Ultrastructural Characterization of Proteinuric Patients Predicts Clinical Outcomes

The prognostic value of electron microscopic (EM) assessment of glomerula in proteinuric patients is still unknown and would require standardization. Four renal pathologists examined over 240 biopsy specimens with minimal change disease (MCD) or focal segmental glomerulosclerosis collected within the NEPTUNE consortium and could correlate twelve ultrastructural descriptors with clinical data. The reproducibility studies show an overall moderate to good inter-rater agreement for most of the descriptors (i.e. foot processes effacement or electron densities…), while some others like the presence of tubuloreticular inclusions are so rare that agreement evaluation was not reliably feasible. Nevertheless, significant outcome prediction was reached by clustering EM lesions into disorder profiles. While the cluster typical for endothelial cell damage is related to a quicker loss of function, the cluster associated with MCD displays higher rates for proteinuria remission. The authors provide insights into the pathophysiological mechanisms of proteinuric diseases and show that besides the amount of foot processes effacement, the description of further ultrastructural parameters offers granularity and pertinent prognostic estimation.