Maastricht, The Netherlands
4
Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Centre, Maastricht University, 6229 ER Maastricht, The Netherlands
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(11), 2428; https://doi.org/10.3390/cells9112428
Received: 27 September 2020 / Revised: 29 October 2020 / Accepted: 4 November 2020 / Published: 6 November 2020
(This article belongs to the Special Issue Research on Vascular Calcification in Cardiovascular Disease)
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. View Full-Text
Keywords: cardiovascular calcification; uremic toxins; chronic kidney disease; cardiovascular disease cardiovascular calcification; uremic toxins; chronic kidney disease; cardiovascular disease
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MDPI and ACS Style

Holmar, J.; de la Puente-Secades, S.; Floege, J.; Noels, H.; Jankowski, J.; Orth-Alampour, S. Uremic Toxins Affecting Cardiovascular Calcification: A Systematic Review. Cells 2020, 9, 2428. https://doi.org/10.3390/cells9112428

AMA Style

Holmar J, de la Puente-Secades S, Floege J, Noels H, Jankowski J, Orth-Alampour S. Uremic Toxins Affecting Cardiovascular Calcification: A Systematic Review. Cells. 2020; 9(11):2428. https://doi.org/10.3390/cells9112428

Chicago/Turabian Style

Holmar, Jana, Sofia de la Puente-Secades, Jürgen Floege, Heidi Noels, Joachim Jankowski, and Setareh Orth-Alampour. 2020. "Uremic Toxins Affecting Cardiovascular Calcification: A Systematic Review" Cells 9, no. 11: 2428. https://doi.org/10.3390/cells9112428

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