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. 2017 Jun 15;376(24):2349-2357.
doi: 10.1056/NEJMoa1614329.

Single-Nephron Glomerular Filtration Rate in Healthy Adults

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Single-Nephron Glomerular Filtration Rate in Healthy Adults

Aleksandar Denic et al. N Engl J Med. .

Abstract

Background: The glomerular filtration rate (GFR) assesses the function of all nephrons, and the single-nephron GFR assesses the function of individual nephrons. How the single-nephron GFR relates to demographic and clinical characteristics and kidney-biopsy findings in humans is unknown.

Methods: We identified 1388 living kidney donors at the Mayo Clinic and the Cleveland Clinic who underwent a computed tomographic (CT) scan of the kidney with the use of contrast material and an iothalamate-based measurement of the GFR during donor evaluation and who underwent a kidney biopsy at donation. The mean single-nephron GFR was calculated as the GFR divided by the number of nephrons (calculated as the cortical volume of both kidneys as assessed on CT times the biopsy-determined glomerular density). Demographic and clinical characteristics and biopsy findings were correlated with the single-nephron GFR.

Results: A total of 58% of the donors were women, and the mean (±SD) age of the donors was 44±12 years. The mean GFR was 115±24 ml per minute, the mean number of nephrons was 860,000±370,000 per kidney, and the mean single-nephron GFR was 80±40 nl per minute. The single-nephron GFR did not vary significantly according to age (among donors <70 years of age), sex, or height (among donors ≤190 cm tall). A higher single-nephron GFR was independently associated with larger nephrons on biopsy and more glomerulosclerosis and arteriosclerosis than would be expected for age. A higher single-nephron GFR was associated with a height of more than 190 cm, obesity, and a family history of end-stage renal disease.

Conclusions: Among healthy adult kidney donors, the single-nephron GFR was fairly constant with regard to age, sex, and height (if ≤190 cm). A higher single-nephron GFR was associated with certain risk factors for chronic kidney disease and certain kidney-biopsy findings. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).

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Figures

Figure 1
Figure 1. Kidney-Biopsy Sample with Structural Measurements
The volume and density of nonsclerotic glomeruli were calculated with the use of stereologic assessments from the area of their cross sections (red outline) and the area of the cortex (green outline) (Panel A). The number of tubules in an area of cortex measuring 1 mm2 (excluding glomeruli, fibrosis, and arteries) was used to calculate the mean cross-sectional tubular area. The volume of the kidney cortex was determined by means of CT scans with the use of contrast material (Panel B) and was multiplied by the nonsclerotic glomerular density to calculate the number of nephrons. Panel C shows a specimen with glomerulosclerosis (in >10% of glomeruli); the number of globally sclerotic glomeruli (pink outlined areas with arrowheads) was divided by the number of both nonsclerotic glomeruli (red outline) and globally sclerotic glomeruli. Panel D shows a specimen with interstitial fibrosis (in >5% of the cortex); the percentage of the cortex that had fibrosis with tubular atrophy (black dashed outline) was estimated by means of visual inspection. Panel E shows a specimen with arteriosclerosis (intimal thickening of >50% of an artery lumen within the biopsy sample; a threshold just met by the specimen shown); the percent of artery luminal stenosis was calculated from the area of intima (shown between the yellow and red outlines) divided by the area of intima plus lumen (inside the red outline).

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