Adult male African Americans with high (>1.1 million) glomerular number (Nglom) have larger individual glomerular volumes (IVglom) than Caucasians with similar Nglom. Quantifying cell numbers in individual glomeruli will provide an indication of the contribution of resident cells to glomerular enlargement.
Four African American adult males, with >1.1 million nephrons per kidney were selected. Paraffin embedded kidneys were serially sectioned through 600um of tissue at 10um thickness. PAS stained, even numbered sections were used to estimate IVglom with the Cavalieri principle. Confocal microscopy was used to capture images of four small and four large glomeruli from each subject that were triple-immunolabelled with DAPI (nuclei), WT1 (podocytes) and vWF (endothelial cells) in remaining kidney sections. The optical disector was used to count podocytes and endothelial cells.
IVglom varied greatly within and between subjects. Podocyte number per glomerulus and endothelial cell number per glomerulus ranged from 176 to 664 and 194 to 1368, 3.8-fold and 7-fold range respectively. Podocyte number was relatively constant within subjects despite large variations in IVglom, but varied significantly between subjects. Endothelial cell number was generally well correlated with IVglom. A significant inverse correlation was observed between podocyte numerical density and IVglom. In contrast, no correlation was seen between endothelial cell numerical density and IVglom.
These results suggest that endothelial cell hyperplasia contributes significantly to hypertrophy of glomeruli, whereas podocyte hyperplasia does not. Larger glomeruli may be more prone to glomerular sclerosis due to reduced podocyte density and an increase in endothelial cell to podocyte numerical density