Urinary single-cell sequence analysis of the urinary macrophage in different outcomes of membranous nephropathy.

Abstract

Great progress has been made in the diagnosis and treatment of membranous nephropathy (MN). However, a significant number of patients do not respond to immunosuppressive therapy and eventually progress to end-stage kidney disease. To investigate the mechanism of different outcome of MN, we performed single-cell sequencing to analyze the urine cells of patients with and without complete remission of MN. Urine single-cell RNA sequencing was performed on 12 healthy controls (HC) and 15 patients with MN. The patients were divided into a complete remission group (CR, n=9) and a no remission group (NR, n=6). (i) Macrophages were the largest group in urine cells, comprising 48.02%, 68.96% and 20.95% in the HC, CR and NR groups, respectively. (ii) Urinary macrophages expressing FIColin-1 and S100 calcium-binding protein A8 were mainly found in the HC and CR groups, indicating that they were derived from bone marrow and peripheral blood, while the urinary macrophages expressing the regulator of G-protein signaling 1 (RGS1) and HLA-DPA1, mainly found in the NR group, were derived from renal resident macrophages. (iii) In healthy adults, urine macrophages expressed the metallothionein family, indicating that they can regulate anti-inflammatory and proinflammatory functions bidirectionally. In the CR group, the urine macrophages showed strong proinflammatory properties. In the NR group, the urinary macrophages mainly associated with the level of proteinuria and the impaired renal function. Our study firstly delineated the differences in urinary cell maps between healthy individuals and MN patients with CR or NR outcomes. Not only the origin but also the function of urine macrophages were different in the HC, CR and NR groups.