uNGAL predicts renal flare in patients with a history of biopsy-proven nephritis with high sensitivity and specificity. Furthermore, uNGAL is a more sensitive and specific forecaster of renal flare in patients with a history of lupus nephritis than anti-dsDNA antibody titres.

Objective The mechanism by which anti-DNA antibodies mediate lupus nephritis has yet to be conclusively determined. Previously, we found that treatment of mesangial cells with anti-DNA antibodies induced high expression of Neutrophil Gelatinase Associated Lipocalin (NGAL), an iron-binding protein upregulated in response to kidney injury. However, whether NGAL is instrumental in pathogenesis, induced as part of repair, or irrelevant to damage/repair pathways, is not known. Methods To investigate the role of NGAL in antibody-mediated nephritis, we induced nephrotoxic nephritis by passive antibody transfer to B6 or 129 mice. To determine if NGAL upregulation is instrumental, we compared the severity of renal damage in NGAL wild-type and knock-out mice following induction of nephrotoxic nephritis. Results We found that kidney NGAL expression, as well as urinary NGAL levels, were significantly increased in nephrotoxic nephritis as compared to control injected mice. Tight correlations were observed between NGAL expression, renal histopathology, and urinary NGAL excretion. NGAL knock-out mice had attenuated proteinuria and improved renal histopathology as compared to wild-type mice. Similarly, following nephritis induction, NGAL injection significantly exacerbated nephritis and decreased survival. NGAL induces apoptosis via caspase-3 activation, and upregulates inflammatory gene expression in kidney cells in vitro and when injected in vivo. Conclusion We conclude that kidney binding of pathogenic antibodies stimulates local expression of NGAL, which plays a crucial role in the pathogenesis of nephritis via promotion of inflammation and apoptosis. NGAL blockade may be a novel therapeutic approach for the treatment of nephritis mediated by pathogenic antibodies, including anti-GBM disease and lupus nephritis.

Drug abusers, particularly those who inject drugs s.c. ("skin popping"), may develop amyloidosis. Chronic infections are thought to play a pathogenetic role in this setting. A patient is presented who had a history of "skin popping" cocaine and heroin and developed nephrotic syndrome, with an elevated serum creatinine and a creatinine clearance of 61 mL/min. Renal biopsy demonstrated amyloidosis. Treatment with colchicine was initiated, and proteinuria decreased to near normal levels after 12 months. Concomitant with the decrease in proteinuria, creatinine clearance improved, although a repeat renal biopsy failed to show any significant improvement in amyloid burden. These observations suggest that colchicine may be a useful treatment in reversing the proteinuria of renal amyloidosis associated with drug abuse. Furthermore, clinical improvement may occur before any demonstrable regression in the amyloidosis.