title: Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model.
abstract: Some studies have reported up to 40% of patients born with a single kidney develop hypertension, proteinuria, and in some cases renal failure. The increased susceptibility to renal injury may be due, in part, to reduced nephron numbers. Notably, children who undergo nephrectomy or adults who serve as kidney donors exhibit little difference in renal function compared with persons who have two kidneys. However, the difference in risk between being born with a single kidney versus being born with two kidneys and then undergoing nephrectomy are unclear. Animal models used previously to investigate this question are not ideal because they require invasive methods to model congenital solitary kidney. In this study, we describe a new genetic animal model, the heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, which demonstrates 50%-75% spontaneous incidence of a single kidney. The HSRA model is characterized by reduced nephron number (more than would be expected by loss of one kidney), early kidney/glomerular hypertrophy, and progressive renal injury, which culminates in reduced renal function. Long-term studies of temporal relationships among BP, renal hemodynamics, and renal function demonstrate that spontaneous single-kidney HSRA rats are more likely than uninephrectomized normal littermates to exhibit renal impairment because of the combination of reduced nephron numbers and prolonged exposure to renal compensatory mechanisms (i.e., hyperfiltration). Future studies with this novel animal model may provide additional insight into the genetic contributions to kidney development and agenesis and the factors influencing susceptibility to renal injury in individuals with congenital solitary kidney.
authors.affiliation: Departments of *Pharmacology and Toxicology.
authors.forename: Xuexiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Departments of *Pharmacology and Toxicology.
authors.forename: Ashley C
authors.initials: AC
authors.lastname: Johnson
authors.affiliation: Departments of *Pharmacology and Toxicology, Medicine (Nephrology).
authors.forename: Jan M
authors.initials: JM
authors.lastname: Williams
authors.affiliation: Departments of *Pharmacology and Toxicology.
authors.forename: Tiffani
authors.initials: T
authors.lastname: White
authors.affiliation: Physiology and Biophysics, Radiology, University of Mississippi Medical Center, Jackson, Mississippi; and.
authors.forename: Alejandro R
authors.initials: AR
authors.lastname: Chade
authors.affiliation: Physiology and Biophysics.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Physiology and Biophysics.
authors.forename: Ruisheng
authors.initials: R
authors.lastname: Liu
authors.affiliation: Departments of *Pharmacology and Toxicology, Medicine (Nephrology).
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Roman
authors.affiliation: Departments of *Pharmacology and Toxicology.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Lee
authors.affiliation: Pathology, and.
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Kyle
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Madison, Wisconsin.
authors.forename: Leah
authors.initials: L
authors.lastname: Solberg-Woods
authors.affiliation: Departments of *Pharmacology and Toxicology, Medicine (Nephrology), mrgarrett@umc.edu.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Garrett
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000503:physiopathology; D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D015984:Causality; D002648:Child; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006984:Hypertrophy / Q000473:pathology; D007668:Kidney / Q000002:abnormalities*; D008297:Male; D008957:Models, Genetic; D009392:Nephrectomy / Q000009:adverse effects; D009399:Nephrons / Q000503:physiopathology*; D011507:Proteinuria / Q000503:physiopathology; D011897:Random Allocation; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000209:etiology* / Q000503:physiopathology; D018570:Risk Assessment; D014564:Urogenital Abnormalities / Q000150:complications* / Q000235:genetics*
keywords: chronic kidney disease; genetics and development; glomerular hyperfiltration; pediatric nephrology; renal agenesis; transcriptional profiling