Abstract P432: The Effect of Carbonyl Stress on Renal Injury Induced by Renal Congestion

Abstract

Background: Due to the functional linkage between cardiac function and renal function, a decline in renal function exacerbates cardiac function and a decline in cardiac function exacerbates renal function. Renal congestion is reported to contribute to the decline of renal function in heart failure patients. Regarding the mechanism of kidney failure caused by congestion, although it is suggested that ischemia is involved due to an increase in venous pressure and a decrease in blood flow, it has not been sufficiently elucidated. Since overexpression of glyoxylose-1 (GLO1), a methylglyoxal (MG) metabolizing enzyme, which is a type of carbonyl stress, has been reported to attenuate impairment due to renal ischemia reperfusion (I/R). In this study, we aimed to investigate the effect of carbonyl stress on kidney damage due to renal congestion using GLO1 overexpressing rats. Methods: Male Wistar wild type (WT) rat and GLO1 transgenic (GLO1) rat were used for experiment. Left kidney was congested by placing silver clip on left renal vein under anesthesia. Two weeks after surgery, renal cortical and outer medullary mRNA markers of fibrosis [transforming growth factor-β (TGF-β) and fibronectin (FN)], tubular injury [osteopontin (OPN) and kidney injury molecule 1 (KIM-1)] and inflammations [monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α)] were measured. Results; Relative mRNA expression of cortical TGF-β (contralateral kidney; 1.00 + 0.09, congested kidney; 2.44 + 0.33, respectively), FN (1.00 + 0.11, 2.71 + 0.46), OPN (1.00 + 0.18, 6.41 + 1.47), KIM-1 (1.00 + 0.59, 21.20 + 6.31), MCP-1 (1.00 + 0.24, 2.93 + 0.56) and TNF-α (1.00 + 0.14, 1.62 + 0.18) were significantly increased in congested kidney compared to contralateral kidney. Relative mRNA expression of cortical TGF-β (GLO1tg; 1.69 + 0.20, WT; 2.44 + 0.33, respectively), FN (1.53 + 0.33, 2.71 + 0.46), TNF-α (1.00 + 0.14, 1.62 + 0.18) in GLO1tg rat were significantly decreased compared to WT rat. No significant change was observed between renal medullary area of WT rat and GLO1tg rat. Conclusion: Renal congestion induces renal fibrosis, tubular injury and inflammation, and carbonyl stress which could contribute to the pathophysiological mechanism on renal injury in cardiac failure.