Urinary biomarkers in lupus nephritis

Abstract

Systemic lupus erythematosus (SLE) is the prototypical autoimmune disease that can affect any organ of the body. Multiple mechanisms may contribute to the pathophysiology of systemic lupus, including failure to remove apoptotic bodies, hyperactivity of self-reactive B and T lymphocytes, abnormal exposure to autoantigens, and increased levels of B-cell stimulatory cytokines. The involvement of the kidney, called lupus nephritis (LN), during the course of the disease affects between 30% and 60% of adult SLE patients, and up to 70% of children. LN is an immune-mediated glomerulonephritis that is a common and serious finding in patients with SLE. Nowadays, renal biopsy is considered the gold standard for classifying LN, besides its degree of activity or chronicity. Nevertheless, renal biopsy lacks the ability to predict which patients will respond to immunosuppressive therapy and is a costly and risky procedure that is not practical in the monitoring of LN because serial repetitions would be necessary. Consequently, many serum and urinary biomarkers have been studied in SLE patients for the complementary study of LN, existing conventional biomarkers like proteinuria, protein/creatinine ratio in spot urine, 24 ​h urine proteinuria, creatinine clearance, among others and non-conventional biomarkers, like Monocyte chemoattractant protein-1 (MCP-1), have been correlated with the histological findings of the different types of LN. In this article, we review the advances in lupus nephritis urinary biomarkers. Such markers ideally should be capable of predicting early sub-clinical flares and could be used to follow response to therapy. In addition, some of these markers have been found to be involved in the pathogenesis of lupus nephritis.

Toll-Like Receptor as a Potential Biomarker in Renal Diseases

“…In the case of SLE, clinical studies indicate that the most common source of biomarker searches is a urine sample. Due to this, numerous proteins, such as cytokines, chemokines, complement proteins, adhesive molecules, and autoantibodies, have been identified as potential biomarkers of disease activity in cross-sectional studies (Figure 7) [128]. Literature data of recent years indicate a special contribution to the etiopathogenesis of this disease of innate immunity elements, mainly TLR.…”

“… Biomarkers associated with lupus nephritis [ 128 ]; CXC16—C-X-C motif chemokine 16; FOXP3—forkhead box protein P3; HMGB1—High mobility group box 1; ICAM—Intercellular Adhesion Molecule 1; IL-6—Urinary Interleukin 6; IL-8—Interleukin 8; IL-17—Urinary Interleukin 17; KIM-1—Urinary kidney injury molecule-1; MCP-1—Monocyte chemoattractant protein-1; NAG—N-Acetyl-β-D Glucosaminidase; NGAL—neutrophil gelatinase-associated lipocalin; RAIL—Renal Activity Index for Lupus; RANTES—Regulated upon Activation, Normal T-cell Expressed, and Secreted; STAT-1—Signal transducer and activator of transcription 1; TGF-β—transforming growth factor beta; Th1—T helper 1; Th2—T helper 2; TNFR1—Tumor necrosis factor receptor 1; TWEAK—Urinary TNF-like weak inducer of apoptosis; VCAM—vascular cell adhesion molecule 1; VEGF—Vascular Endothelial Growth Factor. …”

High-Mobility Group Box 1 Protein (HMGBl): Role in Lupus Nephritis

“…Certainly, the cytoplasmic and extracellular presence of HMGB1 has been found in kidney biopsies of patients with LN HMGB1 can be detected in the urine of patients with LN compared with that of patients without active LN. Additionally, it is positively correlated with serum levels of HMGB1, proteinuria, and SLEDAI [4].…”

“…Nevertheless, these biomarkers may not be useful enough to appropriately predict relapse, accurately monitor response to treatment, or identify the degree of disease activity and chronic damage. For this reason, the investigation of new potential biomarkers that overcome these obstacles are clearly necessary [4].…”

Systemic lupus erythematosus: The search for the ideal biomarker

“…In addition, serial biopsies are impractical in the monitoring of LN due to their invasiveness and potential unacceptable complications. 133,134…”