Renal growth in children with severe vesicoureteral reflux: 10-year prospective study of medical and surgical treatment: the International Reflux Study in Children (European branch).

PURPOSE: To determine whether medical or surgical treatment better promotes renal growth in children with severe vesicoureteric reflux (VUR) and to examine factors influencing renal growth. MATERIALS AND METHODS: Three hundred two children younger than 11 years with urinary tract infection and grade III or IV VUR were randomly assigned to surgical (n = 149) or medical (n = 153) treatment and were followed up at serial intravenous urography for up to 5 years; 223, for up to 10 years (surgical, n = 110; medical, n = 113). Renal size was measured planimetrically on serial intravenous urograms and was related to the virtual height of L1 through L3 by expressing it as an SD score. RESULTS: There was no significant difference in mean renal growth between patients treated surgically or those treated medically after 5- or 10-year follow-up. Bilateral renal size of 80 surgical and 75 medical patients remained within 1 SD score. In patients entering the study at 2 years of age or younger and in those with grade IV VUR, bilateral VUR, or renal scars, there was a trend toward improved renal growth in those treated medically, but this finding was not statistically significant. When renal scarring or thin parenchyma was unilateral, the affected kidney grew less well, irrespective of treatment. Bilateral renal scarring was usually asymmetrical, with a corresponding effect on renal growth. CONCLUSION: There was no significant difference in renal growth during 10 years between surgical and medical treatment in patients with severe reflux.

Growth and weight gain in children with vesicoureteral reflux receiving medical versus surgical treatment: 10-year results of a prospective, randomized study. International Reflux Study in Children (European Branch).

In children with vesicoureteral reflux (VUR) and urinary tract infection, retardation of growth and weight gain at the time of diagnosis and catch-up growth during follow-up, mostly after operating for VUR, have been reported. A controlled trial comparing the effect on growth of surgical treatment and long-term prophylactic antibiotic treatment has not been reported previously. Between 1980 and 1985, 306 children younger than 11 y with non-obstructive grade III or IV VUR, with a history of symptomatic urinary tract infection, were randomly allocated to surgical or medical treatment. Of these, 236 were followed for 10 y, 118 randomized to surgical treatment (mean age at entry 3.5 +/- 2.3 y) and 118 to medical treatment (mean age at entry 3.8 +/- 2.5 y). All children had renal function and blood pressure in the normal range. Body height, measured at start and after 1, 5 and 10 y, was transformed to standard deviation score of height for chronological age (SDSH-CA) and body weight to percentage of ideal body weight for height (%IBW). The evolution of SDSH-CA and %IBW was similar in both treatment groups (SDSH-CA: surgical: start, 0.23 +/- 1.4; 10 y, 0.40 +/- 1.0; medical: start, 0.14 +/- 1.2; 10 y, 0.44 +/- 1.2; %IBW: surgical: start, 99 +/- 9%; 10 y, 107 +/- 14%; medical: start, 98 +/- 10%; 10 y, 105 +/- 16%). While children starting the study below the age of 3 y (SDSH-CA 0.55 +/- 1.34) started significantly taller than those older than 3 y (SDSH-CA -0.1 +/- 1.39), the young ones demonstrated a significant drop in SDSH-CA during the 1st year (SDSH-CA 0.19 +/- 1.23), which was regained up to the 10th year (SDSH-CA 0.6 +/- 1.13), and the older ones steadily gained height up to an SDSH-CA of 0.28 +/- 1.05 at 10 y. During all of the study period, treatment protocol, grade of VUR, renal parenchymal scars at entrance and urinary tract infections did not influence growth and weight gain. Age at entry and gender were the only significant correlates with growth and weight gain.

Five-year study of medical or surgical treatment in children with severe vesico-ureteral reflux dimercaptosuccinic acid findings. International Reflux Study Group in Europe.

UNLABELLED: The results of serial dimercaptosuccinic acid (DMSA) imaging over 5 years are reported in 287 children with severe vesico-ureteral reflux entered into the European Branch of the International Reflux Study in Children. The children were randomly allocated to medical (n=147) or surgical (n=140) management and DMSA studies were performed during the follow up period at least 6 months after any urinary tract infection. Abnormal images were classified into four types: (1) large polar hypodensity with normal renal outline; (2) peripheral photon deficient defect(s) in a non-deformed kidney; (3) small renal image with normal contour; and (4) peripheral defect(s) with resultant irregularity of the renal outline. The DMSA findings were abnormal at entry in 235 (82%) with no difference in incidence or severity between the two treatment groups. During follow up, deterioration was observed in 25 medically and 23 surgically treated patients and comprised image deterioration alone in 17, image deterioration with corresponding reduction in differential function in 16 and reduction in relative function without image change in 15, with similar distribution between the two treatment groups. Deterioration was more frequent in children entering the study under the age of 2 years and in those with grade IV rather than grade III reflux. These findings, showing no difference in outcome between children managed surgically or medically, are consistent with the radiological results already published. CONCLUSION: In the International Reflux Study the DMSA scintigraphic data showed no difference in outcome between children managed surgically or medically.

[Radiologic findings in the kidney of children with severe reflux. Five-year comparative study of conservative and surgical treatment]. / Radiologische Nierenbefunde bei Kindern mit schwerem Reflux. Fünfjahresvergleichsstudie konservativer und chirurgischer Behandlung.

The renal findings revealed by intravenous urography (IVU) in 306 children (73 boys, 233 girls) are reported. The children were seen at eight European centres and enrolled in an international study comparing medical and surgical management of children with urinary tract infection and severe vesico-ureteric reflux who were followed for 5 years. In all, 155 children were randomly allocated to medical and 151 to surgical treatment. The protocol and the investigative techniques were standardized, and randomization, data collection and analysis were performed centrally in Essen, Federal Republic of Germany. At entry 149 (49%) had established renal scarring (79 medical, 70 surgical). Presence of normal kidneys (105), areas of thinned parenchyma (52) and grade of reflux were also evenly distributed. IVU was repeated at 6, 18 and 54 months, and serial urine culture, 99mtechnetium-dimer-captosuccinic acid scans and plasma creatinine estimations were performed. Follow-up was complete in 272 children (89%). In 174 children (57%: 90 medical, 84 surgical) there was renal growth without morphological change. New renal scars developed in 19 children treated medically and 20 treated surgically; 12 (5 medical, 7 surgical) developed in previously normal kidneys. Six followed postoperative obstruction. No significant difference in outcome was found between medical and surgical management in terms of the development of new renal lesions or the progression of established renal scars.

Characteristics at entry of children with severe primary vesicoureteral reflux recruited for a multicenter, international therapeutic trial comparing medical and surgical management. The International Reflux Study in Children.

A total of 532 children, 401 from Europe and 131 from the United States, was recruited into an international multicenter study comparing the results of medical and surgical treatment of children with international grade III or IV vesicoureteral reflux and urinary tract infection. Patient age was less than 11 years, glomerular filtration rate was greater than 70 ml. per minute per 1.73 m.2 and there was no obstruction, renal malformation, previous urinary tract surgery or neuropathic bladder. A total of 80 children had less than grade III vesicoureteral reflux on a second pre-entry cystourethrogram required by the European protocol, and they were followed separately as a sideline group. At entry the age distribution, history of urinary tract infection and proportion of children with grade IV vesicoureteral reflux were similar in Europe and the United States. Of the European and United States children 48% and 54% had renal scarring, and 17% and 14% had parenchymal thinning, respectively. In each group renal length and planimetric area were normal in two-thirds and 5% had small kidneys (<2 standard deviations from normal). Differences included sex distribution (24% boys in Europe and 11% in the United States group), the proportion of children in whom vesicoureteral reflux was previously known (18% Europe and 69% United States) and the proportion of children with bilateral reflux (77% Europe and 57% United States). Randomization and stratification for treatment were successful.

Infection pattern in children with vesicoureteral reflux randomly allocated to operation or long-term antibacterial prophylaxis. The International Reflux Study in Children.

A total of 306 children with grade III to IV vesicoureteral reflux (international classification) and a history of documented urinary tract infection was randomized into medical (155 patients) or surgical (151 patients) treatment arms in the European portion of the International Reflux Study in Children. Children treated medically were maintained on prophylactic antibacterials as long as the reflux persisted, while those treated surgically were covered prophylactically until followup studies at 6 months postoperatively demonstrated the reflux to be corrected. Standard definitions for bacteriuria were used, and the distinction was made clinically among acute pyelonephritis, cystitis and asymptomatic bacteriuria, supported in many instances by additional laboratory testing. Urine was cultured after 3 months and whenever suspicious symptoms occurred. Urinary tract infections developed during the first 5-year followup period in 59 patients (38%) in the medical group and in 59 (39%) in the surgical group but the incidence of pyelonephritis was higher in the medical group (21%) than in the surgical group (10%) (p < 0.01). Pyelonephritis often followed catheterization or cystoscopy but asymptomatic bacteriuria was uncommon after these procedures in either group. Recurrent infections were related to age, sex and treatment center. They were common in boys and girls entering under 1 year of age but were less common in girls and rare in boys entering after 1 year of age. Recurrences were lowest among the Finnish children and highest in the German and Belgian children.

Renal scars and parenchymal thinning in children with vesicoureteral reflux: a 5-year report of the International Reflux Study in Children (European branch).

A total of 321 children less than 11 years old with nonobstructive grade III or IV vesicoureteral reflux and with previous urinary tract infection was randomly allocated to medical or surgical treatment in the European branch of the International Reflux Study in Children. (Randomization was stratified for age, sex, grade of reflux, presence of renal scarring, interval since last urinary tract infection and treating hospital). The results of excretory urography are reported for 233 girls and 73 boys treated according to the random allocation, 89% of whom were followed for 5 years. After 5 years in the medical group (155 children) new renal scars were seen in 19 and new renal parenchymal thinning in 11. The proportions were almost identical among 151 children allocated to surgical treatment with 20 new scars and 15 new thinnings. Progression of established scars was also similar in both groups. However, the new scars developed sooner after surgery than during medical treatment. In 6 surgically treated children postoperative obstruction was followed by the development of new scars. In addition, 12 patients showed new scars approximately 6 months after successful surgery, while in only 2 children scars developed more than 6 months after surgery. In 11 children of the medical group new scars were seen more than 6 months after allocation. More new scars developed in the children with parenchymal thinning at entry (23%) than in those with scarred or normal kidneys at entry (10% each) (p < 0.05). The younger the patients at entry, the higher the frequency of new scars (less than 2 years 19.8%) 2 to 4 years 9.8% and 5 years or more 4.6%, p < 0.05).

Surgical results in the International Reflux Study in Children (Europe).

In the European part of the International Reflux Study in Children (7 participating centers) 151 infants and children were randomly allocated to surgical treatment of primary grades III and IV vesicoureteral reflux. Reimplantation was performed unilaterally in 65 patients and bilaterally in 86, for a total of 237 ureters reimplanted. The patients were followed at regular intervals for 5 years. Reflux was absent in 231 of the reimplanted ureters (97.5%) at the end of 5 years. No patient underwent reoperation for reflux. In 10 ureters (4.2%, 10 patients) obstruction developed postoperatively and 7 needed reoperation. All reoperations were performed on the left side. Of the obstructed kidneys new scars developed in 6 during the 5-year followup. Including these cases, the number of new renal scars was equal in the surgical and medical groups (20 each). The number of pyelonephritic episodes during followup was significantly less in the surgical group (without chemoprophylaxis) than in the medical group (on chemoprophylaxis). No kidneys were lost and no child became hypertensive. If voiding cystourethrography and excretory urography were normal 6 months postoperatively, the reflux had been permanently eradicated and postoperative obstruction could be ruled out. In this study the patients who underwent reimplantation had a 74% (112 of 151) chance of an uncomplicated postoperative course (no persisting reflux, obstruction, pyelonephritis or severe renal damage).

Cessation of vesicoureteral reflux for 5 years in infants and children allocated to medical treatment. The International Reflux Study in Children.

A total of 401 children with severe vesicoureteral reflux (97 with grade III and 304 with grade IV) was entered into the European branch of the International Reflux Study in Children. Of these patients 37 with grade III and 43 with grade IV reflux were allocated to medical treatment as a sideline group because the reflux grade III or IV had improved to grade II or I, or it had disappeared during the preceding 2 to 6 months (median 4). Of the remaining 321 patients with persistent grade III or IV reflux 158 were randomly allocated to medical treatment of whom 3 switched to surgery. We report on 235 children treated medically (155 random medical and 80 sideline), of whom 88% had a complete 5-year followup with x-ray and/or isotope voiding cystourethrography at 6, 18, 30 and 54 months. Seven children dropped out of the study after a followup of 6 months or less, including 6 with persistent vesicoureteral reflux. Cessation of vesicoureteral reflux was observed significantly more often in children with unilateral (40 of 74, 54%) than with bilateral (18 of 154, 12%) reflux (p < 0.001). No significant difference between grades III and IV was noted. Vesicoureteral reflux ceased in 25 of 153 children (16%) from the random medical group and in 32 of 75 children (43%) in the sideline group. Of 194 children with vesicoureteral reflux detected for the first time at entry reflux resolved in 55 (28%). In only 2 of 34 children (6%) in whom vesicoureteral reflux was detected more than 1 year before entry did reflux resolve after 5 years. Among the children in whom vesicoureteral reflux either disappeared, diminished or remained unchanged the proportion with urinary tract infection recurrences was almost the same.

Historical clues to the complex of dysfunctional voiding, urinary tract infection and vesicoureteral reflux. The International Reflux Study in Children.

The prevalence of nonneuropathic bladder/sphincter dysfunction was assessed with a questionnaire in 310 of the 386 children enrolled in the European branch of the International Reflux Study in Children. Despite the exclusion criteria (neuropathic bladder, anatomical malformations other than vesicoureteral reflux and overt dysfunctional voiding or urge incontinence), the prevalence of bladder/sphincter dysfunction was as high as 18%. Four patterns of dysfunction emerged: urge syndrome, staccato voiding, fractionated and incomplete voiding, and voiding postponement. The questionnaire proved helpful in detecting low profile cases of bladder/sphincter dysfunction, as well as indicating the need for further urodynamic studies. A strong correlation was established between recurrences of urinary tract infections, as well as disappearance of vesicoureteral reflux (negative correlation) and nonneuropathic bladder/sphincter dysfunction. This finding implies that detection and treatment of bladder/sphincter dysfunction are essential in every child with the complex of recurrent urinary tract infection and vesicoureteral reflux.

Five-year study of medical or surgical treatment in children with severe reflux: radiological renal findings. The International Reflux Study in Children.

The renal findings on intravenous urography (IVU) are reported in 306 children (73 boys, 233 girls) from eight European centres entered into an international study comparing medical and surgical management of children with urinary tract infection and severe vesico-ureteric reflux followed for 5 years. One hundred and fifty-five children were randomly allocated to medical and 151 to surgical treatment. Protocol and investigative techniques were standardised and randomisation, data collection and analysis were performed centrally in Essen, Germany. At entry 149 (49%) has established renal scarring (79 medical, 70 surgical). Children with normal kidneys (105), areas of thinned parenchyma (52) and grade of reflux were also evenly distributed. IVU was repeated at 6, 18 and 54 months and serial urine culture, 99mtechnetium-dimercaptosuccinic acid scans and plasma creatinine estimations were performed. Two hundred and seventy-two children (89%) completed this follow-up. In 174 children (57%), (90 medical, 84 surgical) there was renal growth without morphological change. New renal scars developed in 19 children treated medically and 20 surgically; 12 (5 medical, 7 surgical) developed in previously normal kidneys. Six followed post-operative obstruction. No significant difference in outcome was found between medical or surgical management in terms of the development of new renal lesions or the progression of established renal scars.

Children with chronic renal failure in the Federal Republic of Germany: II. Primary renal diseases, age and intervals from early renal failure to renal death. Arbeitsgemeinschaft für Pädiatrische Nephrologie.

In a retrospective survey, 623 children with chronic renal failure (CRF) comprising a 7-year period were registered in the Federal Republic of Germany. The primary renal disease could be classified in 91% of the patients. Pyelonephritis was the most frequent diagnosis (31%), followed by glomerulopathies (20%), renal hypoplasia or dysplasia (14%), cystic kidney disease including nephronophthisis (12%), other hereditary nephropathies (7%), and vascular nephropathies (4%). At the time of first presentation, 23% of the children with preterminal chronic renal failure were younger than 5 years, 34% 5 to 10 years and 43% 10 to 16 years old. At the time of renal death, the serum creatinine level was below 10 mg/dl in 84% of the children below 5 years, compared to 5% in the patients older than 10 years. The mean interval from the first presentation of CRF to the terminal stage was 6 months in vascular nephropathies, 19 months in cystic renal disease, 26 months in glomerular disorders, 32 months in pyelonephritis, and 36 months in hereditary nephropathies and in renal hypoplasia or dysplasia. The range of these intervals is so large, even when diagnostic subgroups are considered, that a reliable prediction of the individual course from the underlying kidney disease is not possible.

International system of radiographic grading of vesicoureteric reflux. International Reflux Study in Children.

The classification of grading of vesicoureteric reflux (VUR) agreed to by the participants in the International Reflux Study in Children is described. It combines two earlier classifications and is based upon the extent of filling and dilatation by VUR of the ureter, the renal pelvis and the calyces. A standardised technique of voiding cystography is also described to ensure comparability of results.