Recombinant α-Klotho may be prophylactic and therapeutic for acute to chronic kidney disease progression and uremic cardiomyopathy

Kidney International

Volumn 91, Issue 5, 2017, Pages 1104-1114

  Hu, Ming Chang ^a,b   Shi, Mingjun ^b   Gillings, Nancy ^b   Flores, Brianna ^b   Takahashi, Masaya ^a,c   Kuro o, Makoto ^b,d   Moe, Orson W ^a,b  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^c UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^d JICHI MEDICAL UNIVERSITY   (Japan)

Author keywords

acute kidney injury; cardiovascular disease; chronic kidney disease; ischemia reperfusion; phosphate

Indexed keywords

KLOTHO PROTEIN; PROTEIN ALPHA KLOTHO; RECOMBINANT ALPHA KLOTHO PROTEIN; RECOMBINANT PROTEIN; UNCLASSIFIED DRUG; BETA GLUCURONIDASE;

ACUTE KIDNEY FAILURE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CARDIOMYOPATHY; CHRONIC KIDNEY FAILURE; CONTROLLED STUDY; DISEASE COURSE; DRUG EFFICACY; DRUG SAFETY; FEMALE; KIDNEY FUNCTION; MALE; MOUSE; NONHUMAN; REPERFUSION INJURY; UNINEPHRECTOMY; UREMIC CARDIOMYOPATHY; ACUTE KIDNEY INJURY; ANIMAL; BIOLOGICAL THERAPY; BLOOD; CARDIAC MUSCLE; CARDIOMYOPATHIES; COMPLICATION; DISEASE MODEL; FIBROSIS; HUMAN; INTRAPERITONEAL DRUG ADMINISTRATION; KIDNEY; METABOLISM; PATHOLOGY; PRECLINICAL STUDY; PROCEDURES; RENAL INSUFFICIENCY, CHRONIC; SECRETION (PROCESS); UREMIA;

ACUTE KIDNEY INJURY; ANIMALS; BIOLOGICAL THERAPY; CARDIOMYOPATHIES; DISEASE MODELS, ANIMAL; DISEASE PROGRESSION; DRUG EVALUATION, PRECLINICAL; FEMALE; FIBROSIS; GLUCURONIDASE; HUMANS; INJECTIONS, INTRAPERITONEAL; KIDNEY; MALE; MICE; MYOCARDIUM; RECOMBINANT PROTEINS; RENAL INSUFFICIENCY, CHRONIC; UREMIA;

EID: 85010606448     PISSN: 00852538     EISSN: 15231755     Source Type: Journal    
DOI: 10.1016/j.kint.2016.10.034     Document Type: Article

References (45)

1. 1 Kuro-o, M., Matsumura, Y., Aizawa, H., et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390 (1997), 45–51.
2. 2 Kurosu, H., Yamamoto, M., Clark, J.D., et al. Suppression of aging in mice by the hormone Klotho. Science 309 (2005), 1829–1833.
3. 3 Hu, M.C., Shi, M., Zhang, J., et al. Renal production, uptake, and handling of circulating alphaKlotho. J Am Soc Nephrol 27 (2016), 79–90.
4. 4 Chen, C.D., Tung, T.Y., Liang, J., et al. Identification of cleavage sites leading to the shed form of the anti-aging protein klotho. Biochemistry 53 (2014), 5579–5587.
5. 5 van Loon, E.P., Pulskens, W.P., van der Hagen, E.A., et al. Shedding of klotho by ADAMs in the kidney. Am J Physiol Renal Physiol 309 (2015), F359–F368.
6. 6 Hu, M.C., Shiizaki, K., Kuro-o, M., et al. Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism. Annu Rev Physiol 75 (2013), 503–533.
7. 7 Bian, A., Neyra, J.A., Zhan, M., et al. Klotho, stem cells, and aging. Clin Interv Aging 10 (2015), 1233–1243.
8. 8 Kuro-o, M., A potential link between phosphate and aging–lessons from Klotho-deficient mice. Mech Ageing Dev 131 (2010), 270–275.
9. 9 Lindberg, K., Amin, R., Moe, O.W., et al. The kidney is the principal organ mediating klotho effects. J Am Soc Nephrol 25 (2014), 2169–2175.
10. 10 Barker, S.L., Pastor, J., Carranza, D., et al. The demonstration of alphaKlotho deficiency in human chronic kidney disease with a novel synthetic antibody. Nephrol Dial Transplant 30 (2015), 223–233.
11. 11 Hu, M.C., Shi, M., Cho, H.J., et al. Klotho and phosphate are modulators of pathologic uremic cardiac remodeling. J Am Soc Nephrol 26 (2015), 1290–1302.
12. 12 Hu, M.C., Shi, M., Zhang, J., et al. Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol 22 (2011), 124–136.
13. 13 Ravikumar, P., Li, L., Ye, J., et al. alphaKlotho deficiency in acute kidney injury contributes to lung damage. J Appl Physiol (1985) 120 (2016), 723–732.
14. 14 Hu, M.C., Shi, M., Zhang, J., et al. Klotho deficiency is an early biomarker of renal ischemia-reperfusion injury and its replacement is protective. Kidney Int 78 (2010), 1240–1251.
15. 15 Hu, M.C., Kuro-o, M., Moe, O.W., Klotho and kidney disease. J Nephrol 23:Suppl 16 (2010), S136–S144.
16. 16 Chen, T.H., Kuro, O.M., Chen, C.H., et al. The secreted Klotho protein restores phosphate retention and suppresses accelerated aging in Klotho mutant mice. Eur J Pharmacol 698 (2013), 67–73.
17. 17 Hu, M.C., Shi, M., Zhang, J., et al. Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. FASEB J 24 (2010), 3438–3450.
18. 18 Shi, M., Flores, B., Gillings, N., et al. αKlotho mitigates progression of AKI to CKD through activation of autophagy. J Am Soc Nephrol 27 (2016), 2331–2345.
19. 19 Cha, S.K., Hu, M.C., Kurosu, H., et al. Regulation of renal outer medullary potassium channel and renal K(+) excretion by Klotho. Mol Pharmacol 76 (2009), 38–46.
20. 20 Gansevoort, R.T., Correa-Rotter, R., Hemmelgarn, B.R., et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet 382:9889 (2013), 339–352.
21. 21 London, G.M., Left ventricular alterations and end-stage renal disease. Nephrol Dial Transplant 17:Suppl 1 (2002), 29–36.
22. 22 Aoyagi, T., Kusakari, Y., Xiao, C.Y., et al. Cardiac mTOR protects the heart against ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 303 (2012), H75–H85.
23. 23 Faul, C., Amaral, A.P., Oskouei, B., et al. FGF23 induces left ventricular hypertrophy. J Clin Invest 121 (2011), 4393–4408.
24. 24 Panesso, M.C., Shi, M., Cho, H.J., et al. Klotho has dual protective effects on cisplatin-induced acute kidney injury. Kidney Int 85 (2014), 855–870.
25. 25 Chawla, L.S., Kimmel, P.L., Acute kidney injury and chronic kidney disease: an integrated clinical syndrome. Kidney Int 82 (2012), 516–524.
26. 26 Bian, A., Xing, C., Hu, M.C., Alpha Klotho and phosphate homeostasis. J Endocrinol Invest 37 (2014), 1121–1126.
27. 27 Ravikumar, P., Ye, J., Zhang, J., et al. alpha-Klotho protects against oxidative damage in pulmonary epithelia. Am J Physiol Lung Cell Mol Physiol 307 (2014), L566–L575.
28. 28 Ikushima, M., Rakugi, H., Ishikawa, K., et al. Anti-apoptotic and anti-senescence effects of Klotho on vascular endothelial cells. Biochem Biophys Res Commun 339 (2006), 827–832.
29. 29 Xie, J., Yoon, J., An, S.W., et al. Soluble Klotho protects against uremic cardiomyopathy independently of fibroblast growth factor 23 and phosphate. J Am Soc Nephrol 26 (2015), 1150–1160.
30. 30 Hu, M.C., Kuro-o, M., Moe, O.W., The emerging role of Klotho in clinical nephrology. Nephrol Dial Transplant 27 (2012), 2650–2657.
31. 31 Lau, W.L., Leaf, E.M., Hu, M.C., et al. Vitamin D receptor agonists increase klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet. Kidney Int 82 (2012), 1261–1270.
32. 32 Narumiya, H., Sasaki, S., Kuwahara, N., et al. HMG-CoA reductase inhibitors up-regulate anti-aging klotho mRNA via RhoA inactivation in IMCD3 cells. Cardiovasc Res 64 (2004), 331–336.
33. 33 Hu, M.C., Klotho connects intermedin1-53 to suppression of vascular calcification in chronic kidney disease. Kidney Int 89 (2016), 534–537.
34. 34 Bucaloiu, I.D., Kirchner, H.L., Norfolk, E.R., et al. Increased risk of death and de novo chronic kidney disease following reversible acute kidney injury. Kidney Int 81 (2012), 477–485.
35. 35 Kuro-o, M., Klotho as a regulator of oxidative stress and senescence. Biol Chem 389 (2008), 233–241.
36. 36 Liu, F., Wu, S., Ren, H., et al. Klotho suppresses RIG-I-mediated senescence-associated inflammation. Nat Cell Biol 13 (2011), 254–262.
37. 37 Hu, M.C., Shi, M., Cho, H.J., et al. The erythropoietin receptor is a downstream effector of Klotho-induced cytoprotection. Kidney Int 84 (2013), 468–481.
38. 38 Yamamoto, M., Clark, J.D., Pastor, J.V., et al. Regulation of oxidative stress by the anti-aging hormone klotho. J Biol Chem 280 (2005), 38029–38034.
39. 39 Kim JH, Xie J, Hwang KH, et al. Klotho may ameliorate proteinuria by targeting TRPC6 channels in podocytes [e-bup ahead of print]. J Am Soc Nephrol. http://dx.doi.org/10.1681/ASN.2015080888.
40. 40 Xie, J., Cha, S.K., An, S.W., et al. Cardioprotection by Klotho through downregulation of TRPC6 channels in the mouse heart. Nat Commun, 3, 2012, 1238.
41. 41 Mizuno, M., Mitchell, J.H., Crawford, S., et al. High dietary phosphate intake induces hypertension and augments exercise pressor reflex function in rats. Am J Physiol Regul Integr Comp Physiol 311 (2016), R39–R48.
42. 42 Selamet, U., Tighiouart, H., Sarnak, M.J., et al. Relationship of dietary phosphate intake with risk of end-stage renal disease and mortality in chronic kidney disease stages 3-5: The Modification of Diet in Renal Disease Study. Kidney Int 89 (2016), 176–184.
43. 43 Gutierrez, O.M., Fibroblast growth factor 23, Klotho, and disordered mineral metabolism in chronic kidney disease: unraveling the intricate tapestry of events and implications for therapy. J Ren Nutr 23 (2013), 250–254.
44. 44 Wolf, M., Molnar, M.Z., Amaral, A.P., et al. Elevated fibroblast growth factor 23 is a risk factor for kidney transplant loss and mortality. J Am Soc Nephrol 22 (2011), 956–966.
45. 45 Grabner, A., Amaral, A.P., Schramm, K., et al. Activation of cardiac fibroblast growth factor receptor 4 causes left ventricular hypertrophy. Cell Metab 22 (2015), 1020–1032.