|Year : 2000 | Volume
| Issue : 2 | Page : 106-110
Renal growth in children with vesicoureteral reflux
Anindya Chattopadhyay, Veereshwar Bhatnagar, Arun Kumar Gupta, Dilip Kumar Mitra
Department of Paediatric Surgery and Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India
Department of Paediatric Surgery, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Antireflux surgery (ARS) was performed on 45 renal units during 1991-96. Pre-operative renal length measurements were available in 20 renal units and 23 renal units were evaluated for renal length postoperatively. Preand post-ARS renal length measurements were available in 15 renal units. Renal length measurements were made by real time B mode ultrasonography. The post-ARS renal growth was accelerated in 69.5% units, normal in 13% units and impaired in 17.3% units. Accelerated renal growth occurred mainly in the first year after ARS but continued up to 2 years. Pre-existing renal scars, hypertension, poor renal function and post-operative urinary tract infection did not affect post-ARS renal growth. Failure of ARS resulted in renal growth retardation.
Keywords: Renal Length; Renal Growth; Ultrasonographic Assessment; Vesicoureteral Reflux; Anti-Reflux Surgery.
|How to cite this article:|
Chattopadhyay A, Bhatnagar V, Gupta AK, Mitra DK. Renal growth in children with vesicoureteral reflux. Indian J Urol 2000;16:106-10
| Introduction|| |
Renal growth arrest is one of the manifestations of renal injury in patients with vesicoureteral reflux (VUR). , This reduction in the velocity of renal growth may occur in the absence of demonstrable renal scarring, and has been linked to the presence of high grade VUR and active urinary tract infection.  Control of VUR by medical management or surgery has resulted in accelerated renal Growth .,, However, B abcock in 1976  reported that there is no post-operative renal growth spurt, and Willscher in the same year  linked the likelihood of renal growth resumption to the absence of renal scarring and to the differential function of the kidneys. Thus the precise contribution of surgery to renal growth in patients with VUR remains to be established. Moreover, the different methods adopted by different authors in assessing renal growth has further compounded the problem. Intravenous urography is no longer employed in the evaluation and follow up of patients with VUR, having been supplanted by the non-invasive real time B mode ultrasonography. , The creation of normal renal growth charts for the Indian children by USG in an earlier study  provided the opportunity to study the effects of antireflux surgery (ARS) on renal growth in patients with primary VUR in an effort to answer the following questions: (a) Does renal growth actually resume or accelerate after ARS ? (b) Are there any pre-operative factors which can predict failure of resumption of renal growth in a particular renal unit? (c) Are there any adverse postoperative factors which affect renal growth potential after ARS?
| Material and Methods|| |
All patients who had undergone antireflux surgery for primary vesicoureteral reflux at the All India Institute of Medical Sciences between 1991 and 1996 were entered for the study. Patients operated before 1994 were studied retrospectively, while those operated after 1994 were followed prospectively.
Details regarding age, sex, mode of presentation, anthropometric measurements, record of blood pressure, indication for ARS and operative findings were recorded in every case. Documentation of primary VUR was made on a contrast micturating cystourethrogram (MCU) pre-operatively. Reflux was graded from I to V based upon the recommendations of the International Committee on Vesicoureteral Reflux.  Pre-operative renal function was determined by renal biochemistry as well as dynamic radionuclide scintigraphy (DTPA). The absence or presence of renal scars was documented on glucoheptonate (GHA) or dimercaptosuccinic acid (DMSA) scans. Preoperative renal length evaluation was done by real time B mode ultrasonography using the technique reported previously.  In the early part of the study, pre-operative renal length evaluation was not being done routinely. Where available, this data was retrieved and recorded.
ARS was in the form of Cohen's bilateral reimplantation in all cases irrespective of the side of reflux. Note was made of the postoperative complications if any.
Follow-up protocols consisted of physical examinations with recording of blood pressures and anthropometry, documentation of the success of the ARS on direct radionuclide scintigraphy (DRCG) 6 months after surgery and then yearly. Renal length was evaluated every 6 months using real time B mode USG. Renal functions were monitored biochemically as well as on the DTPA scan. Development of fresh scars or the progression of pre-existing ones were evaluated by the GHA/DMSA scans. Urine culture was done at each follow-up visit or earlier, if the child had any urinary tract symptoms. In all cases prophylactic antimicrobials were given postoperatively for a period of 6 months, or till the DRCG revealed an absence of reflux.
Renal growth was computed by plotting renal length against age at various time intervals in the follow-up on the normal renal growth curve. If the slope of the growth curve in the operated kidney exceeded that of the slope of the normal renal growth curve, then the growth was taken to be accelerated. If the slope of the growth of the operated kidney was less than the slope of the normal renal growth curve, then the growth was deemed to have been retarded. Similarly, if the slope paralleled the normal growth pattern, then renal growth was taken to be normal.
Subsequently, the growth in the operated renal units was correlated to various pre and postoperative factors such as the age of the patient at surgery, the presence of hypertension, the presence of renal scars, occurrence of postoperative urinary tract infection (UTI), impaired renal function and the failure of surgery in an effort to identify factors which were associated with good or poor renal growth postoperatively.
| Results|| |
24 patients underwent bilateral Cohen's reimplantation in the study period. There were 18 males and 6 females (M:F 3:1). The age at presentation ranged from 3 months to 10 years with a mean of 49.5 months. The average age at surgery was 54.3 months with a range of 11 months to 10 years.
3 patients had unilateral reflux (12.5%), while 21 had bilateral VUR (87.5%). This made a total of 45 affected renal units undergoing ARS. Reflux was graded as I in 1 renal unit (2.2%), II in 1 unit (2.2%), III in 4 renal units (8.8%), IV in 34 units (75.5%) and V in 5 renal units (11.1%).
Hypertension was present in 5 patients at diagnosis (20%). All these patients also demonstrated renal scarring on GHA/DMSA scans.
GHA/DMSA scans were not available in 2 patients (4 renal units). Of the remaining 41 affected units, 36 had renal scars at the time of presentation (87.8%). Only 5 renal units were unscarred at presentation (12.2%) -1 unit each had grade I and II reflux, while 3 others had grade IV-V reflux.
20 renal units had been evaluated preoperatively by real time B mode USG. 8 refluxing units had a significantly decreased size (40%) while 2 renal units were abnormally large (10%) when compared with the normal renal length at the appropriate age.
4 patients were lost to follow-up (8 renal units). In 3 others, insufficient data was available to assess renal growth (6 renal units). 2 patients were excluded because of associated renal artery stenosis and duplex system respectively, which would interfere with the evaluation of renal growth (4 units). In 1 additional patient, renal length could not be evaluated postoperatively due to indistinct renal outlines (2 renal units).
The remaining 23 renal units were evaluated for growth after ARS. Of these, 3 patients had unilateral reflux, while 10 had bilateral VUR. Pre and postoperative renal measurements were available in 15 renal units. In 8 other units, renal growth was evaluated on the basis of postoperative USG scans.
Analysis of renal growth on follow-up revealed accelerated growth in 16 of the 23 units (69.5%), normal renal growth in 3 renal units (13%) and impaired renal growth in 4 renal units (17.3%). 1 patient with unilateral reflux had an initial period of accelerated growth, which was followed by a period of renal growth arrest and this coincided with recurrence of reflux.
In 15 renal units where data was available pre and postoperatively, the mean age at the pre-operative USG was 23.5 months and the mean renal length was 5.21 cms (SD 1.56). The mean age at surgery was 31 months for these 15 renal units. The mean age at the follow-up USG was 48.3 months and the mean renal length postoperatively was 6.45 cms (Standard deviation= 1.23 cms). The mean renal length of normal children at the same ages are 6.68 cms (95.5% confidence limits range from 5.66 to 7.49 cms) and 7.09 cms (95.5% confidence limits range from 6.07 cms to 8.11 cms) respectively. On plotting this data on the normal renal growth curve, an increase in the slope of the curve for the operated patients is evident [Figure 1].
[Table 1] shows the distribution of various pre and postoperative factors among the renal units which showed accelerated and impaired growth after ARS. Accelerated renal growth occurred mainly within the first year after ARS. However, 5 renal units (31%) continued to demonstrate faster than normal growth till 24 months after surgery.
Failure of ARS occurred in 3 patients giving a success rate of 87.5% for the procedure. 2 of these patients could not be evaluated for renal growth, as 1 patient had associated renal artery stenosis, and the other patient lacked sufficient data. The 1 patient who was available for growth evaluation showed accelerated growth postoperatively, but then had a period of deceleration when reflux recurred.
| Discussion|| |
The importance of evaluating renal growth in patients with VUR cannot be overemphasised. VUR may lead to the genesis of radiologically apparent scars, but it may also produce renal growth arrest with diffuse cortical thinning which may be missed if renal growth estimations are not done. , The impact of VUR on the kidneys generally leads to growth arrest but the exact cause of this phenomenon and the responsible factors have remained elusive inspite of extensive experimental and clinical work . ,, Factors associated with poor renal growth have included the presence of infected urine in patients with high grade reflux, the presence of pre-existing renal scars and the presence of a contralateral hypertrophied unaffected renal unit. ,
Control of infection by appropriate medical management, or the elimination of reflux by surgery has been reported to lead to resumption of renal growth. ,,,,,
Smellie et al in their landmark paper in 1981  showed that normal renal growth continued in the presence of high grade VUR provided the urine was kept sterile. This finding was confirmed by the Birmingham Reflux Study Group, , who found no difference in renal growth in patients with high grade reflux when they were treated medically or surgically.
Atwell et al  studied renal growth in 26 renal units after ARS and found resumption of renal growth after surgery which was mainly confined to the first postoperative year. Ginalski et al  also confirmed accelerated growth after surgery, but found the growth to remain accelerated for several years after surgery. Both the authors emphasised that the presence of pre-existing scars does not preclude renal growth after surgery, in contrast to their apparent adverse effect on renal growth in patients treated medically.  However Willescher  in a large series of patients showed that accelerated renal growth after surgery was significantly affected by pyelonephritic scarring, especially if the contralateral renal unit was normal. In a dissenting paper, Babcock et al  did not find any enhanced renal growth after successful ARS for VUR, and explained the findings on the basis of intrinsic renal dysplasia associated with abnormal ureteric orifice position as stated by Mackie and Stephens in their famous theory of ureteral bud anomalies. 
Control of VUR by successful ARS led to accelerated growth in 69.5% of the cases in this study, confirming a postoperative renal growth spurt. This occurred in spite of the presence of renal scarring in 75% of the evaluated renal units. Due to the paucity of unscarred units in the study, the effect of a normal contralateral unaffected kidney on renal growth could not be evaluated. The duration of the postoperative renal growth spurt was found to be mainly confined to 12 months after surgery, but as many as 31% of the renal units continued an accelerated growth after that period.
Although there were no factors which could predict the ultimate growth potential of an involved kidney, the mean age at surgery seemed to influence the results. Better postoperative renal growth was seen when the patients were operated earlier, the p value being between 0.05 and 0. 10 (not statistically significant). The Birmingham Reflux Study Group noted that there was a tendency for impaired renal growth to persist if the ARS was performed after the age of 6 years. , This fact was noted by Ginalski et al also who reported better renal growth resumption in younger patients. 
While the presence of breakthrough infections during medical management significantly affects renal growth;  the occurrence of postoperative urinary tract infection appeared to be innocuous in this study. By preventing the ascent of bacilli to the upper urinary tract, ARS mitigates the effect of UTI and allows unimpeded renal growth. Indeed failure of ARS in 1 patient was associated with a recurrence of renal growth arrest in the study.
In conclusion, the findings of this study confirm that ARS performed successfully leads to renal growth acceleration. Renal growth acceleration occurs in spite of the presence of pre-existing renal scars, hypertension, poor renal function and postoperative UTI, and continues for more than 24 months in more than 30% of the cases. There are no pre-operative markers to predict the outcome of ARS on a given renal unit, and the main role of ARS appears to be the protection of the kidneys from ascending infection without recourse to prolonged antimicrobial therapy. The only postoperative factor associated with poor outcome appears to be failure of the surgery.
| References|| |
|1.||Lyon RP. Renal arrest. J Urol 1973: 109: 707-710. |
|2.||Redman JF. Scriber LJ, Bissada NK. Apparent failure of renal growth secondary to vesicoureteral reflux. Urology 1974: 3: 704-707. |
|3.||Smellie JM. Edwards D, Normand ICS, Prescod N. Effects of VUR on renal growth in children with urinary tract infection. Arch Dis Child 1981: 56: 593-600. |
|4.||Atwell JD. Vijay MR. Renal growth following reimplantation of the ureters for reflux. Br J Urol 1970: 50: 367-370. |
|5.||Ginalski JM. Michaud A. Genton N. Follow-up of renal morphology and growth of 141 children operated for vesicoureteric reflux: a retrospective computerised study. J Pediatr Surg. 1986: 21: 697701. |
|6.||Babcock JR. Keats GK, King LR. Renal changes after an uncomplicated antireflux operation. J Urol 1976; 115: 720-721. |
|7.||Willscher MK. Bauer SB. Zammuto PJ. Retik AB. Renal growth and urinary infection following antireflux surgery in infants and children. J Urol 1976; 115: 722-725. |
|8.||Tay JS, Vellayappan K, Tan LK, Wee PH, Wong HB. Paediatric ultrasonography IV: the accuracy of the ultrasound scan in the estimation of renal size in children. J Singapore Paediatr Soc 19: 234-237. |
|9.||Rosenbaum DM, Korngold E, Teele RL. Sonographic assessment of renal length in normal children. AJR 1984; 142: 467-469. [PUBMED] [FULLTEXT]|
|10.||Chattopadhyay A, Bhatnagar V, Gupta AK, Mitra DK. Ultrasonographic assessment of renal growth in normal Indian children. Indian J Urol 1997 (under consideration). |
|11.||Report of the International Reflux Committee. Medical versus surgical treatment of primary vesicoureteral reflux. Pediatrics 1981; 67: 392-400. |
|12.||King LR, Sellards HG. The effect of vesicoureteral reflux on renal growth and development in puppies. Invest Urol 1971; 9: 95-97. [PUBMED] |
|13.||Godley ML, Risdon RA, Ransley PG. Effect of unilateral vesicoureterie reflux on renal growth and the uptake of 99m Tc DMSA by the kidney. An experimental study in the minipig. Br J Urol 1989; 63: 340-347. |
|14.||Birmingham Reflux Study Group. Prospective trial of operative versus non-operative treatment of severe vesicoureteral reflux: 2 years observation in 96 children. Br Med J 1983; 287: 171-174. |
|15.||Birmingham. Reflux Study Group. Prospective trial of operative versus non-operative treatment of severe vesicoureteral reflux: 5 years observation. Br Med J 1987; 295: 237-241. |
|16.||Mackie GG, Stephens FD. Duplex kidneys: a correlation of renal dysplasia with position of ureteral orifice. J Urol 1975; 114: 274-280. [PUBMED] |