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

Abstract

BackgroundTubular 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.MethodsIn 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.ResultsThe 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 A1C (HbA1c). 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.ConclusionsUrinary 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.

Biomarkers in Progressive Chronic Kidney Disease. Still a Long Way to Go

“…Moreover, in this study, urine CLU showed a significant correlation with other urine tubular damage markers like KIM-1, LFABP and NGAL [61]. Despite these promising results, in another study in patients with diabetes, urine CLU showed a lower overall sensitivity and specificity in comparison to urinary NGAL in predicting diabetic kidney disease, although urinary levels of CLU were significantly higher in patients with established diabetic kidney disease [62]. Overall, urine CLU is a reliable candidate for CKD validation with the prospective of predicting CKD progression.…”

Возможности Диагностики И Предупреждения Развития Диабетической Нефропатии У Детей С Сахарным Диабетом 1-Го Типа

“…Високий рівень CLU був виявлений у клітинах тубулярного відділу нирок. Тому сечовий кластерин може бути використаний як маркер тубулярного ураження нирки при розвитку та прогресуванні ДН [33,34].…”

Ramipril and resveratrol co‐treatment attenuates RhoA/ROCK pathway‐regulated early‐stage diabetic nephropathy‐associated glomerulosclerosis in streptozotocin‐induced diabetic rats

“…Moreover, the diagnostic value of microalbuminuria in DN has recently been challenged by many researchers worldwide . Therefore, studies are currently focusing on more efficient diagnostic criteria, such as neutrophil gelatinase‐associated lipocalin (NGAL), serum cystatin C, and Gene Atlas of Type 2 Diabetes Mellitus (DM)‐Associated Complex Disorders (T2DiACoD) …”

“…4 Therefore, studies are currently focusing on more efficient diagnostic criteria, such as neutrophil gelatinase-associated lipocalin (NGAL), serum cystatin C, and Gene Atlas of Type 2 Diabetes Mellitus (DM)-Associated Complex Disorders (T2DiACoD). [5][6][7] Currently, the clinical therapeutic strategy for very early-stage DN patients with microalbuminuria involves management and control of blood glucose levels, including oral hypoglycemic agents or insulin injections. These interventions may slow down disease progression until symptoms of proteinuria appear, when the recommended therapy is angiotensin-converting enzyme inhibitor (ACEi) treatment to reduce proteinuria.…”