Impairment of kidneys by lupus nephritis (LN) is a common and serious complication in patients with systematic lupus erythematous (SLE). Approximately 50 % of the patients with SLE have symptoms of renal dysfunction and 10% of the LN patients are at risk of end-stage renal disease (ESRD). Pathogenesis of LN involves various molecular mechanisms, starting from systematic activation of autoreactive B cells and Fc-mediated activation of macrophages through cell proliferation and increased expression of extracellular matrix (ECM) proteins, proinflammatory cytokines, chemokines and matrix metalloproteinases (MMPs). Clinically, disease activity is monitored by measurements of proteinuria as well as serum creatinine, anti-dsDNA and complement levels. However, early diagnosis based on these parameters is poor and insensitive, making them efficient only in the late or advanced stage of the disease. Better approaches are urgently needed to detect the molecular processes of injury and monitor disease progression and to guide treatment options.
In a case-control study, levels of urinary biomarkers altered during ECM remodeling in LN compared to SLE without LN and healthy individuals were investigated and were subsequently correlated with clinical renal disease parameters (Figure 1). In total, 129 participants were selected from which 36 were LN patients, 35 LN-negative SLE patients and 58 healthy controls. In this way, 300 LN-associated urinary peptides - most of which were derived from collagen chains (n=70) - that were significantly different between LN and non-renal SLE and between LN and healthy individuals were identified. Correlation analysis was performed showing 172 peptides having moderate to strong correlation to at least one of the following clinical parameter: serum creatinine, estimated glomerular filtration rate, urine protein: creatinine ratio, renal SLE disease activity index, biopsy total activity index AI and total chronicity. In addition, 22 proteases (various MMPs) were identified by in silico protease prediction likely responsible for LN-associated urinary peptide generation.
- Wei R, Gao B, Shih F, Ranger A, Dearth A, Mischak H, Siwy J, Wisniacki N, Petri M, Burkly LC. Alternation in urinary collagen peptides in lupus nephritis subjects correlated with renal dysfunction and renal histopathology. Nephrol Dial Transplant 2017, 32(9):1468-1477