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

Hollmen et al. Critical Care Deceased donor neutrophil gelatinase-associated lipocalin and delayed graft function after kidney transplantation: a prospective study Maria E Hollmen 0 Lauri E Kyllnen 0 Kaija A Inkinen 2 Martti LT Lalla 2 Jussi Merenmies 1 Kaija T Salmela 0 0 Division of Transplantation, Helsinki University Hospital , Kasarmikatu 11, 00130 Helsinki , Finland 1 Clinical Laboratory, Finnish Red Cross Blood Service , Kivihaantie 7, 00310, Helsinki , Finland 2 HUSLAB, Helsinki University Hospital, Surgical Hospital , Kasarmikatu 11, 00130, Helsinki , Finland Introduction: Expanding 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. Methods: We 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). Results: Mean 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 SNGAL 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. Conclusions: This 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. - Introduction Deceased kidney donors are expected to have healthy kidneys which will function well in the recipient after transplantation. However, a considerable number of kidney transplantations from deceased donors are complicated by delayed graft function (DGF). There is no consensus on the ultimate effect of short DGF, lasting less than one week, on graft survival; however, when the duration of allograft dysfunction becomes prolonged, the negative effect on kidney graft survival becomes evident [1,2]. The criteria for deceased donors have been expanded because of organ shortages, and consequently DGF has become more common [3,4]. At our center, we have expanded our criteria for acceptable kidney donors since 1995. During the past ten years, the rate of DGF in transplantations from expanded criteria donors (ECDs) has been 42%, compared to 23% in transplantations from standard criteria donors (P = 0.001; unpublished data, Helsinki University Hospital, Division of Transplantation, Kyllnen L and Salmela K). The quality of donor kidneys has a clear impact on long-term kidney allograft outcomes [5-7]. Various algorithms have been designed for the evaluation of deceased donors [8-10]. As these scoring systems also use recipient and transplantation variables such as cold ischemia time and human leukocyte antigen (HLA) matching, they cannot be used when deciding whether to accept or reject the donor. In practice, the judgment relies on the only readily available markers: diuresis and plasma creatinine level. Neutrophil gelatinase-associated lipocalin (NGAL) is a new marker for acute kidney injury (AKI) which has been studied after cardiac surgery, liver transplantation and contrast media administration, as well as in intensive care unit (ICU) patients (in heterogeneous patient groups and in patients with septic vs. nonseptic AKI), in unselected patients who present to the emergency department and in critically ill multiple trauma patients [11-22]. So far, very little is known about NGAL after kidney transplantation [23-26], and there are no published data available on NGAL in deceased kidney donors. We recently found that recipient urine NGAL (U-NGAL) measured the first morning following transplantation predicted DGF, particularly in cases where early graft function (EGF) was expected on the basis of diuresis and decreasing plasma creatinine concentration [27]. In addition, recipient U-NGAL could predict DGF lasting longer than two weeks [27]. Plasma creatinine level is known to be a poor early detector of AKI. Thus, a simple laboratory test revealing AKI early on would be useful for clinicians taking care of potential donors in ICU when evaluating the quality of their kidneys. In this prospective study, we wanted to examine (1) the levels of serum NGAL (S-NGAL) and U-NGAL in deceased kidney donors, (2) whether donor S-NGAL and/or U-NGAL could be used as predictors of DGF and especially (3) prolonged DGF after kidney transplantation. Materials and methods Study design and patients The present study was performed at Helsinki University Hospital, which provides organ transplant service for Finland, which has a population of 5.2 million. For this study, we prospectively enrolled 99 consecutive, deceased, heartbeating donors and their 176 adult kidney recipients between August 2007 and December 2008. The study protocol was approved by the Helsinki University Hospital Ethics Committee and the hospitals Department of Surgery. Written informed consent was obtained from the recipients before enrollment. Altogether 198 kidneys were obtained from the 99 donors. One kidney was not transplanted because of a vascular lesion. Twenty-one kidneys were not included in the study: six were used for pediatric recipients, two were used for recipients who underwent combined kidney and liver transplantation and one was used for a combined kidney and lung transplantation. Nine kidneys were shipped to the other Nordic countries according to the Scandiatransplant exchange rules. Three patients did not consent to participate in the study. The recipients of the remaining 176 kidneys were included in this study. Donor clinical history data were obtained from the hospital records. The following variables were gathered: age, gender, history of hypertension, need for cardiopulmonary resuscitation, need for intracranial surgery, use of vasopressor su (...truncated)