Suramin Attenuates Renal Fibrosis Results Suramin inhibits glomerular and vascular sclerosis in rat remnant kidneys We recently showed that suramin prevented progressive renal injury as demonstrated by inhibition of a rise in 24 hour-protein excretion and a rise in serum creatinine by preserving renal tissue architecture and preventing the development of renal interstitial fibrosis in the rat model of remnant kidney disease [12]. As glomerular and vascular sclerosis are also two major pathogenetic changes in the model of remnant kidneys, we further examined the effect of suramin on those events. As shown in Figure 1 and 2, after 4- weeks of renal ablation, 15% of glomeruli were damaged and displayed segmental and focal solidification and sclerosis of the glomerular tuft (Fig. 1A). Forty percent of renal arteries also show an onion skin-like change, indicating vascular sclerosis in the remnant kidney (Fig. 2A). By comparison, very few sclerotic glomeruli and arteries were observed in the kidney of animals that received suramin treatment. There were no obvious pathological changes in the kidney of both sham and suramin alone-treated animals. Masson trichrome staining showed increased deposition of collagen fibrils in glomeruli and blood vessels following the 5/6 renal ablation (Fig. 1B, 2B). Administration of suramin diminished deposition of collagen fibrils in glomeruli and blood vessels. Perivascular collagen fibril deposition around small arteries also increased, but was suppressed by suramin treatment. Notably, in the normal kidney, expression of ECM protein was seen in perivascular areas (positive on Masson trichome staining) and was not affected by suramin (Fig. 2B). This data, together with our previous observation that suramin inhibits the development of renal interstitial fibrosis, suggests that suramin application has renoprotective properties and is able to prevent the development of fibrotic lesions in all areas including glomeruli and arteries in the remnant kidney. Suramin reduces infiltration of monocytes/macrophages to the remnant kidney Kidney fibrosis is almost always preceded by and closely associated with chronic interstitial inflammation [23,28,29,30]. Macrophage infiltration and proliferation functionally contributes to the fibrotic process after injury [31,32]. To determine the effect of Figure 2. Effect of suramin on vascular sclerosis in rat remnant kidney. (A) Photomicrographs (4006) illustrating periodic acid-Schiff-stained sections of kidney tissue on week 4 after various treatments as indicated. (B) Photomicrographs (4006) illustrating trichrome stained kidney tissue on week 4 after various treatments. RK, remnant kidney. doi:10.1371/journal.pone.0036194.g002 PLoS ONE | www.plosone.org 3 April 2012 | Volume 7 | Issue 4 | e36194