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Biomarkers that Predict Development or Worsening of Lupus Nephritis in Patients with Systemic Lupus Erythematosus

Lupus nephritis is frequently associated with a poor long-term prognosis in patients with systemic lupus erythematosus (SLE). Currently, noninvasive blood or urine tests do not reliably predict the course of lupus nephritis. Therefore, biomarkers that could either predict the development of lupus nephritis or could be used to identify patients with more aggressive disease would be of value in selecting patients for more intensive clinical monitoring and aggressive therapy. At the 2013 annual meeting of the American College of Rheumatology held in San Diego, California from October 25-30, 2 presentations involved biomarkers that may be able to predict the course of renal disease in patients with SLE.

Abulaban and colleagues (Abstract 590) evaluated 3 candidate urine biomarkers that may predict future kidney function in adults and children with lupus nephritis: liver-type fatty acid binding protein (L-FABP), albumin, and monocyte chemoattractant protein 1 (MCP-1). Using the enzyme-linked immunosorbent assay, the levels of these 3 biomarkers were measured in the urine of 70 adults and 29 children with documented lupus nephritis. The association of each biomarker to renal function loss (RFL)—defined as a sustained increase of ≥25% in serum creatinine in adults or a decrease in estimated glomerular filtration rate of ≥20% in children—was determined. After a mean follow-up of 6.1 months for the children and 60 months for the adults, patients with RFL showed significantly higher levels of L-FABP (P = .038), albumin (P = .014), and MCP-1 (P = .014) than patients without RFL. Moreover, the combination of all 3 biomarkers improved the prediction and discrimination of  RFL in patients with lupus nephritis (the area under the receiver operating characteristic curve corresponding to RFL was 0.76).

Autoantibody production against nuclear components is a characteristic feature of SLE, and autoantibody clustering may be of value in predicting SLE disease severity. Jordan and Cruz (Abstract 581) carried out a retrospective case-control study of 180 patients with SLE plus biopsy-proven lupus nephritis and a control group of 179 matched patients with SLE without lupus nephritis, evaluating positivity to the triad of antinuclear autoantibodies (anti-Ro/anti-Sm/anti-RNP). Results showed that patients who had SLE and lupus nephritis were significantly more likely to have this autoantibody triad than patients with SLE without lupus nephritis (12% vs 6%; P = .03). A trend toward a higher rate of progression to end-stage renal disease (KDOQI stages 4 and 5) in patients with lupus nephritis who were antibody triad–positive (19% vs 8%, respectively; P = .052) was noted. Moreover, in mean renal survival was significantly shorter in patients with lupus nephritis  who were antibody triad–positive (14 years vs 21 years; P = .05). However, the researchers did not find an association between the presence of the antibody triad and earlier onset of lupus nephritis in patients with SLE.

Both studies provide noninvasive methods to predict the development of future RFL in patients with lupus nephritis. Patients with SLE and this serum antibody profile or urine biomarkers may represent a subset of patients with more aggressive disease that warrants more intensive clinical monitoring and therapy.

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Last modified: August 30, 2021