Focal segmental glomerulosclerosis: Treatment

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

In work described in a paper by Latt et al, Kidney Int Rep, 2022, we performed single cell RNA-seq on urine cells from FSGS cases, in order to characterize transcriptional profiles. Deidentified samples were received from collaborating medical centers. Results: We identified immune cells, predominantly monocytes, and renal epithelial cells in the urine. Further analysis revealed 2 monocyte subtypes consistent with M1 and M2 monocytes. Shed podocytes in the urine had high expression of marker genes for epithelial-to mesenchymal transition (EMT). We selected the 16 most highly expressed genes from urine immune cells and the 10 most highly-expressed EMT genes from urine podocytes as immune signatures and EMT signatures, respectively. Using kidney biopsy transcriptomic data from the NEPTUNE study, we found that urine cell immune signature and EMT signature genes were more highly expressed in FSGS biopsies compared with MCD biopsies. Conclusions: We conclude that in FSGS, urine immune cells are predominantly monocytes, indicating innate immune activation, and that shed podocytes have undergone epithelial-to-mesenchymal transformation. These findings may have implications for FSGS treatment. We also collaborated with two groups on papers relating to treatments for podocytopathies. Antisense oligonucleotides ameliorate kidney dysfunction in podocyte-specific APOL1 risk variant mice. Yang YW, Poudel B, Frederick J, Dhillon P, Shrestha R, Ma Z, Wu J, Okamoto K, Kopp JB, Booten SL, Gattis D, Watt AT, Palmer M, Aghajan M, Susztak K. Mol Ther. 2022 Jul 6;30(7):2491-2504. PMID: 35450819 LNA-anti-miR-150 alleviates renal interstitial fibrosis by reducing pro-inflammatory M1/M2 macrophage polarization. Hao X, Luan J, Jiao C, Ma C, Feng Z, Zhu L, Zhang Y, Fu J, Lai E, Zhang B, Wang Y, Kopp JB, Pi J, Zhou H. Front Immunol. 2022 Aug 5;13:913007. PMID: 35990680