Targeting the progression of chronic kidney disease
Abstract
Chronic kidney disease (CKD) is a devastating condition that is reaching epidemic levels owing to the increasing prevalence of diabetes mellitus, hypertension and obesity, as well as ageing of the population. Regardless of the underlying aetiology, CKD is slowly progressive and leads to irreversible nephron loss, end-stage renal disease and/or premature death. Factors that contribute to CKD progression include parenchymal cell loss, chronic inflammation, fibrosis and reduced regenerative capacity of the kidney. Current therapies have limited effectiveness and only delay disease progression, underscoring the need to develop novel therapeutic approaches to either stop or reverse progression. Preclinical studies have identified several approaches that reduce fibrosis in experimental models, including targeting cytokines, transcription factors, developmental and signalling pathways and epigenetic modulators, particularly microRNAs. Some of these nephroprotective strategies are now being tested in clinical trials. Lessons learned from the failure of clinical studies of transforming growth factor β1 (TGFβ1) blockade underscore the need for alternative approaches to CKD therapy, as strategies that target a single pathogenic process may result in unexpected negative effects on simultaneously occurring processes. Additional promising avenues include preventing tubular cell injury and anti-fibrotic therapies that target activated myofibroblasts, the main collagen-producing cells.
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Both kidney cells and recruited immune cells of the innate and adaptive immune systems produce proinflammatory factors that damage the kidney.
“Both kidney cells and recruited immune cells of the innate (M1 macrophages) and the adaptive (CD4+ and CD8+ T cells) immune systems produce proinflammatory factors that damage the kidney (42).”
From GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity (2025) · cites this paper as [42]
Cites
Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness
Nishita, M., Park, S.-Y., Nishio, T., Kamizaki, K., Wang, Z., Tamada, K., Takumi, T., Hashimoto, R., Otani, H., Pazour, G. J., et al. (2017) · Scientific Reports · doi:10.1038/s41598-016-0028-x · Cited by 15,947 · see citing works
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144 · see citing works
Brenner, B. M., Cooper, M. E., de Zeeuw, D., Keane, W. F., Mitch, W. E., Parving, H.-H., Remuzzi, G., Snapinn, S. M., Zhang, Z., & Shahinfar, S. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa011161 · Cited by 7,493 · see citing works
Interleukin-10 and the Interleukin-10 Receptor
Moore, K. W., de Waal Malefyt, R., Coffman, R. L., & O'Garra, A. (2001) · Annual Review of Immunology · doi:10.1146/annurev.immunol.19.1.683 · Cited by 6,737 · see citing works
Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy
Perkovic, V., Jardine, M. J., Neal, B., Bompoint, S., Heerspink, H. J. L., Charytan, D. M., Edwards, R., Agarwal, R., Bakris, G., Bull, S., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1811744 · Cited by 6,189 · see citing works
Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation
O'Brien, J., Hayder, H., Zayed, Y., & Peng, C. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00402 · Cited by 5,287 · see citing works
The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes
Parving, H.-H., Lehnert, H., Bröchner-Mortensen, J., Gomis, R., Andersen, S., & Arner, P. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa011489 · Cited by 2,873 · see citing works
Transcriptional regulation of macrophage polarization: enabling diversity with identity
Lawrence, T., & Natoli, G. (2011) · Nature Reviews Immunology · doi:10.1038/nri3088 · Cited by 2,284 · see citing works
Baar, M. P., Brandt, R. M. C., Putavet, D. A., Klein, J. D. D., Derks, K. W. J., Bourgeois, B. R. M., Stryeck, S., Rijksen, Y., van Willigenburg, H., Feijtel, D. A., et al. (2017) · Cell · doi:10.1016/j.cell.2017.02.031 · Cited by 1,454 · see citing works
Emerging regulation and functions of autophagy
Boya, P., Reggiori, F., & Codogno, P. (2013) · Nature Cell Biology · doi:10.1038/ncb2788 · Cited by 1,216 · see citing works
Perivascular Gli1+ Progenitors Are Key Contributors to Injury-Induced Organ Fibrosis
Kramann, R., Schneider, R. K., DiRocco, D. P., Machado, F., Fleig, S., Bondzie, P. A., Henderson, J. M., Ebert, B. L., & Humphreys, B. D. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2014.11.004 · Cited by 922 · see citing works
Ferroptosis, but Not Necroptosis, Is Important in Nephrotoxic Folic Acid–Induced AKI
Martin-Sanchez, D., Ruiz-Andres, O., Poveda, J., Carrasco, S., Cannata-Ortiz, P., Sanchez-Niño, M. D., Ruiz Ortega, M., Egido, J., Linkermann, A., Ortiz, A., et al. (2017) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015121376 · Cited by 564 · see citing works
Self-citationHerrington, W. G., Preiss, D., Haynes, R., von Eynatten, M., Staplin, N., Hauske, S. J., George, J. T., Green, J. B., Landray, M. J., Baigent, C., et al. (2018) · Clinical Kidney Journal · doi:10.1093/ckj/sfy090 · Cited by 237 · see citing works
Cellular senescence in the aging and diseased kidney
Valentijn, F. A., Falke, L. L., Nguyen, T. Q., & Goldschmeding, R. (2018) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-017-0434-2 · Cited by 173 · see citing works
Canaud, G., Brooks, C. R., Kishi, S., Taguchi, K., Nishimura, K., Magassa, S., Scott, A., Hsiao, L.-L., Ichimura, T., Terzi, F., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aav4754 · Cited by 139 · see citing works
Herzog, C., Yang, C., Holmes, A., & Kaushal, G. P. (2012) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00659.2011 · Cited by 82 · see citing works
Role of interleukin 17 in TGF-β signaling-mediated renal interstitial fibrosis
Sun, B., Wang, H., Zhang, L., Yang, X., Zhang, M., Zhu, X., Ji, X., & Wang, H. (2018) · Cytokine · doi:10.1016/j.cyto.2017.10.015 · Cited by 47 · see citing works
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Obesity and chronic kidney disease
Jiang, Z., Wang, Y., Zhao, X., Cui, H., Han, M., Ren, X., Gang, X., & Wang, G. (2023) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00179.2022 · Cited by 267 · see citing works
The Role of Myofibroblasts in Physiological and Pathological Tissue Repair
Schuster, R., Younesi, F., Ezzo, M., & Hinz, B. (2023) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a041231 · Cited by 232 · see citing works
He, Y., Deng, B., Liu, S., Luo, S., Ning, Y., Pan, X., Wan, R., Chen, Y., Zhang, Z., Jiang, J., et al. (2022) · Hypertension · doi:10.1161/hypertensionaha.121.18750 · Cited by 114 · see citing works
Roehlen, N., Saviano, A., El Saghire, H., Crouchet, E., Nehme, Z., Del Zompo, F., Jühling, F., Oudot, M. A., Durand, S. C., Duong, F. H. T., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abj4221 · Cited by 54 · see citing works
GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity
Cooper, M. E., & van Raalte, D. H. (2025) · Journal of Clinical Investigation · doi:10.1172/jci194749 · Cited by 24 · see citing works
“Both kidney cells and recruited immune cells of the innate (M1 macrophages) and the adaptive (CD4 + and CD8 + T cells) immune systems produce proinflammatory factors that damage the kidney (42).”
Emerging epigenetic modifications in renal fibrosis: From mechanisms to treatments
Suo, X., Ge, Q., Peng, L., Zhu, Q., Zhang, M., Cheng, X., Wang, F., Jin, J., Wang, J., & Meng, X. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.09.012 · Cited by 8 · see citing works
- Authors
- Ruiz-Ortega, M., Rayego-Mateos, S., Lamas, S., Ortiz, A., & Rodrigues-Diez, R. R.
- Affiliations
- Centro de Biología Molecular Severo Ochoa (ES)
- Venue
- Nature Reviews Nephrology
- Published
- 2020-02-14
- Volume
- 16
- Issue
- 5
- Pages
- 269-288
- ISSN
- 1745-8323 (ISSN-L)
- 1759-5061
- 1759-507X
- OpenAlex
- W3006609143
- Cited by
- 979
- References
- 17
- Citations by year
- 2026: 135 · 2025: 192 · 2024: 222 · 2023: 173 · 2022: 129 · 2021: 101 · 2020: 27
- FWCI
- 17.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Reviews Nephrology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Keywords
- chronic kidney disease progression, renal fibrosis, antifibrotic therapy, tubular cell injury, myofibroblasts, chronic inflammation, renal protection, microRNA, epigenetic regulators, kidney regeneration, epithelial-mesenchymal transition, nephron loss
- MeSH terms
- Humans, Disease Progression, Renal Insufficiency, Chronic
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