Detection and Clinical Patterns of Nephron Hypertrophy and Nephrosclerosis Among Apparently Healthy Adults

Abstract

Background Even among ostensibly healthy adults, there is often mild pathology in the kidney. The detection of kidney microstructural variation and pathology by imaging and the clinical pattern associated with these structural findings is unclear. Study Design Cross-sectional (clinical-pathological correlation). Setting & Participants Living kidney donors at Mayo Clinic (Minnesota and Arizona sites) and Cleveland Clinic 2000-2011. Predictors Pre-donation kidney function, risk factors, and contrast computed tomography scan of the kidneys. These scans were segmented for cortical volume and medullary volume, reviewed for parenchymal cysts, and scored for kidney surface roughness. Outcomes Nephrosclerosis (glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis) and nephron size (glomerular volume, profile tubular area, and cortical volume per glomerulus) determined from an implantation biopsy of the kidney cortex at donation. Results Among 1520 living kidney donors, nephrosclerosis associated with increased kidney surface roughness, cysts, and smaller cortical to medullary volume ratio. Larger nephron size (nephron hypertrophy) associated with larger cortical volume. Nephron hypertrophy and larger cortical volume associated with higher systolic blood pressure, higher glomerular filtration rate, higher urine albumin excretion, larger body mass index, higher serum uric acid, and family history of end-stage renal disease. Both nephron hypertrophy and nephrosclerosis associated with older age and mild hypertension. The net effect of both nephron hypertrophy and nephrosclerosis associating with cortical volume was that nephron hypertrophy diminished volume loss with age-related nephrosclerosis and fully negated volume loss with mild hypertension-related nephrosclerosis. Limitations Kidney donors are selected on health, restricting the spectrum of pathological findings. Kidney biopsies in living donors are a small tissue sample leading to imprecise estimates of structural findings. Conclusions Among apparently healthy adults, the microstructural findings of nephron hypertrophy and nephrosclerosis differ in their association with kidney function, macrostructure, and risk factors.

New insights on glomerular hyperfiltration: a Japanese autopsy study

“…They found that while nephron number decreased with healthy aging, SNGFR remained relatively constant, and glomerular volume did not increase in association with nephron loss (39). They concluded that this failure to compensate for loss of nephrons in healthy aging might be due to a concurrent decrease in metabolic demand that could influence GFR (22).…”

Single-Nephron Glomerular Filtration Rate in Healthy Adults

“…The presence of nephrosclerosis probably explains the age-related decline in the total GFR over time. 14,15,24 Seemingly healthy persons can also have more nephrosclerosis than expected for their age, yet may not have a further reduction in the total GFR. 14,24 This study showed that nephrosclerosis exceeding that expected for age decreased the number of nephrons but was generally accompanied by a compensatory higher single-nephron GFR, which maintained the total GFR.…”

“…14,15,24 Seemingly healthy persons can also have more nephrosclerosis than expected for their age, yet may not have a further reduction in the total GFR. 14,24 This study showed that nephrosclerosis exceeding that expected for age decreased the number of nephrons but was generally accompanied by a compensatory higher single-nephron GFR, which maintained the total GFR. The apparent failure of the single-nephron GFR to increase with the expected age-related nephron loss, whereas it increased with nephro-sclerosis beyond the level expected for age, may support an age-based approach to the identification of chronic kidney disease.…”

“…[13][14][15] Data sources were all from the usual care of kidney donors, and the study was approved by an institutional review board with a waiver of informed consent.…”

When kidneys get old: an essay on nephro-geriatrics

“…Detailed anatomic and physiologic studies of the healthiest of the healthy, normal living donors for kidney transplantation by the Mayo Clinic and Cleveland Clinic have been particularly revealing. [14][15][16][17][18][19] We are all born with a complement of nephrons determined in large part by the process of nephrogenesis in utero. 20 This process can be influenced, either negatively or positively by the maternal-fetal nexus.…”