Kidney Injury Molecule-1 (KIM-1): an early novel biomarker for Acute Kidney Injury (AKI) in critically - ill patients

Background: Acute Kidney Injury (AKI) is a major cause of morbidity and mortality especially in critically-ill patients. The lack of early biomarkers for AKI in humans has interfered with potentially effective therapies in a timely manner. Kidney Injury Molecule-1 (KIM-1) is a type I cell membrane glycoprotein, which is associated with proximal tubule cell injury/dedifferentiation. Presence of KIM-1 in the urine is highly specific for kidney injury as indicated by absence of its expression in the normal kidney; its marked upregulation with proximal tubular cell injury and/or differentiation. Objective: To investigate the role of KIM-1 as an early marker for AKI in critically-ill patients. Methods: The study was carried out on 20 critically-ill patients who were at risk for developing AKI. Other 20 healthy subjects were included as control. The Sequential Organ Failure Assessment (SOFA) score was chosen to select critically-ill patients. All candidates were subjected to thorough history taking, complete clinical examination including assessment of Glasgow coma scale & urine output as well as laboratory investigations including urinary KIM-1 (by ELISA), blood urea, serum creatinine, arterial blood gases, platelet count and serum bilirubin. Results: The results of our study have shown that there were no significant statistical differences between patient and control group as regards gender (12 females and 8 males for both groups) and age (51.90 +/- 16.32 years for patient group and 51.60 +/- 13.67 years for the control group) with p. value of 0.950 and 0.988 respectively. Our study has shown that KIM-1 becomes significantly elevated before a rise of serum creatinine (p. value 0.001) by a mean of 27.60 +/- 15.62 hours. Urinary KIM-1 was shown to have excellent sensitivity & specificity, 90.9 % and 95.24 % respectively. Also it showed a positive predictive value of 95.24 %, and a negative predictive value of 90.9 %. Our results have also shown that urinary KIM-1 was significantly elevated on admission (7.88 +/- 1.72 ng/mL) as compared with elevation of serum creatinine (0.895 +/- 0.173 mg/dL & p.<0.001), blood urea (37.4 +/- 14.53 mg/dL & p.<0.001) and reduction in estimated glomerular filtration rate (eGFR) (85.2 +/- 21.02 mL/minute/1.73 m(2) & p.<0.001). There was a significant rise of serum creatinine in patient group as compared with control group from the 2nd day (1.425 +/- 0.505 mg/dL & p.<0.001). However this was insignificant at admission (p. value 0.854). Same results apply to blood urea (57.93 +/- 23.1 mg/dL & p.<0.001 on 2nd day and 0.052 at admission). On the other hand, significant reduction in eGFR occurred only on the 3rd day (27 +/- 13.97 mL/minute/1.73 m(2) & p.<0.001); however this reduction was insignificant early in the course of illness with p. value of 0.527 & 0.008 at admission and after 24 hours respectively. In comparison, urinary KIM-1 was significantly elevated before a rise in blood urea & serum creatinine and before a reduction in eGFR at admission (p<0.001) and continued to rise significantly over the next two days. Conclusion: The data presented suggest that urinary KIM-1 is a reliable early marker for AKI with excellent sensitivity and specificity, especially in critically-ill patients, therefore allowing early diagnosis & institution of appropriate therapy. [Gamal F. EL Naggar, Hesham A. El Srogy, Sameh M. Fathy. Kidney Injury Molecule -1 (KIM-1): an early novel biomarker for Acute Kidney Injury (AKI) in critically - ill patients. Life Sci J 2012;9(4):3937-3943]. (ISSN:1097-8135). http://www.lifesciencesite.com. 587