Basic discovery and clinical trials in diabetic kidney disease (DKD) have continued to be reported in 2023 despite the disruption of research activity by COVID-19 in recent years. Advances in clinical trials and emerging ways to diagnose, monitor and treat DKD dominate the current literature.
Key advances
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Preservation of the glomerular endothelial glycocalyx has been established as a key mechanism by which mineralocorticoid receptor antagonists confer renoprotection in diabetic kidney disease (DKD)3.
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Glucagon-like peptide-1 receptor agonists are likely to emerge as alternative or additional therapeutics for cardiorenal protection7.
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Leukocyte methylation correlates with baseline kidney function, and novel methylation sites predict patients with type 2 diabetes who are at risk of kidney failure; these findings may enable the identification of patients who could benefit from early intervention8.
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Mesenchymal stem cell therapy to treat DKD continues to show promise in pre-clinical models, although clinical trials are yet to be progressed9,10.
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References
The EMPA-KIDNEY Collaborative Group. Empagliflozin in patients with chronic kidney disease. N. Engl. J. Med. 388, 117–127 (2023).
Agarwal, R. et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur. Heart J. 43, 474–484 (2022).
Crompton, M. et al. Mineralocorticoid receptor antagonism in diabetes reduces albuminuria by preserving the glomerular endothelial glycocalyx. JCI Insight 8, e154164 (2023).
Bakris, G. L. et al. A prespecified exploratory analysis from FIDELITY examined finerenone use and kidney outcomes in patients with chronic kidney disease and type 2 diabetes. Kidney Int. 103, 196–206 (2023).
Chertow, G. M. et al. Quételet (body mass) index and effects of dapagliflozin in chronic kidney disease. Diabetes Obes. Metab. 24, 827–837 (2022).
Heerspink, H. J. et al. Effects of tirzepatide versus insulin glargine on cystatin C–based kidney function: a SURPASS-4 post hoc analysis. Diabetes Care 46, 1501–1506 (2023).
Zhang, Y. et al. Network meta-analysis on the effects of finerenone versus SGLT2 inhibitors and GLP-1 receptor agonists on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and chronic kidney disease. Cardiovasc. Diabetol. 21, 232 (2022).
Li, K. Y. et al. DNA methylation markers for kidney function and progression of diabetic kidney disease. Nat. Commun. 14, 2543 (2023).
Wang, J. et al. Human placenta-derived mesenchymal stem cells ameliorate diabetic kidney disease by modulating the T helper17 cell/regulatory T-cell balance through the programmed death 1/programmed death-ligand 1 pathway. Diabetes Obes. Metab. https://doi.org/10.1111/dom.15282 (2023).
Han, X. et al. Placental mesenchymal stem cells alleviate podocyte injury in diabetic kidney disease by modulating mitophagy via the SIRT1-PGC-1alpha-TFAM pathway. Int. J. Mol. Sci. 24, 4696 (2023).
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S.J.G. has received honoraria for presentations and advisory board roles from Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly and Novo Nordisk. C.A.P. has received honoraria for presentations and advisory board roles from Astra Zeneca, Bayer, Eli Lilly, Boehringer Ingelheim and Otsuka.
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Glastras, S.J., Pollock, C.A. Targeted identification of risk and treatment of diabetic kidney disease. Nat Rev Nephrol 20, 75–76 (2024). https://doi.org/10.1038/s41581-023-00796-9
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DOI: https://doi.org/10.1038/s41581-023-00796-9