Featured New InvestigatorPrematurity in mice leads to reduction in nephron number, hypertension, and proteinuria
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Animals, housing, and diet
The study was conducted in a 60,000 sq ft Association for Assessment and Accreditation of Laboratory Animal Care accredited animal facility devoted exclusively to housing rodents. All experimental procedures involving animals in the facility were reviewed and approved by the Medical College of Wisconsin Institutional Animal Care and Use Committee. Experimental procedures are performed in compliance with the Guide for the Care and Use of Laboratory Animals.25, 26 Accordingly, relevant ethical
Results
Data from both male and female mice were combined; we did not observe statistically significant sex difference within each group. The error bars in all data represents standard error of mean.
Histopathology
Prior studies from human and mouse models of reduced nephron number showed that the renal lesion was in the form of sclerosis of the glomeruli.35, 36 To assess whether the decrease of nephron number in our model will yield the same histopathologic picture observed in humans and other mouse models, we stained paraffin-embedded kidney sections with PAS. The glomerular surface area was measured electronically in 30 glomeruli per mouse in whole-section images captured on Hamamatsu NanoZoomer. The
Discussion
The mechanism of prematurity-induced reduction in nephron number, hypertension and chronic kidney disease (CKD) remains mostly speculative. “Organ sparing,” as a result of unfavorable intrauterine conditions, is a proposed mechanism for multiorgan underdevelopment including low nephron number,37, 38, 39, 40, 41, 42 whereas mechanical stress and hyperfiltration have been proposed as a mechanism of CKD associated with the low nephron number.35 Meanwhile, placental and environmental programming of
Ashraf El-Meanawy, MD, PhD, is an Assistant Professor of Medicine in the Division of Nephrology at the Medical College of Wisconsin. His article is based on a presentation given at the Combined Annual Meeting of the Central Society for Clinical Research and Midwestern Section American Federation for Medical Research held in Chicago, Ill, April 2011.
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Pregnancy and severely reduced renal mass: A stress model showing renal hyperfiltration
2022, Pregnancy HypertensionCitation Excerpt :To extrapolate total nephron numbers and compare NX to S, calculated ratio is 174 to 987.4 nephrons (1 to 5.7)—confirming 5/6th nephrectomy. Increasing numbers of women with decreased nephron numbers whether congenital or acquired from low birth weight and prematurity [7,8], advanced maternity age [9,10], small kidney [11,12], and renal transplantation [13], make a model in which to study severely deceased nephron numbers valuable. Our findings affirm pregnancy as a stressor in this 5/6th nephrectomy pregnancy model (NX) causing elevated systolic and diastolic blood pressure, serum creatinine, and proteinuria [14,15].
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Ashraf El-Meanawy, MD, PhD, is an Assistant Professor of Medicine in the Division of Nephrology at the Medical College of Wisconsin. His article is based on a presentation given at the Combined Annual Meeting of the Central Society for Clinical Research and Midwestern Section American Federation for Medical Research held in Chicago, Ill, April 2011.
Supported in part by grants HL-29587 and DK-62803 from the National Institutes of Health and by the Kidney Disease Center at the Medical College of Wisconsin.