INTRARENAL REFLUX

Abstract. Seventy-six children with a total of 123 ureters showing vesico-ureteric reflux were reviewed in order to detect intrarenal reflux (pyelotubular backflow) occuring during micturating cystourethrography. This was found in 7 patients (9.2%). Five patients had unilateral and two bilateral intrarenal reflux. In only 7 out of the 9 kidneys with intrarenal reflux was it possible to outline the kidney contour precisely on excretion urography. In 3 cases renal damage corresponded exactly to the areas with intrarenal reflux. One kidney showed damage which did not correspond to the location of intrarenal reflux and 3 were without signs of damage. Renal damage of varying localization was found in 54 of the 123 kidneys with vesico-ureteric reflux and intrarenal reflux was present in 6 of these (11%). The significance of intrarenal reflux as a cause of renal damage and whether intrarenal reflux might be primary or secondary to the renal damage are discussed, and it is concluded that presence of intrarenal reflux is a definite indication for operation.     

Reflux nephropathy in the 1st year of life — the role of infection

The importance of infection and vesico-ureteric reflux in the development of reflux nephropathy is generally accepted. Widespread use of antenatal ultrasound scanning has identified dilated fetal urinary tracts, allowing prompt investigation and treatment in the early post-natal period; some of these children have vesico-ureteric reflux. This study compares renal parenchymal damage, demonstrated by uptake of technetium ^99m dimercaptosuccinic acid (DMSA) in two groups. The first included babies less than 6 months old who had presented with their first urinary tract infection and had vesico-ureteric reflux. The second included those in whom a dilated urinary tract had been identified at antenatal ultrasound and post-natal investigation revealed vesico-ureteric reflux, but who had no evidence of urinary tract infection. Renal damage was present in 68% of group 1 and 29% of group 2 when DMSA scanning was used to detect scarring (P = <0.05). Our results support the proposal that infection is a major factor in development of renal damage in patients with vesico-ureteric reflux. Identification by antenatal ultrasound scanning allows early therapeutic intervention before renal damage occurs. Offprint requests to: D. C. S. Gough     

小儿先天性发育不良肾的临床特点和治疗

目的 探讨小儿先天性发育不良肾的临床特点、诊断和治疗.方法 总结分析1988年至2009年我科收治的83例单侧先天发育不良肾的临床资料.所有患儿术前均行多普勒超声、静脉肾盂照影和99mTc-DTPA肾脏扫描.35例患儿行增强CT检查,39例行IVP后延迟CT检查三维重建.所有病例均行发育不良肾切除,肾切除的指征包括无功能发育不良肾脏合并临床症状55例,无临床症状的无功能多囊发育不良肾,随访不消退或增大27例,无功能发育不良肾合并肾输尿管积水1例.结果 各项术前检查中IVP后延迟CT三维重建技术阳性诊断率最高,达100%.术后病理均提示为发育不良肾脏.4例因高血压行发育不良肾切除的患儿,术后2例仍然有高血压,其他患儿术后临床症状消失,没有恶变者.结论 儿童先天发育不良肾脏发育不良程度不一,合并畸形不同,临床表现各异.IVP后延迟CT检查三维重建技术诊断发育不良肾脏阳性率高.合并临床症状的无功能发育不良肾、多囊发育不良肾长期随访不消退者可手术治疗,随访过程中有明显消退的多囊发育不良可定期观察,有功能的非多囊发育不良肾可以保留.近19%发育不良肾脏可合并对侧肾脏畸形,应密切监测对侧肾脏功能及血压.     

小儿先天性发育不良肾的临床特点和治疗

目的 探讨小儿先天性发育不良肾的临床特点、诊断和治疗.方法 总结分析1988年至2009年我科收治的83例单侧先天发育不良肾的临床资料.所有患儿术前均行多普勒超声、静脉肾盂照影和99mTc-DTPA肾脏扫描.35例患儿行增强CT检查,39例行IVP后延迟CT检查三维重建.所有病例均行发育不良肾切除,肾切除的指征包括无功能发育不良肾脏合并临床症状55例,无临床症状的无功能多囊发育不良肾,随访不消退或增大27例,无功能发育不良肾合并肾输尿管积水1例.结果 各项术前检查中IVP后延迟CT三维重建技术阳性诊断率最高,达100%.术后病理均提示为发育不良肾脏.4例因高血压行发育不良肾切除的患儿,术后2例仍然有高血压,其他患儿术后临床症状消失,没有恶变者.结论 儿童先天发育不良肾脏发育不良程度不一,合并畸形不同,临床表现各异.IVP后延迟CT检查三维重建技术诊断发育不良肾脏阳性率高.合并临床症状的无功能发育不良肾、多囊发育不良肾长期随访不消退者可手术治疗,随访过程中有明显消退的多囊发育不良可定期观察,有功能的非多囊发育不良肾可以保留.近19%发育不良肾脏可合并对侧肾脏畸形,应密切监测对侧肾脏功能及血压.     

Reflux-induced renal parenchymal injury: evaluation by urinary enzyme management

The urinary enzymes N-acetyl-B-D-glucosaminidase (NAG) and gamma-glutamyltransferase (GGT) were measured in four paediatric cohorts. Group 1 (21 children) suffered from severe vesico-ureteric reflux (VUR), group 2 (9 children) had active e urinary sepsis without reflux, group 3 constituted the control group (84 children), and group 4 comprised 21 children who had undergone successful endoscopic corrective surgery for VUR. Excretion of both NAG and GGT was significantly greater in group 1 than in groups 2 and 3 (P < 0.05). Within group 1, those with reflux in association with a single ureteric system demonstrated greater enzyme excretion than those with reflux in a duplex moiety (P < 0.05). Following surgical correction of reflux (group 4), there was a significant reduction in urinary enzyme excretion (P < 0.001). A spectrum of renal tubular damage exists in association with VUR. Urinary enzyme measurement is an invaluable technique in the evaluation of such renal damage in reflux, and in quantitatively assessing the efficacy of treatment.     

Outcome of primary vesicoureteric reflux detected following fetal renal pelvic dilatation

OBJECTIVE: Postnatal investigation of mild degrees of fetal hydronephrosis has allowed subsequent detection of infants with vesicoureteric reflux (VUR). This study was designed to provide short to medium term information on such infants who had primary VUR, the rates of renal damage and progression over time, the risk factors for such damage and to compare the characteristics of those who had mild dilatation of the fetal renal pelvis (4-9 mm) with those who had moderate-severe dilatation (> or = 10 mm). METHODOLOGY: Since June 1989, infants whose antenatal sonography had identified a fetal renal pelvis with an anteroposterior diameter of > 4 mm were investigated postnatally with renal ultrasonography and micturating cystourethrogram (MCU), and placed on antimicrobial prophylaxis. Those with VUR received 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy. Infants were followed until discharge based on resolution of VUR, surgery, or low grade VUR. A 5.5 year cohort between June 1989 and December 1994 formed the study population. A review of notes and clinical review (if still under follow up) was undertaken. Vesicoureteric reflux on MCU was regraded according to the International Classification, and reflux nephropathy on DMSA scans was regraded according to criteria proposed by Goldraich. Regression analysis was used to assess risk factors for renal damage. RESULTS: There were 69 infants (37 girls, 32 boys) who were identified with primary VUR, with 37/69 having bilateral reflux. Eight had a urinary tract infection during the follow-up period. There was a broad distribution of grades of reflux detected (Grades I-3, Grades II-23, Grades III-19, Grades IV - 17, Grades V-7). 99m-Tc-dimercaptosuccinic acid scans on 57/69 (83%) demonstrated renal damage in eight infants (14%). This was predominantly global contraction of function. No progression of renal damage was seen over 2-7 years. Regression analysis showed a strong association between Grades IV, V reflux and the presence of renal damage (P < 0.001). Review of the degrees of fetal renal pelvic dilatation showed that 60/69 infants were detected because of mild (4-9 mm) dilatation. The majority (43/60) had lower grades of reflux (Grades I, II, 3), but there was no obvious cut-off between 4 and 9 mm that could predict high grade VUR (Grades IV, V). CONCLUSIONS: The use of 4 mm to define an abnormal fetal renal pelvis allows a much larger group of infants with high grade primary VUR to be detected than if a higher cut-off measurement is used. Although it also detects many more infants with low grade primary VUR, there is no obvious cut-off point at which this effect predominates. Progressive renal damage was not seen in follow up of up to 7 years of age. Renal damage on DMSA scanning in this group is almost exclusively a pattern of global contraction of function. The presence of high-grade VUR appears to be the only important factor in predicting the presence of renal damage.     

Typical technetium dimercaptosuccinic acid distribution patterns in acute pyelonephritis

Technetium dimercaptosuccinic acid renal scintiscans in 37 children with clinical diagnosis of acute pyelonephritis were reviewed. In 18 children, follow-up scintigraphy was obtained after an interval ranging from 5 to 8 months. Uptake abnormalities were found in 89% of the children (74% of the kidneys). We were able to identify four typical pathological uptake patterns: (i) pole defect(s), usually wedge shaped (60%); (ii) lateral wedge shaped defect (4%); (ii) scattered multiple defects (21Yo); and (iv) swollen kidney without areas of diminished uptake (15%). Remaining pathology at follow-up was found in 52% of the kidneys. Vesicoureteric reflux was present in 33% of the children with scintigraphic signs of pyelonephritis. Frequencies of parenchymal changes in the acute phase and at follow-up were not significantly correlated to the presence of reflux.     

Outcome of the kidney with vesico-ureteral reflux. Apropos of 129 cases

The final status of the kidneys of 129 children suffering from vesico-ureteric reflux was studied. The growth of the kidneys was comparable in the surgically treated and in the medically treated group. However, growth was better when the kidneys had been normal initially than when they presented renal scars. New scars were more frequent in the medically treated group, and/or when scars were already present at diagnosis of vesico-ureteric reflux. Our results are in agreement with those in the literature.     

Dysplastic kidneys in children – Do they grow?

ObjectivesDysplastic kidneys (DK) are a common cause of chronic kidney disease (CKD). Little is known about their growth or how their sonographic appearance changes. This study aimed to test the hypothesis that DK gain little length, and to identify radiologic trends predictive of CKD.MethodsUltrasound scans of children with DK born in 1980–2005 and referred to a single tertiary centre were analysed by a pediatric radiologist. Renal lengths were plotted on standard nomograms and the degree of dysplastic appearance noted. Factors related to DK – bladder outlet obstruction, vesico-ureteric reflux and renal impairment – were noted.ResultsFifty-three children were studied (83 kidneys), of whom 41 were boys; 289 scans were analysed. In 33 children there was associated bladder outlet obstruction or vesico-ureteric reflux. Forty-four DK were noted to fall off their renal length ‘centile’. This correlated well with the development of CKD and is statistically significant. Deterioration occurred in 53% of DK; primarily progressive reduction in corticomedullary differentiation. This also correlated well with development of CKD.ConclusionMore than half of the DK showed poor growth velocity. This, together with the degree of sonographic abnormality, carries a high predictive value for development of CKD. We recommend diligent serial sonography to follow renal growth and dysplastic appearance in children with DK.     

Medical or surgical management for children with vesico-ureteric reflux?

A critical survey of the literature on treatment of children with vesico-ureteric reflux was carried out in order to create a basis for the new Swedish management policy. There are few studies that meet modern standards of scientific methodology and provide adequate patient numbers. The only large investigations that randomized patients to operative or non-operative treatment were the Birmingham Reflux Study and the International Reflux Study in Children. In these studies, long-term outcome of renal status and renal function, as well as the number of recurrent infections, were independent of treatment modality. Although pyelonephritic recurrences were less common in the surgically managed group, this did not influence appearance of renal damage. There is no evidence to indicate clear superiority of either medical or surgical management. Further studies are needed to address such questions as the optimal duration of antibacterial prophylaxis and the effect of a dilating reflux that persists into adulthood.     

Endoscopic treatment of children with vesico-ureteric reflux

Endoscopic subureteric injection of tissue-augmenting substances has become an alternative to long-term antibiotic prophylaxis and open surgery in the treatment of children with vesico-ureteric reflux. Successful elimination of reflux in about 80% of patients after a single injection (and in 90% after a repeat) has been achieved using the foreign-body non-degradable substances Teflon and silicone. Few patients have required open surgery and recurrence of reflux after initial successful treatment has occurred in only 5-10%. Concern has arisen, however, about possible distant migration and granuloma formation after injection of particulate plastic materials. Cross-linked bovine collagen is a biodegradable alternative substance, but with a lower response rate of 60% after the first treatment and a recurrence rate of 10-20%. Dextranomer in sodium hyaluronan is a new biological substance with microparticles with a response rate of 69% after the first injection. Biological substances have caused few complications. Present literature on injection treatment unfortunately focuses on elimination of reflux, with little attention to subsequent frequency of pyelonephritis or to the long-term development of the kidneys. Furthermore, there are no controlled, randomized studies with subureteric injection as one of the treatment alternatives. Thus, although having the advantage of being a minimally invasive procedure that can be performed on an outpatient basis, this technique needs to be tested in a large prospective study with the long-term renal outcome as the main end-point.     

Micturating cystourethrograms are not necessary for all cases of antenatally diagnosed hydronephrosis

ObjectiveSince 1995 we have, at our centre, adopted a selective approach to performing micturating cystourethrograms (MCUGs) on patients with antenatally diagnosed hydronephrosis. This study reviews the outcome of this policy.MethodsWe carry out MCUGs only if any of the following features are present on ultrasound: bilateral hydronephrosis, ureteric dilatation, renal scarring, bladder wall thickness greater than 5 mm, or presence of a duplex system or ureterocele. Patients with simple unilateral hydronephrosis are excluded, and are managed with 6 months’ trimethoprim prophylaxis and ultrasound surveillance with a minimum of 3 years’ follow up.ResultsFifty-five patients were referred with an antenatal diagnosis of hydronephrosis between 1999 and 2002; 26 (47%) did not have an MCUG. Of these, five had increasing hydronephrosis and required surgery for pelvi-ureteric junction obstruction, and three had a multicystic dysplastic kidney on postnatal scanning. In the remaining 18 patients, the hydronephrosis resolved spontaneously, with no renal scars or asymmetry. During follow up, none of these patients had a urinary tract infection.ConclusionWe believe that vesico-ureteric reflux in most antenatally diagnosed hydronephrotic kidneys is physiological rather than pathological, and resolves with time without causing long-term renal damage. This is a separate entity from, rather than a precursor of, the pathological symptomatic refluxing kidney in older, mainly female children. Taking a more conservative approach to the postnatal investigation of antenatally diagnosed hydronephrotic kidneys has not resulted in any missed damaged kidneys, but has reduced the number of invasive investigations performed. A careful protocol and detailed postnatal ultrasonography are important to prevent missed pathological cases.     

Serial 99mTc dimercaptosuccinic acid (DMSA) scans after urinary infections presenting before the age of 5 years.

Forty five children presenting with a first proven urinary tract infection under the age of 5 years were studied by sequential 99mTc dimercaptosuccinic acid (DMSA) scans. Forty nine kidneys in 40 children had definite defects at presentation, and 39 (80%) of these defects were still present when the DMSA scan was repeated. Changes in the appearance of defects were independent of the presence or degree of reflux at presentation and of symptomatic recurrence of infection, though the combination of new infection and grade 3 reflux (reflux reaching the renal calices with distension) was associated with deterioration. No kidney with a relative DMSA uptake of less than 35% showed any improvement in its cortical defects. Only two kidneys that were initially without defects, in a single patient who had bilateral grade 3 reflux and breakthrough infections, developed defects on subsequent scans. The outcome after urinary tract infection is dependent on the effect of the first infection on the kidney. Occasionally children with grade 3 reflux develop damage during subsequent infections. More widespread use of DMSA scans should improve our understanding of the factors that determine the development of renal damage.     

Primary vesicoureteral reflux detected in neonates with a history of fetal renal pelvis dilatation: a prospective clinical and imaging study

OBJECTIVE: To assess the clinical outcome and imaging features of neonatal primary vesicoureteral reflux (VUR). STUDY DESIGN: We prospectively followed 43 infants with primary VUR identified from among a cohort of 497 infants with fetal renal pelvis dilatation. Postnatal renal ultrasound (US) examinations were performed at 5 days and 1, 3, 6, 12, and 24 months of life. Voiding cystourethrography was performed in the neonatal period and repeated at 12 and 24 months when VUR was persistent. Two radioisotopic examinations, including a 99mTc-MAG3 renogram and a plasma clearance of Cr-51 EDTA, were performed in all children with high-grade reflux. RESULTS: The incidence of primary VUR in our study group was 9%. Among the 43 patients followed, 11 (26%) had high-grade (IV-V) VUR and 32 (74%) had low-grade VUR. Resolution of reflux occurred in 2 of 11 (18%) patients with high-grade VUR and in 29 of 32 (90.6%) patients with low-grade VUR at age 2 years (P < .001). At age 2 years, 91% of the low-grade refluxing kidneys were normal on US, compared with only 35% of the high-grade refluxing kidneys. Split renal function was within normal range and single-kidney GFR was significantly increased in 13 of the 17 high-grade refluxing kidneys during follow-up. Furthermore, a strong association between dysplasia on US and poor renal function outcome was found. CONCLUSIONS: In most infants with VUR, the reflux is of low grade and resolves rapidly. In those children with high-grade VUR, spontaneous resolution is rare at age 2 years, but persistent reflux rarely impairs the maturation of renal function.     

Rational use of CT in acute pyelonephritis: Findings and relationships with reflux

Enhanced renal CT scanners were performed in 38 children (82% girls) to rule out acute pyelonephritis. Patients were divided in 2 groups on the basis of clinical presentation and bacteriology data. In patients of group A (n=16, preliminary study), upper urinary tract infection (UTI) was certain. CT confirmed the diagnosis in all but 3 patients (a 2-year-old child and 2 patients with UTI developed on prior obstruction). In subsequently studied patients of group B (n=22), clinical findings or bacteriology data were negative or questionable. CT made the diagnosis of acute pyelonephritis in 11 patients. As well as DMSA scintigraphy, CT scanner can help to diagnose or to rule out upper UTIs in difficult cases. In all boys of both groups, ipsilateral vesico-ureteric reflux (VUR) was found by subsequent voiding cystourethrography (VCUG) on the side of pyelonephritis. In girls, this correlation was shown in only 7 of the 25 kidneys with pyelonephritis. This result supports the hypothesis of a gender-dependent contamination. We believe that absence of radiologic reflux cannot exclude the possibility of bacterial crossings of ureteric meatus capable to lead to genuine upper UTIs.     

Primary vesicoureteral reflux in infants with a dilated fetal urinary tract

Vesicoureteral reflux (VUR) was recognized neonatally by voiding cystography in 25 of 117 infants with a dilated fetal urinary tract. There was a male preponderance (76%) and a high percentage (40%) of associated urinary malformations. Thirtynine refluxing units were studied. All grades of VUR were detected but gross dilating VUR dominated (59%). Spontaneous resolution was excellent in lower grades of VUR but was poor in gross VUR. Surgery was successfully performed in 13 renal units of nine patients with gross reflux [8], additional ipsilateral malformations [4], or pyelonephritis during antibiotic prophylaxis [1]. Segmental renal scars developed in four kidneys after urinary infections, and a diffuse parenchymal lesion was noted in nine kidneys even at birth. One boy with duplication had a non-functioning refluxing system. Our results in a small number of infants show differences to children with VUR detected after urinary infections and seem to support the existence of a congenital reflux nephropathy.     

139例小儿原发性膀胱输尿管反流临床分析

目的 分析小儿原发性膀胱输尿管反流(VUR)的发病情况、肾损害评价、预后等临床资料.方法 回顾性分析974例尿路感染患儿中的139例小儿原发性VUR患儿的反流发生情况、肾瘢痕形成、尿路B超、尿微量蛋白、预后等临床资料.结果 尿路感染患儿中VUR发生率为14.3%(139/974).婴幼儿期(＜2岁)发生率最高为17.2%(79/458),139例患儿中79例(56.8%)患儿年龄＜2岁,且男性所占比例高于女性(P=0.001).轻度(Ⅰ-Ⅱ级)、中度(Ⅲ级)、重度(Ⅳ-Ⅴ级)反流所占比例分别为19.7%(41/208)、35.6%(74/208)、44.7%(93/208).VUR患儿中肾瘢痕发生率为37.O%(50/135),在不同年龄段中婴儿期(＜1岁)发生率最高(42.4%).50例肾瘢痕患儿中30例(60.0%)年龄在2岁之内,随着反流级别加重,发生肾瘢痕危险性亦提高(P＜0.05).尿路B超诊断VUR的灵敏度与特异度分别为24.8%、94.3%.疾病急性感染期尿微量蛋白的升高与肾瘢痕形成无明显相关性(P＞0.05).31例随访患儿中有90%尿路感染控制,44.4%患儿反流消失,57.1%患儿肾瘢痕好转,无肾功能进行性恶化病例.结论 小儿原发性VUR需要及早诊断与治疗,并同时对.肾损害作出正确评估,只有坚持长期的正规治疗与长期随访,才能有效保护肾脏,防止肾瘢痕的形成.     

Intrarenal reflux: diagnosis with contrast-enhanced harmonic US

The objective of this case report is to demonstrate the possibility of visualizing intrarenal reflux (IRR) in children using contrast-enhanced harmonic voiding urosonography (VUS). A 10-month-old girl underwent VUS as part of the work-up of acute pyelonephritis of the right kidney. Before and after intravesical administration of US contrast medium (Levovist) the urinary tract was scanned in harmonic imaging mode. Bilateral vesicoureteric reflux was detected (right grade IV, left grade III). Moreover, at the height of the reflux the right kidney parenchyma turned markedly echogenic, corresponding to massive IRR. The voiding cystourethrography that followed confirmed the results of the VUS.