Currently, the diagnosis of lupus nephritis (LN) is dependent on a renal biopsy, which is an invasive procedure with inherent risk, and the procedure may be contraindicated in a subgroup of patients. Additionally, response to therapy in patients with established LN is currently assessed by measures of urine protein to creatinine ratio (UPCR), which may not reliably change during early treatment periods. Due to these limitations, there is an unmet need for novel biomarkers of histological features and treatment response in LN.
We highlight studies relating to the potential use of serum and urinary biomarkers for use in diagnosis and disease course management in LN presented by Fava et al. during the 2022 American College of Rheumatology Convergence.
Abstract #0333 noted that while autoantibodies in proliferative LN are typically present in LN, a clear understanding of how they relate to different classes and subtypes of LN and treatment response is lacking. Using the Accelerating Medicines Partnership (AMP) LN longitudinal cohort, the authors found that proliferative LN (class III, IV, III+V, or IV+V) had higher positivity rates and higher titers of autoantibodies against dsDNA, chromatin, and C1q, compared to patients with pure membranous LN (class V). Additionally, complete treatment response in proliferative LN led to a significant decline in their levels, whereas, levels remained stable for partial or non-responders, suggesting a possible role in LN pathogenesis. These autoantibodies may serve as noninvasive diagnostic biomarkers of proliferative LN and biomarkers of early treatment response.
Abstract #0636 focused on serum soluble mediators in proliferative LN: Patients with pure proliferative nephritis had higher serum levels of immune mediators such as IFNB or IL-1B compared to non-proliferative LN and syndecan-1 (CD138) and TNF-RII highly correlated with intrarenal LN activity (defined by the NIH activity index), decreased with complete and partial response but not with nonresponse. Conversely, immune mediators with the highest correlation with the NIH chronicity index were stem cell factor (SCF) and TNF-RI.
Abstract #0536 focused on urinary biomarkers. Findings in this abstract suggested that an early decline in 51 urinary proteins, most notably CD163, IL-16, and macrophage mannose receptor (MMR) at 3 months predicted a 1-year treatment response of LN, with no decline among non-responders. This decline even outperformed a decline in UPCR, especially in proliferative LN (ROC analysis with an area under the curve (AUC) for response at 1 year of 91%, 86% and 78% for the 3-month decline in MMR, CD163 and UPCR respectively). This finding is immensely important, and, if validated, would enable early noninvasive monitoring, allowing for clinicians to adjust treatment changes to optimized patient outcomes and obviate for longitudinal repeat biopsies to check on changes at the tissue level.
Dr. Dhital and Dr. Kalunian have no conflicts of interest to report.
Illustration by Jennifer Bogartz