Volume 64, Issue 6, Pages 2172-2181 (December 2003) Cyclooxygenase-2 (COX-2) inhibition limits abnormal COX-2 expression and progressive injury in the remnant kidney  Clarice Kazue Fujihara, Gláucia Rutigliano Antunes, A.N.A. Lúcia Mattar, Natalie Andreoli, Denise Maria Avancini, Costa Malheiros, Irene Lourdes Noronha, Roberto Zatz  Kidney International  Volume 64, Issue 6, Pages 2172-2181 (December 2003) DOI: 10.1046/j.1523-1755.2003.00319.x Copyright © 2003 International Society of Nephrology Terms and Conditions

Figure 1 Parameters of renal injury/inflammation 60days after renal ablation in sham (S) group, sham + celecoxib (S + CEL), renal ablation (Nx), and renal ablation + celecoxib (Nx + CEL). (A) Glomerulosclerosis index (GSI).(B) Fractional cortical interstitial area (%INT). (C) Percent vascular injury (%VASC). (D) Extent of macrophage infiltration (Mφ). *P < 0.05 vs. respective sham group; †P < 0.05 vs. respective untreated group. Kidney International 2003 64, 2172-2181DOI: (10.1046/j.1523-1755.2003.00319.x) Copyright © 2003 International Society of Nephrology Terms and Conditions

Figure 2 Cyclooxygenase-2 (COX-2) expression followed four typical patterns in this study (positive cells appear heavily stained). (A) Macula densa staining observed in all groups. (B) Glomerular infiltration by COX-2–positive cells. Note that in this case the infiltration concentrated at a sclerosing area. (C) Interstitial infiltration by COX-2–positive cells, appearing mostly in inflamed areas. (D) Infiltration of arterial/arteriolar walls by COX-2–positive cells, following an “onion skin” pattern. Patterns exemplified in (B, C, and D) appeared only in renal ablation group and, to a lesser extent, in the renal ablation group given celecoxib. Kidney International 2003 64, 2172-2181DOI: (10.1046/j.1523-1755.2003.00319.x) Copyright © 2003 International Society of Nephrology Terms and Conditions

Figure 3 Graphic representation of the expression of cyclooxygenase-2 (COX-2) at the macula densa (A), glomeruli (B), interstitial area (C) and arteries/arterioles (D) in the four groups studied.*P < 0.05 vs. respective sham group; †P < 0.05 vs. respective untreated group. Abbreviations are: S, sham group; S + CEL, sham + celecoxib; Nx, renal ablation, and Nx + CEL, renal ablation + celecoxib. Kidney International 2003 64, 2172-2181DOI: (10.1046/j.1523-1755.2003.00319.x) Copyright © 2003 International Society of Nephrology Terms and Conditions

Figure 4 Parameters of renal injury represented as a function of cyclooxygenase-2 (COX-2) expression. The extent of injury at the glomeruli, cortical interstitium, and vessels correlated positively and significantly with the respective “ectopic” expression of COX-2, but not with the expression of COX-2 at the macula densa (data not shown). (A) Glomerulosclerosis index (GSI) vs. the intensity of COX-2 staining at the glomerular tuft (expressed as stained cells/100 glomerular profiles). (B) Fraction of the cortical area occupied by interstitial matrix (%INT) vs. the intensity of COX-2 staining at the interstitium (expressed as stained cells/mm2). (C) Percent of arterial/arteriolar profiles exhibiting wall injury (%VASC) vs. intensity of COX-2 staining at the vessels (expressed as stained cells/100 vascular profiles). Kidney International 2003 64, 2172-2181DOI: (10.1046/j.1523-1755.2003.00319.x) Copyright © 2003 International Society of Nephrology Terms and Conditions