Progressive Nephron Loss in Aging Kidneys: Clinical–Structural Associations Investigated by Two Anatomical Methods

Two major studies of structural changes associated with aging in human kidneys are reviewed and new information presented. The studies are the Monash University stereologically analyzed series of 319 autopsy kidneys from the United States in which 44% were white and the Mayo Clinic CT angiogram/biopsy analysis of 1,388 US kidney donors in which 97% were white. Hypertension rates in the Monash series were 48% and included moderate and severe hypertension. In the Mayo Clinic study, 12% had mild hypertension. The studies showed no relationship between glomerular number and hypertension except for a weak relationship with older white women in the Monash series. An inverse relationship was present between glomerular number and glomerular volume, a reciprocity that tended to enhance glomerular mass and by inference filtration capacity with lower nephron numbers. This relationship seemed to be present whether low nephron numbers were intrinsic or acquired. In the Mayo Clinic studies, pretransplant iothalamate clearances demonstrated that single nephron (SN) glomerular filtration rates (GFR) were similar throughout the range of glomerular number in subjects younger than 70 years, but that increased SNGFR correlated with nephron hypertrophy and increased nephrosclerosis particularly at 70 years of age and over. Hypertension at least through middle age cannot be related to a deficiency of glomeruli, but glomeruli are lost with later aging in association with adaptive nephron hypertrophy that can maintain GFR near normal. These studies help define an age‐related nephropathy that overlaps with hypertension as a potential cause of end‐stage renal disease when glomerulosclerosis is advanced.