Evaluation of fibroblast growth factor-23 and alpha klotho levels in patients with sarcoidosis

Esra Özen Engin; Tansu Sav; Kürşat Öneç; Peri Meram Arbak

doi:10.18203/2320-6012.ijrms20243351

Authors

Esra Özen Engin Department of Medical Oncology, Sakarya University Faculty of Medicine, Sakarya, Turkey
Tansu Sav Department of Nephrology, Duzce University Faculty of Medicine, Duzce, Turkey
Kürşat Öneç Department of Nephrology, Duzce University Faculty of Medicine, Duzce, Turkey
Peri Meram Arbak Department of Chest Diseases, Duzce University Faculty of Medicine, Duzce, Turkey

DOI:

https://doi.org/10.18203/2320-6012.ijrms20243351

Keywords:

Sarcoidosis, Alpha klotho, FGF-23

Abstract

Background: Sarcoidosis is a systemic granulomatous disease. In its pathology, it is thought that 1-alpha hydroxylase production and activation as well as 1,25-hydroxy vitamin D production from active macrophages take place. FGF-23 and alpha klotho are proteins that play a key role in the bone-parathyroid-kidney axis, regulation of phosphate and calcium metabolism, and vitamin D metabolism. We aimed to demonstrate the effects of pathologic conditions on bone metabolism and the occurrence of vascular calcification since vitamin D can be activated in non-kidney patterns and hypercalcemia and hypercalciuria can be seen in these patients.

Methods: The study was designed as a prospective case-control study. The study included 42 patients with sarcoidosis and 41 healthy volunteers who were admitted to Düzce University Medical Faculty Hospital. Age, gender, comorbidity information, BMD measurement data within the last 6 months, 24-hour urine and blood samples were taken from the patient and control groups.

Results: FGF-23 and alpha klotho levels were significantly higher in the patient group. There was a positive correlation between FGF-23 and alpha klotho. A negative correlation was found between FGF-23 and urea levels while positive correlation was found between alpha klotho and L1-L4 T-score.

Conclusions: These results suggested that there may be a relationship between sarcoidosis progression and FGF-23 and alpha klotho levels. Positive correlation between alpha klotho and L1-L4 T score in all groups suggests that alpha klotho may be associated with osteoporosis.

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References

Silverman KJ, Hutchins GM, Bulkley BH. Cardiac sarcoid: a clinicopathologic study of 84 unselected patients with systemic sarcoidosis. Circulation. 1978;58(6):1204-11.

Berliner AR, Haas M CM. Sarcoidosis: the nephrologist’s perspective. Am J Kidney Dis. 2006;48(5):856-70.

Hilderson I, Van Laecke S, Wauters A, Donck J. Treatment of renal sarcoidosis: is there a guideline? Overview of the different treatment options. Nephrol Dial Transpl. 2014;29(10):1841-7.

Sharma OP. Hypercalcemia in granulomatous disorders: a clinical review. Curr Opin Pulmon Med. 2000;6(5):442-7.

Kovesdy CP QL. Fibroblast growth factor-23: what we know, what we don’t know, and what we need to know. Nephrol Dial Transplant. 2013;28(9):2228-36.

Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V, Goetz R, Kuro-o M, Mohammadi M, et al. The parathyroid is a target organ for FGF23 in rats. J Clin Invest. 2007;117(12):4003-8.

Martin A, David V, Quarles LD. Regulation and function of the FGF23/klotho endocrine pathways. Physiol Rev. 2012;92(1):131-55.

McCort JJ, Wood RH, Hamilton JB, Eherlich DE. Sarcoidosis: a clinical and roentgenographic study of 28 proven cases. Arch Intern Med. 1947;80:293-321.

Mayock RL, Bertrand P, Morrison CE SJ. Manifestations of sarcoidosis: analysis of 145 patients with a review of nine series selected from literature. Am J Med. 1963;35:67-89.

James DG, Neville E S LE. A worldwide review of sarcoidosis. Ann NY Acad Sci. 278AD;321-34.

Adams JS, Singer FR, Gacad MA, Sharma OP, Hayes MJ, Vouros P, Holick MF. Isolation and structural identification of 1, 25-dihydroxyvitamin D3 produced by cultured alveolar macrophages in sarcoidosis. J Clin Endocrinol Metab. 1985;60(5):960-6.

Zeimer HJ, Greenaway TM, Slavin J, Hards DK, Zhou H, Doery JC, et al. Parathyroid-hormone-related protein in sarcoidosis. Am J Pathol. 1998;152(1):17.

Unsal A, Basturk T, Koc Y, Sakacı T, Ahbap E, Ozagarı A, et al. Renal sarcoidosis with normal serum vitamin D and refractory hypercalcemia. Int Urol Nephrol. 2012;25:1779-83.

Baughman RP, Janovcik J, Ray M, Sweiss N, Lower EE. Calcium and vitamin D metabolism in sarcoidosis. Sarcoidosis Vasc Diffus Lung Dis. 2013;30(11):113-20.

Berlin JL, Shantha GP, Yeager H, Thomas-Hemak L. Serum vitamin D levels may not reflect tissue-level vitamin D in sarcoidosis. Case Rep. 2014;2014:bcr2014203759.

Lebacq E, Verhaegen H, Desmet V. Renal involvement in sarcoidosis. Postgrad Med J. 1970;46(538):526-9.

Sen N, Ermis H KM. Clinical features and diagnostic methods of sarcoidosis according to stages: an evaluation of 55 cases. Eurasian Pulmonol. 2008;10(2):89-96.

Mitchell TH, Stamp TC, Jenkins MV, Mawer EB, Berry JL. Hypercalcaemic sarcoidosis in hypoparathyroidism. Br Med J. 1983;286(6367):764.

Vucinic V, Skodric-Trifunovic V, Ignjatovic S. How to diagnose and manage difficult problems of calcium metabolism in sarcoidosis: an evidence based review. Curr Opin Pulmon Med. 2011;17(5):297-302.

Grekin RH, Curtis A. Sarcoidosis II. Chemical and functional studies. J Invest Dermatol. 1948;11:299-304.

Harrell GT, Fisher S. Blood chemical changes in Boeck’s sarcoidosis with particular reference to protein, calcium and phosphatase values. J Clin Invest. 1939;18:687-93.

Sexton DJ, O’Reilly MW, Geoghegan P, Kinsella SM, Moran PJ, O’Regan AW. Serum Fibroblastic Growth Factor 23 in Acute Sarcoidosis and Normal Kidney Function. Sarcoidosis Vasc Diffus Lung Dis. 2016;33(2):139-42.

Silva AP, Mendes F, Pereira L, Fragoso A, Gonçalves RB, Santos N, et al. Klotho levels: association with insulin resistance and albumin-to-creatinine ratio in type 2 diabetic patients. Int Urol Nephrol. 2017;49(10):1809-14.

Sarmento-Dias M, Santos-Araújo C, Poínhos R, Oliveira B, Silva IS, Silva LS, et al. Fibroblast growth factor 23 is associated with left ventricular hypertrophy, not with uremic vasculopathy in peritoneal dialysis patients. Clin Nephrol. 2016;85(3):135-41.

Raafat M, Madkour M, Metwaly A, Nasr FM, Mosbah O, El-Sheikh N. Clinical significance of FGF-23 in chronic kidney disease patients. Schol J Appl Med Sci. 2015;3:741-50.

Kuro-o M. Klotho as a regulator of fbroblast growth factor signalling and phosphate/calcium metabolism. Curr Opin Nephrol Hypertens. 2006;(15):437-41.

Zheng S, Chen Y, Zheng Y, Zhou Z, Li Z. Correlation of serum levels of fibroblast growth factor 23 and Klotho protein levels with bone mineral density in maintenance hemodialysis patients. Eur J Med Res. 2018;23(1):18.