Determinants of glomerular hypofiltration in aging humans

Background. The purpose of the present study was to confirm the extent to which glomerular filtration rate (GFR) is depressed in healthy, aging subjects and to elucidate the mechanism of such hypofiltration. Methods. Healthy volunteers aged 18 to 88 years (N = 159) underwent a determination of GFR, renal plasma flow (RPF), afferent oncotic pressure, and arterial pressure. Glomeruli in renal biopsies of healthy kidney transplant donors aged 23 to 69 years (N = 33) were subjected to a morphometric analysis, so as to determine glomerular hydraulic permeability and filtration surface area. The aforementioned GFR determinants were then subjected to mathematical modeling to compute the glomerular ultrafiltration coefficient (K-f) for two kidneys and individual glomeruli. Results. GFR was significantly depressed (P < 0.0001) by 22% in aging (≥55 years old) compared to youthful subjects (≤40 years old). Corresponding reductions of the following GFR determinants in the aging vs. youthful subsets were RPF by 28% (P < 0.0001), two-kidney K-f by 21% to 53% (P < 0.005), glomerular hydraulic permeability by 14% (P = 0.03), and the single-nephron K-f (SNKf) by 30% (P = 0.09). There were no significant differences between aging and youthful subsets for afferent oncotic pressure and filtration surface area per glomerulus. Conclusion. We conclude that a reduction in overall, two-kidney K-f contributes to GFR depression in aging subjects. We infer that this is due in part to structural changes that lower SNKf, and in part to the reduction in the actual number of functioning glomeruli that has been demonstrated by others at autopsy.