The Role of Soluble Klotho in Diabetic Nephropathy Patients
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Keywords
Soluble Klotho ; Diabetic Nephropathy Patients
Abstract
Diabetic nephropathy (DN) is serious microvascular complication of diabetes which may be complicated by renal failure, cardiovascular disease and premature mortality. Objective: to evaluate the role of soluble Klotho in diabetic nephropathy patients and its relation with albuminuria and determine its ability to slow down the progression of renal disease and reduce the risk of cardiovascular diseases. Patients and methods: this this case control study included seventy patients with type 2 diabetes, at the diabetic outpatient clinic of Zagazig University Hospitals, as well as 20 healthy controls. All laboratory investigations were done in clinical pathology department in Zagazig University Hospitals. Results: There was highly statistically significant difference between diabetic and control groups regarding presence of hypertension and between the 3 diabetic subgroups regarding duration of DM and type of the antidiabetic therapy. Macroalbuminuria group had the longest duration of DM and the highest proportion ofpatients on insulin therapy. However, no statistically significant difference was found regarding presence of hypertension between diabetic subgroups. We found an interesting decrease in hemoglobin concentration from 12.9 g/dl in normoalbuminuria group and 13.1 g/dl in microalbuminuria group to 11.2 g/dl in macroalbuminuria group (p value <0.001).There were highly statistically significant differences among diabetic and control groups regarding fasting blood sugar level, HbA1c, hematocrit and urinary creatinine. A highly statistically significant differences among the studied groups regarding urinary albumin/creatinine ratio. Conclusion: Serum klotho concentrations are negatively associated with renal function. Serum klotho could serve as a biomarker for predicting the risk of developing diabetic nephropathy. Klotho may be involved in the pathogenesis of kidney disease, not only DN. Future studies performed in patients with another kidney disease are needed to explain the precise role of klotho in kidney disease. Our findings that urine klotho correlates with nephropathy markers in type 2 diabetic subjects, suggest that elevation of urine klotho could be an independent predictive marker for the progression of diabetic nephropathy.
References
2- Association, A.D. (2017): Standards of Medical Care in Diabetes—2017 Abridged for Primary Care Providers. Clinical diabetes: a publication of the American Diabetes Association, 35(1), 5-26.
3- Karalliedde J, Vibert GC (2011): In Davies MAS ed. Diabetic nephropathy, 2nd edn. Oxford University Press, Oxford.
4- Maltese G, Fountoulakis N, Siow RC. (2017): Perturbations of the anti-ageing hormone Klotho in patients with type 1 diabetes and Microalbuminuria. Diabetologia; 60:911–914.
5- Nakatani T, Sarraj B, Ohnishi M. (2009): In vivo genetic evidence for Klotho- dependent, fibroblast growth factor 23 (Fgf23)-mediated regulation of systemic phosphate homeostasis. FASEB J 2009; 23: 433–41.
6- Karalliedde J, Maltese G, Hill B. (2013): Effect of Renin-Angiotensin System Blockade on Soluble Klotho in Patients with Type 2 Diabetes, Systolic Hypertension, and Albuminuria. Clin J Am Soc Nephrol 8: 1899–1905.
7- Asai O, Nakatani K, Tanaka T, Sakan H, Imura A, Yoshimoto S (2012): Decreased renal alpha-klotho expression in early diabetic nephropathy in humans and mice and its possible role in urinary calcium excretion. Kidney Int 81(6):539–47.
8- Lee EY, Kim SS, Lee J-S, Kim IJ, Song SH, et al. (2014): Soluble a-Klotho as a Novel Biomarker in the Early Stage of Nephropathy in Patients with Type 2 Diabetes. PLoS ONE 9(8): e102984.
9- Kasper DL, Fauci AS, Hauser SL et al. (2015) :Harrison's principles of internal medicine (19th edition). New York: McGraw Hill, 2399-2429.
10- Berl T. and Henrich W. (2006): Kidney-heart interactions: epidemiology, pathogenesis, and treatment. Clin J AmSoc Nephrol 1(1), 8–18.
11- Budhiraja P, Thajudeen B, Popovtzer M (2013): Absence of albuminuria in type 2 diabetics with classical diabetic nephropathy: clinical pathological study. Journal of Biomedical Science and Engineering 6(5):20-25.
12- MacIsaac BJ and Jerums G (2011): Diabetic kidney disease with and without albuminuria. Current Opinion in Nephrology and Hypertension 20(3):246–257.
13- Jayakumar C, Mohamed R, Ranganathan PV. (2011): Intracellular Kinases Mediate Increased Translation and Secretion of Netrin-1 from Renal Tubular Epithelial Cells. PLoS ONE 6:e26776.
14- Nauta FL, Boertien WE, Bakker JL, et al. (2011): Glomerular and tubular damage markers are elevated in patients with diabetes. Diabetes Care 34(4):975–981.
15- VaidyaVS, Niewczas MA, Ficociello LH.(2011): Regression of microalbuminuria in type 1 diabetes is associated with lower levels of urinary tubular injury biomarkers, kidney injurymolecule-1,andN-acetyl-[beta]-Dglucosaminidase. Kidney Int 79:464–470.
16- Kuro-o M. (2010): A potential link between phosphate and aging–lessons from klotho-deficient mice. Mech Ageing Dev 131 (4):270–5.
17- Hu M.C., Kuro-o M., Moe O.W. (2012): Secreted klotho and chronic kidney disease. Adv. Exp. Med. Biol.728:126–157.
18- Lang F, Lang E, FollerM (2012): Physiology and pathophysiology of eryptosis. Transfus Med Hemother 39: 308–314.
19- Kempe DS, Ackermann TF, Fischer SS, et al. (2009): Accelerated suicidal erythrocyte death in Klotho-deficient mice. Pflugers Arch 458: 503–512.
20- Inci A, Olmaz R, Sari F, Coban M, Ellidag HY, Sarikaya M. (2016): Increased oxidative stress in diabetic nephropathy and its relationship with soluble klotho levels. Hippokratia 20 (3): 198–203.
21- Haruna Y, Kashihara N, Satoh M.(2007): Amelioration of progressive renal injury by genetic manipulation of Klotho gene. Proc Nat Acad Sci USA 104:2331–6.
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