Kidney Injury Molecule-1 Correlates With Kidney Function in Renal Allograft Recipients

Abstract

Introduction KIM-1 (kidney injury molecule-1) is responsible for the clearance of debris from damaged renal tubules. KIM-1 can be expressed and excreted in urine within 12 hours after the initial ischemic insult and before regeneration of the epithelium, persisting over time thereafter. Urinary KIM-1 has been reported to be a noninvasive, rapid, sensitive, and reproducible biomarker of experimental nephrotoxic and ischemic acute kidney injury. Renal KIM-1 expression is significantly increased in human kidney tissue among patients with a wide range of kidney diseases, including various types of glomerulonephritis, chronic allograft nephropathy, acute rejection, hypertension, and Wegener's granulomatosis. Both renal and urinary KIM-1 correlate with kidney damage and negatively with renal function, but not with proteinuria. The aim of this study was to assess whether urinary KIM-1 correlated with kidney function in kidney allograft recipients. Methods Serum NGAL, creatinine and estimated glomerular filtration rate (eGFR) were evaluated in 170 kidney allograft recipients on therapy with a calcineurin inhibitor plus mycophenolate mofetil or azathioprine and prednisone as well as in healthy volunteers. KIM-1 was estimated in urine using a commercially available kit. Results Kidney transplant recipients showed significantly higher KIM-1 values than the control group. Normotensive kidney allograft recipients displayed significantly lower NGAL results than hypertensive subjects. Urinary KIM-1 was significantly higher among diabetic than nondiabetic subjects, whereas creatinine did not differ significantly between them. Upon univariate analysis urinary KIM-1 strongly correlated with serum creatinine ( r = .64) and eGFR ( r = −.71), and only weakly with other parameters. Upon multiple regression analysis, the best predictor of urinary KIM-1 was eGFR (beta −0.61), which explained 61% of KIM-1 concentrations. Conclusion Even a successful kidney transplantation is associated with kidney injury as reflected by elevated urinary KIM-1 and lower eGFR. Therefore, KIM-1 needs to be investigated as a potential early marker for impaired renal function/kidney injury, especially in patients with other risk factors for damage such as hypertension or diabetes.