Serum Klotho protein level in type 2 diabetic patients depending on the renal function

  • I. Topchii Government Institution “L.T.Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine” https://orcid.org/0000-0002-7690-6787
  • P. Semenovykh Government Institution “L.T.Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine” https://orcid.org/0000-0003-0475-8524
  • T. Shcherban Government Institution “L.T.Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine” https://orcid.org/0000-0003-1095-5241
  • V. Galchinska Government Institution “L.T.Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine”
  • K. Savicheva Government Institution “L.T.Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine” https://orcid.org/0000-0003-1015-8832
Keywords: diabetes mellitus, diabetic nephropathy, Klotho protein

Abstract

The study aimed to assess serum Klotho protein level in type 2 diabetic patients depending on kidney function.

Methods. This observational study included 72 patients with diabetes mellitus (DM) and 26 patients with acute coronary syndrome. The control group consisted of 20 healthy subjects. Depending on the presence of albuminuria and glomerular filtration rate (GFR), the diabetics were divided into the following groups: group I included the patients with normal GFR and without albuminuria (n = 25); group ІІ consisted the patients with normal GFR and albuminuria (n = 23); group III – the patients with reduced GFR and albuminuria (n = 24) and group ІV included the patients with acute coronary syndrome (n = 26).

The GFR was calculated using the CKD EPI formula (KDIGO 2012). The concentration of Klotho protein was determined by enzyme-linked immunosorbent assay.

Results. The development of diabetic nephropathy in type 2 diabetic patients accompanied by a significant decrease of soluble Klotho compared with the controls and the patients of the1-st group. The level of Klotho protein in the group of patients with albuminuria decreased to (490.66 ± 58.76) pg/ml (p <0.05). The lowest concentration of Klotho (443.58 ± 46.92) pg/ml was found in the advanced stages of diabetic nephropathy, namely in patients with albuminuria and impaired renal function. Moreover, a significantly decreased serum Klotho was observed in acute coronary syndrome group in comparison with the control group (p <0.05). There were inverse correlations of Klotho concentration with urinary albumin and blood creatinine levels and a direct correlation between Klotho and GFR.

Conclusions. The obtained data indicated the key role of Klotho protein in the formation of renal pathology in type 2 diabetes and the feasibility of practical use of Klotho determination as an early diagnostic marker of renal disorders and cardiovascular risk assessment. The strategies improving Klotho production may be useful in the reduction of both renal and vascular lesions progression in type 2 diabetic patients.

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References

Shaw JE, Sicree R, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030.  Diabetes Res. Clin. Pract. 2010; 87(1): 4–14. doi: 10.1016/j.diabres.2009.10.007.

Reddy MA, Natarajan R. Role of epigenetic mechanisms in the vascular complications of diabetes. Subcell Biochem. 2013; 61: 435-454. doi: 10.1007/978-94-007-4525-4_19.

Khutorska LA. Poshyrenist, absoliutnyi i vidnosnyi ryzyk rozvytku diabetychnoi nefropatii u khvorykh na tsukrovyi diabet. Bukovynskyi medychnyi visnyk. 2012; 16(4): 170-175. Dostupno: http://dspace.bsmu.edu.ua/bitstream/123456789/14982/1/BMV4_181.pdf [In Ukrainian].

Fox CS, Matsushita K. Woodward M. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet. 2012; 380 (9854): 1662–1673. doi: 10.1016/S0140-6736(12)61350-6.

Li L, Zhang X. et al. Renal pathological implications in type 2 diabetes mellitus patients with renal involvement . J. Diabetes Complications. 2017. 31(1): 114-121. doi: 10.1016/j.jdiacomp.2016.10.024.

Duru OK, Middleton T. et al. The Landscape of Diabetic Kidney Disease in the United States. Curr. Diab. Rep. 2018. 18(3):14.  doi: 10.1007/s11892-018-0980-x.

Phillips A, Steadman R. Diabetic nephropathy: the central role of renal proximal tubular cells in tubulointerstitial injury. Histol. Histopathol. 2002. 17(1):247-252. doi: 10.14670/HH-17.247.

Couser WG, Remuzzi G, Mendis S et al. The contribution of chronic kidney disease to the global burden of major noncommunicable diseases. Kidney int. 2011. 80(12): 1258-1270. doi: 10.1038/ki.2011.368.

Dedov YY, Shestakova MV. Dyabetycheskaia nefropatyia. Unyversum pablyshynh. 2000. 240 s. [In Russian].

Mise K, Imamura M. et al. Identification of Novel Urinary Biomarkers for Predicting Renal Prognosis in Patients With Type 2 Diabetes by Glycan Profiling in a Multicenter Prospective Cohort Study: U-CARE Study 1. Diabetes Care. 2018. 41(8): 1765-1775. doi: 10.2337/dc18-0030.

Radcliffe NJ, Seah JM et al. Clinical predictive factors in diabetic kidney disease progression. J. Diabetes Investig. 2017. 8(1): 6-18. doi: 10.1111/jdi.12533.

Nie F, Wu D, Du H. et al. Serum klotho protein levels and their correlations with the progression of type 2 diabetes mellitus. J. Diabetes Complications. 2017. 31(3): 594-598. doi: 10.1016/j.jdiacomp.2016.11.008.  

Yu L, Kang L, Ren X-Z. et al. Circulating α-Klotho levels in hemodialysis patients and their relationship to atherosclerosis. Kidney Blood Press. Res. 2018. 43: 1174-1182. doi: 10.1159/000492245.

KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Kidney Int Suppl. 2009 Aug;(113):1-130. doi: 10.1038/ki.2009.188.

Pavik I, Jaeger P et al. Secreted Klotho and FGF23 in chronic kidney disease Stage 1 to 5: a sequence suggested from a cross-sectional study. Nephrol. Dial. Transplant. 2013. 28(2): 352–359. doi: 10.1093/ndt/gfs460.

 Topchii I, Semenovykh P, Galchiskaya V, Yakymenko Yu, Shcherban T. Association of fibroblast growth factor 23 with markers of inflammation and fibrosis in diabetic nephropathy. Georgian Medical News. 2019. 7-8(292-293):44-49. Dostupno: http://www.geomednews.org/shared/issues/med292-293.pdf [In Russian].

Wan M, Smith C. Fibroblast growth factor 23 and soluble klotho in children with chronic kidney disease. Nephrol. Dial. Transplant. 2013. 28(1): 153–161. doi: https://doi.org/10.1093/ndt/gfs411.  

Fountoulakis N, Maltese G, Gnudi L et al. Reduced levels of anti-ageing hormone Klotho predict renal function decline in type 2 diabetes. J. Clin. Endocrinol. Metab. 2018. 103(5): 2026–2032. doi: 10.1210/jc.2018-00004.

Lee EY., Kim SS, Lee J-S, et al. Soluble a-Klotho as a novel biomarker in the early stage of nephropathy in patients with type 2 diabetes. PLOS ONE. 2014. 9(8): e102984. doi:10.1371/journal.pone.0102984.


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Published
2020-06-27
How to Cite
Topchii, I., Semenovykh, P., Shcherban, T., Galchinska, V., & Savicheva, K. (2020). Serum Klotho protein level in type 2 diabetic patients depending on the renal function. Ukrainian Journal of Nephrology and Dialysis, (3(67), 60-66. https://doi.org/10.31450/ukrjnd.3(67).2020.08