The Kidney Precision Medicine Project (KPMP) and the Nephrotic Syndrome Study Network (NEPTUNE) recently published a landmark study in the journal JCI Insight. This work highlights the relevance of a new and emerging technology in exposing underlying mechanisms involved in kidney disease progression. In this paper, the power of RNA sequencing technology was leveraged to group single cells derived from reference adult human kidney biopsy samples into 31 distinct cell clusters. Three of these were identified as endothelial cell clusters mapping to distinct vascular beds in the kidney.

For the first time, based on the single cell data, differences in expression patterns of glomerular endothelial cell (GEC) specific transcripts were investigated in tissue samples from two large patient cohorts representing ten different glomerular diseases. Highest GEC scores were observed in patients with focal segmental glomerulosclerosis (FSGS). Endothelial signatures further grouped patients with FSGS into two groups, with kidney expression levels of alpha-2 macroglobulin (A2M) as a key distinguishing feature. Finally, patients with more A2M expressed in the glomerulus were associated with lower proteinuria remission rates, linking endothelial function with long-term outcome in FSGS.

The single cell data described in this paper can now also be viewed at http://nephrocell.miktmc.org