Comparison of urine and blood NGAL for early prediction of delayed graft function in adult kidney transplant recipients: a meta-analysis of observational studies

Abstract

Background Neutrophil gelatinase-assoicated lipocalin (NGAL) appears to be a promising proximal tubular injury biomarker for early prediction of delayed graft function (DGF) in kidney transplant recipients. However, its predictive values in urine and blood were varied among different studies. Here, we performed the meta-analysis to compare the predictive values of urine NGAL (uNGAL) and blood NGAL (bNGAL) for DGF in adult kidney transplant recipients. Methods We systematically searched Medline, Cochrane library and Embase for relevant studies from inception to May 2018. The summary receiver operating characteristic (SROC) curves, the pooled sensitivity, specificity and diagnostic odds ratio (DOR) were used to evaluate the prognostic performance of uNGAL and bNGAL for the identification of DGF. Results A total of 1036 patients from 14 eligible studies were included in the analysis. 8 studies focused on NGAL in urine and 6 reported NGAL in serum or plasma. The composite area under the ROC (AUC) for 24 h uNGAL was 0.91 (95% CI, 0.89–0.94) and the overall DOR for 24 h uNGAL was 24.17(95% CI, 9.94–58.75) with a sensitivity of 0.88 (95% CI, 0.75–0.94) and a specificity of 0.81 (95% CI, 0.68–0.89). The composite AUC for 24 h bNGAL was 0.95 (95% CI, 0.93–0.97) and the overall DOR for 24 h bNGAL was 43.11 (95% CI, 16.43–113.12) with a sensitivity of 0.91 (95% CI, 0.81–0.96) and a specificity of 0.86 (95% CI, 0.78–0.92). Conclusions Urine and serum/plasma NGAL were valuable biomarkers for early identification of DGF in kidney transplantation. In addition, the bNGAL was superior to uNGAL in early prediction of DGF. Electronic supplementary material The online version of this article (10.1186/s12882-019-1491-y) contains supplementary material, which is available to authorized users.

Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction

“…A metanalysis first demonstrated that elevated serum and urine NGAL levels can predict DGF and 1-year graft function [ 22 ]; a second, more recent one, including 1036 patients from 14 studies, confirmed that both bNGAL—performed on serum/plasma—and uNGAL were robust biomarkers for DGF (AUC 0.91 and 0.95, respectively), with superior predictive value of bNGAL over uNGAL [ 23 ].…”

Prediction Value of Serum NGAL in the Diagnosis and Prognosis of Experimental Acute and Chronic Kidney Injuries

“…Experimental kidney injury (KI) animal models are very helpful in screening potential nephrotoxic reagents and possible anti-KI compounds in vivo, and they also can provide research tools to study renal pathophysiology. However, traditional biomarkers measuring renal functions in the human study, such as blood urea nitrogen (BUN) and serum creatinine (Scr), are not sensitive enough to detect early or slight damages in experimental animals [ 1 , 2 ]. Urine-derived biomarkers such as albumin, vanin-1, N-acetyl-β- d -glucosamininidase, and kidney injury molecule-1 might be effective biomarkers [ 3 , 4 ]; however, in some conditions, especially when a large number of animals are used in the same experiment batch, serum-derived KI biomarkers might be more advantageous becaue of their shorter identification time and simple extraction.…”

“…Several roles have been ascribed to NGAL, including iron trafficking and chemotactic and bacteriostatic effects [ 8 ]. Current knowledge suggests that NGAL is a promising KI biomarker, especially in the early stages of AKI [ 2 ]. For example, NGAL is one of the most highly induced proteins in the kidney after ischemic or nephrotoxic AKI, both in clinical studies and animal models, and it increases in urine before the rise in serum creatinine concentration [ 9 , 10 ].…”

Urinary Biomarkers for Diagnosis and Prediction of Acute Kidney Allograft Rejection: A Systematic Review

“…Confounding outcomes need always to be considered due to potential overlap in diagnosis. For example, urinary chemokines are also elevated in allograft BK virus nephropathy (as discussed below), urinary NGAL was proposed as early predictor of DGF [56], and as a biomarker of CNI toxicity [57], while urinary miRNAs dysregulation has been linked to interstitial inflammation and tubular atrophy [58]. For the first time Tinel and colleagues demonstrated that considering (instead of excluding) potential confounding factors (i.e., urinary tract infection and BK virus reactivation) in a diagnostic multi-parametric model could optimize its performance [16].…”