Single-Nephron Glomerular Filtration Rate in Healthy Adults

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.)

Uromodulin and Nephron Mass

“…The 24-hour urine uromodulin excretion increased at higher birth weight ( Figure 1A). In multiple linear regression analysis, 24-hour urine uromodulin excretion was associated with the same predictors of nephron mass as identified in the study by Denic et al (4). Age, female sex, and uric acid were negative predictors whereas height and birth weight were positive predictors of 24-hour urine uromodulin excretion.…”

New insights on glomerular hyperfiltration: a Japanese autopsy study

“…The associations described above between glomerular number, glomerular volume, and SNeGFR in normotensive, hypertensive, and CKD subjects are somewhat different from those of Denic et al who measured these parameters in healthy adult kidney donors (22,23). 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 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).…”

“…Glomerular hypertrophy also occurs with hypertension and obesity, suggesting that increased metabolic and excretory demands can contribute to compensatory glomerular growth (16)(17)(18). Although the effect of increased glomerular volume on glomerular function is unclear (18-21), Denic et al recently found that single-nephron glomerular filtration rate (SNGFR; measured GFR divided by the number of nephrons) in healthy adult kidney donors was fairly constant with regard to age, sex, and height (if < 190 cm) (22). However, these authors found that higher SNGFR was independently associated with larger nephrons on biopsy and more glomerulosclerosis and arteriosclerosis than would be expected for the donors' age.…”

Renal Hyperfiltration in Adolescents with Type 2 Diabetes: Physiology, Sex Differences, and Implications for Diabetic Kidney Disease

“…In adults with T2D, the reduction in intraglomerular hypertension was reflected by a mean reduction in eGFR of 2–4 ml/min/1.73m 2 after treatment initiation, followed by a stabilisation of eGFR decline compared to placebo during long-term treatment (15). Therefore, the initial decline in eGFR likely reflects attenuation of single-nephron hyperfiltration, which is associated with subsequent long-term renal function preservation (46). It is not known whether these renal hemodynamic effects occur in youth-onset T2D, as there are no published studies to date examining the effect of SGLT2 inhibitors on intrarenal hemodynamic function in this patient population.…”