Urinary Tumor Necrosis Factor-Like Weak Inducer of Apoptosis (uTWEAK) and Urinary Monocyte Chemo-attractant Protein-1 (uMCP-1): Promising Biomarkers of Lupus Nephritis Activity?

Current Insights on Biomarkers in Lupus Nephritis: A Systematic Review of the Literature

“…TWEAK has been linked to LN pathogenesis and represents a possible target of renoprotective agents [ 28 , 29 ]. Pathological effects mediated by TWEAK/Fn14 signalling include the enhancement of apoptosis of parenchymal renal cells and induction of proinflammatory cytokines and chemokines, which, in turn, might serve as emerging biomarkers of kidney injury in LN [ 27 , 30 ]. Both serum and urinary TWEAK hold promise as useful diagnostic markers of LN, with the latter displaying outstanding overall metrics in most studies (see Table 1 for the detailed metrics) [ 26 , 27 , 30 ], although two studies reported the superiority of serum TWEAK over urinary TWEAK in the ability to differentiate between LN and non-renal SLE [ 31 , 32 ].…”

“…MCP-1 is another low molecular weight CC chemokine implicated in the recruitment of leukocytes and a mediator of inflammation and injury in LN [ 30 , 82 ]. MCP-1 expression is upregulated by several proinflammatory cytokines, including those belonging to the TNF superfamily.…”

“…MCP-1 expression is upregulated by several proinflammatory cytokines, including those belonging to the TNF superfamily. It has been shown that the TNF𝛼/TNF receptor II (TNFRII) and TWEAK/Fn14 axes both induce the production of MCP-1, which, in turn, amplifies the inflammatory response [ 30 , 72 , 83 ]. This provides biological advocacy for a link between MCP-1 and other widely investigated biomarkers of LN, such as TWEAK and TNFRII [ 30 , 56 , 83 ].…”

“…It has been shown that the TNF𝛼/TNF receptor II (TNFRII) and TWEAK/Fn14 axes both induce the production of MCP-1, which, in turn, amplifies the inflammatory response [ 30 , 72 , 83 ]. This provides biological advocacy for a link between MCP-1 and other widely investigated biomarkers of LN, such as TWEAK and TNFRII [ 30 , 56 , 83 ]. MCP-1 was evaluated in several studies [ 11 , 30 , 41 , 65 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ], and its value as a urinary marker of LN activity was further strengthened in a meta-analysis conducted by Xia et al, which reported a pooled sensitivity of 89% and pooled specificity of 63% (AUC = 0.90; pooled OR = 19.4) for distinguishing patients with active LN from patients with inactive LN [ 91 ].…”

“…This provides biological advocacy for a link between MCP-1 and other widely investigated biomarkers of LN, such as TWEAK and TNFRII [ 30 , 56 , 83 ]. MCP-1 was evaluated in several studies [ 11 , 30 , 41 , 65 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ], and its value as a urinary marker of LN activity was further strengthened in a meta-analysis conducted by Xia et al, which reported a pooled sensitivity of 89% and pooled specificity of 63% (AUC = 0.90; pooled OR = 19.4) for distinguishing patients with active LN from patients with inactive LN [ 91 ]. Moreover, Urrego-Callejas et al found that the urine levels of MCP-1 were significantly increased in patients with a National Institutes of Health (NIH) renal pathology chronicity index (CI) score ≥ 4, fibrous crescents, tubular atrophy, and interstitial fibrosis, underscoring the potential utility of this molecule as a less invasive, complementary biomarker of kidney damage in real-life clinical settings [ 92 ].…”