BACKGROUND Renal involvement in systemic lupus erythematosus (SLE), known as lupus nephritis (LN), is a common and severe complication and a major predictor of poor outcome. Long-term survival in SLE can be improved with early diagnosis and prompt treatment of LN. A number of biochemical markers are currently used to clinically assess disease activity in patients; however, they lack sensitivity and specificity for differentiating renal activity and damage in LN. A reliable clinical biomarker that can forecast LN flare and which could be sequentially followed would help to optimize initiation and escalation of therapy at the time of active or relapsing disease. OBJECTIVE This study was carried out to investigate the value of urinary tumor necrosis factor (TNF)-like weak inducer of apoptosis (uTWEAK) as a biomarker for active lupus nephritis. METHODS A total of 44 patients with SLE fulfilling the 1997 revised criteria for the classification of SLE as well as 11 age and sex-matched healthy controls were included in this study and subjected to full medical history taking, clinical examination, routine laboratory investigations, measurement of uTWEAK level as well as renal biopsy for patients with active LN. RESULTS The uTWEAK levels were significantly higher in SLE patients with active LN compared to those without or with inactive renal disease and normal healthy subjects.