Nephron Hypertrophy and Glomerulosclerosis and Their Association with Kidney Function and Risk Factors among Living Kidney Donors

Abstract

Background and objectives The relationship of kidney function and CKD risk factors to structural changes in the renal parenchyma of normal adults is unclear. This study assessed whether nephron hypertrophy and nephrosclerosis had similar or different associations with kidney function and risk factors.Design, setting, participants, & measurements From 1999 to 2009, 1395 living kidney donors had a core needle biopsy of their donated kidney during transplant surgery. The mean nonsclerotic glomerular volume and glomerular density (globally sclerotic and nonsclerotic) were estimated using the Weibel and Gomez stereologic methods. All tubules were counted in 1 cm 2 of cortex to determine a mean profile tubular area. Nephron hypertrophy was identified by larger glomerular volume, larger profile tubular area, and lower nonsclerotic glomerular density. Nephrosclerosis was identified by higher globally sclerotic glomerular density.Results The mean (6SD) age was 44612 years, 24-hour urine albumin excretion was 567 mg, measured GFR was 103617 ml/min per 1.73 m 2 , uric acid was 5.261.4 mg/dl, and body mass index was 2865 kg/m 2 . Of the study participants, 43% were men, 11% had hypertension, and 52% had a family history of ESRD. Larger glomerular volume, larger profile tubular area, and lower nonsclerotic glomerular density were correlated. Male sex, higher 24-hour urine albumin excretion, family history of ESRD, and higher body mass index were independently associated with each of these measures of nephron hypertrophy. Higher uric acid, higher GFR, and older age were also independently associated with some of these measures of nephron hypertrophy. Hypertension was not independently associated with measures of nephron hypertrophy. However, hypertension and older age were independently associated with higher globally sclerotic glomerular density.Conclusions Nephron hypertrophy and nephrosclerosis are structural characteristics in normal adults that relate differently to clinical characteristics and may reflect kidney function and risk factors via separate but inter-related pathways.

New insights on glomerular hyperfiltration: a Japanese autopsy study

“…Low nephron count in humans has previously been associated with tubular hypertrophy (43). In response to the increased filtered load, compensatory cellular hypertrophy in proximal tubules increases Na + reabsorption, which restores NaCl delivery to distal tubules via tubuloglomerular feedback (44).…”

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.…”

“…19 However, albuminuria does highly correlate with glomerular enlargement, the latter of which may be a manifestation of nephron endowment rather than nephron loss with aging. 14 Disentangling the different effects of low nephron endowment and the physiologic loss of nephrons with aging will required additional study.…”

Evaluation of Kidney Function and Structure in Potential Living Kidney Donors: Implications for the Donor and Recipient

“…In living donors, the prevalence of glomerulo-nephrosclerosis increases linearly with age from 2.7 % for donors aged 18-29 years, to 73 % for donors aged 70-77 years [45]. Elsherbiny et al found correlations between some donor characteristics with structural changes in the renal parenchyma [46]. Male sex, high kidney function, albuminuria, family history of renal disease, and high BMI were independently associated with features of nephron hypertrophy (large glomerular volume, large tubular area, and low nonsclerotic glomerular density).…”