NMR-Based Serum Metabolomics Reveals Reprogramming of Lipid Dysregulation Following Cyclophosphamide-Based Induction Therapy in Lupus Nephritis

Abstract

Lupus nephritis (LN) is a major cause of morbidity and mortality in lupus. Renal biopsy is the gold standard for classification of nephritis but due to its impracticality, new approaches for improving patient prognostication and monitoring treatment efficacy are needed. In the present study, we aimed to evaluate the potential of metabolic profiling in identifying biomarkers to distinguish disease and monitor treatment efficacy in patients with LN. Serum samples from patients with LN (n=18) were profiled on NMR based metabolomics platforms at diagnosis and after six months of treatment. LN patients had a different metabolomic fingerprint as compared to healthy controls with increased lipoproteins, lipids and reduced acetate and amino acids. Using multivariate statistical analysis, we found that the metabolic changes observed in naïve LN patients at diagnosis displayed a variation in the opposite direction upon responding to treatment. Increased levels of lipid metabolites including low and very-low density lipoproteins (LDL/VLDL) in LN patients significantly decreased after six months of treatment, while the serum levels of acetate increased. These levels correlated significantly with SLE Disease Activity Index (SLEDAI 2K), renal SLEDAI, serum C3 and C4 levels. The result presented in this pilot longitudinal study revealed the reprogramming of metabolome in LN patients on immunosuppressive therapy using NMR based metabolomics and thus this approach may be used to monitor response to treatment.