Complete Unilateral Ureteral Obstruction Research Articles

EVALUATION OF RENAL FUNCTION IN NORMAL AND HYDRONEPHROTIC KIDNEYS IN RATS USING GADOLINIUM DIETHYLENETETRAMINE-PENTAACETIC ACID ENHANCED DYNAMIC MAGNETIC RESONANCE IMAGING

Magnetic resonance imaging (MRI) is becoming established as a modality complementary to computerized tomography and ultrasound for evaluating kidney function. The evaluation of renal function during ureteral obstruction may be improved by contrast enhanced MRI. We evaluated dynamic changes in relative signal intensity in normal and hydronephrotic rat kidneys after intravenous injection of gadolinium (Gd) diethylenetetramine-pentaacetic acid (DTPA). Using Gd-DTPA enhanced dynamic MRI we evaluated 35, 1-year-old rats, including 10 with partial and complete unilateral ureteral obstruction, respectively, and 15 with sham operated nonobstructed kidneys. Partial obstruction was created in 2-day-old rats by embedding the left ureter into the psoas muscle. Complete obstruction was created 10 days before MRI by placing a ligature around the upper third of the left ureter. MRI was performed before and 0.1 to 60 minutes after and intravenous injection of Gd-DTPA. We calculated relative signal intensity per time interval in the renal cortex, medulla and pelvis. Dynamic relative signal intensity patterns differed significantly among normal, and partially and completely obstructed kidneys. In normal kidneys signal intensity changes were divided into 3 phases after Gd-DTPA administration. During phase 1 rapid parenchymal uptake of Gd-DTPA within the initial minute after injection produced a rapid signal intensity decrease in the cortex, which achieved a minimum of 28% of pre-injection intensity. During phase 2 signal intensity decreased in the medulla and pelvis to a minimum of 18% and 22%, respectively, of pre-injection intensity within 5 minutes. During phase 3 significant relative signal intensity recovery began in the cortex at 7 minutes, and in the medulla and pelvis at 10 to 15 minutes, and lasted 30 to 60 minutes. In partially obstructed kidneys the 3 phases were significantly slower than in controls. In completely obstructed kidneys only phase 1 occurred within 60 minutes. Gd-DTPA enhanced dynamic MRI provides useful information for distinguishing obstructed from nonobstructed and partially from completely obstructed kidneys.

RECOVERY OF RENAL FUNCTION AFTER 153 DAYS OF COMPLETE UNILATERAL URETERAL OBSTRUCTION

The length of time that a human kidney may tolerate complete obstruction and yet recover useful function is unknown. There have been few reports of the recovery of renal function in humans after prolonged complete unilateral ureteral obstruction.1.2 In a literature review Shapiro and Bennet noted that the longest period was 150 days.1 We report on a woman in whom renal function recovered after 153 days of complete unilateral ureteral obstruction. CASE REPORT A 42-year-old woman underwent abdominal complete hysterectomy and left salpingo-oophorectomy for leiomyoma of the uterus and endometrial cyst of the left ovary on April 12, 1994. The procedure was uneventful. Sutures of 2-zero silk were used for hemostasis. She was referred to our hospital for right hydronephrosis found at a general evaluation in July. The patient was asymptomatic. Excretory urography (IVP) showed a right nonvisualizing kidney. 99”Technetium dimercaptosuccinic acid renal scintigraphy revealed severely decreased uptake on the right side with the right kidney accounting for 11.4% of total renal function. Retrograde pyelography demonstrated complete obstruction of the distal ureter (fig. 1, A). Computerized tomography (CT) showed well preserved, enhanced right renal parenchyma (fig. 1, B). A percutaneous nephrostomy tube was placed on September 12. Urine volume from the nephrostomy tube was 1,000 to 1,200 ml. daily. Creatinine clearance of the right kidney was 6.8 ml. per minute. Antegrade pyelography also revealed complete distal ureteral obstruction. The patient underwent surgical exploration of the right ureter on September 21. Severe fibrosis was noted around the stenotic portion of the ureter. Although no suture remnants were detected, we concluded that ureteral stricture had probably been caused by suture entrapment. We excised the ureteral stricture and performed right ureteroneocystos

Interstitial Fibrosis in Chronic Hydronephrosis is Modulated by Angiotensinogen Expression • 1797

The renin-angiotensin system (RAS) may serve pathogenic as well as salutary roles in the development of renal disease, and angiotensin II has been implicated to regulate cellular mechanisms of fibrosis. To advance the understanding of the contribution of the RAS to the progression of renal disease, chronic obstructive nephropathy was studied in neonatal mice having 0, 1, 2 or 4 functional copies of the angiotensinogen gene (Agt) since: 1) all components of RAS are stimulated in obstructive nephropathy; and 2) these mice have genetically determined gradations in their steady-state plasma angiotensinogen levels. Two day-old mice underwent complete unilateral ureteral obstruction (UUO) or a sham operation (n=27 each). Obstructed (UUO), intact opposite (IO), and sham (S) kidneys were examined 28 d later for tubular atrophy and interstitial fibrosis, both hallmarks of chronic obstructive nephropathy. Sham and obstructed zero-copy mice exhibited a similar 20-30% reduction in body weight (P<0.05). In all genotypes, UUO induced a 40-80% reduction in renal mass compared to S, and IO demonstrated compensatory growth of 127-155% (both P<0.05). Compared to S, UUO increased tubular atrophy 100-fold in 1-4 copy mice. The elevated tubular atrophy in S of zero-copy mice was reduced in IO (both P<0.05). Interstitial collagen deposition, an index of fibrosis, increased in UUO linearly with Agt copy number, from 25.4 ± 9.6% in 0-copy mice to 54.2 ± 14.2% in 2-copy mice (R=0.723, slope=14.3 ± 3.3%, P<0.001), but fibrosis was not further elevated by UUO in 4-copy mice (58.5 ± 9.6%). Thus, in chronic neonatal UUO, less than normal levels of angiotensinogen decrease interstitial fibrosis. In contrast, tubular atrophy in the absence of Agt is prominent and not synergistic with UUO. We conclude: 1) Compensatory renal growth is independent of RAS activity; 2) Tubular integrity (measured by severity of tubular atrophy) is impaired in the absence of Atg; 3) Most importantly, this study demonstrates conclusively that the renal fibrotic response to chronic UUO is attenuated by decreasing angiotensinogen expression. It is likely that angiotensin-dependent fibrosis is a mechanism common to the progression of many forms of renal disease or injury.

Hemodynamic Changes After Complete Unilateral Ureteral Obstruction in the Young Lamb

Purpose We studied renal hemodynamic changes after complete acute unilateral ureteral obstruction in the young lamb. Materials and Methods Seven 4-week-old lambs underwent unilateral complete ureteral obstruction and renal blood flow was monitored in both kidneys with ultrasonic flow transducers. Ureteral and arterial blood pressure was measured. Results In the obstructed kidney renal blood flow was stable for 5 hours and then decreased thereafter to 71% of baseline at 5 days (p <0.05). In the contralateral kidney the pattern of renal blood flow constituted a mirror image, although the magnitude of the increase was decreased (122% of baseline at 5 days, not statistically significant). Mean arterial blood pressure did not change in 5 days. Mean ureteral pressure increased from a baseline of 9 to 37 mm. Hg (p <0.001) 2 hours after obstruction but gradually decreased to 24 mm. Hg after 24 hours and remained elevated for 5 days (p <0.001). Conclusions The pattern of renal blood flow and ureteral pressure response to obstruction in the young lamb is different from that previously reported. Renal blood flow does not increase after obstruction and it is relatively preserved at 5 days. This unexpected response may be a result of the compound caliceal sheep kidney, immaturity of the young vascular system or developmental differences in the mechanism of spontaneous decompression of the collecting system.

Hemodynamic changes after complete unilateral ureteral obstruction in the young lamb.

We studied renal hemodynamic changes after complete acute unilateral ureteral obstruction in the young lamb. Seven 4-week-old lambs underwent unilateral complete ureteral obstruction and renal blood flow was monitored in both kidneys with ultrasonic flow transducers. Ureteral and arterial blood pressure was measured. In the obstructed kidney renal blood flow was stable for 5 hours and then decreased thereafter to 71% of baseline at 5 days (p < 0.05). In the contralateral kidney the pattern of renal blood flow constituted a mirror image, although the magnitude of the increase was decreased (122% of baseline at 5 days, not statistically significant). Mean arterial blood pressure did not change in 5 days. Mean ureteral pressure increased from a baseline of 9 to 37 mm. Hg (p < 0.001) 2 hours after obstruction but gradually decreased to 24 mm. Hg after 24 hours and remained elevated for 5 days (p < 0.001). The pattern of renal blood flow and ureteral pressure response to obstruction in the young lamb is different from that previously reported. Renal blood flow does not increase after obstruction and it is relatively preserved at 5 days. This unexpected response may be a result of the compound caliceal sheep kidney, immaturity of the young vascular system or development differences in the mechanism of spontaneous decompression of the collecting system.

Lipid Peroxidation Assessment of Free Radical Production Following Release of Obstructive Uropathy

Purpose To identify if free radicals were released following relief of ureteric obstruction. Materials and Methods Free radical production was assessed by a high performance liquid chromatography assay of malondialdehyde (MDA) in a 24-hour complete unilateral ureteric obstruction model in Wistar rats. Results In the first experiment, a rise greater than 20 percent above prerelease levels in renal venous malondialdehyde levels was observed at 8, 15, 22, and 30 minutes following release. At 45 and 60 minutes, levels were similar to the prerelease levels. In the second experiment, renal venous samples taken before release and at 10 and 20 minutes after release in control and obstructed groups (n = 7) identified a significant difference (T = 10 minutes p = 0.006 and T = 20 minutes p = 0.045). A significant MDA rise following release occurred only in the obstructed group (obstruction group: MDA level T = 0 min. 1.01 micromole/l. plus/minus 0.13, T = 10 min. 2.12 micromole/l. plus/minus 0.3 p = 0.016, T = 20 min. 2.09 micromole/l. plus/minus 0.28 p = 0.016. Control group: T = 0 min. 1.13 micromole/l. plus/minus 0.23, T = 10 min. 1.05 micromole/l. plus/minus 0.18 p = 0.95, T = 20 min. 1.23 micromole/l. plus/minus 0.19 p = 0.67). In the third experiment, an attempt was made to block free radical release with allopurinol. No statistical difference between the control and obstructed groups with allopurinol was noted at 20 minutes after release. A Kruskal Wallace two-way analysis identified a significant difference between experiments two and three at both time periods (p = 0.049). Conclusion This study suggests, for the first time, that free radicals are released after relief of ureteric obstruction and that this release is partially attenuated by allopurinol pretreatment.

Eicosanoid Excretion from the Contralateral Kidney in Pigs with Complete Unilateral Ureteral Obstruction

Eicosanoid Excretion from the Contralateral Kidney in Pigs with Complete Unilateral Ureteral Obstruction

Eicosanoid Excretion from the Contralateral Kidney in Pigs with Complete Unilateral Ureteral Obstruction

Purpose Eicosanoid excretion from the contralateral kidney in pigs with unilateral ureteral occlusion (UUO) was examined, and the effects of blockade of angiotensin II synthesis and cyclooxygenase inhibition were investigated. Materials and Methods Urine obtained from contralateral kidneys in pigs with UUO and from the right kidney in sham-operated pigs was examined for prostaglandin E 2 (PGE 2) and thromboxane B 2 (TxB 2) by radioimmunoassay. Results Excretion rate of PGE 2 increased from 307 plus/minus 69 pg. per minute to 542 plus/minus 149 pg. per minute (p less than 0.05) during UUO. Indomethacin blocked the synthesis of both PGE 2 and TxB 2. Administration of an inhibitor of the angiotensin I converting enzyme resulted in a significant (p = 0.02) reduction of PGE 2 excretion as well as a decrease in TxB 2 excretion which was significantly lower 15 hours after UUO. Blockade of angiotensin II synthesis in the sham-operated pigs did not affect prostanoid excretion from their kidneys. Conclusion This study demonstrates that the presence of angiotensin is important for a full expression of these prostanoids in the contralateral kidney during UUO

Ureteral obstruction in the neonatal rat: Renal nerves modulate hemodynamic effects

In the neonate, chronic unilateral ureteral obstruction (UUO) reduces renal blood flow (RBF) of the ipsilateral kidney and increases RBF of the opposite kidney. To determine whether renal nerves mediate or modulate these responses, complete left UUO in the neonatal rat was used as a model of severe obstructive uropathy, and was compared with sham-operated controls. At 24-28 days of age, animals underwent left or right mechanical renal denervation or left sham renal denervation. One week after denervation, animals were anesthetized and blood pressure and heart rate were measured. Cardiac output and RBF were determined by the radioactive microsphere technique. UUO increased blood pressure and heart rate, and decreased RBF in the obstructed kidney, regardless of denervation. While left UUO increased RBF to the intact opposite kidney in rats with left renal denervation, this was attenuated by right renal denervation. Thus, in the neonatal rat, UUO modulates systemic renal hemodynamics, possibly through activation of the renin-angiotensin system. While renal nerves do not mediate the vasoconstriction of the obstructed kidney, renal nerves modulate vascular tone of the kidney contralateral to UUO.

Insulin-Like Growth Factor Improves Renal Architecture of Fetal Kidneys with Complete Ureteral Obstruction

Others have previously demonstrated that the administration of insulin-like growth factor-I accelerates recovery from ischemic acute tubular necrosis in the rat kidney. We investigated the effect of insulin-like growth factor-I on the histology of unilaterally obstructed kidneys in the pouch young of the North American opossum, Didelphis virginiana. In this model complete unilateral ureteral obstruction reliably induces statistically significant degrees of caliceal dilatation, tubular cystic change, and cortical and medullary fibrosis in kidneys examined 1 week after the creation of complete obstruction. Cortical and medullary inflammation is also increased after 1 week of obstruction in this model but not to a degree that is statistically different than control (sham operated) animals. We administered insulin-like growth factor-I to opossum pups with complete unilateral obstruction created at a length of 5 cm. (age 25 days, human equivalent 18 to 20 weeks). Insulin-like growth factor-I (400 mcg./kg.) was injected subcutaneously on the day of operation and again on days 2 and 4 postoperatively. The animals were sacrificed 1 week after obstruction and the formalin fixed, paraffin embedded kidneys were assessed histologically. In the obstructed kidney insulin-like growth factor-I ameliorated the development of fibrosis (cortical and medullary) and caliceal dilatation such that these characteristics did not differ significantly from those of sham operated animals. Tubular cystic change in the obstructed kidneys was also decreased by insulin-like growth factor-I administration but not to significant levels. Insulin-like growth factor-I treatment in obstructed animals resulted in significantly more inflammation (cortical and medullary) than in the sham operated animals. We also administered insulin-like growth factor-I to normal pups with no other intervention. These insulin-like growth factor-I treated pups did not differ from sham pups for any characteristic studied. Our study suggests that there is a protective effect of insulin-like growth factor-I on renal architecture when administered in the setting of experimental fetal ureteral obstruction.

Insulin-like growth factor improves renal architecture of fetal kidneys with complete ureteral obstruction.

Others have previously demonstrated that the administration of insulin-like growth factor-I accelerates recovery from ischemic acute tubular necrosis in the rat kidney. We investigated the effect of insulin-like growth factor-I on the histology of unilaterally obstructed kidneys in the pouch young of the North American opossum, Didelphis virginiana. In this model complete unilateral ureteral obstruction reliably induces statistically significant degrees of caliceal dilatation, tubular cystic change, and cortical and medullary fibrosis in kidneys examined 1 week after the creation of complete obstruction. Cortical and medullary inflammation is also increased after 1 week of obstruction in this model but not to a degree that is statistically different than control (sham operated) animals. We administered insulin-like growth factor-I to opossum pups with complete unilateral obstruction created at a length of 5 cm. (age 25 days, human equivalent 18 to 20 weeks). Insulin-like growth factor-I (400 mcg/kg.) was injected subcutaneously on the day of operation and again on days 2 and 4 postoperatively. The animals were sacrificed 1 week after obstruction and the formalin fixed, paraffin embedded kidneys were assessed histologically. In the obstructed kidney insulin-like growth factor-I ameliorated the development of fibrosis (cortical and medullary) and caliceal dilatation such that these characteristics did not differ significantly from those of sham operated animals. Tubular cystic change in the obstructed kidneys was also decreased by insulin-like growth factor-I administration but not to significant levels. Insulin-like growth factor-I treatment in obstructed animals resulted in significantly more inflammation (cortical and medullary) than in the sham operated animals. We also administered insulin-like growth factor-I to normal pups with no other intervention. These insulin-like growth factor-I treated pups did not differ from sham pups for any characteristic studied. Our study suggests that there is protective effect of insulin-like growth factor-I on renal architecture when administered in the setting of experimental fetal ureteral obstruction.

Renal clearance of atrial natriuretic peptide during acute unilateral complete ureteral obstruction in the pig.

Renal extraction and renal plasma clearance of atrial natriuretic peptide from pigs with complete unilateral ureteral obstruction (UUO) and from intact anaesthetized pigs were determined from arteriovenous differences in plasma atrial natriuretic peptide and measured renal plasma flow. The effect of administration of either a cyclooxygenase inhibitor or an angiotensin converting enzyme inhibitor was examined during UUO. Renal extraction ratio and renal clearance rate of plasma atrial natriuretic peptide (ANP) in the intact pig was stable during the 15 h observation period. UUO resulted in a significant (P < 0.05) temporary increase in renal extraction ratio and a significant (P < 0.05) reduction in the renal clearance rate of atrial natriuretic peptide. During cyclooxygenase inhibition there was a significant increase in the renal extraction ratio of ANP. During angiotensin II converting enzyme inhibition, renal handling of atrial natriuretic peptide did not differ from that observed in control animals. The present data demonstrate that atrial natriuretic peptide is extracted by the obstructed kidney. Despite the significant reduction in renal blood flow during indomethacin administration, renal clearance of ANP was unaltered. The increase in ipsilateral renal extraction of atrial natriuretic peptide immediately after ureteral obstruction and indomethacin administration could be explained either by a direct influence of PGE2 on the renal haemodynamics altering renal extraction of ANP, or by a compensatory mechanism attempting to preserve renal function.

Experimental Ureteral Obstruction in the Fetal Opossum: Histologic Assessment

In the North American opossum, Didelphis virginiana unilateral complete ureteral obstruction (ECO) and partial unilateral (EPO) ureteral obstruction were created during the early meta- nephric stage of kidney development in pups attached to the teat (approximately 4.5cm. long, 20 days old). At 70 days of pouch life (full-term equivalent in the human) some completely obstructed ureters were unobstructed with reanastomosis to the bladder (RECO). Other pups underwent unilateral complete ureteral ligation at this full-term equivalent (70 days of pouch life) and constituted the late obstruction (LCO) group. Unoperated animals constituted the control (C) group. All animals were harvested when full grown (.7 to 2.2kg.), and paraffin sections of the kidneys were stained with hematoxylin and eosin and Masson’s Trichrome. In each a semiquantitative assessment of 24 histologic features was made and a digital score assigned. All experimental groups except EPO demonstrated significant epithelial and mesenchymal alterations. The changes can be broadly categorized as those secondary to obstruction of urine flow (dilation and cystic changes), those affecting epithelial differentiation in both cortex and medulla and those affecting mesenchymal differentiation.The EPO group demonstrated significantly fewer glomerular generations than did control kidneys. For all other characteristics studied, the EPO group did not differ from control. The ECO group demonstrated significant changes when compared with control for most parameters studied. Medullary dysplasia was more prominent in kidneys obstructed early. Reanastomosis (RECO) at a full-term equivalent did ameliorate the changes of medullary dysplasia and cortical atrophy. More collecting duct hyperplasia, cortical and medullary aplasia were present in the LCO group compared with the ECO. The LCO group also had less primitive duct formation and less medullary dysplasia than the ECO group. Renal blastema, previously unreported in experimental obstruction, was present in 41% of experimental kidneys.

Effects of experimental ureteral obstruction on platelet-derived growth factor-A and type I procollagen expression in fetal metanephric kidneys.

Complete ureteral obstruction in fetal opossum kidneys has been used as an experimental method to induce tubulointerstitial damage and interstitial fibrosis. However, the molecular events underlying extracellular matrix deposition are currently unknown. Cytokines such as platelet-derived growth factor (PDGF) are considered possible participants in these processes. In this study we used a marsupial model of ureteral obstruction to examine the expression of PDGF-A and type I procollagen mRNAs by in situ hybridization. Complete unilateral ureteral obstruction was performed in six animals at midtrimester human equivalent. Obstructed kidneys, as well as the contralateral and age-matched sham kidneys, were harvested at 1, 3, 5, 10, and 20 days post obstruction. Morphological assessment of the obstructed kidneys harvested between 1 and 5 days post obstruction showed mild tubulocystic changes, interstitial fibrosis, and inflammation compared with controls. Kidneys harvested at days 10 and 20 showed moderate tubulointerstitial damage compared with kidneys harvested after 1 and 5 days. PDGF-A mRNA signal of low abundance was detected within renal interstitial cells, urothelial cells of the pelvis, and focally within epithelial cells of immature distal convoluted tubules in non-obstructed kidneys. Type I procollagen mRNA expression was spatially co-distributed with PDGF-A-expressing interstitial cells. PDGF-A and type I procollagen signal intensities in obstructed kidneys harvested 10 and 20 days post obstruction were increased several fold compared with controls and kidneys harvested 1-5 days post obstruction. Both PDGF-A and type I procollagen mRNA increases correlated with morphological features of tubulointerstitial damage. Our results suggest that PDGF-A may participate in this form of fetal kidney damage.

The Effect of Indomethacin Infusion on Renal Hemodynamics and on the Renin-Angiotensin System During Unilateral Ureteral Obstruction of the Pig

Obstruction of the urinary tract is associated with an increase in pelvic pressure (PP) and a decline in ipsilateral renal blood flow (RBF). To investigate the influence of the renal prostaglandins on these parameters, pigs with complete unilateral ureteral obstruction (UUO) were studied under general anesthesia after administration of indomethacin 30 minutes before obstruction. Pelvic pressure increased to a maximum of 41.1 ± 2.4cm. H2O after 6 hours, but maximum pressure, as well as the rate of pressure increase, was significantly reduced after indomethacin. A transient but significant increase in mean aortic blood pressure was seen, together with a bilateral decrease in RBF immediately after indomethacin administration. Ipsilaterally RBF decreased by 25% from 319 ± 21ml. per minute to 237 ± 16ml. per minute and contralaterally by 23% from 300 ± 20ml. per minute to 231 ± 25ml. per minute. After 15 hours a further decline was measured in ipsilateral RBF to 136 ± 20ml. per minute but, on the contralateral side, RBF was only slightly reduced to 281 ± 36ml. per minute after 15 hours. Following indomethacin a sustained increase in ipsilateral renal vascular resistance (RVR) was observed from 37.6 ± 3.6mm. Hg × ml.−1 × min. × gm. to 130.5 ± 42.3mm. Hg × ml.−1 × min. × gm. compared with a much smaller increase from 37.4 ± 3.2mm. Hg × ml.−1 × min. × gm. to 55.1 ± 9.2mm. Hg × ml.−1 × min. × gm. in the control group. Renal secretion rate of angiotensin II was significantly reduced 2 and 6 hours after indomethacin administration on the obstructed side, and was not significantly changed on the contralateral side. It can be concluded that inhibition of prostaglandin synthesis during unilateral ureteral obstruction in pigs results in reduced pelvic pressure, renal blood flow and angiotensin II secretion rate from the affected kidney, and that renal prostaglandin synthesis plays an important role for the perfusion of the kidney during ureteral obstruction.

Can Renal Blood Flow, Glomerular Filtration Rate or 99mTc‐DMSA Uptake Predict Outcome in Experimental Unilateral Renal Obstruction?

Single kidney glomerular filtration rate (SK GFR), single kidney blood flow (SK BF) and differential renal function (DRF), using both technetium labelled diethylene-pentaacetic acid (99mTc-DTPA) and dimercaptosuccinic acid (99mTc-DMSA), were examined as predictors of outcome in a pig model of complete unilateral ureteric obstruction. SK GFR and SK BF were unable to predict outcome following relief of obstruction but there was a high curvilinear correlation between DRF assessed at the end of defined periods of obstruction and after relief of obstruction using 99mTc-DMSA. Functional recovery was near complete using DMSA when the loss in DRF did not exceed 30%, after which there was an exponential decline in expected recovery. There was no difference between DRF using 99mTc-DTPA or 99mTc-DMSA in controls or before or after obstruction but significant differences between assessment by these radionuclides existed in the obstructed kidney at 24 h, 5 days, 10 days and 20 days. 99mTc-DMSA is a sensitive agent in the prediction of outcome following acute complete obstruction in the pig but its assessment of DRF in the obstructed kidney differs markedly from that of 99mTc-DTPA.

The effect of unilateral ureteral obstruction on the contralateral renal growth in weanling rats

The effect of unilateral hydronephrosis on the growth of contralateral kidney were evaluated with weanling rats of which kidneys were in growing stage (body weighted between 80 g and 90 g). These rats underwent complete unilateral ureteral obstruction (CUUO) on day 0. They were divided into 3 groups and went through second operations on day 3 (CUUO-3) as follows; a) CUUO released, b) nephrectomy performed and c) CUUO continued. Sham-operation was performed on day 0 and on day 3 to the controls. Wet weights and bromodeoxy-uridine (BrdU) labeling index (L.I.) (index for cell proliferation in the uriniferous tubules) of the contralateral kidneys were measured for the evaluation. The wet weights were significantly higher in all the groups than that of the controls throughout the observation period on and after the day 3. The group that underwent nephrectomy demonstrated a sharp rise in L.I. after the day 7. In the group that was continued in CUUO, the L.I. started to rise later than its rise in nephrectomised group but the index caught up at the time when the blood flow completely disappeared in the kidneys of the ligated side. L.I. in the group of which CUUO was released became significantly higher than that of controls on the day 7 and remained its significance until the day 21 in spite of resolution of the hydronephrosis. To reveal the effect of length of obstructed term, the same trial was carried out that rats endured in CUUO for 5 days (CUUO-5) till the second operation. This turned out lower L.I. in the CUUO-5 than the CUUO-3. These results suggest that the presence of hydronephrosis made by CUUO suppress the growth (cell proliferation) of contralateral kidney and also duration of obstruction can be critical on the renal growth that shorter obstructed period turns out preferable for cell proliferation after relief of CUUO.

An experimental study of PAH clearance in chronic unilateral and completely obstructed kidney

The following experiment was performed to estimate PAH clearance of chronic unilateral and completely obstructed kidney and to explore its change during obstruction period. Thirty adult male mongrel dogs were used. Unilateral complete ureteral obstruction was made by ligation of the left ureter proximal to the bladder. After 3, 5, 10, 20 and 40 days of obstruction, an experiment was performed. Under laparotomy, the left kidney was exposed and polyethylene catheter was inserted into the renal pelvis. Intrapelvic pressure was monitored by pressure transducer. In a condition that PAH (p-aminohippurate) was constantly infused intravenously, intrapelvic urine of the obstructed kidney was exchanged for physiological saline. After the exchange, intrapelvic PAH concentration was measured at hourly intervals for 4 hours. At each midpoint of the measurements, plasma PAH concentration was measured. At the end of the experiment, the obstructed kidney was resected and pelvic capacity was measured. PAH of the obstructed pelvis increased at hourly intervals after the exchange. The result showed that the clearance ability was maintained in the completely obstructed kidney. PAH clearance values were 16.3, 13.6, 1.0, 0.9, 0.9 ml/hr/kg b.w. at 3, 5, 10, 20 and 40 days obstruction respectively. PAH clearance decreased sharply during early stage of obstruction and tended to reach a fixed low value at over 10 days of obstruction. Our experimental method seemed to be available to estimate the clearance ability of chronically, unilaterally and completely obstructed kidney.

Effect of hydronephrosis on the contralateral blood flow and glomerular volume

We designed a following experiment to appraise the effect of unilateral hydronephrosis on the contralateral kidney using weanling rats whose kidneys were in a growing stage. Rats were divided into 4 groups. Complete unilateral (left) ureteral obstruction (CUUO) was made on the experiment rats, and these went through the following procedures on the day 3 after CUUO; 1) Group R: CUUO released, 2) Group N: left nephrectomy performed, 3) Group S: CUUO continued. Sham-operations were performed on the days 0 and 3 to the controls. Renal cortical blood flow and glomerular volume of the contralateral (right) kidneys were determined on the days 5, 7, 9, 14 and 21. Blood flow to the renal cortex per unit volume (ml/min/100 cm3; measured with Laser blood perfusion monitor) in the contralateral kidneys increased gradually in the all groups, but statistical significance was not confirmed in the observed period between any groups. Increases in total renal blood flow (wet kidney weight times renal cortical blood flow per unit volume; g x ml/min/100 cm3) were proportional to the measured wet kidney weight in the all groups. Notably in the group N, a significant increase was noted compared to the group R and the controls. Glomerular volume (GV) of the contralateral kidneys did not show significant changes on the day 3 compared to the controls. GV significantly grew up during the day 5 to the day 14 (2 to 11 days after the relief of CUUO) in the group R and then it settled to the level of the controls on the day 21.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced intrarenal angiotensin II generation in response to obstruction of the pig ureter.

The effect of acute unilateral complete ureteral obstruction (UUO) on renal hemodynamics has been examined in a pig model. Pigs were operated on under general anesthesia, electromagnetic flow probes were inserted around renal arteries, and catheters were implanted in renal veins and aorta for blood sampling. The influence of 15 h of obstruction on the physiological variation in immunoreactive angiotensin II (ANG II) was measured together with detailed analysis of the renal handling of ANG II in anesthetized animals. Pelvic pressure rose significantly within 2 h to a maximum of 59.9 +/- 2.9 cmH2O (n = 10). The ipsilateral renal blood flow (RBF) was reduced by 30% from 319 +/- 35 to 241 +/- 42 ml/min (P = 0.001), whereas contralateral RBF did not change. A temporary significant increase in mean aortic blood pressure was seen during the first 2 h after UUO. Renal vascular resistance increased by 44% in the obstructed kidney from 37 +/- 3 to 55 +/- 9 mmHg.ml-1.min.g during the course of obstruction. Concomitantly, the plasma concentration of immunoreactive ANG II increased from all three sample sites by 8-15 times. This increase was highly significant compared with the sham-operated group. The results show that the pig kidney responds to UUO by a net secretion of ANG II from the ipsilateral kidney. Our observations on the ANG II renal secretion rate suggest that part of the immunoreactive ANG II in the renal venous effluent originated de novo from intrarenal generation.