Correlation of Urine Immune Cells with Renal Histological Features in Lupus Nephritis: Lessons from the Accelerating Medicines Partnership (AMP) in SLE Consortium

Abstract Text: Lupus nephritis (LN) is a complex autoimmune disease with unknown cause that is associated with severe morbidity and mortality. Recent research suggested a benefit of serial kidney biopsies in managing LN. Studying immune cells in the urine of LN patients offers the prospect of minimizing the need for invasive kidney biopsies. We performed analysis of single cell RNA-sequencing data of urine immune cells collected from patients with active LN. We identified 101,787 high quality immune cells from 146 patients including myeloid, dendritic, B, T, NK, and dividing cells. The median number of cells per patient was 315 (IQR 42-1,071). The majority of cells were myeloid (91,215 cells, 89.6%); Still, most immune cell subsets identified in the kidneys of LN patients, including lymphocyte subsets, were also found in the urine. Approximately 39% of urine samples yielded higher numbers of immune cells compared to the corresponding kidney biopsies. Proliferative and mixed nephritis were associated with higher percentages of phagocytic myeloid cells (Kruskal Wallis q value < 0.001). The NIH Activity Index positively correlated with phagocytic myeloid fractions (Spearman rho=0.40, q value=0.002) and negatively correlated with that of dendritic cells (Spearman rho=-0.29, q value=0.030); while the NIH Chronicity Index correlated positively with B cells (Spearman rho=0.32, q value=0.012), negatively with phagocytic myeloid cells (Spearman rho=-0.28, q value=0.035), and positively with inflammatory myeloid cells (Spearman rho=0.32, q value=0.012). This work describes the complex immune cells present in urine during LN, and paves the way for additional work to predict renal histological features from urine samples.