Predictive Performance of Postoperative Neutrophil Gelatinase-Associated Lipocalin for Development of Chronic Kidney Disease After Liver Transplantation.

evaluating predictive ability of serial urinary neutrophil gelatinase-associated lipocalin (uNGAL) pre and post liver transplantation (LT) for the development of perioperative acute kidney injury (AKI). By a retrospective analysis for their previously published prospective cohort using multivariable regression analysis, they showed that uNGAL at 24 hours postreperfusion was an independent predictor of the development of chronic kidney disease (CKD), an important risk factor affecting the long-termoutcomes of LT patients. Although the valuable research has been conducted, some methodological issues seem important to avoid any optimistic interpretation or misinterpretation of results. In our view, there were several issues in this study that were not well addressed. First, this study only assessed the association of post-LT uNGAL with CKD by multivariable regression analysis, but not predictive ability of post-LTuNGAL for the development of CKD by further Harrell's concordance index (C-index). The C-index is the number of patients who experience events within a classification threshold when compared with the number of patients who do not experience events within the same classification threshold. Predictive ability is considered adequate when the C-index exceeds 0.7 and strong when the C-index exceeds 0.8. Second, the receiver operating characteristic (ROC) curve analysis showed that the mean area under the ROC curve (AUC-ROC) of post-LT uNGAL for the prediction of CKD at 4 years post-LT was only 0.65 (0.52-0.78). It is well believed that an AUC-ROC value of 0.90 to 1.0 indicates excellent (0.75-0.89), good (0.60-0.74), fair (0.50-0.59), or no predictive value. Furthermore, the AUC-ROC of post-LT uNGAL was not significantly different from those of the Modification of Diet in Renal Disease–estimated glomerular filtration rates pre-LT, post-LT, and 24 hours post-LT. It suggests that predictive performance of post-LT uNGAL for the development of CKD at 4 years post-LT does not surpass the perioperative Modification of Diet in Renal Disease– estimated glomerular filtration rates. After obtaining the cutoff of post-LT uNGAL by the ROC curve analysis, the authors did not further provide its sensitivity, specificity, and positive and negative predictive values. In this way, the readers cannot determine whether there is a good overall agreement between predicted probabilities and observed frequencies in the development and the validation sets. Finally, the incidence of AKI in the early postoperative period after LT is very high, but most of them are transient and do not develop into CKD. The available evidence shows that pre-LT kidney dysfunction is themost important determinant of post-LT CKD, and the most common cause of post-LT CKD is calcineurin inhibitor toxicity. Furthermore, both the duration of post-LTAKI and degree of residual kidney function at the late postoperative period are important for the development of CKD. When post-LT kidney function continues to gradually deteriorate over months to years, kidney biopsies usually demonstrate multifactorial etiology with the 3 most important causes being calcineurin inhibitor nephrotoxicity, diabetes, and hypertension. Perhaps, this is a possible reason for finding of this study that post-LT uNGAL has only a moderate predictive ability for the development of post-LT CKD.