High Incidence of Glomerular Sclerosis in Rats Subjected to Uninephrectomy at Young Age

Okuda, Seiya; Motomura, Kinsi; Sanai, Toru; Onoyama, Kaoru; Fujishima, Masatoshi

doi:10.1159/000185063

Cited by 26 publications

(21 citation statements)

References 6 publications

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“…The HSRA model offers a distinct advantage to investigate the consequences of having a single kidney as other studies have done so through invasive procedures, such as nephrectomy [8][9][10] and renal ablation 11-13 using two-kidney rats. The major findings of this study are as follows.…”

Section: Discussionmentioning

confidence: 99%

“…Many experimental animal models have investigated the consequences of having a single kidney, but most have used invasive procedures, such as early nephrectomy [9][10][11] or renal ablation. [12][13][14] These studies suggest that compensatory renal changes (due to reduced nephron number) lead to progressive damage and loss of renal function in the remaining kidney and hypertension over time.…”

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confidence: 99%

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Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

Wang¹,

Johnson²,

White³

et al. 2015

Journal of the American Society of Nephrology

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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.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

Wang¹,

Johnson²,

White³

et al. 2015

Journal of the American Society of Nephrology

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show abstract

“…23 A reduction of 50% of the nephrons by uninephrectomy in neonatal rats causes hypertension and progressive renal disease. 12 However, uninephrectomy in adult rats does not cause hypertension or renal injuries, 20,24 and, therefore, neonatal and adult nephrectomy appear to have different effects on blood pressure regulation. In the present study, nephrectomy was performed in postnatal animals, which all developed various degrees of hypertension in adulthood.…”

Section: Discussionmentioning

confidence: 99%

Uninephrectomy in Young Age or Chronic Salt Loading Causes Salt-Sensitive Hypertension in Adult Rats

et al. 2007

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Abstract-The importance of nephron endowment and salt intake for the development of hypertension is under debate. The present study was designed to investigate whether reduced nephron number, after completion of nephrogenesis, or chronic salt loading causes renal injury and salt-sensitive hypertension in adulthood. Rats were operated at 3 weeks of age (after completed nephrogenesis) and then subjected to either normal or high-salt diets for 6 to 8 weeks. Four different experimental groups were used: sham-operated animals raised with normal-salt diet (controls) or high-salt diet (HS) and uninephrectomized animals raised with normal-salt diet (UNX) or high-salt diet (UNXϩHS). In the adult animals, renal and cardiovascular functions were evaluated and blood pressure recorded telemetrically under different sodium conditions (normal, high, and low). Hypertension was present in UNXϩHS (122Ϯ9 mm Hg), UNX (101Ϯ3 mm Hg), and HS (96Ϯ1 mm Hg) groups on normal-salt diets compared with the controls (84Ϯ2 mm Hg), and the blood pressure was salt sensitive (high-versus normal-salt diet; 23Ϯ3, 9Ϯ2, 7Ϯ2, and 1Ϯ1 mm Hg, respectively). The hypertensive groups (UNXϩHS, UNX, and HS) had increased diuresis and reduced ability to concentrate urine. The glomerular filtration rate (milliliters per minute) in anesthetized rats was reduced in the UNXϩHS (2.36Ϯ0.30) and UNX animals (2.00Ϯ0.31) compared with both HS animals (3.55Ϯ0.45) and controls (3.01Ϯ0.35). Hypertensive groups displayed reduced plasma renin concentrations during high sodium conditions and hypertrophic kidneys and hearts with various degrees of histopathologic changes. In conclusion, at a young age after completed nephrogenesis, uninephrectomy or chronic salt loading causes renal and cardiovascular injury with salt-sensitive hypertension. (Hypertension.

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“…5,6 Long-term complications, in theory, could be glomerulosclerosis, renal dysfunction, proteinuria, and hypertension. As to longterm postsurgical repercussions, glomerulosclerosis, hyperinfiltration, and renal dysfunction have been observed in animal experimentation, [7][8][9] whereas studies conducted on 3000 human donors have not…”

Section: Introductionmentioning

confidence: 99%

Resistive Index of the Remaining Kidney in Allograft Kidney Donors

Nekouei

Ahmadnia²,

Abedi³

et al. 2012

Exp Clin Transplant

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Objectives: Kidney transplant is the last resort in patients with end-stage renal disease. In living-kidney donors undergoing nephrectomy for transplant; however, morphologic and hemodynamic changes may occur in the remaining kidney with time. If there would be such a change, then it may alter the diagnostic utility of Doppler ultrasound in evaluating diseased conditions of the solitary kidney. Using Doppler ultrasound, this study sought to determine whether there are hemodynamic changes in the remaining kidney. Materials and Methods: Forty-one patients (38 men, 3 women) for kidney donation were examined using a MyLab 50 color Doppler apparatus with a convey 3.5-to 5-MHz probe. Resistive index values of the main renal, interlobar, and interlobular arteries in the remaining kidney were assessed before, and at 7 and 90 days after nephrectomy. The size and parenchymal thickness of the remaining kidney also were measured before and after nephrectomy. Results: At day 90, a statistically significant increase (P < .001) in resistive index was seen at all levels, compared with before and 7 days after nephrectomy. No significant changes, however, could be noticed on the day 7, when compared with before the nephrectomy. Renal size and parenchymal thickness remained constant over the time studied. Conclusions: Although a statistically significant increase in resistive index values of the remaining kidney was seen 90 days after the nephrectomy, these values have remained within the normal limits of renal resistive index. So, our findings indicate that resistive index measurement is useful in assessing the diseased condition of the remaining kidney after removing the contralateral kidney.

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High Incidence of Glomerular Sclerosis in Rats Subjected to Uninephrectomy at Young Age

Cited by 26 publications

References 6 publications

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

Nephron Deficiency and Predisposition to Renal Injury in a Novel One-Kidney Genetic Model

Uninephrectomy in Young Age or Chronic Salt Loading Causes Salt-Sensitive Hypertension in Adult Rats

Resistive Index of the Remaining Kidney in Allograft Kidney Donors

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