Background
Great progresses have been made in diagnosis and treatment of membranous nephropathy (MN). However, a significant number of patients do not respond to immunosuppressive therapy and eventually progress to ESRD. To investigate the mechanism of different outcome of MN, we performed single-cell sequencing to analysis the urine cells of patients with and without complete remission of MN.
Methods
Urine single-cell RNA sequencing was performed on 12 healthy controls (HC) and 15 patients with MN. The patients were divided into complete remission group (CR, n = 9) and no remission group (NR, n = 6).
Results
1) Macrophages were the largest group in urine cells, they were 48.02%, 68.96% and 20.95% in the HC, CR and NR group, respectively. 2) Urinary macrophages expressing FIColin-1 and S100 calcium binding protein A8 were mainly in HC group and CR group, indicating that they were derived from bone marrow and peripheral blood, while the urinary macrophages expressing the regulator of G-protein signaling 1 and HLA-DPA1, mainly in the NR group, were derived from renal resident macrophages. 3) 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.
Conclusions
Our study firstly delineated the differences of urinary cell maps between healthy individuals and the MN patients with CR or NR outcomes. Not only in origin but also in function of urine macrophages were different in the HC, CR and NR group.