5.2.2. MCP-1

MCP-1, a 13 kDa protein, is a potent attractant of monocytes and a member of the CC subfamily [56]. It is produced by many types of cells, including epithelial, endothelial, and smooth muscle cells; fibroblasts, astrocytes, and monocytes; and microglial cells. MCP-1 recruits monocytes, memory T-cells, and dendritic cells to sites of tissue injury and infection; monocytes and macrophages are the major sources of MCP-1 [57]. MCP-1 mRNA is undetectable in the normal kidney, but MCP-1 gene expression is markedly increased at the tubulointerstitial level in UPJO biopsy samples and correlates with the extent of monocyte infiltration [58,59]. In one experimental study, mice deficient in MCP-1 exhibited significantly decreased survival and increased renal damage after ischemia/reperfusion-induced renal tubular injury in the absence of macrophage accumulation [60]. Kidneys and primary tubular epithelial cells from such mice exhibited increased apoptosis after ischemia, which indicates that MCP-1 protects the kidney from the acute inflammatory response that develops after kidney injury. MCP-1 is one of the most promising biomarkers of kidney injury [61]. Elevated MCP-1 levels are associated with immune system-mediated kidney injury [62,63], diabetic nephropathy [64], and autosomal-dominant polycystic kidney disease [65]. In a mouse model of UUTO, serum and urine MCP-1 levels increased significantly compared to those of control mice [66]. mRNA expression and urinary excretion of MCP-1 correlate with the extent of the obstruction, subsequent renal damage, and hydronephrosis. Urine levels of MCP-1 decrease after release of the obstruction [67]. Urine MCP-1 levels are significantly increased in UPJO groups compared to controls and fall significantly after surgery [24,36,46,59,68–70]. The AUC-ROC values in terms of the presence of UUTO are 0.70–0.93 for bladder urine MCP-1 and 0.89 for renal pelvic urine MCP-1 (Table 1) [24,36,46,68,69]. An inverse correlation is evident between the level of MCP-1 in renal pelvic urine and mertiatide clearance by the affected kidney [59,69]. Urine MCP-1 levels usefully distinguish between UPJO (which requires pyeloplasty) and the absence of an obstructive dilation of the renal pelvis. They can be used to monitor the resolution of kidney

damage after surgery for UUTO [36]. Serum MCP-1 levels increase in patients with AKI after cardiac surgery and in those with chronic kidney damage [60,71,72], but no study has yet evaluated the serum MCP-1 level as a biomarker of UUTO in a clinical setting.
