87 Mapping disease severity and progression of renal involvement in patients with systemic lupus erythematosus

Abstract

Background Despite recent advances in the treatment of systemic lupus erythematosus (SLE) and lupus nephritis (LN), understanding of their pathogenesis and the interrelation between disease states remains incomplete. A pragmatic review (GSK study LS3178) was conducted to map disease severity and progression of renal involvement in SLE, focusing on: LN development among patients with SLE, within-LN progression, and progression to end-stage renal disease (ESRD). Methods A keyword based literature search was conducted using PubMed, Google and Google Scholar and supplemented with a bibliography search relevant to the focus area. The following publications were screened and prioritized for inclusion: high quality; published after 2010; addressed a topic of focus or an information gap; data were from the USA or Europe. High-quality pre-2010 and non-USA/Europe publications were permitted. Results Overall, 248 citations were identified (keyword based search, n=117; bibliography search, n=131). Following full text screening, 144 publications were considered relevant to the review and 26 were selected for inclusion (21 primary studies, 3 narrative reviews and 2 systematic literature reviews). An overview of the results is provided in the Figure. This review identified that 726% of patients had LN at the time of SLE diagnosis, and 3148% of patients with SLE developed LN in the disease course, most (8090%) within 5 years of diagnosis. Class IV nephritis was the most common LN class found at first (3560%) and repeat (3563%) biopsy and had the worst prognosis. Histological transformation from one LN class to another was reported in 4076% of patients, most commonly in patients with nonproliferative lesions in the first biopsy. Overall, the proportion of patients who subsequently developed ESRD was 36% (SLE) and 428% (LN). Limited data existed for time to progression within LN and from SLE/LN to ESRD, and for renal signs present before LN diagnosis. Conclusions This review highlights risk factors for developing LN and progressing from SLE/LN to ESRD. Male patients, patients of non white ethnicities, and patients of a younger age at SLE diagnosis had the highest risk for developing LN and progressing from SLE/LN to ESRD. Of the renal parameters, elevated serum creatinine was identified as the best predictor of worsening disease state. A higher risk of worse outcomes is seen in the earlier SLE/LN disease stages, demonstrating the importance of early diagnosis and the need for effective disease modifying treatments for SLE and LN. Funding Source(s): Study funded by GSK.