Received March 9, 2009
Accepted on July 26, 2009

CLINICAL RESEARCH

IL-18 and Urinary NGAL Predict Dialysis and Graft Recovery after Kidney Transplantation

Isaac E. Hall ^*, Sri G. Yarlagadda , Steven G. Coca ^*, Zhu Wang ^*, Mona Doshi , Prasad Devarajan ^||, Won K. Han ^¶, Richard J. Marcus ^**, and Chirag R. Parikh ^*1

*Department of Medicine, Section of Nephrology, Yale University School of Medicine, New Haven, Connecticut; Clinical Epidemiology Research Center, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut; Department of Medicine, Division of Nephrology and Hypertension, University of Kansas School of Medicine, Kansas City, Kansas; Department of Medicine, Division of Nephrology, Wayne State University School of Medicine, Detroit, Michigan; ||Division of Nephrology and Hypertension, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio; ¶Department of Medicine, Division of Nephrology, Thomas Jefferson University, Jefferson Medical College, Philadelphia, Pennsylvania; and **Department of Medicine, Division of Nephrology and Hypertension, Allegheny General Hospital, Drexel University College of Medicine, Pittsburgh, Pennsylvania

¹ To whom correspondence should be addressed. E-mail: Chirag.Parikh{at}Yale.edu.

	Abstract

Current methods for predicting graft recovery after kidney transplantation are not reliable. We performed a prospective, multicenter, observational cohort study of deceased-donor kidney transplant patients to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL), IL-18, and kidney injury molecule-1 (KIM-1) as biomarkers for predicting dialysis within 1 wk of transplant and subsequent graft recovery. We collected serial urine samples for 3 d after transplant and analyzed levels of these putative biomarkers. We classified graft recovery as delayed graft function (DGF), slow graft function (SGF), or immediate graft function (IGF). Of the 91 patients in the cohort, 34 had DGF, 33 had SGF, and 24 had IGF. Median NGAL and IL-18 levels, but not KIM-1 levels, were statistically different among these three groups at all time points. ROC curve analysis suggested that the abilities of NGAL or IL-18 to predict dialysis within 1 wk were moderately accurate when measured on the first postoperative day, whereas the fall in serum creatinine (Scr) was not predictive. In multivariate analysis, elevated levels of NGAL or IL-18 predicted the need for dialysis after adjusting for recipient and donor age, cold ischemia time, urine output, and Scr. NGAL and IL-18 quantiles also predicted graft recovery up to 3 mo later. In summary, urinary NGAL and IL-18 are early, noninvasive, accurate predictors of both the need for dialysis within the first week of kidney transplantation and 3-mo recovery of graft function.