Age-related changes in glomerular volume and hydroxyproline content in rat and human

Total 4-hydroxyproline content and volume were measured in the same sample of microdissected glomeruli obtained fro rat and human outer or inner cortex. Glomerular volume was determined by computer-assisted image analysis, and 4-hydroxyproline was measured by a highly sensitive gas-liquid chromatographic method. Results were expressed as weight of basement membrane material by comparison with the amount of 4-hydroxyproline in purified basement membrane/mesangial matrix preparations. Microanalyses were possible in samples containing as few as eight human glomeruli. Rat glomerular size increased sevenfold between 5 wk and 2 yr of age, with volume being consistently 36 to 45% greater in inner than in outer cortex glomeruli. Basement membrane material content per glomerulus markedly increased with age (12-fold); however, when expressed per unit volume, this change was greatly reduced (2-fold). Expressed per volume, inner and outer cortex glomerular content of basement membrane material was always similar, regardless of age. Therefore, a greater glomerular size, in itself, does not accelerate the rate of basement membrane material deposition. Glomerular size distributions (measured by skewness and kurtosis) did not change, indicating that, although glomerular volume increases with age, aging does not appear to cause the emergence of distinct glomerular populations within an age group. Basement membrane material accumulation is probably a generalized change. Human glomeruli increased sevenfold in size from infancy to adulthood and then declined during senescence. Contrary to that in the rat, glomerular basement membrane material content appeared to closely follow size changes, thus, varying little from infancy to senescence if expressed per unit of glomerular volume.