The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Klotho deficiency is an early biomarker of renal ischemia–reperfusion injury and its replacement is protective
Open accessAbstract
Klotho is an antiaging substance with pleiotropic actions including regulation of mineral metabolism. It is highly expressed in the kidney and is present in the circulation and urine but its role in acute kidney injury (AKI) is unknown. We found that ischemia–reperfusion injury (IRI) in rodents reduced Klotho in the kidneys, urine, and blood, all of which were restored upon recovery. Reduction in kidney and plasma Klotho levels were earlier than that of neutrophil gelatinase-associated lipocalin (NGAL), a known biomarker of kidney injury. Patients with AKI were found to have drastic reductions in urinary Klotho. To examine whether Klotho has a pathogenic role, we induced IRI in mice with different endogenous Klotho levels ranging from heterozygous Klotho haploinsufficient, to wild-type (WT), to transgenic mice overexpressing Klotho. Klotho levels in AKI were lower in haploinsufficient and higher in transgenic compared with WT mice. The haploinsufficient mice had more extensive functional and histological alterations compared with WT mice, whereas these changes were milder in overexpressing transgenic mice, implying that Klotho is renoprotective. Rats with AKI given recombinant Klotho had higher Klotho protein, less kidney damage, and lower NGAL than rats with AKI given vehicle. Hence, AKI is a state of acute reversible Klotho deficiency, low Klotho exacerbates kidney injury and its restoration attenuates renal damage and promotes recovery from AKI. Thus, endogenous Klotho not only serves as an early biomarker for AKI but also functions as a renoprotective factor with therapeutic potential.
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Cites
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
Self-citationMishra, J., Dent, C., Tarabishi, R., Mitsnefes, M. M., Ma, Q., Kelly, C., Ruff, S. M., Zahedi, K., Shao, M., Bean, J., et al. (2005) · The Lancet · doi:10.1016/s0140-6736(05)74811-x · Cited by 2,394
Suppression of Aging in Mice by the Hormone Klotho
Kurosu, H., Yamamoto, M., Clark, J. D., Pastor, J. V., Nandi, A., Gurnani, P., McGuinness, O. P., Chikuda, H., Yamaguchi, M., Kawaguchi, H., et al. (2005) · Science · doi:10.1126/science.1112766 · Cited by 1,935
Self-citationKlotho converts canonical FGF receptor into a specific receptor for FGF23
Urakawa, I., Yamazaki, Y., Shimada, T., Iijima, K., Hasegawa, H., Okawa, K., Fujita, T., Fukumoto, S., & Yamashita, T. (2006) · Nature · doi:10.1038/nature05315 · Cited by 1,850
Mishra, J., Ma, Q., Prada, A., Mitsnefes, M., Zahedi, K., Yang, J., Barasch, J., & Devarajan, P. (2003) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000088027.54400.c6 · Cited by 1,749
Regulation of Fibroblast Growth Factor-23 Signaling by Klotho
Kurosu, H., Ogawa, Y., Miyoshi, M., Yamamoto, M., Nandi, A., Rosenblatt, K. P., Baum, M. G., Schiavi, S., Hu, M.-C., Moe, O. W., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.c500457200 · Cited by 1,366
Self-citationMori, K., Lee, H. T., Rapoport, D., Drexler, I. R., Foster, K., Yang, J., Schmidt-Ott, K. M., Chen, X., Li, J. Y., Weiss, S., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23056 · Cited by 954
Dual Action of Neutrophil Gelatinase–Associated Lipocalin
Schmidt-Ott, K. M., Mori, K., Li, J. Y., Kalandadze, A., Cohen, D. J., Devarajan, P., & Barasch, J. (2007) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006080882 · Cited by 772
Acute renal failure: definitions, diagnosis, pathogenesis, and therapy
Schrier, R. W., Wang, W., Poole, B., & Mitra, A. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22353 · Cited by 683
Acute renal failure: definitions, diagnosis, pathogenesis, and therapy
Schrier, R. W., Wang, W., Poole, B., & Mitra, A. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200422353 · Cited by 642
Cited by
The Klotho proteins in health and disease
Kuro-o, M. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0078-3 · Cited by 707
Self-citationHu, M. C., Shiizaki, K., Kuro-o, M., & Moe, O. W. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183727 · Cited by 587
Self-citationAKI on CKD: heightened injury, suppressed repair, and the underlying mechanisms
He, L., Wei, Q., Liu, J., Yi, M., Liu, Y., Liu, H., Sun, L., Peng, Y., Liu, F., Venkatachalam, M. A., et al. (2017) · Kidney International · doi:10.1016/j.kint.2017.06.030 · Cited by 448
Parathyroid hormone activates the orphan nuclear receptor Nurr1 to induce FGF23 transcription
Meir, T., Durlacher, K., Pan, Z., Amir, G., Richards, W. G., Silver, J., & Naveh-Many, T. (2014) · Kidney International · doi:10.1038/ki.2014.215 · Cited by 152
Inflammaging and Complement System: A Link Between Acute Kidney Injury and Chronic Graft Damage
Franzin, R., Stasi, A., Fiorentino, M., Stallone, G., Cantaluppi, V., Gesualdo, L., & Castellano, G. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00734 · Cited by 93
Metadata
- Authors
- Hu, M.-C., Shi, M., Zhang, J., Quiñones, H., Kuro-o, M., & Moe, O. W.
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 78
- Issue
- 12
- Pages
- 1240-1251
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W2040380840
- Cited by
- 386
- References
- 49
- FWCI
- 11.26
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hu, M.-C., Shi, M., Zhang, J., Quiñones, H., Kuro-o, M., & Moe, O. W. (2010). Klotho deficiency is an early biomarker of renal ischemia–reperfusion injury and its replacement is protective. Kidney International. https://doi.org/10.1038/ki.2010.328
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