Neutrophil-gelatinase Associated Lipocalin As A Biomarker Of Disease Activity And Pathology Classification In Lupus Nephritis

ObjectiveTo study plasma and urinary neutrophil-gelatinase associated lipocalin (pNGAL and uNGAL) in patients with systemic lupus erythematosus (SLE), and investigate their possible value as markers of disease activity and pathology classification in lupus nephritis (LN).Methods1. The plasma and urine samples of104SLE patients and60controls were collected. SLE patients were further devided into lupus nephritis (LN, n=63) and non-renal SLE (n=41), while the controls consisted of30patients with non-SLE autoimmune diseases (DC) and30healthy volunteers (NC). The concentration of pNGAL and uNGAL was measured by a latex-enhanced turbidimetric immunoassay method.2. Disease activity was measured by the Systemic Lupus Erythmatosus Disease Activity Index (SLEDAI). The LN patients were further devided into active LN (n=41) and inactive LN (n=22). pNGAL and uNGAL were assessed in LN patients, additionally, the clinical and laboratory data of the patients were also collected. To access the sensitivity and specificity of uNGAL in predicting kidney disease activity of uNGAL, ROC curves were constructed using the previous visit’s uNGAL level.3. For the subgroup analysis of LN patients on biopsy, the pNGAL and uNGAL levels of LN patients with different renal pathology classifications were comparedResults1. Plasma and urinary NGAL were significantly increased in subjects with SLE compared with those with non-SLE autoimmune disease or with healthy controls (P<0.01). Levels of pNGAL and uNGAL were significantly higher in patients with LN than those without LN (P<0.05,P<0.01).2. In patients with LN, pNGAL levels of active group were not significantly different from controls (216.05±133.67ng/mL vs172.75±91.68ng/mL, P>0.05), but the uNGAL levels were higher in active LN than those in inactive LN (0.76±0.40ng/mg Cr vs0.45±0.29ng/mg Cr,P<0.01).3. uNGAL correlated with the renal score of the Systemic Lupus Erythmatosus Disease Activity Index (r=0.364, P<0.01) but not with pNGAL (P>0.05).4. The ROC curve of uNGAL showed:the level of uNGAL at cut-off point was0.585ng/mg Cr, with a high sensitivity and specificity,70.73%and77.27%respectively (P<0.01). Area under the ROC curve was0.756.5. A comparison of pNGAL levels with different WHO classes of LN yielded no significant difference between the groups (P>0.05). The patients with class Ⅲ and Ⅳ had elevated uNGAL, but the difference was not statistically significant (P>0.05). Neither pNGAL nor uNGAL levels were significanty different between patients with proliferative vs membranous disease (P>0.05).Conclusions1. Both uNGAL and pNGAL levels will be elevated promptly in SLE patients with renal involvement.2. NGAL in urine but not in plasma represents a sensitively novel biomarker for predicting disease activity in LN.3. There is no significant difference in pNGAL and uNGAL levels among different types of LN. Neither of them can be used to monitor patients with proliferative renal disease.