Chronic Kidney Disease is a serious and pervasive condition. In the United States alone, it affects approximately 15 percent of the population.  90 percent of these people do not know they have it. This disease causes a gradual loss of function and often goes undetected until serious damage or kidney failure results. 

Fortunately, within the kidneys is a protein called Klotho, aptly named after a Greek goddess who spins the thread of life. With gene therapy, Klotho can keep our kidneys healthy and our lives long.

Klotho is a remarkable protein primarily synthesized in the kidneys. Research continues to unveil the powerful effects it has on health. It displays remarkable properties, enhancing cognition and increasing life span. 

When Klotho is deficient in the body, it often leads to both acute kidney injury and chronic kidney disease (Izquierdo, 2012). Genetic Klotho deficiency is a serious and debilitating issue. It is not only linked with direct detriment to the kidneys themselves, but due to the age-accelerating and pervasive processes of CKD, to vascular calcification, bone disease, left ventricular hypertrophy, and premature death (Zoccali, 2017).

The impact of Klotho deficiency has been rigorously studied. First identified in animal models as an ineluctable driver of premature aging. Klotho deficient mice averaged a mere 60 days of life in comparison to the over three year lifespan of mice without disrupted Klotho levels. Moreover, a plethora of physical, morphological, and biochemical features associated with rapid aging were observed. These conditions ranged from kyphosis, skeletal muscle wasting, osteopenia, and atrophy of organs among other ailments. (Ohnishi, 2010)

A large contributor to the ill-effects of aging and Kidney disease is inflammation. Proper Klotho levels downregulate inflammation, and inflammation will downregulate Klotho. Kidney Klotho is diminished in models of renal injury precipitated by inflammation. However, studies have shown that decreased Klotho expression is reversible by the introduction of an antioxidant (Cheng, 2010).

Klotho is decreased even in the fist stage of CKD. Although at this early stage, renal function is preserved, there is usually a degree of kidney injury, such as albuminuria (Hu, 2010).  It has been hypothesized, considering the insignificant loss of tubular cells in the first stage of CKD, rather inflammation is the force behind the decreased Klotho expression. (Izquierdo, 2012)

The problems with low Klotho are legion, but as mentioned before, gene therapy holds a key, not only to mitigate damage due to deficiency but to possibly reverse it. A single injection in an animal model of recombinant Klotho protein improved acute kidney injury (Hu, 2010). Gene therapy via adenovirus-mediated Klotho gene transfer also resulted in improvements in renal morphological damage while reducing apoptosis (Sugiura, 2005).

At the cutting-edge of gene therapy stands Integrated Health Systems. Dedicated to allowing patients to secure the most advanced gene therapies available and consisting of renowned specialists in the field, IHS brings the future of medicine to us today. Klotho is one of the gene therapies IHS offers. 

References and Suggested Reading

María C. Izquierdo, María V. Perez-Gomez, María D. Sanchez-Niño, Ana B. Sanz, Olga Ruiz-Andres, Jonay Poveda, Juan Antonio Moreno, Jesús Egido, Alberto Ortiz, Klotho, phosphate and inflammation/ageing in chronic kidney disease, Nephrology Dialysis Transplantation, Volume 27, Issue suppl_4, December 2012, Pages iv6–iv10,

Zoccali C, Vanholder R, Massy ZA, Ortiz A, Sarafidis P, Dekker FW, Fliser D, Fouque D, Heine GH, Jager KJ, Kanbay M, Mallamaci F, Parati G, Rossignol P, Wiecek A, London G; European Renal and Cardiovascular Medicine (EURECA-m) Working Group of the European Renal Association – European Dialysis Transplantation Association (ERA-EDTA). The systemic nature of CKD. Nat Rev Nephrol. 2017 Jun;13(6):344-358. doi: 10.1038/nrneph.2017.52. Epub 2017 Apr 24. PMID: 28435157.

Ohnishi M, Razzaque MS. Dietary and genetic evidence for phosphate toxicity accelerating mammalian aging. FASEB J. 2010 Sep;24(9):3562-71. doi: 10.1096/fj.09-152488. Epub 2010 Apr 23. PMID: 20418498; PMCID: PMC2923352.

Cheng MF, Chen LJ, Cheng JT. Decrease of Klotho in the kidney of streptozotocin-induced diabetic rats. J Biomed Biotechnol. 2010;2010:513853. doi: 10.1155/2010/513853. Epub 2010 Jun 27. PMID: 20625492; PMCID: PMC2896693.

Hu MC, Shi M, Zhang J, Quiñones H, Griffith C, Kuro-o M, Moe OW. Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol. 2011 Jan;22(1):124-36. doi: 10.1681/ASN.2009121311. Epub 2010 Nov 29. PMID: 21115613; PMCID: PMC3014041.

Hu MC, Shi M, Zhang J, Quiñones H, Kuro-o M, Moe OW. Klotho deficiency is an early biomarker of renal ischemia-reperfusion injury and its replacement is protective. Kidney Int. 2010 Dec;78(12):1240-51. doi: 10.1038/ki.2010.328. Epub 2010 Sep 22. PMID: 20861825; PMCID: PMC3237296.

Sugiura H, Yoshida T, Tsuchiya K, Mitobe M, Nishimura S, Shirota S, Akiba T, Nihei H. Klotho reduces apoptosis in experimental ischaemic acute renal failure. Nephrol Dial Transplant. 2005 Dec;20(12):2636-45. doi: 10.1093/ndt/gfi165. Epub 2005 Oct 4. PMID: 16204278.

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