Antithrombin III prevents progression of chronic kidney disease following experimental ischaemic-reperfusion injury
Jianyong Yin, Feng Wang, Yiwei Kong, Rui Wu, Guangyuan Zhang, Niansong Wang, Ling Wang, Zeyuan Lu, Mingyu Liang, Jianyong Yin, Feng Wang, Yiwei Kong, Rui Wu, Guangyuan Zhang, Niansong Wang, Ling Wang, Zeyuan Lu, Mingyu Liang
Abstract
Acute kidney disease (AKI) leads to increased risk of progression to chronic kidney disease (CKD). Antithrombin III (ATIII) is a potent anticoagulant with anti-inflammatory properties, and we previously reported that insufficiencies of ATIII exacerbated renal ischaemia-reperfusion injury (IRI) in rats. In this study, we examined the characteristic of AKI-CKD transition in rats with two distinct AKI models. Based on our observation, left IRI plus right nephrectomy (NX-IRI) was used to determine whether ATIII had therapeutic effects in preventing CKD progression after AKI. It was observed that NX-IRI resulted in significant functional and histological damage at 5 weeks after NX-IRI compared with sham rats, which was mitigated by ATIII administration. Besides, we noticed that ATIII administration significantly reduced NX-IRI-induced interstitial fibrosis. Consistently, renal expression of collagen-1, α-smooth muscle actin and fibronectin were substantial diminished in ATIII-administered rats compared with un-treated NX-IRI rats. Furthermore, the beneficial effects of ATIII were accompanied with decreased M1-like macrophage recruitment and down-regulation of M1-like macrophage-dependent pro-inflammatory cytokines such as tumour necrosis factor α, inducible nitric oxide synthase and interleukin-1β, indicating that ATIII prevented AKI-CKD transition via inhibiting inflammation. Overall, ATIII shows potential as a therapeutic strategy for the prevention of CKD progression after AKI.
Keywords: acute kidney injury; antithrombin III; chronic kidney disease.
© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
Figures
References
- Ruiz‐Criado J, Ramos‐Barron MA, Fernandez‐Fresnedo G, et al Long‐term mortality among hospitalized non‐ICU patients with acute kidney injury referred to nephrology. Nephron. 2015; 131: 23–33.
- Coca SG, Yusuf B, Shlipak MG, et al Long‐term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta‐analysis. Am J Kidney Dis. 2009; 53: 961–73.
- Brown JR, Rezaee ME, Marshall EJ, et al Hospital mortality in the United States following acute kidney injury. Biomed Res Int. 2016; 2016: 4278579.
- Xue JL, Daniels F, Star RA, et al Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001. J Am Soc Nephrol. 2006; 17: 1135–42.
- Waikar SS, Curhan GC, Wald R, et al Declining mortality in patients with acute renal failure, 1988 to 2002. J Am Soc Nephrol. 2006; 17: 1143–50.
- Coca SG, Singanamala S, Parikh CR. Chronic kidney disease after acute kidney injury: a systematic review and meta‐analysis. Kidney Int. 2012; 81: 442–8.
- Chawla LS, Eggers PW, Star RA, et al Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med. 2014; 371: 58–66.
- Basile DP, Bonventre JV, Mehta R, et al Progression after AKI: understanding Maladaptive Repair Processes to Predict and Identify Therapeutic Treatments. J Am Soc Nephrol. 2016; 27: 687–97.
- Venkatachalam MA, Weinberg JM, Kriz W, et al Failed tubule recovery, AKI‐CKD transition, and kidney disease progression. J Am Soc Nephrol. 2015; 26: 1765–76.
- Bonventre JV. Maladaptive proximal tubule repair: cell cycle arrest. Nephron Clin Pract. 2014; 127: 61–4.
- Tanaka S, Tanaka T, Nangaku M. Hypoxia as a key player in the AKI‐to‐CKD transition. Am J Physiol Renal Physiol. 2014; 307: F1187–95.
- Mehrotra P, Patel JB, Ivancic CM, et al Th‐17 cell activation in response to high salt following acute kidney injury is associated with progressive fibrosis and attenuated by AT‐1R antagonism. Kidney Int. 2015; 88: 776–84.
- Lech M, Grobmayr R, Ryu M, et al Macrophage phenotype controls long‐term AKI outcomes–kidney regeneration versus atrophy. J Am Soc Nephrol. 2014; 25: 292–304.
- Kinsey GR. Macrophage dynamics in AKI to CKD progression. J Am Soc Nephrol. 2014; 25: 209–11.
- Dunzendorfer S, Kaneider N, Rabensteiner A, et al Cell‐surface heparan sulfate proteoglycan‐mediated regulation of human neutrophil migration by the serpin antithrombin III. Blood. 2001; 97: 1079–85.
- Kellner P, Nestler F, Leimert A, et al Antithrombin III, but not C1 esterase inhibitor reduces inflammatory response in lipopolysaccharide‐stimulated human monocytes in an ex‐vivo whole blood setting. Cytokine. 2014; 70: 173–8.
- Ozden A, Sarioglu A, Demirkan NC, et al Antithrombin III reduces renal ischemia‐reperfusion injury in rats. Res Exp Med (Berl). 2001; 200: 195–203.
- Harada N, Okajima K, Uchiba M, et al Antithrombin reduces ischemia/reperfusion‐induced liver injury in rats by activation of cyclooxygenase‐1. Thromb Haemost. 2004; 92: 550–8.
- Wang F, Zhang G, Lu Z, et al Antithrombin III/SerpinC1 insufficiency exacerbates renal ischemia/reperfusion injury. Kidney Int. 2015; 88: 796–803.
- Hagiwara S, Iwasaka H, Shingu C, et al Antithrombin III prevents cerulein‐induced acute pancreatitis in rats. Pancreas. 2009; 38: 746–51.
- Xu J, Li PX, Wu J, et al Involvement of the Hippo pathway in regeneration and fibrogenesis after ischaemic acute kidney injury: YAP is the key effector. Clin Sci. 2016; 130: 349–63.
- Yin J, Lu Z, Wang F, et al Renalase attenuates hypertension, renal injury and cardiac remodelling in rats with subtotal nephrectomy. J Cell Mol Med. 2016; 20: 1106–17.
- Wang F, Cai H, Zhao Q, et al Epinephrine evokes renalase secretion via alpha‐adrenoceptor/NF‐kappaB pathways in renal proximal tubular epithelial cells. Kidney Blood Press Res. 2014; 39: 252–9.
- Chawla LS, Amdur RL, Amodeo S, et al The severity of acute kidney injury predicts progression to chronic kidney disease. Kidney Int. 2011; 79: 1361–9.
- Ishani A, Xue JL, Himmelfarb J, et al Acute kidney injury increases risk of ESRD among elderly. J Am Soc Nephrol. 2009; 20: 223–8.
- Palant CE, Amdur RL, Chawla LS. The acute kidney injury to chronic kidney disease transition: a potential opportunity to improve care in acute kidney injury. Contrib Nephrol. 2016; 187: 55–72.
- Heung M, Chawla LS. Predicting progression to chronic kidney disease after recovery from acute kidney injury. Curr Opin Nephrol Hypertens. 2012; 21: 628–34.
- Shi M, Flores B, Gillings N, et al Alphaklotho mitigates progression of AKI to CKD through activation of autophagy. J Am Soc Nephrol. 2016; 27: 2331–45.
- Ishani A, Nelson D, Clothier B, et al The magnitude of acute serum creatinine increase after cardiac surgery and the risk of chronic kidney disease, progression of kidney disease, and death. Arch Intern Med. 2011; 171: 226–33.
- Basile DP, Friedrich JL, Spahic J, et al Impaired endothelial proliferation and mesenchymal transition contribute to vascular rarefaction following acute kidney injury. Am J Physiol Renal Physiol. 2011; 300: F721–33.
- Basile DP, Leonard EC, Tonade D, et al Distinct effects on long‐term function of injured and contralateral kidneys following unilateral renal ischemia‐reperfusion. Am J Physiol Renal Physiol. 2012; 302: F625–35.
- Ostrovsky L, Woodman RC, Payne D, et al Antithrombin III prevents and rapidly reverses leukocyte recruitment in ischemia/reperfusion. Circulation. 1997; 96: 2302–10.
- Yamashiro K, Kiryu J, Tsujikawa A, et al Inhibitory effects of antithrombin III against leukocyte rolling and infiltration during endotoxin‐induced uveitis in rats. Invest Ophthalmol Vis Sci. 2001; 42: 1553–60.
- Souter PJ, Thomas S, Hubbard AR, et al Antithrombin inhibits lipopolysaccharide‐induced tissue factor and interleukin‐6 production by mononuclear cells, human umbilical vein endothelial cells, and whole blood. Crit Care Med. 2001; 29: 134–9.
- Zuo XJ, Okada Y, Nicolaidou E, et al Antithrombin III inhibits T and B lymphocyte activation in vitro and improves parameters of inflammation in a rat model of acute lung allograft rejection. Transpl Proc. 1999; 31: 847–8.
- Oelschlager C, Romisch J, Staubitz A, et al Antithrombin III inhibits nuclear factor kappaB activation in human monocytes and vascular endothelial cells. Blood. 2002; 99: 4015–20.
- Baek JH, Zeng R, Weinmann‐Menke J, et al IL‐34 mediates acute kidney injury and worsens subsequent chronic kidney disease. J Clin Investig. 2015; 125: 3198–214.
- Szeto HH, Liu S, Soong Y, et al Mitochondria protection after acute ischemia prevents prolonged upregulation of IL‐1beta and IL‐18 and arrests CKD. J Am Soc Nephrol. 2016; 28: 1437–49.
Source: PubMed