Renal caveolin-1 expression in children with unilateral ureteropelvic junction obstruction

Caveolae are plasma membrane invaginations that contain a variety of signal transduction molecules and receptors for growth factors and cytokines. This study was performed to examine the in vivo expression and localization of caveolin-1 in kidneys from 19 children who underwent surgery release of ureteropelvic junction obstruction (UPJO) in relation to renal function and degree of tubulointerstitial fibrosis. Renal biopsies were carried out at the time of surgery for obstruction release. Kidney tissue from children of similar age removed because of carcinoma was used as control. Expression of caveolin-1 at the protein level in renal tissue and urine was demonstrated in patients with technetium 99 m labeled diethylene triamine pentaacetate (⁹⁹Tc DTPA) renal scan 28.8±2% and increased tubular interstitial fibrosis in seven patients at the time of obstruction release. Colocalization staining of AT₁ angiotensin II receptor with caveolin-1 in basolateral membrane of epithelial tubule cells, enhanced AT₁ messenger ribonucleic acid (mRNA) and decreased endothelial nitric oxide synthase (eNOS), were shown in these patients. In contrast, absence of association of caveolin-1 with AT₁ receptor expression in proximal and collecting tubule membranes with AT₁ receptor mRNA and eNOS mRNA expression near control were demonstrated in 12 patients, with ⁹⁹Tc DTPA renal scan 39.7+2.1% and no evidence of tubulointerstitial fibrosis. From our results, the role of caveolin-1 as a factor contributing to the severity of the tubulointerstitial process resulting from obstructive nephropathy could be suggested.     

神经型一氧化氮合酶在肾盂输尿管连接部梗阻中的表达及意义

目的研究神经型一氧化氮合酶(nNOS)在肾盂输尿管连接部梗阻(UPJO)中的表达及意义。方法病例组36例,均为非管腔外压迫所致的UPJO狭窄段标本,且镜下具有UPJO基本特征:管壁肌层平滑肌稀疏,肌束变细,其间纤维结缔组织堆积。对照组20例为肾肿瘤、肾盂输尿管连接部(UPJ)切缘无肿瘤细胞浸润的UPJ标本。采用免疫组化SABC法对2组UPJ组织进行nNOS染色,并用图像分析进行定量分析比较。结果nNOS主要表达于UPJ肌层平滑肌细胞胞质。UP-JO组与对照组肌层表达的平均吸光度A值分别为0.208±0.014和0.230±0.016,2组比较差异有统计学意义(P<0.01)。结论UPJO中nNOS表达减少,提示NO合成减少可能参与UPJO发病过程。     

Factors associated with the outcomes of children with unilateral ureteropelvic junction obstruction

PURPOSE: Children with congenital unilateral ureteropelvic junction obstruction were evaluated with 99mtechnetium-labeled diethylenetriaminepentaacetic acid furosemide renal scans (DTPA) to determine the correlation of tubular function tests, growth factors and renal function. MATERIALS AND METHODS: A total of 38 children diagnosed with congenital unilateral ureteropelvic junction obstruction and recipients of dismembered pyeloplasty were prospectively studied. Before pyeloplasty split renal tubular function, creatinine clearance, urinary growth factors and a marker for apoptosis of each kidney were examined. Renal function of the obstructed kidney was evaluated by DTPA before and after pyeloplasty. Initially patients with DTPA greater than 40% were designated group 1 and those with DTPA 40% or less were assigned to group 2. After surgery followup patients with DTPA greater than 40% were designated the well preserved group and those with DTPA 40% or less were assigned to the poorly preserved group. Statistical analyses were performed to determine the best predictive variable for treatment. RESULTS: Mean initial DTPA split renal function values of groups 1 and 2 were 47.3% and 28.8%, respectively and subsequently, they were 48.4% and 35.3%. Initial DTPA on the obstructed side of less than 35% had a 100% sensitivity and 100% positive predictive rate for a poorly preserved renal outcome. Among the various tubular functions, only percent fractional excretion of sodium and percent fractional excretion of chloride correlated with post-pyeloplasty DTPA. Urinary epidermal growth factor/creatinine correlated with preservation of renal function on postoperative DTPA renal scans. Although urinary transforming growth factor/creatinine levels and apoptosis ratios were higher on the obstructed side, they were not significantly different between the groups. CONCLUSIONS: Proximal tubular dysfunction, such as increased percent fractional excretion of sodium and chloride, and initial DTPA 35% or less, suggest a high possibility of poorly preserved renal outcome. Urinary transforming growth factor-beta1 and apoptosis are not correlated with renal outcome. A high urinary level of epidermal growth factor might be a potential indicator of preservation of renal growth.     

Endoscopic management of ureteropelvic junction obstruction in children

A variety of endoscopic methods are available for managing ureteropelvic junction obstruction in children, and these methods can be considered for use in selected circumstances.     

Endopyelotomy for secondary ureteropelvic junction obstruction in children

Percutaneous endopyelotomy has been shown to be successful in treating ureteropelvic junction obstruction in adults. Little data have been published regarding this procedure in children. We describe 4 patients 6.5 weeks to 5.5 years old who underwent percutaneous endopyelotomy to treat ureteropelvic junction obstruction following failed open dismembered pyeloplasty. Preoperative obstruction was demonstrated by a nephrostogram, diuretic renogram and/or ultrasonography. Percutaneous endopyelotomy was successful in relieving the obstruction in all 4 patients, although 2 required secondary endoscopic procedures. One patient had persistent obstruction 40 days after endopyelotomy at the ureteropelvic junction and, subsequently, required percutaneous resection of a persistent flap of obstructing tissue. In another patient a ureterovesical stricture was noted at the time of stent removal, which was treated by endoscopic incision. All patients have been followed from 1.5 to 3 years postoperatively. Followup diuretic renograms, ultrasound and/or excretory urography demonstrated a patent ureteropelvic junction in all patients and all have remained asymptomatic. Endopyelotomy appears to be safe and effective in treating secondary ureteropelvic junction obstruction in children.     

Fibroepithelial polyps causing ureteropelvic junction obstruction in children

PURPOSE: Fibroepithelial polyps are benign mucosal projections that can be found throughout the urinary system. We review our experience with fibroepithelial polyps of the ureteropelvic junction in children to define more clearly this entity and its outcome following treatment. METHODS: We reviewed the records of all children with fibroepithelial polyps causing ureteropelvic junction obstruction treated at our institution between December 1967 and February 2002. RESULTS: Nine patients 6 weeks to 9 years old had 11 ureteropelvic junction obstructions secondary to fibroepithelial polyps, representing a 0.5% incidence of all ureteropelvic junction obstructions seen during that period. The majority of the patients were male (89%) and had obstruction on the left side (78%). Only 22% of the patients had a diagnosis of obstructing polyps suggested preoperatively. All patients underwent dismembered pyeloplasty but 1 required subsequent nephrectomy due to progressive loss of renal function. All lesions were characterized microscopically by polypoid projections of fibrous tissue covered by epithelium and demonstrating varying degrees of inflammation. No recurrences were seen during a mean followup of 44 months. CONCLUSIONS: Fibroepithelial polyps are rare lesions that cause ureteropelvic junction obstruction in children, primarily in males and on the left side. Filling defects were diagnosed preoperatively in 22% of the patients in this series. Excision and dismembered pyeloplasty were curative, and recurrences were not observed. The etiology of this disease remains obscure.     

Hypertension in unilateral atrophic kidney secondary to ureteropelvic junction obstruction.

A patient with atrophic unilateral hydronephrosis due to ureteropelvic junction obstruction associated with hypertension was successfully treated by nephrectomy. Preoperatively, plasma renin activity was elevated in both the peripheral vein and affected renal vein. Renin concentration in the resected kidney was high, and immunohistochemical localization of renin was observed along the afferent arterioles of the juxtaglomerular apparatus and in arterioles at some distance from the glomeruli.     

Surgical indications for unilateral neonatal hydronephrosis in considering ureteropelvic junction obstruction

Prenatal hydronephrosis is one of the most common urological congenital abnormalities detected by ultrasound. The incidence ranges from 0.59% to 0.69%. Approximately 50% of these fetuses do not have hydronephrosis on postnatal examination, whereas 25–33% of the rest have persistent hydronephrosis leading to the diagnosis of ureteropelvic junction (UPJ) obstruction. Renal ultrasonography and renal radionuclide scanning are the major modalities used for assessment and follow-up. Three main criteria used to determine the presence of obstruction are: (1) the magnitude of hydronephrosis present on ultrasound, (2) the relative renal function (RRF) measured by renography, and (3) the response of radionuclide washout with furosemide. Unfortunately, it is not always easy to determine obstruction; different types of management have been developed. Without depending on the severity of renal pelvis dilation, percentage of RRF, and response of radionuclide washout in the initial presentation, early surgery to preserve renal function and aggressive observation to prevent unnecessary surgery are two extremes on the spectrum of management for neonatal UPJ obstruction. Relying on renal function in renography, <35–40% or 5–10% of a decrease in the percentage of RRF or on the enlarging of hydronephrosis, respectively, and parenchymal thinning on ultrasonography are the indications for the surgical management to recover renal function in time. In addition to renal function change and imaging progression, the follow-up protocol and family compliance are the other considerations in prevention of impaired renal function. Through more than 40 years of development in the field of UPJ obstruction in infants, there have been several advances in management but controversies remain to be resolved. In this review, we focus on the surgical indications for the UPJ obstruction in this cohort.     

Partial unilateral ureteropelvic junction obstruction induced in 2-week-old piglets.

PURPOSE: We examined effects on kidney function and morphology of a partial ureteropelvic junction obstruction induced late in the postnatal nephrogenesis period of the pig. We compared the results to a similar study on pigs with obstruction induced early in the nephrogenesis period. MATERIALS AND METHODS: A total of 20 14-day-old pigs were included in the study. Fifteen animals were randomized to partial unilateral obstruction and 5 were sham operated. Kidney function and morphology were analyzed regarding glomerular filtration rate, renographic functional share and total kidney volume at the age of 4, 12 and 24 weeks. RESULTS: At age 4 weeks hydronephrosis was found in all obstructed kidneys included in the study. Four obstructed kidneys had renographic functional share 40% or greater and 1 deteriorated to less than 40% at 24 weeks. A total of 11 obstructed kidneys had a functional share less than 40%, 5 increased to a share greater than 40% at age 24 weeks and 3 had decreasing share from age 4 to 24 weeks. Single kidney glomerular filtration rate of the contralateral kidneys was significantly increased at all ages. Volume of the contralateral kidney was significantly increased at age 4 and 12 weeks. CONCLUSIONS: The variability and course of renographic functional share in kidneys subjected to partial obstruction at age 2 weeks was similar to findings obtained in pigs obstructed at age 2 days. In contrast to these our study showed compensatory increase in function and size of the contralateral kidney, suggesting that contralateral compensation is an ability gained late in the nephrogenesis period.     

Laparoscopic dismembered pyeloplasty for ureteropelvic junction obstruction in children

Objectives:   To present our initial experience with laparoscopic pyeloplasty and to evaluate the safety and short-term outcome of this technique in children.
Methods:   Thirteen kidney units in twelve children underwent laparoscopic dismembered pyeloplasty for the management of ureteropelvic junction obstruction (UPJO) at our institution between 2005 and 2008. Patient age at surgery was 18–177 months (mean 89.8 months). There were six boys and six girls. Ten had unilateral UPJO with a normal contralateral kidney, one had bilateral UPJO and one had UPJO of a solitary kidney. We used 3- and 5-mm instruments for grasping, blunt dissection, incising and suturing to facilitate safe and precise surgery. The outcome was measured by the operative time and resolution of obstruction and symptoms.
Results:   Median operative time was 275 min (range 154–420). There was a slight relationship between age and operative time. No major perioperative complications occurred in any cases. Median renal pelvic anterior–posterior diameter at ultrasonography significantly decreased from 8.6 cm (range 3.8–22.0) preoperatively to 3.9 cm (1.0–8.9) postoperatively ( P  < 0.05). The median pre- and postoperative split renal function on diuretic renography in unilateral cases was 37.3% (range 29.7–46.4) and 39.5% (27.8–48.0), respectively. Overall, successful resolution of UPJO was observed in 12 of 13 kidneys (92.3%).
Conclusions:   Laparoscopic pyeloplasty represents a safe and effective option in the surgical treatment of children with UPJO.     

Role of nitric oxide in renal tubular apoptosis of unilateral ureteral obstruction

BACKGROUND: The obstructed kidney in unilateral ureteral obstruction (UUO) is characterized by renal atrophy and tissue loss, which is mediated by renal tubular apoptosis. We sought to determine whether NO is involved in renal tubular apoptosis in vitro and in vivo. METHODS: Rat renal tubular epithelial cells (NRK-52E) were subjected to mechanical stretch, and apoptosis and cell size were analyzed by flow cytometry. Furthermore, we studied UUO in mice lacking the gene for inducible nitric oxide synthase (iNOS-/-) and their wild-type littermates. Tubular apoptosis and proliferation were detected by immunostaining. NOS activity and NOS expression were assessed by a citrulline assay and Western blot, respectively. RESULTS: Stretching-induced apoptosis in NRK-52E, which was reduced when NO was increased; conversely, stretch-induced apoptosis was increased when a NOS inhibitor was added to the cells. Stretched cells are larger and more apoptotic than unstretched cells. In UUO, the obstructed kidney of iNOS-/- mice exhibited more apoptotic renal tubules than the wild-type mice through 14 days of UUO. The obstructed kidney of iNOS-/- mice at day 3 showed more proliferative tubules compared with wild type. The obstructed kidney of wild-type mice exhibited higher total NOS activity until day 7 after UUO compared with iNOS-/- mice. However, the obstructed kidney of day 14 wild-type mice exhibited significantly lower iNOS activity and protein compared with the day 0 kidney. CONCLUSION: These results suggest that mechanical stretch is related to renal tubular apoptosis and that NO plays a protective role in this system in UUO.     

肾盂输尿管交界部功能性梗阻

自１９８５～１９９１年间共收治先天性肾盂输尿管交界部（ＵＰＪ）功能性梗阻患者３７例，病理检查而确诊，均经手术治疗。其中近期７例手术标本作了电镜检查，结果证实本病的病因为ＵＰＪ处平滑肌细胞之间有大量胶原纤维组织堆积，平滑肌细胞本身发育不良所致传导功能障碍。治疗应尽量切除病变的ＵＰＪ组织。     

Dominantly inherited ureteropelvic junction obstruction

We report on siblings from two families with unilateral ureteropelvic junction obstruction. HLA studies were undertaken and found to be a useful marker between affected members. We believe that incomplete penetrance with variable expression is the most probable mode of transmission of this disorder.     

腹腔镜手术治疗肾盂输尿管连接部狭窄19例

目的 评价腹腔镜手术治疗肾盂输尿管连接部狭窄（ureteropelvic junctiono bstruction，UPJO）的疗效。方法 采用经腹路径对19例UPJO行离断式。肾盂输尿管成形术。打开侧腹膜，以。肾下极为标志游离出。肾盂输尿管连接部，切除狭窄部分，端端吻合肾盂输尿管并留置双J管。结果 19例手术全部成功，手术时间110～240min，平均150min。术中出血量50～100ml，平均80ml，无严重并发症发生。术后住院6～10d，平均7．8d。19例随访3～15个月，平均6个月，14例静脉尿路造影（intrarenous urography，IVU）无吻合口狭窄。结论 腹腔镜下离断式肾盂输尿管成形术治疗UPJO有效、可行，可以替代开放手术。     

后腹腔镜肾盂成形术治疗儿童肾盂输尿管连接部狭窄15例报告

目的探讨后腹腔镜下离断性肾盂成形术即Anderson-Hynes手术治疗儿童肾盂输尿管连接部梗阻（UPJ0）的疗效。方法采用后腹腔镜下Anderson-Hynes手术治疗肾盂输尿管连接部梗阻所致中、重度肾积水的患者15例。病程2周～5年,均为腰部钝痛不适就诊,所有患者均经影像学明确UPJ0诊断。结果后腹腔镜离断式肾盂成形术耗时120～230（155．0±37．4）min,术中出血20-55（35．0±9．2）mL。无中转开放手术。术后2～4d拔出腹膜后引流管,切口均一期愈合,术后8～10周拔出D-J管,无漏尿及吻合口狭窄,随访3～24（18．0±4．1）个月,B超及静脉肾盂造影（IVU）提示积水改善、肾功能恢复。结论后腹腔镜离断式肾盂成形术在手术创伤、住院时间、术后恢复等方面优于开放手术,有望替代开放术式。