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Circulating non-coding RNAs in chronic kidney disease and its complications

Nature Reviews Nephrology volume 19, pages 573–586 (2023)Cite this article

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Abstract

Post-transcriptional regulation by non-coding RNAs (ncRNAs) can modulate the expression of genes involved in kidney physiology and disease. A large variety of ncRNA species exist, including microRNAs, long non-coding RNAs, piwi-interacting RNAs, small nucleolar RNAs, circular RNAs and yRNAs. Despite early assumptions that some of these species may exist as by-products of cell or tissue injury, a growing body of literature suggests that these ncRNAs are functional and participate in a variety of processes. Although they function intracellularly, ncRNAs are also present in the circulation, where they are carried by extracellular vesicles, ribonucleoprotein complexes or lipoprotein complexes such as HDL. These systemic, circulating ncRNAs are derived from specific cell types and can be directly transferred to a variety of cells, including endothelial cells of the vasculature and virtually any cell type in the kidney, thereby affecting the function of the host cell and/or its response to injury. Moreover, chronic kidney disease itself, as well as injury states associated with transplantation and allograft dysfunction, is associated with a shift in the distribution of circulating ncRNAs. These findings may provide opportunities for the identification of biomarkers with which to monitor disease progression and/or the development of therapeutic interventions.

Key points

  • Circulating non-coding RNAs (ncRNAs) are mediators of cell–cell communication; evidence suggests that they have important roles in kidney disease.

  • Circulating ncRNAs are selectively loaded into their carriers; selective uptake by recipient cells suggests that transported ncRNAs may have very specific functions in specific cell types.

  • ncRNAs in specific carriers may serve as better biomarkers than total levels of circulating ncRNAs.

  • A variety of circulating ncRNA species beyond microRNAs, including long non-coding RNAs, piwi-interacting RNAs, small nucleolar RNAs, circular RNAs and yRNAs, as well as tRNA fragments, may have important functions, but their role in kidney physiology and disease remains to be explored.

  • Selective modulation of carrier–ncRNA complexes may provide novel therapeutic targeting strategies for various kidney diseases.

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Fig. 1: Types of circulating non-coding RNAs and their carriers.
Fig. 2: Functional role of carrier-associated non-coding RNAs in kidney disease.
Fig. 3: Biomarker potential of carrier-associated non-coding RNAs in patients with kidney disease.

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Acknowledgements

The authors acknowledge funding from the Dutch Kidney Foundation (KOLLF grant 20OK015, to R.B.) and the European Foundation for the Study of Diabetes (to A.J.V.Z. and R.B.). The authors also thank Manon Zuurmond (LUMC, Leiden, the Netherlands) for generating the concept figures used in this Review.

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  1. Department of Internal Medicine (Nephrology), Leiden University Medical Center, Leiden, the Netherlands

    Anton Jan van Zonneveld, Qiao Zhao, Joris I. Rotmans & Roel Bijkerk

  2. Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands

    Anton Jan van Zonneveld, Qiao Zhao, Joris I. Rotmans & Roel Bijkerk

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Q.Z. and R.B researched data for the article. All authors contributed substantially to discussion of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Roel Bijkerk.

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Nature Reviews Nephrology thanks Benjamin Humphreys, Valérie Metzinger-Le Meuth and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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van Zonneveld, A.J., Zhao, Q., Rotmans, J.I. et al. Circulating non-coding RNAs in chronic kidney disease and its complications. Nat Rev Nephrol 19, 573–586 (2023). https://doi.org/10.1038/s41581-023-00725-w

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