Article Text

Download PDFPDF

PO.5.104 Evaluation of traditional laboratory markers as predictors of renal flares: a post-hoc analysis of four phase iii clinical trials of SLE
  1. S Jägerback,
  2. A Gomez and
  3. I Parodis
  1. Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital ~ Stockholm ~ Sweden


Purpose In patients with systemic lupus erythematosus (SLE), renal involvement is associated with high morbidity, and renal flare is a major contributing factor to poor long-term prognosis. Lupus nephritis (LN) still leads to end-stage kidney disease in approximately 10–20% of SLE patients. Identification of patients with susceptibility to develop a renal flare despite immunosuppressant therapy is needed toward individualised treatment optimisation, which was the scope of the present investigation.

Methods In this study, we used pooled data from four phase III randomised controlled trials of belimumab in patients with SLE, i.e. BLISS-52 (NCT01597622; N=865), BLISS-76 (NCT00410384; N=819), BLISS Northeast Asia (NCT1597622; N=677), and BLISS-SC (NCT01484496; N=836). SLE patients with moderate to severe disease activity were recruited while active severe LN was an exclusion criterion. Participants were on non-biologic standard therapy, and were assigned to IV belimumab (1 mg/kg or 10 mg/kg every fourth week), SC belimumab 200 mg weekly, or placebo. The outcome of this investigation was development of renal flares, defined as a reproducible (i) increase in proteinuria to >1 g/day if the baseline value was <0.2 g/d, >2 g/day if the baseline value was 0.2–1.0 g/d, or >2 times the baseline value if the baseline value was >1g/d, (ii) increase in serum creatinine ≥20% or 0.3 mg/dL, accompanied by proteinuria, haematuria or red blood cell (RBC) casts, or (iii) new haematuria of glomerular origin, accompanied by proteinuria or RBC casts. Cox proportional hazards regression models were employed. We next adjusted the models for age, sex, ethnicity, BMI, organ damage, baseline SLE disease activity, previous renal involvement, baseline prednisone equivalent dose, and use of immunosuppressants and belimumab.

Results The mean age of the patients was 36.7 years, 94% were women, and 192 developed a renal flare after a median of 141 days. The proportion of patients with a history of renal involvement was 54.6%. In univariable Cox regression analysis, low C3 levels at baseline were associated with an increased risk to develop a renal flare (hazard ratio, HR: 2.6; 95% confidence interval, CI: 1.9–3.5; p<0.001; figure 1), as did anti-dsDNA positivity (HR: 1.8; 95% CI: 1.3–2.6; p=0.001), anti-Sm positivity (HR: 1.6; 95% CI: 1.1–2.5; p=0.022), plasma albumin levels (HR: 0.9; 95% CI: 0.8–0.9; p<0.001), and proteinuria (HR: 1.5; 95% CI: 1.4–1.6; p<0.001). Low C4 levels were not associated with renal flare development. In adjusted analysis, the association with low C3 levels, plasma albumin and proteinuria remained significant.

Conclusions Low C3, plasma albumin and proteinuria levels at baseline were associated with renal flare development in a clinical trial setting encompassing patients with active SLE yet no severe active LN, as were anti-dsDNA and anti-Sm positivity yet only in unadjusted models. While C3 and anti-dsDNA are markers of known importance for surveillance of renal SLE, anti-Sm and plasma albumin are not established markers of renal flare; investigation of potential complemental predictive properties across these traditional biomarkers has merit.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.