Lupus Nephritis Risk Factors and Biomarkers: An Update

Abstract

Lupus nephritis (LN) represents the most severe organ manifestation of systemic lupus erythematosus (SLE) in terms of morbidity and mortality. To reduce these risks, tremendous efforts have been made in the last decade to characterize the different steps of the disease and to develop biomarkers in order to better (i) unravel the pre-SLE stage (e.g., anti-nuclear antibodies and interferon signature); (ii) more timely initiation of therapy by improving early and accurate LN diagnosis (e.g., pathologic classification was revised); (iii) monitor disease activity and therapeutic response (e.g., recommendation to re-biopsy, new urinary biomarkers); (iv) prevent disease flares (e.g., serologic and urinary biomarkers); (v) mitigate the deterioration in the renal function; and (vi) reduce side effects with new therapeutic guidelines and novel therapies. However, progress is poor in terms of improvement with early death attributed to active SLE or infections, while later deaths are related to the chronicity of the disease and the use of toxic therapies. Consequently, an individualized treat-to-target strategy is mandatory, and for that, there is an unmet need to develop a set of accurate biomarkers to be used as the standard of care and adapted to each stage of the disease.

Keywords: autoantibodies; biomarkers; lupus nephritis; renal biopsy; urinary markers.

Figure 1

Pathogenic mechanisms and related biomarkers in lupus nephritis (LN). Accumulation of immune complexes (IC) containing nucleic acids is reported at pre-LN stage, and this process is driven by the presence of anti-nucleic acid antibodies (Abs). Next, the half-life of the renal nucleic acid immune complexes is abnormally increased that results, in part, to the polarization of macrophages implicated in renal repair and sclerosis. Activation of the classical complement is also important for tissular injury through intrarenal complement deposition, and when present, anti-C1q Abs amplify this process. This figure was produced using images from Servier Medical Art.

Figure 2

Lupus nephritis (LN) biomarkers and their level of performance used to monitor the different steps of the disease; dotted lines represent negative associations. Adapted from [37,116].