Neutrophil Gelatinase Associated Lipocalin Is an Early and Accurate Biomarker of Graft Function and Tissue Regeneration in Kidney Transplantation from Extended Criteria Donors

Abstract

BackgroundDelayed graft function (DGF) is an early complication of kidney transplantation (KT) associated with increased risk of early loss of graft function. DGF increases using kidneys from extended criteria donors (ECD). NGAL is a 25KDa protein proposed as biomarker of acute kidney injury. The aim of this study was to investigate the role of NGAL as an early and accurate indicator of DGF and Tacrolimus (Tac) toxicity and as a mediator of tissue regeneration in KT from ECD.MethodsWe evaluated plasma levels of NGAL in 50 KT patients from ECD in the first 4 days after surgery or after Tac introduction.ResultsPlasma levels of NGAL at day 1 were significantly higher in DGF group. In the non DGF group, NGAL discriminated between slow or immediate graft function and decreased more rapidly than serum creatinine. NGAL increased after Tac introduction, suggesting a role as marker of drug toxicity. In vitro, hypoxia and Tac induced NGAL release from tubular epithelial cells (TEC) favoring an autocrine loop that sustains proliferation and inhibits apoptosis (decrease of caspases and Bax/Bcl-2 ratio).ConclusionsNGAL is an early and accurate biomarker of graft function in KT from ECD favoring TEC regeneration after ischemic and nephrotoxic injury.

The impact of calcineurin inhibitors on neutrophil gelatinase‐associated lipocalin and fibroblast growth factor 23 in long‐term kidney transplant patients

“…Use of TAC in kidney‐transplant recipients, resulted in a significant rise in NGAL levels without any changes in serum creatinine . In a cohort of 80 kidney‐transplant patients, of whom all used CyA, NGAL levels were significantly higher when compared to CKD patients stages 2‐4 and healthy volunteers and was associated to the dose of CyA .…”

“…Delayed graft function (DGF) may be regarded as a form of AKI occurring after kidney transplantation usually defined as the need for dialysis during the first week after transplantation. NGAL levels were significantly higher in patients with DGF day 1 after transplantation compared to those who did not require dialysis in a study of 50 kidney transplant recipients from extended criteria donors . The acute rise in NGAL levels has been hypothesized as essential for protection against infection and as part of the regenerative proliferation that follows an AKI .…”

Furosemide Stress Test as a Predicting Biomarker for Delayed Graft Function in Kidney Transplantation

“…Indeed, IRI involves a complex interplay between leukocyte activation, autophagy, complement activation, oxidative stress, and endothelial cell injury [31]. Several biomarkers including serum NGAL [32,33], urine NGAL [34,35], urine interleukine-18 [34,35], urine clustering [36], and urine insulin-like growth factor-binding protein-7 and tissue inhibitor of metalloproteinases-2 [37] could affect the above mechanisms and showed promising results of AUC for predicting DGF, ranging from 0.7 to 0.9, depending on the timing of biomarkers sampling and the definition of DGF. In the present study, the FST outperformed urine NGAL, RI of renal arteries, and ERPF in the prediction of DGF (Table 3).…”

Endogenous factors and mechanisms of renoprotection and renal repair

“…HIF1A upregulation along with HMOX1 activation after donor preconditioning with fenoldopam was shown to have positive effects on renal function in a rat kidney transplantation model. 43,44 The reader is referred to a review on ischaemic kidney injury and mechanisms of tissue repair by El Sabbahy and Vaidya, who discuss mechanisms of ischaemic injury and repair in acute and chronic kidney diseases. Part of these effects could be attributed to a downregulation of miR-127-3p.…”