Determinants of glomerular hypofiltration in aging humans

Area of Science:

• Nephrology
• Gerontology
• Physiology

Background:

• Aging is associated with a decline in kidney function.
• Glomerular filtration rate (GFR) is a key indicator of kidney health.
• The mechanisms behind age-related GFR reduction require further elucidation.

Purpose of the Study:

• To quantify the decline in GFR in healthy aging individuals.
• To identify the underlying mechanisms contributing to age-related hypofiltration.
• To investigate changes in renal plasma flow, glomerular hydraulic permeability, and filtration coefficients.

Main Methods:

• Assessed GFR, renal plasma flow (RPF), and arterial pressure in 159 healthy volunteers aged 18-88.
• Performed morphometric analysis on kidney biopsies from 33 donors (aged 23-69) to assess glomerular hydraulic permeability and filtration surface area.
• Utilized mathematical modeling to compute the glomerular ultrafiltration coefficient (Kf) and single-nephron Kf (SNKf).

Main Results:

• A 22% significant depression in GFR was observed in aging subjects (≥55 years) compared to younger subjects (≤40 years).
• Reductions were noted in RPF (28%), two-kidney Kf (21-53%), and glomerular hydraulic permeability (14%) in older adults.
• No significant differences in afferent oncotic pressure or filtration surface area per glomerulus were found between age groups.

Conclusions:

• Reduced overall two-kidney Kf is a significant contributor to GFR depression in aging.
• Structural changes lowering SNKf and a decreased number of functioning glomeruli likely underlie age-related hypofiltration.
• These findings highlight the impact of intrinsic kidney changes on renal function during aging.