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.)
Glomerular volume increases when demand exceeds nephron supply, which may lead to glomerulosclerosis. It is unclear if determinants of glomerular volume are consistent between populations that differ by severity of comorbidities. We studied kidney biopsy specimens from living kidney donors (=2453) and patients who underwent radical nephrectomy for a renal tumor (=780). We scanned specimen sections into high-resolution digital images, manually traced glomerular profiles, and calculated mean glomerular volumes using the Weibel-Gomez stereologic formula (separately for nonsclerosed glomeruli and globally sclerosed glomeruli). We then assessed the relationship of glomerular volume with age, clinical characteristics, and nephrosclerosis on biopsy specimen. Compared with kidney donors, patients with tumors were older and more frequently men, obese, diabetic, or hypertensive, had more glomerulosclerosis and interstitial fibrosis on biopsy specimen, and had 12% larger nonsclerosed glomeruli (<0.001). In both populations, male sex, taller height, obesity, hypertension, and proteinuria associated with larger nonsclerosed glomeruli to a similar extent. In patients with tumors, diabetes, glomerulosclerosis >25%, and interstitial fibrosis >25% also associated with larger nonsclerosed glomeruli. Independent clinical predictors of larger nonsclerotic glomeruli were family history of ESRD, male sex, taller height, obesity, diabetes, and proteinuria. After adjustment for these characteristics, nonsclerotic glomerular volume did not differ between populations and was stable up to age 75 years, after which it decreased with age. Many of these findings were also evident with globally sclerotic glomerular volume. Characteristics associated with glomerular volume are consistent between patient populations with low and high levels of comorbidity.
Background: Non-invasive biomarkers that detect occult pathology in patients with normal glomerular filtration rate (GFR) and normal urine albumin excretion may help identify patients at risk for chronic kidney diseases. Methods: Two promising biomarkers of interstitial fibrosis, urinary monocyte chemoattractant protein 1 (MCP-1) and collagen IV, were assayed among 634 living kidney donors from 2005 to 2011, who had both a frozen pre-donation spot urine sample and a core needle biopsy of their donated kidney at transplantation (‘time zero biopsy'). The association of urine MCP-1 and collagen IV with kidney function (GFR and urine albumin excretion), kidney volume on computed tomographic imaging and histological findings was assessed. Results: The mean ± SD age was 45 ± 12 years, 24-hour urine albumin was 4 ± 7 mg and measured GFR (mGFR) was 102 ± 18 ml/min/1.73 m2. The median (25th-75th percentile) urine level of MCP-1 was 146 (54-258) pg/ml and of collagen IV was 2.0 (1.0-3.5) µg/l. Higher urine MCP-1 associated with higher 24-hour urine albumin excretion; higher urine collagen IV associated with male gender. On kidney biopsy, any interstitial fibrosis was present in 22% and fibrosis >5% in 4% of donors. The mean MCP-1/Cr ratio was 1.49 pg/mg for 0% fibrosis, 1.80 pg/mg for 1-5% fibrosis, 2.33 pg/mg for 6-10% fibrosis and 4.33 pg/mg for >10% fibrosis. After adjustment for age, sex, mGFR and 24-hour urine albumin, higher urine MCP-1 but not collagen IV associated with interstitial fibrosis and tubular atrophy. Conclusion: Urine MCP-1 may detect early tubulointerstitial fibrosis in adults with normal kidney function.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.