IL-18 and urinary NGAL predict dialysis and graft recovery after kidney transplantation

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.

Figures

Figure 1.

Mean (and SE) for urinary biomarker values after kidney transplant by level of allograft recovery: (A) urinary NGAL, (B) urinary IL-18, and (C) urinary KIM-1. DGF (solid black line) defined by dialysis within 1 wk of transplant. SGF (dashed red line) defined by creatinine reduction ratio less than 0.7 by day 7 without need for dialysis. IGF (dotted black line) defined by absence of SGF without need for dialysis. POD, postoperative day. *P < 0.05, †P < 0.01, and ‡P < 0.001.

Figure 2.

Receiver-operating characteristic curves for urinary biomarkers and changes in serum creatinine on the first postoperative day for predicting dialysis within 1 wk of kidney transplant. Absolute change of Scr is the difference between Scr within 1 h postoperatively and the first postoperative day Scr. Relative change of Scr is the absolute change divided by Scr within 1 h postoperatively.

Figure 3.

(A) Mean serum creatinine over the first 3 d after transplant separated by tertiles of urinary NGAL on the first postoperative day: upper tertile of values (solid black line), middle tertile of values (dashed red line), and lower tertile of values (dotted black line). (B) Mean serum creatinine over the first 3 d after transplant separated by medians of urinary IL-18 on the first postoperative day: upper median (solid black line) and lower median (dotted black line). (C) Mean 3-mo serum creatinine separated by NGAL tertiles (left) and IL-18 medians (right) from the first postoperative day. *P < 0.05, †P < 0.01, and ‡P < 0.001.