Determinant of histopathological findings of kidney parenchyma by day 60 after CRS procedure. A-F: Light microscopic findings (400 ×) of HE stain illustrating remarkably increased in loss of brush border in renal tubules (yellow arrows), tubular necrosis (green arrows), tubular dilatation (red asterisk) protein cast formation (black asterisk), and dilatation of Bowman’s capsule (blue arrows) in CRS group than in other groups. G: Kidney injury score, * vs. other groups with different symbols (†, ‡, §, ¶, #), P<0.0001. Scale bars in right lower corner represent 20 µm. All statistical analyses were performed by one-way ANOVA, followed by Bonferroni multiple comparison post hoc test (n = 8 for each group). Symbols (*, †, ‡, §, ¶, #) indicate significance (at 0.05 level). SC = sham control; CKD = chronic kidney disease; CRS = cardiorenal syndrome; Mel = melatonin; Ex4 = exendin-4.