Non-inferiority of creatinine excretion rate to urinary L-FABP and NGAL as predictors of early renal allograft function

Abstract

BackgroundWe evaluated accuracy of urinary liver type fatty acid-binding protein (L-FABP) for prediction of early allograft function and compared it to neutrophil gelatinase associated lipocalin (NGAL), diuresis and urinary creatinine excretion rate (UCr).MethodsUrine samples from 71 consecutive patients were taken 4, 10, 24 and 48 h after transplantation. We classified recipients into two groups: immediate graft function (IGF), with more than 70% reduction of serum Cr at 7th day post-transplant, and delayed graft function (DGF)/slow graft function (SGF) group (DGF - the need for hemodialysis procedure in the first week, SGF - less than 70% reduction of serum Cr in the first week).ResultsThirty-one recipients had IGF and 40 had DGF/SGF. L-FABP was only useful 48 h post-transplant with ROC AUC of 0.85 (95% C.I. 0.74-0.92); NGAL 24 h post-transplant had ROC AUC of 0.82 (0.7-0.91). Sensitivity, specificity, PPV and NPV for prediction of DGF/SGF with L-FABP > 9.5 mg/mmol Cr and NGAL > 33.1 μg/mmol Cr were: 86, 80, 83 and 83% (L-FABP), and 68, 93, 91, and 73% (NGAL). The difference in urine output between the groups was largest 4 h post-transplant (p = 0.001), later on the difference diminished. There were no significant differences in ROC AUC between L-FABP at 48 h, NGAL at 24 h, urine output at 4 h and UCr excretion rate at 10 h post-transplant. UCr < 0.56 mmol/h 10 h post-transplant predicted DGF/SGF with 94% sensitivity, 84% specificity, 89% PPV and 91% NPV, ROC AUC was 0.9. Classification tree with urine output 4 h and UCr 10 h post-transplant accurately predicted 89% of outcomes. When L-FABP or NGAL were added, the prediction was accurate in 92 or 90%, respectively.ConclusionsL-FABP is comparable to NGAL for prediction of first week allograft function, however UCr and diuresis were non-inferior.

Kidney Transplantation: Which Variables Should Be Improved?

“…It is also well known that the level of diuresis after the surgical procedure is one of the most clinically used predictors of early allograft function [25]. Reinforcing this evidence we encountered the same predictive value for this parameter.…”

Biomarkers of acute kidney injury: the pathway from discovery to clinical adoption

“…Many investigators have examined various patient populations and determined the performance of NGAL. Its performance has been evaluated in various settings, such as for prediction of AKI in pediatric [22] and adult cardiac surgery patients [72,76], in critically ill patients [8,24], in patients in the emergency department [20,21], and in patients in the kidney transplant setting [77][78][79]. A recent meta-analysis by Ho et al including 16 studies with a total of 2906 patients investigated urine NGAL as a biomarker for the prediction of AKI after cardiac surgery in adult patients.…”

Neutrophil gelatinase-associated lipocalin in kidney transplantation: A review

“…Pajek et al found that a urinary creatinine excretion rate of less than 0.56 mmol/h 10 hours posttransplant predicted DGF and slow graft function with 94% sensitivity and 84% specificity (AUC ROC of 0.90, 95% confidence interval [CI] 0.80-0.96) whilst a uNGAL:creatinine ratio N33.1 mcg/mmol had 68% sensitivity and 93% specificity and similar AUC ROC of 0.82, 95% CI 0.70-0.91) [33].…”

“…However, although in theory urinary NGAL might be expected to be more specific for kidney injury than sNGAL (as NGAL can be secreted into circulation from other organs), this hypothesis is not borne out in practice due to the high frequency of oliguria and anuria post-operatively (between 12-38% of KTRs of deceased donors are anuric in the postoperative period) [33,34]. Furthermore, differences in glomerular filtration of sNGAL derived from extrarenal tissues and urine from residual functioning native kidneys may modify the uNGAL signal from graft tubules.…”