Placental growth factor, pregnancy-associated plasma protein-A, soluble receptor for advanced glycation end products, extracellular newly identified receptor for receptor for advanced glycation end products binding protein and high mobility group box 1 levels in patients with acute kidney injury: a cross sectional study

BMC Nephrology

Marta Kalousova¹  Vladimir Tesar⁴  Tomas Zima¹  Jan Vachek²  Vitezslav Kriha³  Oskar Zakiyanov¹ 

[1] Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic;Institute of Pharmacology, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic;Department of Physics, Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic;Department of Nephrology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic

关键词: Soluble receptor for advanced glycation end products;    Pregnancy-associated plasma protein-A;    Placental growth factor;    Haemodialysis;    Extracellular newly identified receptor for advanced glycation end products binding protein;    Chronic kidney disease;    Biomarkers;    Acute kidney injury;   

Others  :  1082794
DOI  :  10.1186/1471-2369-14-245

 received in 2013-07-30, accepted in 2013-10-23,  发布年份 2013

【 摘 要 】

Background

Placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A), soluble receptor for advanced glycation end products (sRAGE), extracellular newly identified receptor for RAGE binding protein (EN-RAGE) and high mobility group box 1 (HMGB-1) are novel biomarkers in chronic kidney disease (CKD). However, their clinical significance in acute kidney injury (AKI) is unknown. The aim of this cross-sectional study was to determine whether selected biomarkers are changed in AKI patients.

Methods

Serum PlGF, PAPP-A, sRAGE, EN-RAGE and HMGB-1 levels were assessed in 40 patients with AKI, 42 CKD 5 patients, 31 haemodialysis patients (HD) and 39 age-matched healthy controls.

Results

PAPP-A was elevated in AKI (20.6 ± 16.9 mIU/L) compared with controls (9.1 ± 2.3 mIU/L, p < 0.001). PlGF was not increased in AKI (11.7 ± 7.4 pg/mL) versus controls (8.5 ± 2.4 pg/mL, n.s.), as well as sRAGE was not elevated in AKI (2400 ± 1400 pg/mL) compared with controls (1760 ± 730 pg/mL, n.s), but was lower compared with CKD 5 (3200 ± 1500 pg/mL, p < 0.05); EN-RAGE was elevated in AKI 480 ± 450 ng/mL in comparison with controls (60 ± 62 ng/mL), CKD 5 (190 ± 120 ng/mL), and HD (120 ± 100 ng/mL), all p < 0.001. Similarly, HMGB-1 was increased in AKI (5.8 ± 7.5 ng/mL) versus controls (1.7 ± 1.4 ng/mL), CKD 5 (3.2 ± 3.1 ng/mL) and HD (2.5 ±2.1 ng/mL), all p < 0.001.

In AKI group, in multivariate regression analysis: PAPP–A levels were associated with transferrin (p <0.001), negatively with albumin (p < 0.01) and prealbumin (p < 0.05); PlGF levels were associated with C - reactive protein (p < 0.001). EN-RAGE levels were associated with ferritin (p < 0.01) and orosomucoid (p = 0.02), and HMGB-1 levels with leukocyte count (p < 0.01) and negatively with proteinuria (p = 0.02).

Conclusions

In AKI patients, PAPP-A, EN-RAGE and HMGB1 are elevated, but sRAGE and PlGF are not increased. Whereas PAPP-A correlates with markers of nutrition; PlGF, EN-RAGE and HMGB-1 are related to inflammatory parameters.

【 授权许可】

   
2013 Zakiyanov et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 1.

Figure 4.

Figure 5.

【 参考文献 】

• [1]Bagshaw SM, Laupland KB, Doig CJ, Mortis G, Fick GH, Mucenski M, Godinez-Luna T, Svenson LW, Rosenal T: Prognosis for long-term survival and renal recovery in critically ill patients with severe acute renal failure: a population-based study. Crit Care 2005, 9(6):R700-R709.
• [2]Wald R, Quinn RR, Luo J, Li P, Scales DC, Mamdani MM, Ray JG, Group UoTAKIR: Chronic dialysis and death among survivors of acute kidney injury requiring dialysis. JAMA 2009, 302(11):1179-1185.
• [3]Malyszko J, Bachorzewska-Gajewska H, Sitniewska E, Malyszko JS, Poniatowski B, Dobrzycki S: Serum neutrophil gelatinase-associated lipocalin as a marker of renal function in non-diabetic patients with stage 2–4 chronic kidney disease. Ren Fail 2008, 30(6):625-628.
• [4]Autiero M, Luttun A, Tjwa M, Carmeliet P: Placental growth factor and its receptor, vascular endothelial growth factor receptor-1: novel targets for stimulation of ischemic tissue revascularization and inhibition of angiogenic and inflammatory disorders. J Thromb Haemost 2003, 1(7):1356-1370.
• [5]Luttun A, Tjwa M, Moons L, Wu Y, Angelillo-Scherrer A, Liao F, Nagy JA, Hooper A, Priller J, De Klerck B, et al.: Revascularization of ischemic tissues by PlGF treatment, and inhibition of tumor angiogenesis, arthritis and atherosclerosis by anti-Flt1. Nat Med 2002, 8(8):831-840.
• [6]Onoue K, Uemura S, Takeda Y, Somekawa S, Iwama H, Imagawa K, Nishida T, Morikawa Y, Takemoto Y, Asai O, et al.: Reduction of circulating soluble fms-like tyrosine kinase-1 plays a significant role in renal dysfunction-associated aggravation of atherosclerosis. Circulation 2009, 120(24):2470-2477.
• [7]Zakiyanov O, Kalousová M, Zima T, Tesař V: Placental growth factor in patients with decreased renal function. Ren Fail 2011, 33(3):291-297.
• [8]Lawrence JB, Oxvig C, Overgaard MT, Sottrup-Jensen L, Gleich GJ, Hays LG, Yates JR, Conover CA: The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proc Natl Acad Sci U S A 1999, 96(6):3149-3153.
• [9]Lin TM, Galbert SP, Kiefer D, Spellacy WN, Gall S: Characterization of four human pregnancy-associated plasma proteins. Am J Obstet Gynecol 1974, 118(2):223-236.
• [10]Bayes-Genis A, Conover CA, Overgaard MT, Bailey KR, Christiansen M, Holmes DR, Virmani R, Oxvig C, Schwartz RS: Pregnancy-associated plasma protein A as a marker of acute coronary syndromes. N Engl J Med 2001, 345(14):1022-1029.
• [11]Kalousová M, Benáková H, Kuběna AA, Dusilová-Sulková S, Tesař V, Zima T: Pregnancy-associated plasma protein A as an independent mortality predictor in long-term hemodialysis patients. Kidney Blood Press Res 2012, 35(3):192-201.
• [12]Basta G: Receptor for advanced glycation endproducts and atherosclerosis: From basic mechanisms to clinical implications. Atherosclerosis 2008, 196(1):9-21.
• [13]Schmidt AM, Yan SD, Yan SF, Stern DM: The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Invest 2001, 108(7):949-955.
• [14]Thornalley PJ: Advanced glycation end products in renal failure. J Ren Nutr 2006, 16(3):178-184.
• [15]Jandeleit-Dahm KA, Lassila M, Allen TJ: Advanced glycation end products in diabetes-associated atherosclerosis and renal disease: interventional studies. Ann N Y Acad Sci 2005, 1043:759-766.
• [16]Kalousová M, Hodková M, Kazderová M, Fialová J, Tesar V, Dusilová-Sulková S, Zima T: Soluble receptor for advanced glycation end products in patients with decreased renal function. Am J Kidney Dis 2006, 47(3):406-411.
• [17]Basta G, Leonardis D, Mallamaci F, Cutrupi S, Pizzini P, Gaetano L, Tripepi R, Tripepi G, De Caterina R, Zoccali C: Circulating soluble receptor of advanced glycation end product inversely correlates with atherosclerosis in patients with chronic kidney disease. Kidney Int 2010, 77(3):225-231.
• [18]Moroz OV, Antson AA, Dodson EJ, Burrell HJ, Grist SJ, Lloyd RM, Maitland NJ, Dodson GG, Wilson KS, Lukanidin E, et al.: The structure of S100A12 in a hexameric form and its proposed role in receptor signalling. Acta Crystallogr D Biol Crystallogr 2002, 58(Pt 3):407-413.
• [19]Zakiyanov O, Kalousová M, Kříha V, Zima T, Tesař V: Serum S100A12 (EN-RAGE) levels in patients with decreased renal function and subclinical chronic inflammatory disease. Kidney Blood Press Res 2011, 34(6):457-464.
• [20]Nakashima A, Carrero JJ, Qureshi AR, Miyamoto T, Anderstam B, Bárány P, Heimbürger O, Stenvinkel P, Lindholm B: Effect of circulating soluble receptor for advanced glycation end products (sRAGE) and the proinflammatory RAGE ligand (EN-RAGE, S100A12) on mortality in hemodialysis patients. Clin J Am Soc Nephrol 2010, 5(12):2213-2219.
• [21]Andersson U, Erlandsson-Harris H, Yang H, Tracey KJ: HMGB1 as a DNA-binding cytokine. J Leukoc Biol 2002, 72(6):1084-1091.
• [22]Klune JR, Dhupar R, Cardinal J, Billiar TR, Tsung A: HMGB1: endogenous danger signaling. Mol Med 2008, 14(7–8):476-484.
• [23]Yu M, Wang H, Ding A, Golenbock DT, Latz E, Czura CJ, Fenton MJ, Tracey KJ, Yang H: HMGB1 signals through toll-like receptor (TLR) 4 and TLR2. Shock 2006, 26(2):174-179.
• [24]Ivanov S, Dragoi AM, Wang X, Dallacosta C, Louten J, Musco G, Sitia G, Yap GS, Wan Y, Biron CA, et al.: A novel role for HMGB1 in TLR9-mediated inflammatory responses to CpG-DNA. Blood 2007, 110(6):1970-1981.
• [25]Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, Frazier A, Yang H, Ivanova S, Borovikova L, et al.: HMG-1 as a late mediator of endotoxin lethality in mice. Science 1999, 285(5425):248-251.
• [26]Taniguchi N, Kawahara K, Yone K, Hashiguchi T, Yamakuchi M, Goto M, Inoue K, Yamada S, Ijiri K, Matsunaga S, et al.: High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine. Arthritis Rheum 2003, 48(4):971-981.
• [27]Inoue K, Kawahara K, Biswas KK, Ando K, Mitsudo K, Nobuyoshi M, Maruyama I: HMGB1 expression by activated vascular smooth muscle cells in advanced human atherosclerosis plaques. Cardiovasc Pathol 2007, 16(3):136-143.
• [28]Wu H, Ma J, Wang P, Corpuz TM, Panchapakesan U, Wyburn KR, Chadban SJ: HMGB1 contributes to kidney ischemia reperfusion injury. J Am Soc Nephrol 2010, 21(11):1878-1890.
• [29]Bruchfeld A, Qureshi AR, Lindholm B, Barany P, Yang L, Stenvinkel P, Tracey KJ: High mobility group box protein-1 correlates with renal function in chronic kidney disease (CKD). Mol Med 2008, 14(3–4):109-115.
• [30]Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P, workgroup ADQI: Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004, 8(4):R204-R212.
• [31]Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med 1999, 130(6):461-470.
• [32]Shlipak MG, Fried LF, Crump C, Bleyer AJ, Manolio TA, Tracy RP, Furberg CD, Psaty BM: Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency. Circulation 2003, 107(1):87-92.
• [33]Xie Q, Zhou Y, Xu Z, Yang Y, Kuang D, You H, Ma S, Hao C, Gu Y, Lin S, et al.: The ratio of CRP to prealbumin levels predict mortality in patients with hospital-acquired acute kidney injury. BMC Nephrol 2011, 12:30.
• [34]Perez Valdivieso JR, Bes-Rastrollo M, Monedero P, de Irala J, Lavilla FJ: Impact of prealbumin levels on mortality in patients with acute kidney injury: an observational cohort study. J Ren Nutr 2008, 18(3):262-268.
• [35]Zoccali C, Mallamaci F, Tripepi G, Cutrupi S, Parlongo S, Malatino LS, Bonanno G, Rapisarda F, Fatuzzo P, Seminara G, et al.: Fibrinogen, mortality and incident cardiovascular complications in end-stage renal failure. J Intern Med 2003, 254(2):132-139.
• [36]Goicoechea M, de Vinuesa SG, Gómez-Campderá F, Aragoncillo I, Verdalles U, Mosse A, Luño J: Serum fibrinogen levels are an independent predictor of mortality in patients with chronic kidney disease (CKD) stages 3 and 4. Kidney Int Suppl 2008, 111:S67-S70.
• [37]Malyszko J, Malyszko JS, Pawlak D, Pawlak K, Buczko W, Mysliwiec M: Hemostasis, platelet function and serotonin in acute and chronic renal failure. Thromb Res 1996, 83(5):351-361.
• [38]Kalousová M, Zima T, Tesar V, Sulková S, Fialová L: Relationship between advanced glycoxidation end products, inflammatory markers/acute-phase reactants, and some autoantibodies in chronic hemodialysis patients. Kidney Int Suppl 2003, 84:S62-S64.
• [39]Kalousová M, Bartosová K, Zima T, Skibová J, Teplan V, Viklický O: Pregnancy-associated plasma protein a and soluble receptor for advanced glycation end products after kidney transplantation. Kidney Blood Press Res 2007, 30(1):31-37.
• [40]Fialová L, Kalousová M, Soukupová J, Sulková S, Merta M, Jelínková E, Horejsí M, Srámek P, Malbohan I, Mikulíková L, et al.: Relationship of pregnancy-associated plasma protein-a to renal function and dialysis modalities. Kidney Blood Press Res 2004, 27(2):88-95.
• [41]Sadik NA, Mohamed WA, Ahmed MI: The association of receptor of advanced glycated end products and inflammatory mediators contributes to endothelial dysfunction in a prospective study of acute kidney injury patients with sepsis. Mol Cell Biochem 2012, 359(1–2):73-81.
• [42]Kalousová M, Jáchymová M, Mestek O, Hodková M, Kazderová M, Tesar V, Zima T: Receptor for advanced glycation end products–soluble form and gene polymorphisms in chronic haemodialysis patients. Nephrol Dial Transplant 2007, 22(7):2020-2026.
• [43]Kim JK, Park S, Lee MJ, Song YR, Han SH, Kim SG, Kang SW, Choi KH, Kim HJ, Yoo TH: Plasma levels of soluble receptor for advanced glycation end products (sRAGE) and proinflammatory ligand for RAGE (EN-RAGE) are associated with carotid atherosclerosis in patients with peritoneal dialysis. Atherosclerosis 2012, 220(1):208-214.
• [44]Shiotsu Y, Mori Y, Nishimura M, Sakoda C, Tokoro T, Hatta T, Maki N, Iida K, Iwamoto N, Ono T, et al.: Plasma S100A12 level is associated with cardiovascular disease in hemodialysis patients. Clin J Am Soc Nephrol 2011, 6(4):718-723.
• [45]Kalousová M, Kuběna AA, Benáková H, Dusilová-Sulková S, Tesař V, Zima T: EN-RAGE (extracellular newly identified receptor for advanced glycation end-products binding protein) and mortality of long-term hemodialysis patients: A prospective observational cohort study. Clin Biochem 2012, 45(7–8):556-560.
• [46]Hochepied T, Berger FG, Baumann H, Libert C: Alpha(1)-acid glycoprotein: an acute phase protein with inflammatory and immunomodulating properties. Cytokine Growth Factor Rev 2003, 14(1):25-34.
• [47]Osikov MV: Role of orosomucoid in the regulation of plasma proteolytic systems during experimental renal failure. Bull Exp Biol Med 2009, 148(1):20-22.
• [48]Yang H, Ochani M, Li J, Qiang X, Tanovic M, Harris HE, Susarla SM, Ulloa L, Wang H, DiRaimo R, et al.: Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci USA 2004, 101(1):296-301.
• [49]Wang H, Liao H, Ochani M, Justiniani M, Lin X, Yang L, Al-Abed Y, Metz C, Miller EJ, Tracey KJ, et al.: Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis. Nat Med 2004, 10(11):1216-1221.
• [50]Bonaldi T, Talamo F, Scaffidi P, Ferrera D, Porto A, Bachi A, Rubartelli A, Agresti A, Bianchi ME: Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J 2003, 22(20):5551-5560.
• [51]Lotze MT, Tracey KJ: High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol 2005, 5(4):331-342.
• [52]Wang H, Zhu S, Zhou R, Li W, Sama AE: Therapeutic potential of HMGB1-targeting agents in sepsis. Expert Rev Mol Med 2008, 10:e32.
• [53]Scaffidi P, Misteli T, Bianchi ME: Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 2002, 418(6894):191-195.
• [54]Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, et al.: Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005, 294(7):813-818.
• [55]Lauzurica R, Pastor C, Bayés B, Hernández JM, Romero R: Pretransplant pregnancy-associated plasma protein-a as a predictor of chronic allograft nephropathy and posttransplant cardiovascular events. Transplantation 2005, 80(10):1441-1446.
• [56]Zhang Z, Dai H, Yu Y, Yang J, Chen J, Wu L: Elevated pregnancy-associated plasma protein A predicts myocardial dysfunction and death in severe sepsis. Ann Clin Biochem 2013. 10.1177/0004563213489275
• [57]Yano K, Okada Y, Beldi G, Shih SC, Bodyak N, Okada H, Kang PM, Luscinskas W, Robson SC, Carmeliet P, et al.: Elevated levels of placental growth factor represent an adaptive host response in sepsis. J Exp Med 2008, 205(11):2623-2631.
• [58]Yano K, Liaw PC, Mullington JM, Shih SC, Okada H, Bodyak N, Kang PM, Toltl L, Belikoff B, Buras J, et al.: Vascular endothelial growth factor is an important determinant of sepsis morbidity and mortality. J Exp Med 2006, 203(6):1447-1458.
• [59]Narvaez-Rivera RM, Rendon A, Salinas-Carmona MC, Rosas-Taraco AG: Soluble RAGE as a severity marker in community acquired pneumonia associated sepsis. BMC Infect Dis 2012, 12:15.
• [60]Bopp C, Hofer S, Weitz J, Bierhaus A, Nawroth PP, Martin E, Büchler MW, Weigand MA: sRAGE is elevated in septic patients and associated with patients outcome. J Surg Res 2008, 147(1):79-83.
• [61]Achouiti A, Föll D, Vogl T, van Till JW, Laterre PF, Dugernier T, Wittebole X, Boermeester MA, Roth J, van der Poll T, et al.: S100A12 And soluble receptor for advanced glycation end products levels during human severe sepsis. Shock 2013, 40(3):188-194.
• [62]Mantell LL, Parrish WR, Ulloa L: Hmgb-1 as a therapeutic target for infectious and inflammatory disorders. Shock 2006, 25(1):4-11.
• [63]Ulloa L, Messmer D: High-mobility group box 1 (HMGB1) protein: friend and foe. Cytokine Growth Factor Rev 2006, 17(3):189-201.
• [64]Sundén-Cullberg J, Norrby-Teglund A, Rouhiainen A, Rauvala H, Herman G, Tracey KJ, Lee ML, Andersson J, Tokics L, Treutiger CJ: Persistent elevation of high mobility group box-1 protein (HMGB1) in patients with severe sepsis and septic shock. Crit Care Med 2005, 33(3):564-573.