ELEVATED CONCENTRATION OF SERUM CYCLOPHILIN A IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Keywords:
Cyclophilin A, serum, chronic kidney disease, biomarkerAbstract
Cyclophilin A (CypA) is a secreted protein which is produced from various kinds of cell types in response to oxidative stress. The elevation of CypA is related to pathogenesis of chronic inflammatory diseases, such as chronic kidney disease (CKD), and may be used as a prognosis marker for the advanced stage of the disease. This study aimed to investigate the associated factors which affect the serum CypA levels and measure those levels among non-CKD and CKD groups. We examined the levels of serum CypA from 358 cases (137, 105, and 116 cases from the non-CKD group, early stage of CKD group, and late stage of CKD group, respectively) using an indirect ELISA technique. The associated factors were analyzed by multiple linear regression analysis. The levels of the CypA concentration were statistically significantly higher in developing renal inflammation patients (the late stage of CKD group) than in the non-CKD group (p<0.001). Fasting blood sugar (FBS), HbA1c, systolic blood pressure (SBP), and estimated glomerular filtration rate (eGFR) were associated with the elevation of serum CypA levels. The multivariate analysis revealed that the early (adjusted OR 1.350, 95%CI: 1.093, 1.667) and late (adjusted OR 1.415, 95%CI: 1.103,1.811) stages of CKD had higher serum CypA levels than the non-CKD group. Therefore, the levels of CypA in a serum could be associated with a progression of CKD and be related to other.
References
Bidin, M.Z., Shah, A.M., Stanslas, J., and Seong, C.L.T. (2019). Blood and urine biomarkers in chronic kidney disease: An update. Clin. Chim. Acta, 495:239-250.
Chang, C.S., Su, S.L., Chang, C.C., Lee, K.W., Kuo, C.L., Huang, C.S., Tseng, W.M., and Liu, C.S. (2013). Cyclophilin A: a novel biomarker for untreated male essential hypertension. Biomarkers, 18:716-720.
Daenen, K., Andries, A., Mekahli, D., Van Schepdael, A., Jouret, F., and Bammens, B. (2019) Oxidative stress in chronic kidney disease. Pediatr. Nephrol., 34:975-991.
Dang, J., Jia, R., Tu, Y., Xiao, S., and Ding, G. (2010). Erythropoietin prevents reactive oxygen species generation and renal tubular cell apoptosis at high glucose level. Biomed. Pharmacother., 64(10):681rmac.
Daum, S., Schumann, M., Mathea, S., Aumüller, T., Balsley, M.A., Constant, S.L., de Lacroix, B.F., Kruska, F., Braun, M., and Fischer, C.S. (2009). Isoform-specific inhibition of cyclophilins. Biochemistry, 48(26):6,268-6,277.
Dronavalli, S., Duka, I., and Bakris, G.L. (2008). The pathogenesis of diabetic nephropathy. Nat. Clin. Pract. Endoc., 4(8):444-452.
Duni, A., Liakopoulos, V., Rapsomanikis, K.P., and Dounousi, E. (2017). Chronic kidney disease and disproportionally increased cardiovascular damage: does oxidative stress explain the burden? Oxid. Med. Cell Longev., 9036450.
Earley, A., Miskulin, D., Lamb, E.J., Levey, A.S., and Uhlig, K. (2012). Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review. Ann. Intern. Med., 156(11):785-795.
GBD 2015 Mortality and Causes of Death Collaborators. (2016). Global, regional, and national life expectancy, all-cause and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet, 388:1,459-1,544.
Harris, R.D., Steffes, M.W., Bilous, R.W., Sutherland, D.E., and Mauer, S.M. (1991). Global glomerular sclerosis and glomerular arteriolar hyalinosis in insulin dependent diabetes. Kidney Int., 40(1):107-114.
Heilig, C.W., Concepcion, L.A., Riser, B.L., Freytag, S.O., Zhu, M., and Cortes, P. (1995). Overexpression of glucose transporters in rat mesangial cells cultured in a normal glucose milieu mimics the diabetic phenotype. J. Clin. Invest., 96(4):1,802-1,814.
Hemmelgarn, B.R., Zhang, J., Manns, B.J., James, M.T., Quinn, R.R., Ravani, P., Klarenbach, S.W., Culleton, B.F., Krause, R., Thorlacius, L., Jain, A.K., and Tonelli, M. (2010). Nephrology visits and health care resource use before and after reporting estimated glomerular filtration rate. J. Amer. Med. Assoc., 303(12):1,151-1,158.
Hohman, R.J. and Hultsch, T. (1990). Cyclosporin A: new insights for cell biologists and biochemists. New Biol., 2:663-672.
Jha, V., Garcia-Garcia, G., Iseki, K., Li, Z., Naicker, S., Plattner, B., Saran, R., Wang, A.Y.M., and Yang, C.W. (2013). Chronic kidney disease: global dimension and perspectives. Lancet, 382:260-272.
Jin, K. and Vaziri, N.D. (2017). Elevated plasma cyclophillin A in hemodialysis and peritoneal dialysis patients: a novel link to systemic inflammation. Iran. J. Kidney Dis., 11(1):44-49.
Jin, Z.G., Melaragno, M.G., Liao, D.F., Yan, C., Haendeler, J., Suh, Y.A., Lambeth, J.D., and Berk, B. (2000). Cyclophilin A is a secreted growth factor induced by oxidative stress. Circ. Res., 87(9):789-796.
Kazancioglu, R. (2013). Risk factors for chronic kidney disease: an update. Kidney Int., 3:368-371.
Kidney Disease Improving Global Outcomes (KDIGO). (2013). Chapter 1: Definition and classification of CKD. Kidney Int. Suppl., 3:19-62.
Levey, A.S. (1990). Measurement of renal function in chronic renal disease. Kidney Int., 38(1):167-184.
Levey, A.S., Atkins, R., Coresh, J., Cohen, E.P., Collins, A.J., Eckardt, K.U., Nahas, M.E., Jaber, B.L., Jadoul, M., Levin, A., Powe, N.R., Rossert, J., Wheeler, D.C., Lameire, N., and Eknoyan, G. (2007). Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes. Kidney Int., 72:247-259.
Liu, M.C., Lee, Y.W., Lee, P.T., Chang, C.S., Tai, Y.L., Yu, J.R., Su, X.T., Hsu, L.W., Lin, S.H., Wu, C.H., and Liu, P.Y. (2015). Cyclophilin A is associated with peripheral artery disease and chronic kidney disease in geriatrics: The Tianliao Old People (TOP) study. Sci. Rep., 5:9,937.
Lu, G.W., Lu, D.W., and Zhang, Y.X.(2018). Predictive value of serum cyclophilin A concentrations after acute pancreatitis. Clin. Chim. Acta, 484:237-245.
Mihai, S., Codrici, E., Popescu, I.D., Enciu, A.M., Albulescu, L., Necula, L.G., Mambet, C., Anton, G., and Tanase, C. (2018). Inflammation and chronic kidney disease: Current approaches and recent advances. In: Chronic Kidney Disease - from Pathophysiology to Clinical Improvements. Rath, T., (ed). IntechOpen, Ltd., London, UK, p. 131-151.
Mishra, R., Emancipator, S.N., Kern, T., and Simonson, M.S. (2005). High glucose evokes an intrinsic proapoptotic signaling pathway in mesangial cells. Kidney Int., 67(1):82-93.
Mitsuo, K., Harmon, J.E., Robert, E.L., Marvin, L.R., and Harry, R.H. (1980). Metabolic activity of diabetic monocytes. Diabetes, 29(4):251-256.
Nagareddy, P.R., Murphy, A.J., Stirzaker, R.A., Hu, Y., Yu, S., Miller, R.G., Ramkhelawon, B., Distel, E., Westerterp, M., Huang, L.S., Schmidt, A.M., Orchard, T.J., Fisher, E.A., Tall, A.R., and Goldberg, I.J. (2013). Hyperglycemia promotes myelopoiesis and impairs the resolution of atherosclerosis. Cell Metab., 17(5):695-708.
Neuen, B.L., Chadban, S.J., Demaio, A.R., Johnson, D.W., and Perkovic, V. (2017). Chronic kidney disease and the global NCDs agenda. BMJ Glob. Health, 2:e000380.
Nigro, P., Pompilio, G., and Capogrossi, M.C. (2013). Cyclophilin A: a key player for human disease. Cell Death Dis., 4:e888
Ong-ajyooth, L., Vareesangthip, K., Khonputsa, P., and Aekplakorn, W. (2009). Prevalence of chronic kidney disease in Thai adults: a national health survey. BMC Nephrol., 10:35.
Ramachandran, S., Venugopal, A., Sathisha, K., Reshmi, G., Charles, S., Divya, G., Chandran, N.S.P, Mullassari, A., and Pillai, M.R. (2012). Proteomic profiling of high glucose primed monocytes identifies cyclophilin A as a potential secretory marker of inflammation in type 2 diabetes. Proteomics, 12(18):2,808-2,821.
Ramachandran, S., Venugopal, A., Kutty, V.R., Chitrasree, V., Mullassari, A., Pratapchandran, N.S., Santosh, K.R., Pillai, M.R., and Kartha, C.C. (2014). Plasma level of cyclophilin A is increased in patients with type 2 diabetes mellitus and suggests presence of vascular disease. Cardiovasc. Diabetol., 13:38.
Satoh, K., Matoba, T., Suzuki, J., O'Dell, M.R., Nigro, P., Cui, Z., Mohan, A., Pan, S., Li, L., Jin, Z.G., Yan, C., Abe, J., and Berk, B.C. (2008). Cyclophilin A mediates vascular remodeling by promoting inflammation and vascular smooth muscle cell proliferation. Circulation, 117:3,088-3,098.
Satoh, K., Nigro, P., and Berk, B.C. (2010). Oxidative stress and vascular smooth muscle cell growth: a mechanistic linkage by cyclophilin A. Antioxid. Redox Sign., 12(5):675-682.
Schlondorff, D. (1987). The glomerular mesangial cell: an expanding role for a specialized pericyte. FASEB J., 1(4):272-281.
Shlipak, M.G., Katz, R., Sarnak, M.J., Fried, L.F., Newman, A.B., Stehman-Breen, C., Seliger, S.L., Kestenbaum, B., Psaty, B., Tracy, R.P., and Siscovick, D.S. (2006). Cystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease. Ann. Intern. Med., 145(4):237-246.
Soe, N.N., Sowden, M., Baskaran, P., Kim, Y., Nigro, P., Smolock, E.M., and Berk, B.C. (2013). Acetylation of cyclophilin A is required for its secretion and vascular cell activation. Cardiovasc. Res., 101:444-453.
Stevens L.A. and Levey A.S. (2009). Measured GFR as a confirmatory test for estimated GFR. J. Am. Soc. Nephrol., 20(11):2,305-2,313.
Suzuki, J., Jin, Z.G., Meoli, D.F., Matoba, T., and Berk, B.C. (2006). Cyclophilin A is secreted by a vesicular pathway in vascular smooth muscle cells. Circ. Res., 98(6):811-817.
Takahashi, N., Hayano, T., and Suzuki, M. (1989). Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin. Nature, 337:473-475.
Tang, F.C., Wang, H.Y., Ma, M.M., Guan, T.W., Pan, L., Yao, D.C., Chen, Y.L., Chen, W.B., Tu, Y.S., and Fu, X.D. (2015). CyPA-CD147-ERK1/2-cyclin D2 signaling pathway is upregulated during rat left ventricular hypertrophy. Sheng Li Xue Bao, 67(5):393-400.
Thanakiggaru, P. (2015). Current Situation of chronic kidney disease in Thailand. Journal of the Department of Medical Services, 40:5-18.
Tsai, S.F., Su, C.W., Wu, M.J., Chen, C.H., Fu, C.P., Liu, C.S., and Hsieh, M. (2015). Urinary cyclophilin A as a new marker for diabetic nephropathy: a cross-sectional analysis of diabetes mellitus. Medicine, 94:e1802.
Weiner, D.E. (2009). Public health consequences of chronic kidney disease. Clin. Pharmacol. Ther., 86(5):566-569.
Xue, C., Sowden, M., and Berk, B.C. (2017). Extracellular cyclophilin A, especially acetylated, causes pulmonary hypertension by stimulating endothelial apoptosis, redox stress, and inflammation. Arterioscler. Throm. Vas., 37:1,138–1,146.
Zhu, X., Song, Z., Zhang, S., Nanda, A., and Li, G. (2014). CD147: a novel modulator of inflammatory and immune disorders. Curr. Med. Chem., 21(19):2,138.
