SERUM NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN (NGAL) IS A PREDICTOR OF GRAFT FUNCTION AND CALCINEURIN INHIBITOR (CNI) NEPHROTOXICITY IN KIDNEY TRANSPLANTATION (KT) FROM EXTENDED CRITERIA DONORS (ECD)

INTRODUCTION AND AIMS: The incidence of delayed graft function (DGF), defined as need for dialysis in the first week after KT, has been increasing for the use of kidneys from ECD. NGAL has been proposed as early biomarker of DGF. However, the evaluation of NGAL in KT from ECD has not been performed yet. The aims of this study were to evaluate: 1) NGAL in 50 patients in the first 24 hr after KT from ECD; 2) the relationship between NGAL and DGF, slow graft function (SGF) and immediate graft function (IGF); 3) the trend of serum creatinine (sCr) and NGAL in the first 5 days after KT; 4) NGAL before and after the introduction of CNI; 5) the correlation between initial NGAL levels and renal function at 6 months after KT. METHODS: 50 patients were enrolled in the study (standard immunodepression with basiliximab, mycophenolate mophetil and steroids: CNI were introduced only when sCr <2.5 mg%). Patients were divided in 3 groups: DGF, SGF (sCr >3 mg% at day 6 after KT) and IGF (sCr <3 mg% at day 6 after KT). Five patients with living donor (LD) KT were enrolled as controls. Serum NGAL levels were measured by a fluorimetric method (Biosite, San Diego, CA) at different time points. RESULTS: Patients demographics and clinical features were: male 67%, recipient age 57.65 yrs, donor age 65 yrs, cold ischemia time 16.8 hr, HLA mismatches 3.46, recipient BMI 24.2, donor hypertension 64.4%, donor eGFR 88.66 ml/min. The incidence of DGF was 28%: in the 72% of patients without DGF, SGF occurred in 55%, IGF in 45%. These data were similar to those observed in our total KT population from ECD in 2008-2010 (n=189). NGAL (24 hr after KT) were significantly higher in DGF than in SGF and IGF groups (DGF 654±96.24 pg/ml; SGF 439,75±67.14 pg/ml; IGF 357,37±52.74 pg/ml). NGAL levels in control LD KT were 93,2±20.46 pg/ml. No significant differences between the 3 groups were observed for donor/recipient age and gender, donor eGFR, donor/recipient hypertension, recipient BMI and HLA mismatches. Cold ischemia time was higher in DGF than SGF/IGF groups (DGF 18.11±2.63 hr; SGF 16.17±4.48 hr; IGF 16.98±2.32 hr). In selected patients of the SGF/IGF groups (n=24), a decline of serum NGAL but not of sCr levels was already detectable at day 2 after KT with a further decrease at day 3, 4 and 5. Moreover, NGAL increased after 24 hr from CNI introduction (before CNI: 120.12±34.58 pg/ml; after CNI: 188.25±44,83 pg/ml). Last, sCr at 6 months after KT was higher in the DGF (1.94±0.46 mg%) than in SGF (mean 1.64±0.26 mg%) and IGF (1.48±0.26 mg%) groups. CONCLUSIONS: NGAL is an early predictor of graft function after KT from ECD. Elevated levels of NGAL associated with DGF, whereas in the SGF/IGF groups, the decline of NGAL occurred earlier than sCr in the first 5 days after KT. Last, our data indicated NGAL as a potential biomarker of CNI nephrotoxicity and of renal function impairment 6 months after KT.