5.2.3. KIM-1

KIM-1 is a type I membrane protein of 104 kDa composed of a 14 kDa membrane-bound fragment and a 90 kDa soluble portion [73]. It was isolated from T-cells, exhibits various functions, and was termed T-cell immunoglobulin-and-mucin-domain-containing molecule-1 (TIM-1) [73]. Normal kidney tissue rarely expresses KIM-1, but kidneys acutely injured by ischemia, hypoxia, toxicity, or renal tubular interstitial/polycystic kidney disease do [74]. The ectodomain of KIM-1 (90 kD) is cleaved by matrix metalloproteinases and is found in urine after injury to the kidney proximal tubules [75]. Acute KIM-1 overexpression in proximal, renal tubular epithelial cells after ischemia, hypoxia, or toxicity promotes the transformation of these cells into semi-professional phagocytic cells. KIM-1 is a phosphatidylserine receptor of the liposome surface and identifies both apoptotic bodies and phosphatidylserine, triggering further phagocytosis [74,76]. The upregulation of KIM-1 by injured tubular epithelial cells facilitates the clearance of apoptotic cells, protecting against AKI. Apart from mediating phagocytosis, KIM-1 assists in repairing injury to cells [77]. It is a valuable biomarker of AKI. Urine and/or serum KIM-1 levels increase after ischemic kidney injury [75] and in patients with diabetic nephropathy [78], IgA nephropathy [79], and kidney injury after renal transplantation [80]. In an animal model, serum and urine KIM-1 levels were useful for the early diagnosis of obstructive nephropathy-induced AKI [81,82]. In a mouse model, serum KIM-1 levels increased after UUTO, peaking on day 3, and remained detectable for 14 days [82]. In a rat model, the urine KIM-1 level began to increase on day 1 after UUTO and remained high until day 7 [81]. In children with UUTO, urine KIM1 levels correlated inversely with worsening obstruction and decreased after surgery [34,36,45,48,49]. The AUC-ROC value for the prediction of childhood UUTO is 0.65–0.89 for the bladder urine KIM-1 level (Table 1) [34,36,45,49]. In adults with UUTO, the urine KIM-1 level is a useful marker of obstructive nephropathy (AUCs of 0.57–0.73 for bladder urine and 0.88 for renal pelvic urine) [23,50,51]. Xie found that the urine KIM-1 level after surgery to treat UUTO predicted renal function deterioration [83].
