Performance of urinary neutrophil gelatinase-associated lipocalin, clusterin, and cystatin C in predicting diabetic kidney disease and diabetic microalbuminuria: a consecutive cohort study

Background: Tubular biomarkers have been regarded as emerging and promising markers for early diagnosis of diabetic kidney disease (DKD). The study was to determine the diagnostic capabilities of tubular biomarkers (urinary neutrophil gelatinase-associated lipocalin [NGAL], clusterin, and cystatin C) for DKD and diabetic microalbuminuria, and whether or not the tubular biomarkers appear earlier than microalbuminuria. Methods: In this consecutive cohort study, 146 type 2 diabetes mellitus (T2DM) patients with a disease duration of >= 6 years were enrolled. Thirty age-and gender-matched subjects without any systemic diseases were recruited as the control group. Urinary samples collected before treatment were tested for NGAL, clusterin, and cystatin C. Results: The levels of biomarkers were higher in patients with DKD (p < 0.001); and positively correlated with the urinary albumin creatinine ratio (UACR; p < 0.001). With respect to the diagnosis of DKD, the areas under the receiver operating characteristic curve (AUCs) for urinary NGAL, clusterin, and cystatin C were 0.816 (95% confidence interval [CI], 0.741-0.891), 0.775 (95% CI: 0.694-0.857), and 0.803 (95% CI: 0.722-0.884), respectively. The levels of urinary NGAL and cystatin C in the normoalbuminuria group (UACR < 30 mg/g.Cr) were elevated compared with the control group, unlike urinary clusterin. There was no statistical difference in the levels of the three biomarkers between groups with different levels of haemoglobin A(1c) (HbA(1c)). The diagnostic AUCs for urinary NGAL, clusterin, and cystatin C in patients with diabetic microalbuminuria were 0.841 (95% CI: 0.775-0.907), 0.783(95% CI: 0.710-0.856), and 0.805 (95% CI: 0.733-0.877), respectively. Conclusions: Urinary NGAL, clusterin, and cystatin C may be promising biomarkers for diagnosing DKD and diabetic microalbuminuria. It is possible that urinary NGAL and cystatin C increase before the onset of microalbuminuria in T2DM patients.