Evaluation of urinary N-acetyl-beta-D-glucosaminidase as a marker of early renal damage in patients with type 2 diabetes mellitus

Abstract

Objective: To evaluate the clinical usefulness of urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion for the detection of early tubular damage in type 2 diabetes mellitus (T2DM). Subjects and methods: Thirty six patients with T2DM were divided into two groups based on urinary albumin to creatinine ratio (ACR): normoalbuminuria (ACR < 30 mg/g; n = 19) and microalbuminuria (ACR = 30-300 mg/g; n = 17). The following parameters were determined in both groups: urinary NAG and albumin, serum and urine creatinine, fasting plasma glucose and glycated hemoglobin (HbA 1c ). Results: Urinary NAG levels [Units/g creatinine; median (range)] were significantly increased in microalbuminuria group [17.0 (5.9 -23.3)] compared to normoalbuminuria group [4.4 (1.5 -9.2)] (P < 0.001). No differences between groups were observed in fasting glucose, HbA 1c , serum creatinine levels and estimated glomerular filtration rates (eGFR). Urinary NAG positively correlated with ACR (r = 0.628; p < 0.0001), while no significant association was observed between NAG and glycemia, HbA 1c , serum creatinine and eGFR. RESUMOObjetivo: Avaliar a utilidade clínica da excreção urinária da N-acetil-beta-D-glucosaminidase (NAG) para a detecção de dano tubular precoce no diabetes melito tipo 2 (DM2). Sujeitos e méto-dos: Foram estudados trinta e seis pacientes com DM2 que se dividiram em dois grupos com base na excreção urinária de albumina (EUA): normoalbuminúrico (EUA < 30 mg/g de creatinina; n = 19) e microalbuminúrico (EUA = 30-300 mg/g de creatinina; n = 17). Em ambos os grupos foram determinados os seguintes parâmetros: NAG e albumina urinária, creatinina sérica e urinária, glicemia de jejum e hemoglobina glicada (HbA 1c ). Resultados: Os níveis de NAG urinária [unidades/g de creatinina; mediana (intervalo interquartílico)] foram significativamente maiores no grupo microalbuminúrico [17,0 (5,9 -23,3)] em comparação com o grupo normoalbuminúrico [4,4 (1,5 -9,2)] (p < 0,001). Não se observaram diferenças significativas entre os dois grupos nos níveis de glicemia de jejum, HbA 1c , creatinina sérica e taxa de filtração glomerular estimada (TFGe). A NAG urinária se correlacionou positivamente com o EUA (r = 0,628, p < 0,0001), não sendo observada associação significativa da NAG com glicemia, HbA 1c , creatinina sérica e TFGe. Conclusões: O aumento da NAG urinária na fase de microalbuminúria da nefropatia diabética (ND) sugere que a disfunção tubular já está presente nesse período. A associação positiva significativa entre a excreção urinária da NAG e EUA indica a possível aplicação clínica da NAG urinária como marcador complementar para a detecção precoce da ND no DM2. Arq Bras Endocrinol Metab. 2014;58(8):798-801 Descritores Nefropatia diabética; diabetes melito tipo

The prognostic value of inflammatory and vascular endothelial dysfunction biomarkers in microvascular and macrovascular complications in type 1 diabetes

“…It is a very important marker of glomerular alteration. Microalbuminuria provides the first clinical evidence for diabetic nephropathy and is a predictor of its progression [9,10]. However, researchers emphasise the fact that, despite the improvement of glycaemic control, in a certain percentage of patients, microalbuminuria constitutes an advanced, practically irreversible stage of microangiopathy [11].…”

“…However, researchers emphasise the fact that, despite the improvement of glycaemic control, in a certain percentage of patients, microalbuminuria constitutes an advanced, practically irreversible stage of microangiopathy [11]. Furthermore, the relatively frequent failure of angiotensin-converting-enzyme inhibitor (ACEI) treatment has been revealed [11,12]. In a study conducted on the paediatric population, microalbuminuria was diagnosed in 25.7% of patients after 10 years of the disease and in as many as 50.7% after 19 years [13].…”

“…Researchers underline the fact that subclinical changes of retinal vessels, such as disrupted blood-retina barrier and increased retinal blood flow, may precede the first clinical signs [12]. New circulating biomarkers could enable the detection of subclinical disease and may be helpful in monitoring the progression of retinopathy [15].…”

Peer Review #1 of "The role of serum and urinary biomarkers in the diagnosis of early diabetic nephropathy in patients with type 2 diabetes (v0.2)"

“…NAG is a lysosomal enzyme expressed in proximal tubules and was previously found to be a sensitive marker of tubular injury 30 . Urinary NAG was increased in type 2 diabetic patients compared to nondiabetic subjects, with higher levels in patients with microalbuminuria than those with normoalbuminuria levels 31,32 . The α1MG protein is freely filtered and reabsorbed through renal tubules.…”

Frutosamina como principal parâmetro glicêmico do paciente diabético em hemodiálise

“…Williams et al 49 The glycemic indices in dialysis evaluation (GIDE) study: 24 , sendo uma condição que resulta na alteração dos vasos sanguíneos renais, levando à perda de proteína na urina. Nessa ordem, quando não controlada, pode levar o órgão à redução de sua função lenta e progressivamente.…”