Background TNF-like Weak Inducer of Apoptosis (TWEAK) 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 urinary TWEAK as a biomarker in SLE to differentiate renal from non-renal activity and its relation to conventional parameters of renal lupus activity.
Methods 50 SLE and 20 healthy age and sex matched controls were included. All patients had active SLE based on SLE DAI. 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 (n=30) whereas those with renal index of 0 were considered as non LN (n=20). Investigations included blood urea, serum creatinine, urine protein/creatinine ratio and 24 hour urine protein, complete urine analysis (for proteinuria, pyuria, hematuria and casts), anti-double stranded (ds) DNA, complement (C) 3, C4, and erythrocyte sedimentation rate (ESR). uTWEAK 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 30 SLE had active LN and 20 had active non-LN. The mean total SLEDAI was significantly higher in LN than non-LN (24.5±8.2 and 16.2±7.2 respectively, P<0.001). In LN, the mean renal SLEDAI was 9.3±4.2. There was significant impairment of renal functions, higher anti-dsDNA, lower C3 and C4 in LN compared to non-LN but no significant difference in ESR. The mean uTWEAK was significantly higher in LN (13.8±7.5) than in non-LN (4.8±1.8, P<0.001) and controls (2.7±1.2, P<0.001). Furthermore, there was no significant difference in the mean uTWEAK among the different histologic classes of LN. uTWEAK correlated significantly with total SLEDAI (r=0.428, P<0.018) in LN but not in non-LN patients. In LN, uTWEAK was positively correlated with renal SLEDAI (P<0.001), When the extrarenal SLEDAI was considered, the correlation with uTWEAK was lost (P=0.622) confirming that the correlation between uTWEAK and SLEDAI is mainly due to its renal component. There was a significant correlation between uTWEAK and anti-dsDNA, C3 and C4 in LN but not in non-LN patients. Furthermore, in LN there was a significant correlation between uTWEAK and 24 hour urinary proteins, urine protein/creatinine ratio as well as with the level of hematuria, pyuria, proteinuria, casts, and with the pathological activity index of renal biopsy. Meanwhile, there was no statistically significant correlation between uTWEAK level and the blood urea, serum creatinine, SLE damage index, histological class of renal biopsy or pathological chronicity index of renal biopsy.
Conclusions uTWEAK is significantly elevated in SLE patients with active LN but not in active non-LN. uTWEAK is strongly correlated with the renal and total SLEDAI in LN patients only. In addition, uTWEAK is significantly correlated with the conventional parameters of disease activity as well as with the pathological activity index of renal biopsy. Accordingly, uTWEAK is a biomarker that can differentiate renal from non-renal activity in SLE. Since uTWEAK 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