**6. Conclusions**

Persistent low-grade inflammation and premature ageing are hallmarks of the uremic phenotype and contribute to impaired health status, reduced quality of life, and premature mortality. Several potential treatment options targeting distinct features of the uremic phenotype may attenuate the risk of progression and poor outcome. Because the burden of disease due to CKD is huge, systemic treatment approaches targeting the underlying hallmarks of CKD, that is, inflammation and premature ageing, are currently being investigated. The NRF2–KEAP1 signaling pathway, the endocrine klotho axis, increased cellular senescence, and impaired mitochondrial biogenesis are currently the most promising candidates, and di fferent pharmaceutical compounds are already in evaluation. If randomized controlled trials show beneficial e ffects, patients with distinct CKD phenotypes can benefit from them. **Author Contributions:** T.E. and S.-C.P. wrote the manuscript and researched the literature. M.B., P.S., A.W., S.A., S.H., K.K., and P.G.S. contributed to the discussion and reviewed/edited the manuscript. All authors have read and agreed to the published version of the manuscript.

**Funding:** T.E. was supported by a Novo Nordisk postdoctoral fellowship run in partnership with Karolinska Institutet, Stockholm, Sweden. This work was further supported by the Swedish Heart and Lung Foundation (no. 20180571 and 20160384), King Gustaf V and Queen Victoria Freemason Foundation, Professor Nanna Svartz Foundation, the Stockholm County Council (20170365), Njurfonden (Swedish Kidney Foundation), as well as the Strategic Research Programme in Diabetes at Karolinska Institutet (Swedish Research Council gran<sup>t</sup> no. 2009-1068) and other grants from the Swedish Research Council (no. 2018–00932).

**Conflicts of Interest:** Peter Stenvinkel serves on scientific advisory boards of Baxter, Reata, and Astra Zeneca. The other authors of this manuscript have nothing to declare.
