Recovery from release of ureteral obstruction in the rat: Relationship to nephrogenesis

Chevalier, Robert L.; Thornhill, Barbara A.; Chang, Alice Y.W.; Cachat, François; Lackey, Adam

doi:10.1046/j.1523-1755.2002.00359.x

Cited by 81 publications

(74 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…Decreases in urinary K + levels in the obstructed kidney likely reflect a reduced GFR rate and are also a product of urinary dilution [24]. Cl -excretion should be expected to increase in both the contralateral and obstructed kidneys, due to natriuresis.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Urinary and Plasma Electrolytes in a Rat Model of Unilateral Ureteric Obstruction (UUO)

Quinlan¹,

Pérez‐Barriocanal²,

Wright³

et al. 2008

TOUNJ

View full text Add to dashboard Cite

Abstract:Following unilateral ureteric obstruction (UUO), hydronephrosis is associated with long term reductions in renal blood flow (RBF) and glomerular filtration rate (GFR), tubular resistance to arginine-vasopressin (AVP), and reduced expression of aquaporin water channels and sodium (Na + ) and urea transporters. During UUO, renal function is contingent upon adaptive changes in the contralateral kidney. In the short term this response is associated with an increased GFR and a reduced expression of Na + transporters. We aimed to assess global renal function in UUO, including a comparison between the obstructed and non-obstructed kidneys.Adult male rats were subjected to UUO of either 3 or 10 days duration. Control rats underwent sham surgery. Before release of the ureteric ligature, blood and both bladder and obstructed renal pelvis urine was sampled, then both kidneys harvested. Urinary and plasma electrolytes and osmolality, and kidney weights, were measured.We observed i) mild uraemia in the obstructed animals, ii) extreme dilution of urine from the pelvis of the obstructed kidney in the absence of noteworthy alterations in plasma ions, and iii) evidence indicative of a contralateral diuresis/natriuresis.To the best of our knowledge, this is the first study simultaneously examining such an extensive range of urinary (bladder and obstructed renal pelvis) and plasma markers of renal function in UUO. The results demonstrate that UUO is associated with a small deterioration in overall renal function and marked changes in renal electrolyte handling, leading to changes in the composition of urinary output from both the non-obstructed and obstructed kidneys.

show abstract

“…Such short-term obstruction does not induce TBM destruction and EMT ( Figure 5). However, renal structure and function is permanently impaired when relief of obstruction occurs after a sustained injury (more than 5 days) (44)(45)(46), a time when TBM integrity is impaired and EMT is prominent. Hence, EMT not only actively participates in the pathogenesis of interstitial fibrogenesis, but also may function as an intrinsic determinant for irreversible progression of chronic fibrotic lesions.…”

Section: Discussionmentioning

confidence: 99%

Disruption of tissue-type plasminogen activator gene in mice reduces renal interstitial fibrosis in obstructive nephropathy

Yang¹,

Shultz²,

Mars³

et al. 2002

J. Clin. Invest.

220

155

View full text Add to dashboard Cite

Tissue-type plasminogen activator (tPA) is one of the major components in the matrix proteolytic network whose role in the pathogenesis of renal interstitial fibrosis remains largely unknown. Here, we demonstrate that ablation of tPA attenuated renal interstitial fibrotic lesions in obstructive nephropathy. Mice lacking tPA developed less morphological injury and displayed a reduced deposition of interstitial collagen III and fibronectin as well as total tissue collagen in the kidneys after sustained ureteral obstruction, when compared with their wild-type counterparts. Deficiency of tPA selectively blocked tubular epithelial-to-myofibroblast transition (EMT), but did not affect myofibroblastic activation from interstitial fibroblasts. A marked decrease in matrix metalloproteinase-9 (MMP-9) induction was found in the obstructed kidneys of tPA -/-mice, which led to a dramatic preservation of the structural and functional integrity of tubular basement membrane (TBM). In vitro, tPA induced MMP-9 gene expression and protein secretion in renal interstitial fibroblasts. Thus, increased tPA is detrimental in renal interstitial fibrogenesis through a cascade of events that lead to MMP-9 induction, TBM destruction, and promotion of EMT. Our findings establish a crucial and definite importance of EMT in the pathogenesis of renal interstitial fibrosis at the whole-animal level.

show abstract

Recovery from release of ureteral obstruction in the rat: Relationship to nephrogenesis

Abstract: In the period immediately following nephrogenesis, the kidney is particularly susceptible to long-term injury from temporary UUO. This suggests that a delay in relief of significant ureteral obstruction should be avoided if diagnosed in the perinatal or neonatal period.

Cited by 81 publications

References 55 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

Analysis of Urinary and Plasma Electrolytes in a Rat Model of Unilateral Ureteric Obstruction (UUO)

Disruption of tissue-type plasminogen activator gene in mice reduces renal interstitial fibrosis in obstructive nephropathy

Contact Info

Product

Resources

About