The aim of the present study was to evaluate levels of neutrophil gelatinase-associated lipocalin (NGAL), a stress protein increased after renal and systemic stimuli, in a cohort of 15 patients with severe proteinuria secondary to idiopathic membranous nephropathy and conserved renal function. Neutrophil gelatinase-associated lipocalin levels and the fractional excretion of this protein were higher in patients than in healthy controls. Furthermore, a close correlation was found between serum NGAL and urinary (uNGAL) (r = 0.81; P < 0.01) and between uNGAL and daily proteinuria (r = 0.44; P < 0.03). One hour after infusion of a single high-dose bolus of intravenous immunoglobulin (0.4 g/kg), a new and promising therapy for several kidney diseases, a marked reduction was found in NGAL levels (serum NGAL 194.1 +/- 121 vs 370.1 +/- 180.5 ng/mL, P < 0.05; urinary NGAL 153.3 +/- 108.6 vs 502.2 +/- 293.4 ng/mL, P < 0.03); this was maintained 24 hours after the treatment. The findings made suggest that the NGAL balance is altered in patients with severe proteinuria who have not yet developed overt chronic renal failure, thus confirming the potential use of this protein as an early biomarker of kidney damage preceding the increase in serum creatinine levels. Furthermore, also extra-renal cells (neutrophils, endothelium) may hyper-release NGAL, expressing systemic stress related to severe proteinuria. This would explain the impressive decrease occurring in NGAL values after intravenous immunoglobulin infusion, thus providing further evidence of the antiinflammatory properties of this particular therapeutic approach and indicating the possible value of NGAL measurement in monitoring the efficacy of treatment of renal diseases.