Recovery following relief of unilateral ureteral obstruction in the neonatal rat

Chevalier, Robert L.; Kim, Andrew; Thornhill, Barbara A.; Wolstenholme, Jennifer T.

doi:10.1046/j.1523-1755.1999.055003793.x

Cited by 123 publications

(114 citation statements)

References 36 publications

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“…We reported previously that renal maturation is delayed by chronic complete UUO. This includes persistence of an immature pattern of glomerular maturation (7,8), microvascular renin distribution (7), and of tubular (25) and interstitial markers (11,38). In the present study, we showed that glomerular maturation is also delayed in the neonatal rat following partial UUO.…”

Section: Discussionsupporting

confidence: 52%

Angiotensin-converting enzyme inhibition aggravates renal interstitial injury resulting from partial unilateral ureteral obstruction in the neonatal rat

Chen¹,

Park²,

Forbes³

et al. 2007

American Journal of Physiology-Renal Physiology

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Congenital urinary tract obstruction is the most important cause of renal insufficiency in infants and children, and angiotensin-converting enzyme (ACE) inhibitors attenuate the progression of renal disease in adults. ACE inhibitors are increasingly utilized in children with progressive renal disease. Because angiotensin is necessary for normal renal development, we examined the effects of ACE inhibition both during and immediately following the period of postnatal nephrogenesis in the neonatal rat subjected to sham operation or partial unilateral ureteral obstruction (UUO) under general anesthesia within the first 48 h of life. Rats in group I received enalapril 30 mg/kg body wt (or vehicle) daily for the first 10 days, while in group II, the 10 days of treatment began 10 days after surgery. Kidneys were harvested at day 21 and analyzed for apoptosis (TUNEL), interstitial macrophages (ED-1 immunohistochemistry), myofibroblasts (α-smooth muscle actin), and collagen (Sirius red). Partial UUO delayed glomerular maturation and increased ipsilateral renal macrophage infiltration, α-smooth muscle actin and Sirius red staining. In group I, enalapril increased myofibroblast accumulation in sham-operated kidneys, but not in obstructed kidneys. In contrast, in group II, enalapril further increased macrophage, myofibroblast, and collagen accumulation following partial UUO. The relative abundance of components of the kallikrein-kinin system, measured by Western blot, was not altered by partial UUO in the 14- and 28-day-old rat. Thus, in contrast to its salutary effects at later ages, ACE inhibition can worsen injury to the partially obstructed kidney during renal maturation even after the completion of nephrogenesis.

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Section: Discussionsupporting

confidence: 52%

Angiotensin-converting enzyme inhibition aggravates renal interstitial injury resulting from partial unilateral ureteral obstruction in the neonatal rat

Chen¹,

Park²,

Forbes³

et al. 2007

American Journal of Physiology-Renal Physiology

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“…Although statistically significant, renal interstitial collagen accumulation 7 days after UUO was Ͻ4% of the parenchymal area and returned to normal levels after release of UUO. Release of temporary UUO in the neonatal rat attenuates, but does not completely reverse interstitial collagen accumulation (6). Although there are reports of reversible fibrotic lesions (2,3), the increase in renal collagen concentration due to UUO correlates with a decrease in renal tissue dry weight (8).…”

Section: Discussionmentioning

confidence: 99%

Renal functional decline and glomerulotubular injury are arrested but not restored by release of unilateral ureteral obstruction (UUO)

Chaabane

Praddaude

Buléon

et al. 2013

American Journal of Physiology-Renal Physiology

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Chaabane W, Praddaude F, Buleon M, Jaafar A, Vallet M, Rischmann P, Galarreta CI, Chevalier RL, Tack I. Renal functional decline and glomerulotubular injury are arrested but not restored by release of unilateral ureteral obstruction (UUO). Am J Physiol Renal Physiol 304: F432-F439, 2013. First published December 5, 2012; doi:10.1152/ajprenal.00425.2012.-Murine unilateral ureteral obstruction (UUO), a major model of progressive kidney disease, causes loss of proximal tubular mass and formation of atubular glomeruli. Adult C57BL/6 mice underwent a sham operation or reversible UUO under anesthesia. In group 1, kidneys were harvested after 7 days. In group 2, the obstruction was released after 7 days, and a physiological study of both kidneys was performed 30 days later. Renal blood flow (RBF), glomerular filtration rate (GFR), urine protein, and albumin excretion were measured after ligation of either the left or right ureter. Glomerular volume (periodic acidSchiff), glomerulotubular integrity and proximal tubular mass (Lotus tetragonolobus lectin), and interstitial collagen (Sirius red) were measured by histomorphometry. Obstructed kidney weight was reduced by 15% at 7 days but was not different from sham after a 30-day recovery. Glomerular volume and proximal tubular area of the obstructed kidney were reduced by 55% at 7 days, but normalized after 30 days. Interstitial collagen deposition increased 2.4-fold after 7 days of UUO and normalized after release. However, GFR and RBF were reduced by 40% and urine albumin/protein ratio was increased 2.8-fold 30 days after release of UUO. This was associated with a 50% reduction in glomerulotubular integrity despite a 30-day recovery (P Ͻ 0.05 for all data). We conclude that release of 7-day UUO can arrest progression but does not restore normal function of the postobstructed kidney. Although the remaining intact nephrons have hypertrophied, glomerular injury is revealed by albuminuria. These results suggest that glomerulotubular injury should become the primary target of slowing progressive kidney disease. glomerular filtration rate; albuminuria; renal hypertrophy; atubular glomeruli; proximal tubule; fibrosis PARENCHYMAL LOSS AND PROGRESSIVE interstitial fibrosis are common features of chronic kidney disease (23). Unilateral ureteral obstruction (UUO) is the animal model most widely used to study the development of tissue damage and fibrosis. In addition, release of obstruction permits examination of renal repair (for a review, see Ref. 5). The renal impact of UUO varies with animal species, and until the past decade rabbits, dogs, and rats have been mostly used (21). However, most studies are currently performed in mice, which offer a variety of genetically engineered animals (9, 12, 16). Because of its technical difficulty, the use of reversible models of UUO in mice remains limited and little information is available regarding the renal functional impact of UUO and its relief. As in humans, most species exhibit a compensatory renal growth of the nonobstructed kidney ...

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“…Longer term obstruction, however, has led to only a partial recovery of renal function after the relief of UUO (34,35). Recovery of GFR after UUO is most likely dependent on several factors, including the duration of obstruction with studies in neonatal rats suggesting that early relief of obstruction in the developing kidney allows greater preservation of renal function (17,36). Clinically, recovery of renal function after relief of obstruction has been linked to patient age, duration of obstruction, function of the contralateral kidney, and compliance of the ureter and renal pelvis (37).…”

Section: Discussionmentioning

confidence: 99%

“…Chevalier et al (16) demonstrated recovery of renal structure in neonatal rats after reversal of 2 to 5 d of UUO. Although the neonatal kidneys of rats after R-UUO have a normal GFR, this may be due to an initial hyperfiltration in the postobstructed kidney (17,18). Our study describes a new model of renal injury and repair in the adult mouse after R-UUO.…”

mentioning

confidence: 91%

Renal Structural and Functional Repair in a Mouse Model of Reversal of Ureteral Obstruction

Cochrane

Kett²,

Samuel³

et al. 2005

Journal of the American Society of Nephrology

141

146

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The end point of immune and nonimmune renal injury typically involves glomerular and tubulointerstitial fibrosis. Although numerous studies have focused on the events that lead to renal fibrosis, less is known about the mechanisms that promote cellular repair and tissue remodeling. Described is a model of renal injury and repair after the reversal of unilateral ureteral obstruction (UUO) in male C57bl/6J mice. Male mice (20 to 25 g) underwent 10 d of UUO with or without 1, 2, 4, or 6 wk of reversal of UUO (R-UUO). UUO resulted in cortical tubular cell atrophy and tubular dilation in conjunction with an almost complete ablation of the outer medulla. This was associated with interstitial macrophage infiltration; increased hydroxyproline content; and upregulated type I, III, IV, and V collagen expression. The volume density of kidney occupied by renal tubules that exhibited a brush border was measured as an assessment of the degree of repair after R-UUO. After 6 wk of R-UUO, there was an increase in the area of kidney occupied by repaired tubules (83.7 ؎ 5.9%), compared with 10 d UUO kidneys (32.6 ؎ 7.3%). This coincided with reduced macrophage numbers, decreased hydroxyproline content, and reduced collagen accumulation and interstitial matrix expansion, compared with obstructed kidneys from UUO mice. GFR in the 6-wk R-UUO kidneys was restored to 43 to 88% of the GFR in the contralateral unobstructed kidneys. This study describes the regenerative potential of the kidney after the established interstitial matrix expansion and medullary ablation associated with UUO in the adult mouse. R enal injury and repair comprises a delicate balance between cell loss and proliferation and extracellular matrix (ECM) accumulation and remodeling. Although many studies have focused on the cellular and molecular events that lead to the development of renal fibrosis, less is understood about the process of endogenous renal repair.We have characterized a model of reversal of unilateral ureteral obstruction (R-UUO) in the mouse to assess the regenerative potential of the kidney after interstitial matrix expansion and medullary ablation. UUO initiates a marked increase in numbers of interstitial macrophages that contribute to the cascade of events that lead to the development of fibrosis and renal cell loss. The facilitation and recruitment of macrophages into the renal interstitium is coupled to the upregulated expression of an array of chemokines and adhesion molecules (1,2). After R-UUO in the rat, both cortical (3) and medullary (4) interstitial macrophages are found to decrease gradually in number toward control values by 4 wk after release.A marked decline in GFR and renal plasma flow is observed by 24 h after UUO in dogs, rabbits, and rats (5-7). The duration of UUO and the extent of cell loss play a pivotal role in the recovery of GFR and subsequent renal remodeling and repair. Whereas short-term UUO in rats seems to be completely reversible (8), UUO for Ͼ72 h may lead to renal fibrotic and apoptotic changes culminating in a perm...

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Recovery following relief of unilateral ureteral obstruction in the neonatal rat

Cited by 123 publications

References 36 publications

Angiotensin-converting enzyme inhibition aggravates renal interstitial injury resulting from partial unilateral ureteral obstruction in the neonatal rat

Angiotensin-converting enzyme inhibition aggravates renal interstitial injury resulting from partial unilateral ureteral obstruction in the neonatal rat

Renal functional decline and glomerulotubular injury are arrested but not restored by release of unilateral ureteral obstruction (UUO)

Renal Structural and Functional Repair in a Mouse Model of Reversal of Ureteral Obstruction

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