Background Urinary Neutrophil gelatinase-associated lipocalin (uNGAL) is one of the recently studied biomarkers gaining interest in systemic lupus erythematosus (SLE), with increasing evidence on its relation to lupus nephritis (LN).
Objectives To investigate uNGAL as a biomarker in SLE to differentiate renal from non-renal activity and its relation to conventional parameters of disease activity.
Methods Sixty two SLE patients and 20 healthy controls were included. All patients had active SLE based on SLEDAI. Patients were classified into active LN and active non-LN according to renal SLEDAI. Patients with renal index of 4 or more were considered as LN and underwent renal biopsy, whereas those with renal index of 0 were considered as non-LN. All patients were subjected to history and clinical examination. Investigations performed included renal functions (blood urea, serum creatinine, urine protein/creatinine ratio), complete urine analysis (for proteinuria, pyuria, hematuria and casts), anti-double stranded (ds) DNAtitre, complement (C) 3, C4, and erythrocyte sedimentation rate (ESR). uNGAL was measured by ELISA in all patients and controls. Renal biopsies were done within one week of urine collection, SLEDAI and renal SLEDAI were assessed on the same day.
Results Fourty-two SLE had active LN and 20 had active non-LN. The mean total SLEDAI was significantly higher in LN than non-LN (19.1±3.9 and 11.3±2.5 respectively, P<0.0001). In LN, the mean renal SLEDAI was 11.3±2.6 and mean extra-renal SLEDAI (total minus renal SLEDAI) was7.7 ±2.3. There was significant impairement of renal functions, higher anti-dsDNA titre, and lower C3 in LN compared to non-LN but no significant difference in C4 or ESR. The mean uNGAL was significantly higher in LN (22.6±2.4) than in non-LN (3.1±1.7, P <0.0001) and controls (2.0±1.4, P <0.0001), but was not statistically different between the latter two groups. Furthermore, there was no significant difference in the mean uNGAL level among the different histologic classes of LN. LN with higher renal index scores had significantly higher mean uNGAL than those with lower scores, with a significant positive correlation (r=0.874, P <0.0001).uNGAL correlated significantly with total SLEDAI(r=0.684, P<0.0001) in LN but not in non-LN patients. In LN, uNGAL was positively correlated with renal SLEDAI(r=0.874, P<0.0001), as well as with the level of proteinurea, pyuria, hematuria and casts. When the extrarenal SLEDAI was considered, the correlation with uNGAL was lost (r=0.072, P =0.649) confirming that the correlation between uNGAL and SLEDAI is mainly due to its renal component. In both active LN and non-LN patients there was no correlation between uNGAL and the different conventional parameters of disease activity and with the renal function tests, except for urine protein/creatinine ratio in LN.
Conclusions uNGAL is significantly elevated in SLE patients with active LN but not in active non-LN.uNGAL is strongly correlated with the renal and total SLEDAI in LN patients only, but not with any of the conventional parameters of disease activity. Accordingly, uNGAL is a biomarker that can differentiate renal from non-renal activity in SLE. Since uNGAL is significantly correlated with all urine sediment abnormalities, which reflect local changes in the kidneys, it can be used as an early predictor of renal lupus activity to guide therapeutic decisions.
Disclosure of Interest None Declared