Changes of renal resistive index in response to hydration and diuretic administration in normal subjects and in patients with small ureteral stone.
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The renal resistive index has been measured before and after hydration and administration of diuretics in persons with normal kidneys and in kidneys with small ureteral stone, either obstructing or nonobstructing, to assess induced flow changes and to identify features differentiating obstructing from nonobstructing stones. In normal kidneys the resistive index was normal (mean, 0.62+/-0.03); no changes in the resistive index occurred within 15 to 60 min after hydration alone, whereas the resistive index rose within 15 min after hydration plus administration of diuretics and then returned to initial values within 30 min. In both cases the resistive index decreased below basal values after 75 to 90 min. Similar changes were observed in kidneys with a nonobstructing ureteral stone. In kidneys with an obstructing ureteral stone the resistive index was higher than in normal subjects (mean, 0.73+/-0.02, P<0.01), increased further within 15 min after hydration and administration of diuretics (P<0.01), and remained higher than basal values during the following 90 min. In conclusion, different resistive index changes have been observed in response to hydration and diuretics in normal and obstructed kidneys. Duplex Doppler sonography and diuresis duplex Doppler sonography seem promising diagnostic tools to identify obstructing stones. (+info)
Increased expression of TGF-beta1 but not of its receptors contributes to human obstructive nephropathy.
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Increased expression of TGF-beta1 but not of its receptors contributes to human obstructive nephropathy. BACKGROUND: Previous studies have revealed an increased expression of transforming growth factor-beta1 (TGF-beta1) and deposition of extracellular matrix in the kidney of animals with ureteral obstruction. However, these relationships have not been elucidated in the hydronephrotic kidney of humans. METHODS: We analyzed the tissue expression of extracellular matrix proteins, TGF-beta1, and its receptors in the human kidney with ureteral obstruction by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Obstructed kidneys (OBKs) were obtained from patients with ureteral tumors. A kidney specimen from patients with a renal tumor was used as control (CNKs). RESULTS: The interstitial volume was significantly increased in OBKs in comparison with CNKs. OBKs showed increased deposition of collagen types I and IV and fibronectin in the renal interstitium. RT-PCR revealed overexpression of collagen alpha1(IV) mRNA and fibronectin mRNA in OBKs. OBKs showed a significantly increased mRNA expression of TGF-beta1 in comparison with CNKs. The immunoreactivity for TGF-beta1 increased markedly in the interstitium of OBKs. There was a significant correlation between the TGF-beta1 mRNA level and the interstitial volume. However, there was no significant difference between OBKs and CNKs in the relative mRNA level nor in immunoreactivity for TGF-beta receptors. CONCLUSIONS: These data suggest that TGF-beta1 may contribute to the interstitial fibrosis found in the human kidney with ureteral obstruction, mainly because of an increase in the expression of this cytokine without significant changes to its receptors. (+info)
Tubulointerstitial renal injury induced by unilateral ureteric obstruction (UUO) is characterized by marked cell proliferation and apoptosis. Proliferation requires cell cycle transit that is positively regulated by cyclins and cyclin-dependent kinases (CDKs) and inhibited by the CIP/KIP family of cyclin-dependent kinase inhibitors (CKIs: p21, p27, and p57). We have shown that the absence of p27 results in markedly increased tubular epithelial cell proliferation and apoptosis following UUO (V. Ophascharoensuk, M. L. Fero, J. Hughes, J. M. Roberts, and S. J. Shankland. Nat. Med. 4: 575-580, 1998). Since p21 mRNA is upregulated following UUO, we hypothesized that p21 would also serve to limit cell proliferation and apoptosis. We performed UUO in p21 +/+ and p21 -/- mice. Cell proliferation [bromodeoxyuridine (BrdU), proliferating cell nuclear antigen (PCNA)], apoptosis [terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method], interstitial myofibroblast accumulation (actin), macrophage infiltration (F4/80), and collagen I expression were quantified at days 3, 7, and 14. In contrast to p27 -/- mice, there was no difference in tubular epithelial cell proliferation or apoptosis between p21 -/- and p21 +/+ mice at any time point. However, interstitial cell proliferation at day 3 was significantly increased in p21 -/- mice [BrdU, 40.7 +/- 1.9 cells/high-power field (cells/hpf) vs. 28.8 +/- 2, P < 0.005], although, interestingly, no difference was seen in interstitial cell apoptosis. Actin/BrdU double staining demonstrated increased interstitial myofibroblast proliferation at day 3 in p21 -/- animals (10 +/- 0.12 vs. 5.8 +/- 0. 11 cells/hpf, P < 0.05), which was followed by increased myofibroblast accumulation at day 7 in p21 -/- mice. No differences were detected in interstitial macrophage infiltration, collagen I deposition or transforming growth factor-beta1 mRNA (in situ hybridization) expression. In conclusion p21, unlike p27, is not essential for the regulation of tubular epithelial cell proliferation and apoptosis following UUO, but p21 levels do serve to limit the magnitude of the early myofibroblast proliferation. This study demonstrates a differential role for the CKI p21 and p27 in this model. (+info)
Effects of beta-adrenergic stimulation on the acutely obstructed ureter in dogs.
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The objective of the present study was to evaluate the effects of a selective beta(3)-adrenoceptor agonist, (R, R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]-1, 3-benzodioxole-2,2-dicarboxylate (CL 316243), on the acutely obstructed ureter in anesthetized dogs. After a complete ureteral obstruction produced by the inflation of a balloon catheter placed within the left lower ureter, the intraluminal ureteral pressure gradually rose to reach a plateau of approximately 52.5 mm Hg. Intravenous administration of isoproterenol (a nonselective beta-adrenoceptor agonist; 10 microg/kg) and CL 316243 (1 microg/kg) significantly decreased this elevated ureteral pressure (by 74.1 and 77.2%, respectively), with the reduction more sustained with CL 316243 than with isoproterenol. In addition, under both isoproterenol and CL 316243, urine flow (which had been interrupted by the balloon) was resumed, resulting in further sustained decreases in ureteral pressure. The mean blood pressure decreased and heart rate increased after the administration of both drugs, but these changes were greater in the isoproterenol group than in the CL 316243 group. In contrast, i.v. administration of butylscopolamine (an anticholinergic agent; 1000 microg/kg) had no evident effects on ureteral pressure or on urine flow. The increase in left kidney weight seen after ureteral obstruction was suppressed by CL 316243. We conclude that the selective beta(3)-adrenoceptor agonist tested appears to be more useful than isoproterenol for reducing ureteral pressure above the obstructed site and for promoting ureteral relaxation and increasing urine flow around the point of obstruction in dogs. (+info)
Effects of ICAM-1 antisense oligonucleotide on the tubulointerstitium in mice with unilateral ureteral obstruction.
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Effects of ICAM-1 antisense oligonucleotide on the renal tubulointerstitium in mice with unilateral ureteral obstruction. BACKGROUND: To extend our previous study of the therapy of the renal lesions of unilateral ureteral obstruction (UUO) in mice by an inhibitor of intercellular adhesion molecule-1 (ICAM-1), we investigated the blocking effects of ICAM-1 antisense oligonucleotides (ASONs) on the ICAM-1 expression in mouse kidney. METHODS: First, ICAM-1 ASON was transducted into mouse renal tubular epithelial cells to investigate the effects of ICAM-1 ASON in vitro. Second, fluorescein isothiocyanate (FITC)-labeled ICAM-1 ASON was injected intravenously to determine the distribution of the ASON in vivo. Third, the expression of ICAM-1 in kidney and the changes of renal morphology were observed to investigate the therapeutic effects of ICAM-1 ASON on the UUO mice in vivo. RESULTS: The expressions of ICAM-1 in the epithelial cells induced by interleukin-1beta were inhibited by ICAM-1 ASON at the dosages of 100 and 200 nmol/L. Twenty-four hours after an introvenous injection with FITC-labeled ICAM-1 ASON, the highest level of fluorescein was detected within the proximal tubules in mouse kidney. Results of immunohistology and Northern blot showed that the ICAM-1 expression was markedly reduced in the obstructed kidney after treatment with ICAM-1 ASON. The ASON also alleviated the infiltration of inflammatory cells and accumulation of the extracellular matrix in the tubulointerstitium of UUO mice without apparent side effects. CONCLUSION: Our data demonstrate that ICAM-1 ASON is taken up primarily by the proximal tubular cells of mouse kidney. ICAM-1 ASON can selectively inhibit the ICAM-1 expression of the renal tubular cells both in vitro and in vivo. (+info)
Heparin-binding EGF-like growth factor is up-regulated in the obstructed kidney in a cell- and region-specific manner and acts to inhibit apoptosis.
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The expression of certain growth factors in the epidermal growth factor (EGF) family is altered in response to renal injury. Recent studies have demonstrated that heparin binding EGF-like growth factor (HB-EGF) expression may be cytoprotective in response to apoptotic signals. The purpose of this study was to investigate the potential role of HB-EGF in the upper urinary tract following unilateral ureteral obstruction. We present evidence that: i) ureteral obstruction induced cell-specific but transient activation of HB-EGF gene expression; ii) HB-EGF expression in renal epithelial cells increased under conditions where mechanical deformation, such as that caused by hydronephrotic distension, induces apoptosis, but HB-EGF expression did not increase in renal pelvis smooth muscle cells under identical conditions; and iii) enforced expression of HB-EGF served to protect renal epithelial cells from stretch-induced apoptosis. These results suggest a potential mechanism by which the kidney protects itself from apoptosis triggered by urinary tract obstruction. (+info)
Renal tubulointerstitial injury from ureteral obstruction in the neonatal rat is attenuated by IGF-1.
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BACKGROUND: The administration of insulin-like growth factor-1 (IGF-1) has been shown to ameliorate the renal injury resulting from ischemic acute renal failure. As there are a number of similarities between acute renal failure and obstructive nephropathy, we examined the effects of IGF-1 on the renal cellular response to unilateral ureteral obstruction (UUO) in the neonatal rat. METHODS: Forty-five rats were subjected to UUO or sham operation within the first 48 hours of life and received IGF-1 (2 mg/kg/day) or saline for the following three or seven days, after which kidneys were removed for study by morphometry and immunohistochemistry. To determine the effects of UUO on endogenous expression of IGF-1 and its receptor, six additional rats were subjected to UUO or sham operation, and mRNA was measured by solution hybridization. RESULTS: There was no effect of seven days of UUO on the renal expression of endogenous IGF-1 or its receptor. Moreover, seven days of exogenous IGF-1 did not improve the suppression of nephrogenesis, the delay in glomerular maturation, or the reduction in tubular proliferation induced by ipsilateral UUO. However, in the obstructed kidney, IGF-1 reduced tubular expression of vimentin, apoptosis, and tubular atrophy by 38 to 50% (P < 0.05). In addition, IGF-1 also decreased renal interstitial collagen deposition in the obstructed kidney by 44% (P < 0.05). Following three days of UUO, the administration of IGF-1 also reduced tubular apoptosis (P < 0.05), but did not alter tubular proliferation. CONCLUSIONS: IGF-1 has a profound salutary effect on the tubular and interstitial response to UUO in early development, without affecting glomerular injury or development. These results suggest that IGF-1 may have therapeutic potential in the management of congenital obstructive nephropathy. (+info)
Enhanced expression of vsmNOS mRNA in glomeruli from rats with unilateral ureteral obstruction.
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BACKGROUND: The vasodilatory/cytotoxic gas, nitric oxide (NO), is associated with an alteration in glomerular hemodynamics seen after the induction of ureteral ligation. As yet the type of nitric oxide synthase (NOS) protein involved in the mechanism has not been clearly established in the unilateral ureteral obstruction (UUO) model. METHODS: Using reverse transcription (RT)-polymerase chain reaction (PCR), the expression and localization of vascular smooth muscle-derived nitric oxide synthase (vsmNOS) mRNA were examined in glomeruli from sham-operated control (SOC) rats and rats with UUO of three hours duration. Moreover, the effect of endogenous angiotensin II on the expression of vsmNOS mRNA in glomeruli was explored using SOC rats and rats with UUO that were pretreated or not with enalapril, an angiotensin-converting enzyme inhibitor. RESULTS: The expression of vsmNOS mRNA was significantly greater in glomeruli of rats with UUO than in those of SOC rats. In rats with UUO, the expression of vsmNOS mRNA was substantially increased in glomeruli of the obstructed kidney (OK) compared to the contralateral, nonobstructed kidney (CLK). Suppression of angiotensin II production in vivo with enalapril restored the expression of vsmNOS mRNA in glomeruli of the CLK and OK from rats with UUO to levels comparable to that seen in glomeruli from SOC rats. In addition, the in situ RT-PCR analysis, a novel method for mRNA identification in cells and tissue, revealed that vsmNOS mRNA was expressed in the cytoplasm of glomerular mesangial and epithelial cells in SOC rats and rats with UUO. CONCLUSIONS: An increase in vsmNOS mRNA expression in glomeruli of the CLK and OK from rats with UUO may be mediated by increased action of endogenous angiotensin II that occurs after the onset of ureteral obstruction. Enhanced expression of vsmNOS mRNA in glomeruli of the OK compared to the CLK may be due to differences in levels of angiotensin II acting on the two kidneys in vivo. Additionally, the expression of vsmNOS mRNA in glomeruli originates in mesangial and epithelial cells in SOC rats and rats with UUO. (+info)