Deceased donor neutrophil gelatinase-associated lipocalin and delayed graft function after kidney transplantation: a prospective study

Abstract

IntroductionExpanding the criteria for deceased organ donors increases the risk of delayed graft function (DGF) and complicates kidney transplant outcome. We studied whether donor neutrophil gelatinase-associated lipocalin (NGAL), a novel biomarker for acute kidney injury, could predict DGF after transplantation.MethodsWe included 99 consecutive, deceased donors and their 176 kidney recipients. For NGAL detection, donor serum and urine samples were collected before the donor operation. The samples were analyzed using a commercial enzyme-linked immunosorbent assay kit (serum) and the ARCHITECT method (urine).ResultsMean donor serum NGAL (S-NGAL) concentration was 218 ng/mL (range 27 to 658, standard deviation (SD) 145.1) and mean donor urine NGAL (U-NGAL) concentration was 18 ng/mL (range 0 to 177, SD 27.1). Donor S-NGAL and U-NGAL concentrations correlated directly with donor plasma creatinine levels and indirectly with estimated glomerular filtration rate (eGFR) calculated using the modification of diet in renal disease equation for glomerular filtration rate. In transplantations with high (greater than the mean) donor U-NGAL concentrations, prolonged DGF lasting longer than 14 days occurred more often than in transplantations with low (less than the mean) U-NGAL concentration (23% vs. 11%, P = 0.028), and 1-year graft survival was worse (90.3% vs. 97.4%, P = 0.048). High U-NGAL concentration was also associated with significantly more histological changes in the donor kidney biopsies than the low U-NGAL concentration. In a multivariate analysis, U-NGAL, expanded criteria donor status and eGFR emerged as independent risk factors for prolonged DGF. U-NGAL concentration failed to predict DGF on the basis of receiver operating characteristic curve analysis.ConclusionsThis first report on S-NGAL and U-NGAL levels in deceased donors shows that donor U-NGAL, but not donor S-NGAL, measurements give added value when evaluating the suitability of a potential deceased kidney donor.

Associations between Deceased-Donor Urine Injury Biomarkers and Kidney Transplant Outcomes

“…In a cohort of 99 deceased donors and 176 kidney transplant recipients, Hollmen et al found NGAL measured in deceased-donor urine samples did not predict DGF as defined by any dialysis in the first week of transplant, but higher donor urine NGAL concentrations were associated with a longer duration of post-transplant dialysis and lower 1-year allograft survival. 28 A potential explanation for the contrasting findings is that our cohort had substantially greater power to detect the association with DGF. We also did not have detailed data on duration of post-transplant dialysis in the entire cohort, precluding our ability to examine DGF severity.…”

A comparison of the analytical performance of five commercially available assays for neutrophil gelatinase-associated lipocalin using urine

“…12 Additionally an association with delayed graft function following renal transplantation is now emerging. 13,14 Critical evaluations of the literature highlighting the potential of NGAL and other markers now recommend larger, clearly designed prospective studies and with attention to issues such as thorough statistical analysis, assays used and confounding factors such as chronic kidney disease. 8,11 Currently (as at 1 September 2012) on the www.clinicaltrials.gov website alone there are 73 studies involving measurement of NGAL.…”

Pre-transplant biomarkers and prediction of post-transplant outcomes in kidney transplantation

“…However, failed to predict DGF in the receiver operating characteristic (ROC) analysis. Reese et al (35) also documented the association of donor uNGAL with consequent DGF, but with lower incidence in comparison to the findings of Hollmen et al (34). Furthermore, both uNGAL and uL-FABP were in association with a lower estimated GFR (eGFR) at sixmonths, but only in recipients in absence of DGF.…”

“…In contrast, considering the current restrictions to allograft quality appraisal, donor urinary biomarker analysis could serve as a valuable assessment tool to decide on allograft selection and in addition make decisions on early perioperative recipient management. Hollmen et al (34) examined the predictive value of uNGAL levels in deceased donors for the first time. None of the donors had clinically established AKI previous to death.…”