Kidney pathological findings of MYH9-related disease: a cross-sectional nationwide survey in Japan

Background MYH9-related disease (MYH9-RD) is characterized by macrothrombocytopenia, hearing loss, and progressive kidney dysfunction. However, kidney biopsy is seldom performed because of low platelet counts. Although a review based on case reports described pathological findings of MYH9-RD included focal segmental glomerulosclerosis (FSGS) and glomerular basement membrane (GBM) abnormalities similar to those in Alport syndrome, no comprehensive studies of MYH9-RD have been performed. Methods We conducted a nationwide survey of MYH9-RD patients and collected kidney pathological samples, and immunofluorescence and electron microscopy images. All pathological samples were examined by multiple pediatric nephrologists and pathologists. Results Nine kidney biopsy samples from eight patients were included. Mesangial matrix expansion was observed in all nine samples (100%), and two samples (22%) had FSGS. Segmental foot process effacement was observed in all nine samples (100%), accompanied by irregularly aggregated podocyte dense material in seven samples (78%). Immunofluorescence analysis revealed three samples (33%) had immunoglobulin and/or complement deposition. Electron dense deposits (EDD) in the mesangium and GBM were observed in five samples (56%), including three samples with positive immunofluorescence. Electron microscopy also demonstrated endothelial cell swelling in seven samples (78%) and GBM abnormalities in five samples (55%), including thinning, thickening and splitting of the lamina densa. Conclusions Mesangial matrix expansion and segmental foot process effacement were commonly observed in MYH9-RD patients. In addition, various pathological findings including immunoglobulin and complement deposition with EDD and GBM abnormalities were also observed. These results may have important implications for the disease mechanism and treatment of MYH9-RD.