Indicators of renal fibrosis in children receiving conservative treatment for chronic kidney disease
More details
Hide details
Katedra i Klinika Nefrologii Pediatrycznej, Wrocławski Uniwersytet Medyczny
Corresponding author
Kinga Musiał
Katedra i Klinika Nefrologii Pediatrycznej, Wrocławski Uniwersytet Medyczny, ul. Borowska 213, 50-556 Wrocław
Med Og Nauk Zdr. 2013;19(1):41-44
Background and Objective:
Matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs), adhesion molecules and heat shock proteins (hsp) may play an essential role in the process of renal fibrosis, but the data concerning such influence in the patients with chronic kidney disease (CKD) on conservative treatment are scarce. The objective of the study was to assess the concentrations of Hsp90a, sE-selectin, MMP-2, TIMP-1 and TIMP-2 in the predialysis CKD children and potential relations between these parameters.

Material and Methods:
65 children were enrolled in the study and divided into those with CKD stage 3-4 (CKD I) and CKD stage 5 (CKD II). 30 age-matched subjects with primary nocturnal enuresis and normal kidney function served as controls. The serum concentrations of Hsp90a, sE-selectin, MMP-2, TIMP-1 and TIMP-2 were assessed by ELISA.

The median values of Hsp90a, sE-selectin, MMP-2, TIMP-1 and TIMP-2 were significantly elevated in CKD patients vs. controls. The concentrations kept growing together with the progressing renal failure in the case of sE-selectin and MMP-2, remained unchanged in the case og TIMP-1 and TIMP-2, whereas diminished in the case of Hsp90a. Several correlations between examined parameters were noticed.

Conclusions. The increased concentrations of Hsp90a, sE-selectin, MMP-2, TIMP-1 and TIMP-2 indicate the enhanced cell damage, aggravation of inflammatory and proteolytic processes, responsible for progression of interstitial renal fibrosis in CKD children. Differences in behaviour of selected parameters in the course of renal failure progression suggest the diversity of their engagement in various stages of CKD

Sharma AK, Mauer SM, Kim Y, Michael AF. Altered expression of matrix metalloproteinase-2, TIMP-1 and TIMP-2 in obstructive nephropathy. J Lab Clin Med. 1995; 125(6): 754–761.
Iimura O, Takahashi H, Yashiro T, Madoiwa S, Sakata Y, Asano Y, Kusano E. Effect of ureteral obstruction on matrix metalloproteinase-2 in rat renal cortex. Clin Exp Nephrol. 2004; 8(3): 223–229.
Lopez-Hernandez FJ, Lopez-Novoa JM. Role of TGF-b in chronic kidney disease: an integration of tubular, glomerular and vascular effects. Cell Tissue Res. 2012; 347(1): 141–154.
Musiał K, Zwolińska D, Polak-Jonkisz D, Berny U, Szprynger K, Szczepańska M. Serum VCAM-1, ICAM-1 and L-selectin levels in children and young adults with chronic renal failure. Pediatr Nephrol. 2005; 20(1): 52–55.
Mosser DM, Edwards JP. Exploring the full spectrum of macrophage activation. Nat Rev Immunol. 2008; 8(12): 958–969.
Sean Eardley K, Cockwell P. Macrophages and progressive tubulointerstitial disease. Kidney Int. 2005; 68(2): 437–455.
Du X, Shimizu A, Masuda Y, Kuwahara N, Arai T, Kataoka M, Uchiyama M, Kaneko T, Akimoto T, Iino Y, Fukuda Y. Involvement of matrix metalloproteinase-2 in the development of renal interstitial fibrosis in mouse obstructive nephropathy. Lab Invest. 2012; 92(8): 1149–1160.
Noh H, Kim HJ, Yu MR, Kim WY, Kim J, Ryu JH, Kwon SH, Jeon JS, Han DC, Ziyadeh F. Heat shock protein 90 inhibitor attenuates renal fibrosis through degradation of transforming growth factor-b type II receptor. Lab Invest. 2012; 92(11): 1583–1596.
Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009; 20(3): 629–637.
Musiał K, Zwolińska D. Matrix metalloproteinases (MMP-2,9) and their tissue inhibitors (TIMP-1,2) as novel markers of stress response and atherogenesis in children with chronic kidney disease (CKD) on conservative treatment. Cell Stress Chaperones 2011; 16(1): 97–103.
Lutz J, Yao Y, Song E, Antus B, Hamar P, Liu S, Heemann U. Inhibition of matrix metalloproteinases during chronic allograft nephropathy in rats. Transplantation 2005; 79(6): 655–661.
Nishida M, Okumura Y, Ozawa S, Shiraishi I, Itoi T, Hamaoka K. MMP-2 inhibition reduces renal macrophage infiltration with increased fibrosis in UUO. Biochem Biophys Res Commun. 2007; 354(1): 133–139.
Joly AL, Wettstein G, Mignot G, Ghiringhelli F, Garrido C. Dual role of heat shock proteins as regulators of apoptosis and innate immunity. J Innate Immun. 2010; 2(3): 238–247.
Srivastava P. Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses. Annu Rev Immunol. 2002; 20: 395–425.
Rosin DL, Okusa MD. Dangers within: DAMP responses to damage and cell death in kidney disease. J Am Soc Nephrol. 2011; 22(3): 416–425.
Journals System - logo
Scroll to top