Podocyte number and density changes during early human life

Background Podocyte depletion, which drives progressive glomerulosclerosis in glomerular diseases, is caused by a reduction in podocyte number, size or function in the context of increasing glomerular volume. Methods Kidneys obtained at autopsy from premature and mature infants who died in the first year of life ( n = 24) were used to measure podometric parameters for comparison with previously reported data from older kidneys. Results Glomerular volume increased 4.6-fold from 0.13 ± 0.07 μm 3 x10 6 in the pre-capillary loop stage, through 0.35 μm 3 x10 6 at the capillary loop, to 0.60 μm 3 x10 6 at the mature glomerular stage. Podocyte number per glomerulus increased from 326 ± 154 per glomerulus at the pre-capillary loop stage to 584 ± 131 per glomerulus at the capillary loop stage of glomerular development to reach a value of 589 ± 166 per glomerulus in mature glomeruli. Thus, the major podocyte number increase occurs in the early stages of glomerular development, in contradistinction to glomerular volume increase, which continues after birth in association with body growth. Conclusions As glomeruli continue to enlarge, podocyte density (number per volume) rapidly decreases, requiring a parallel rapid increase in podocyte size that allows podocyte foot processes to maintain complete coverage of the filtration surface area. Hypertrophic stresses on the glomerulus and podocyte during development and early rapid growth periods of life are therefore likely to play significant roles in determining how and when defects in podocyte structure and function due to genetic variants become clinically manifest. Therapeutic strategies aimed at minimizing mismatch between these factors may prove clinically useful.