Neutrophil gelatinase-associated lipocalin作為貓隻腎臟疾病的生物標記

Abstract

Neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a potential biomarker for early prediction of acute kidney injury (AKI), differentiation of AKI from chronic kidney disease (CKD), and the prognosis of AKI and CKD in human and canine medical studies. Nevertheless, the role of NGAL in feline kidney disease has never been studied. The purpose of this study was to determine the relationship between NGAL and different renal diseases in cats. From Sep 2014 to Mar 2016, 92 cats with azotemia were enrolled. According to the International Renal Interest Society (IRIS) staging system, the cats were categorized into five groups, (1) healthy cats, (2) cats with IRIS CKD stage II, (3) cats with IRIS CKD stage III, (4) cats with IRIS CKD stage IV, and (5) cats with AKI stages II-V. Urine and plasma samples of cats were collected at admission and tested for NGAL concentrations by our in-house sandwich ELISA system. The urinary NGAL (uNGAL) to creatinine ratio (UNCR) was also calculated. Simultaneously, hematologic and serum biochemical data of each case were also recorded. Statistically the uNGAL and UNCR of azotemic cats are significantly higher than those of healthy cats (i.e., uNGAL：Median [IQR] 1.8 [3.48] ng/mL in azotemic cats vs. 0.95 [1.35] ng/mL in healthy cats; UNCR：Median [IQR] 2.58 [8.23]% in azotemic cats vs. 0.23 [0.59]% in healthy cats), while plasma NGAL(pNGAL) had no statistical significance (p=0.113) between two groups. Unlike previous studies that increased pNGAL was associated with AKI in human medicine, the present findings indicated that only uNGAL and UNCR had significantly difference between AKI and healthy cats. Among CKD groups, cats with CKD grade 3, 4 had higher uNGAL and UNCR compared with cats with CKD grade 2 and healthy cats. For all patients, UNCR value was significantly correlated with uNGAL, plasma creatinine, hematocrit, segment and phosphorus concentrations. However, uNGAL concentration and UNCR were not associated with pNGAL concentration for all cases. According to the Receiving operative charaterstic (ROC) analysis, uNGAL and UNCR are useful to predict clinical progression for cats with CKD. Area under ROC (AUROC) for uNGAL in predicting the progression of CKD was 0.71 and the best cutoff value of 2.06 ng/mL had a sensitivity of 76.9% and specificity of 75％, whereas AUROC for UNCR in predicting the progression of CKD was 0.79 and the best cutoff value of 4.08% had a sensitivity of 76.9% and specificity of 79.2%. Above these values, patients experienced significantly faster deterioration within 19-20 days. In conclusion, uNGAL and UNCR could serve as useful biomarkers in cats with renal diseases. Furthermore, the CKD cats with higher concentration of uNGAL and UNCR tended to have poor clinical progression.