Urinary N-Acetyl-Beta-D Glucosaminidase Activity is Associated with Inflammation and Proteinuria in Diabetic and Non-Diabetic Patients with Different Stages of Chronic Kidney Disease

Abstract

OBJECTIVE:Clinical studies have demonstrated that tubulointerstitial rather than glomerular pathology correlates with the degree and progression of renal impairment. Urinary n-acetyl-beta-D-glucosaminidase (NAG) is a biomarker of tubular damage, shown to be elevated in patients with glomerulonephritis and acute kidney injury. However, it has not been assessed longitudinally in chronic kidney disease (CKD). The aim of the present study was to determine urinary NAG activity and its possible associations with metabolic and inflammatory parameters in CKD. MATERIAL and METHODS:A total of 72 patients (mean age: 64.5±15.7) with stage 1-5 CKD were included. Of the 72 patients 23 (32%) had diabetic nephropathy and 49 (68%) had different types of primary glomerular diseases. Fasting blood samples were collected to analyse complete blood count, urea, creatinine, albumin, lipid parameters, C-reactive protein, uric acid and parathyroid hormone. 24-hour urine was collected to determine protein excretion. Urinary NAG and creatinine levels were analysed from the first morning urine samples. The NAG index (urinary NAG/ creatinine) was used to exclude dilutional errors. RESULTS:Mean eGFR was 38.3±21.7 ml/min. The urinary NAG index was significantly higher in stage 3 compared to stage 2 (32.1±23.5 vs. 7.5±3.3 U/gr-creatinine; p=0.002) and lower in stage 5 compared to stage 3 CKD (8.2±7.6 vs. 32.1±23.5; p=0.017). The urinary NAG index was positively correlated with 24-hour urine protein excretion (r=0.43; p=0.0001) and serum CRP (r=0.549; p=0.04) and negatively correlated with hemoglobin levels (r-0.394; p=0.004). CONCLUSION:The present study demonstrated that urinary NAG correlates with systemic inflammation and proteinuria and may be associated with progression of CKD. KEY WORDS:Chronic kidney disease, Proteinuria, Inflammation, N-acetyl-beta-D-glucosaminidase ÖZ AMAÇ: Klinik çalışmalar glomerüler patolojiden ziyade tubulointerstisyel hasarın böbrek yetmezliği derecesi ve ilerlemesi ile ilişkili olduğunu göstermiştir. İdrarda saptanan n-asetil-beta-D-glukosaminidaz (NAG) enzimi glomerülonefrit ve akut böbrek hasarında yükselen bir tübüler hasar biyomarkeridir ancak NAG düzeyi, kronik böbrek hastalığının (KBH) değişen aşamalarında değerlendirilmemiştir. Çalışmada, farklı evrelerdeki kronik böbrek hastalarında idrar NAG aktivitesi, NAG aktivitesi ile metabolik ve inflamatuvar parametreler arasında olası ilişki araştırılmıştır. GEREÇ ve YÖNTEMLER:Evre 1-5 KBH tanılı toplam 72 hasta (ortalama yaş:64,5 ± 15,7) çalışmaya alındı. Hastaların 23'ünde (% 32) diyabetik nefropati ve 49'una (% 68) farklı türde primer glomerüler hastalıklar mevcuttu. Açlık kan örneklerinde C-reaktif protein, ürik asit ve paratiroid hormon, hemogram, üre, kreatinin, albümin, lipid parametreleri çalışıldı. Kantitatif protein analizi için 24 saatlik idrar örnekleri kullanıldı. İdrar NAG ve kreatinin seviyeleri sabah ilk idrar örneklerinden analiz edildi. Dilüsyonel hataları dışlamak için NAG indeksi (idrar NAG / kreatinin:mg/gr) hesaplanarak değerlendiri...

Urinary biomarkers in lupus nephritis

“…NAG is a hydrolase-class enzyme, found abundantly in the lysosomes of cells located in the proximal tubules [ 116 ]. Normally it is not filtered through the glomerulus and is only excreted in the urine when there is dysfunction in the tubular epithelial cells [ 117 ].…”

“…These elevated levels can also be observed in the urine of patients with glomerulonephritis of any cause but mainly secondary to primary glomerular disease [ 119 ]. It has also been linked to proteinuria and CKD (particularly stage 3) [ 116 ].…”

Early detection of subclinical nephritis in systemic lupus erythematosus patients

“…(26) The IL-6 production in mesangial cells, tubule epithelial cells, endothelial cells, and podocytes, have linked this cytokine to CKD, acute kidney disease (AK-D) and LN. (27) N-acetyl-b-D-glucosaminidase (NAG) is a hydrolase-class enzyme, found abundantly in the lysosomes of cells located in the proximal tubules (28). Elevated urinary levels of NAG have been found in patients with LN compared with healthy individuals.…”