Pathological and Prognostic Value of Urinary Neutrophil Gelatinase-Associated Lipocalin in Macroproteinuric Patients with Worsening Renal Function

Abstract

Background/Aims: Persistent proteinuria is a sign of renal damage caused by several factors, but it is itself a cause of tubular injury leading to chronic renal failure. Neutrophil gelatinase-associated lipocalin (NGAL) is a stress protein released by tubular cells which urinary excretion (uNGAL) increases in response to various stimuli. Methods: In the present study we analyzed uNGAL levels in 23 macroproteinuric patients with membranous glomerulonephritis. Results: In these subjects, uNGAL concentrations were significantly higher than in controls, directly correlated with proteinuria and inversely related to residual renal function. Patients were further categorized into two groups, according to a cut-off baseline uNGAL value of 350 ng/ml and evaluated during a 1-year follow-up period. After 12 months, subjects with higher uNGAL levels showed a significant worsening in baseline renal function and a 3.36 risk ratio of developing a severe decrease in GFR (≧50% of baseline values) compared with others. Conclusions: These findings suggest that NGAL may play a key role in tubular adaptations to persistent macroproteinuria. Furthermore, a new, interesting application of NGAL measurement could be proposed in clinical nephrology as a predictor of worsening renal function in patients affected by chronic kidney disease.

Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Progression of Chronic Kidney Disease

“…In a recent study (8), we pointed out that subjects with membranous nephropathy and impaired renal function showed exaggeratedly increased baseline levels of neutrophil gelatinase-associated lipocalin (NGAL), a small 25-kD protein massively released from renal tubular cells after various injuring stimuli. Moreover, subjects with higher baseline NGAL showed a considerably increased risk of worsening residual renal function within 1 yr compared with those with lower baseline NGAL values.…”

Hubungan Kadar Albumin Serum dengan Neutrophil Gelatinase-Associated Lipocalin Urine pada Penderita Sindrom Nefrotik Anak

“…2,7 Penelitian ini bertujuan untuk menilai hubungan antara kadar albumin dan NGAL urine pada penderita SN anak. …”

“…3,4 Hipoalbuminemia menyebabkan hipovolemia yang menurunkan RBF dan LFG, penurunan RBF dan LFG menyebabkan selsel tubulus proksimal menjadi iskemik, 6 yang secara aktif memproduksi NGAL. 7,10 Iskemia pada sel-sel tubulus dan obstruksi pada lumen tubulus menyebabkan peningkatan kadar NGAL urine, peningkatan ini telah terjadi saat iskemia tubulus yaitu saat fase inisiasi dari acute kidney injury. 12 Penelitian pada anak dengan SN sensitif dan resisten steroid didapatkan hubungan negatif yang bermakna pada estimasi LFG dan NGAL urine, menunjukkan NGAL meningkat sejalan dengan penurunan fungsi ginjal pada SN.…”

“…13 Pada penderita SN dengan makroproteinuria, kadar NGAL urine meningkat dibandingkan dengan subjek sehat. 7 Pada laporan kasus SN dewasa dengan edema yaitu saat terjadi proteinuria masif dan hipoalbuminemia, kadar NGAL lebih tinggi dibandingkan dengan saat terjadi perbaikan klinis. 2 Keterbatasan penelitian ini yaitu diagnosis SN yang tidak homogen.…”

Surgery with and without extracorporeal circulation in patients aged above 65 and kidney injury assessed by NGAL concentration

“…Moreover, numerous data indicate a relationship between early post-operative urinary and serum NGAL concentration and the severity of AKI, patient hospitalization, dialysis therapy and increased mortality [9][10][11][12]. Accordingly, urinary NGAL concentration after 2 h correlates with AKI intensification and duration [13,14].…”