November 1976
TheJournalofPEDIATRICS
743
Infection of the urinary tract after anti-reflux surgery Two hundred twenty-three children who underwent anti-reflux surgery were evaluated Pyelonephritic scarring was more apt to occur with greater degrees" of reflux. Postoperative infection was principally confined to the bladder and occurred primarily in females. The beneficial effect of anti-reflux surgery is discussed
Max K. Willscher, M.D., Stuart B. Bauer, M.D., Peter J. Zammuto, M.S., and Alan B. Retik, M.D.,* Boston, Mass.
R E F L U X is commonly associated with urinary infection and pyelonephritis.' There has been speculation concerning the effect successful antireflux surgery has on the incidence of recurrent urinary infection and the progression of pyelonepfiritic scarring? ~ Herein we describe the effect of anti-reflux surgery on these clinical manifestations in a large number of children. VESICOURETERAL
MATERIALS AND METHODS Anti-reflux surgery was performed on 223 children-48 males and 175 females-at the Boston Floating Hospital for Infants and Children between 1967 and 1973. The children were followed for periods ranging from six months to seven years. The study excluded those children with other associated anatomic abnormalities; e.g., p0ster!or urethral valves, ectopic ureterocele, primary megaureter, and neurogenic bladder dysfunction. The great majority of children were referred to us because of recurrent urinary infection. The presence of pyelonephritis" and/or hydronephrosis, grade of reflux, and ureteral orifice position and configuration 7 were determined during the initial evaluation. The children, who ranged in age from six months to 14 years, underwent surgery for one or more of the following reasons~: (1) recurrence of infection despite the use of antibiotics; (2) From the Department of Urology, Boston Floating Hospital for Infants and Children, Boston, Mass. 02111. *Reprint address." 171 Harrison Ave., Boston, Mass. 02111.
persistent reflux with a basic anatomic abnormality at the ureteral orifice; or (3) severe reflux with pyelonephritis. Average age at the time of surgery was 3.4 years. A modified Politano-Leadbetter procedure was performed in most children." Foilowing surgery, each child received maintenance therapy with an appropriate anti'biotic for four to six months. A postoperative excretory urogram was obtained at six weeks, again at four months along with a voiding cystourethrogram, and repeated yearly thereafter. Subsequent voiding cystourethrograms were obtained when indicated. Urine was cultured at monthly intervals during the first postoperative year and periodical!y thereafter. Preoperative reflux was graded according to degree TM (Fig. 1). Grade I, lower ureteral filling; Grade IIa, total reflux without calyceal distention; Grade IIb, ureteral and pelvic filling with mild calyceal blunting; Grade llI, marked distention of the pelvis, calyces and ureter; Grade IV, massive reflux associated with severe hydroureteronephrosis. RESULTS Of the 223 patients who underwent anti-reflux surgery, 104 had unilateral reimplantation and 119 had bilateral surgery. Thirty-nine patients had a complete duplication of the collecting system--27 unilateral and 12 bilateral. In concurrence with Dwoskin and Perlmutter," pyelonephritic scarring occurred more often with greater degrees of reflux (P = 0.01) (Fig. 2). The severity of reflux and the presence of pye!onephritis were found to be independent of age and sex, and unrelated to the existence of a duplicate system.
Vol. 89, No. 5, pp. 743-746
744
Willscher et al.
The Journal of Pediatrics November 1976
PYELONEPHRITIC
SCARRING
VS GRADE OF REFLUX ( :542 URETERS ) 100ZO')
wV_. rr __ .~ ~
75-
r
,o, o
w i-->z Bm (..)-1Crl-Ld
5025-
1
2A GRADE
2B
3
4
OF REFLUX
Fig. 2. Pyelonephritic scarring is more likely with greater degrees of reflux.
COMPLICATIONS OF ANTI-REFLUX SURGERY PERSISTENT REFLUX
Ipsilateral
Contralateral
Fig. 1. The grades of reflux as described in the text and labeled according to degree.
Following surgery, ureteral obstruction occurred in four patients (1.2%). Transient postoperative reflux was observed on the operated (ipsilateral) side in ten of the 342 ureters (3%), but spontaneously subsided in each case within one year. In 104 unilateral operations, 17 patients (16%) developed reflux on the nonoperated (contralateral) side. Within one year, this reflux stopped in all but two children, each of whom had demonstrated transient preoperative reflux (Fig. 3). Postoperative infection occurred in 21% of the patients (Fig. 3). There were only two boys in this group, each of whom clinically had Cystitis. The majority of postoperative infections occurred in girls (45 of the 175 females), and clinically all but three (1.7%) were confined to the bladder. No patient with transient or persistent postoperative reflux developed an infection. The presence of a duplicate system did not influence the rate of postoperative infection. One-third of all postoperative infections occurred in the first six months while the child was still receiving antibiotics (Fig. 4). The later occurring infections were in those' children not taking antibiotics. With each infection there is less chance for development of a subsequent infection (Fig. 4). The incidence of postoperative infection was
.2Oo)
(
[ 342 Ureters
104 Unilateral Operations
POSTOP INFECTIONS - 2 1 %
o 1.7%
48 Males
175 Females
Fig. 3. No ipsilateral reflux occurred in 342 operated ureters. Contralateral reflux developed in two patients following unilateral surgery. Postoperative infection was rare in males, more common in females, and usually confined to the bladder.
neither related to the preoperative presence of pyelonephritis nor hydronephrosis (Fig. 5). Interestingly, one-third of all patients with greater than Grade IIa reflux had normal excretory urograms~ In addition, greater degrees of preoperative reflux did not predispose the patient to a higher incidence of postoperative infection (Fig. 5).
Volume 89 Number 5
Urinary infection after anti-reflux surgery
POST OPERATIVE INFECTIONS IN 4 5 FEMALES ( TIME OF FIRST INFECTION ) 20
Z
INFECTIONS
_-J '15 ..,r
IN 45 FEMALES
( COMPARISON TO PRE-OPERATIVE
I,,-
UROGRAM
[]INFECTIONS
~_ t0oz uJ
ILl
II.. O
POST OPERATIVE
74 5
[]
NO INFECTIONS
75-
h Q
t0-
50-
re" z
W m
:Ig
w u
5
"
w o_
z
0.5
i
YEARS
2
5
25-
Normal
>5
T.VP
POST OPERATIVE
Pyelone )hritis Hydronephrosis
(COMPARISON TO PRE-OPERATIVE REFLUX )
( DISTRIBUTION )
50
Ioo llJ
z 4O n," d
oc
~"
5o
~-
n- 2 0
(x.
[]
INFECTIONS
[]
NO INFECTIONS
75
DO
50
Z bJ
[a= 0
n~
"'
ILl
25
:E "~ Z
I0 i
2A GRADE
2
3
4
5
NUMBER OF INFECTIONS
Fig. 4. Most infections occurred early in the postoperative period, with recurrences being less frequent with each reinfection. Less than one quarter had more than one infection. DISCUSSION The association of pyelonephritic scarring, as seen by excretory urography and infection, with vesicoureteral reflux is well known. There is recent evidence to suggest that even subclinical infections in infants followed prospectively will produce progressive renal scarring despite subsequent cessation of reflux? 1 Although the argument has been advanced that infection is necessary for pyelonephritic scarring to occur in the kidney with reflux, it is apparent that reflux alone can be a major factor in the development of parenchymal damage. It has been shown that pyelonephritic scarring occurs most frequently in those areas of the kidney where there are patent papillary ducts without check valves to prevent intrarenal reflux. '~ 1:~In this manner, the "water h a m m e r " effect of persistent reflux is said to reach and damage the k i d n e y ? ' ~:' With time, intrarenal reflux may result in pyelonephritic scarring in some children. 1~ Similarly, we have demonstrated that pyelonephritic scarring is most closely associated with the degree of reflux and not with other preoperative clinical factors.
2B
5
4
OF REFLUX
Fig. 5. Comparison of preoperative excretory urogram and voiding cystogram to the occurrence of postoperative infection. Postoperative infection was not dependent on radiographic appearance or grade of reflux.
The postoperative rate of infection in this series is 21% which conforms to the generally reported figure, l; ~" These children rarely developed pyelonephritis, with 98% of infections clinically confined to the bladder. Following an episode of pyelonephritis, a renal scar (as visualized by excretory urography) may take up to two years to become maximally evident? ~ Therefore, successful anti-reflux surgery may not halt the initial progression of renal scarring, -'~ but will protect the kidney against future parenchymal reinfection. Boys rarely developed a postoperative infection presumably because of the protective effect of the longer male urethra. The greater n u m b e r of postoperative infections in girls most likely represents anatomic and physiologic factors peculiar to the female lower urinary tract, rather than to the presence of old pyelonephritis. Thus, successful antireflux surgery returns these female children to that group of patients who get recurrent bladder infection for reasons other than reflux. A b n o r m a l perineal flora may play a role in producing recurrent infection in these children TM ~-~ Neither the severity of reflux nor the radiologic
746
Willscher et al.
evidence of preoperative pyelonephritis predisposes the patient to postoperative infection. Postoperative recurrences tend to be less f r e q u e n t t h e longer the child r e m a i n s free o f infection. W i t h each reinfection, a child is less likely to develop another. 23 Finally, successful anti-reflux surgery m a y h a v e a beneficial effect on the growing kidney. We have f o u n d a statistically significant renal growth spurt in some children, following correction of reflux5 ~ By preventing recurrent infection, the d a m a g e d kidney m a y be able to recuperate from prior n e p h r o n loss by c o m p e n s a t o r y h y p e r t r o p h y o f existing p a r e n c h y m a . REFERENCES
1. Scott JES, and Stansfeld JM: Ureteric reflux and kidney scarring in children, Arch Dis Child 43:468, 1968. 2. Bailey RR: Relationship of vesicoureteric reflux to urinary tract infection and chronic pyelonephritis-reflux nephropathy, Clin Nephrol 1:132, 1973. 3. Blank E: Caliectasis and renal scars in children, J Urol 110:255, 1973. 4. Hodson CJ, and Craven JD: The radiology of obstructive atrophy of the kidney, Clin Radiot 17:355, 1966. 5. Rolleston GL, Shannon FT, and Utley WL: Relationship of infantile vesicoureteric reflux to renal damage, Br Med J 1:460, 1970. 6. Hodson CJ: The radiologic diagnosis of pyelonephritis, Proc R. Soc Med 52:669, 1959. 7. Lyon RP, Marshal S, and Tanagho EA: The ureteral orifice: Its configuration and competency, J Urol 102:504, 1969. 8. Retik AB: Urinary reflux in children: An approach to management, Hosp Prac 9:125, 1974. 9. Politano VA, and Leadbetter WF: An operative technique for correction of vesicoureteral reflux, J Urol 79:932, 1958.
The Journal of Pediatrics November t976
10. Dwoskin JY, and Perlmutter AD: Vesicoureteral reflux in -children: A computerized review, J Urol 109:888, 1973. 11. Randolph MF, Morris KE, and Gould BS: The first urinary tract infection in the female infant, J PEDIATR 86:342, 1975. 12. Ransley PG, and Risdon RA: Renal papillae and intrarenal reflux in the pig, Lancet 2:1114, 1974. 13. Ransley PG, and Risdon RA: Renal papillary morphology in infants and young children (in press). 14. Editorial: V.P.R. + I.R.R. = C.P.N.? Lancet 2:1120, 1974. 15. Evans EJ: Urinary reflux in chronic pyelonephritis, Lancet 2:t259, 1974. 16. Rolleston GL, Maling TMJ, and Hodson CJ: Intrarenal reflux in the scarred kidney, Arch Dis Child 49:531, 1974. 17. Hendren WH: Ureteral reimplantation in children, J Pediatr Surg 3:649, 1968. 18. Williams DI, and Eckstein HB: Surgical treatment of reflux in children, Br J Urol 37:13~ 1965. 19. Filly R, Friedland GW, Govan DE, and Fair WR: Development and progression of clubbing and scarring in children with recurrent urinary tract infections, Radiology 113:145, 1974. 20. Govan DE, and Palmer JM: Urinary tract infections in children: The influence of successful anti-reflux operations and morbidity from infection, Pediatrics 44:677, 1969. 21. Leadbetter (3, and Slavin S: Pediatric urinary tract infection: Significance of vaginal bacteria, Urology 3:58l, 1974. 22. Stamey TA, and Sexton CC: Role of vaginal colonization with enterobacteriacae in recurrent urinary infections, J Urol 113:214, 1975. 23. Kunin CM: The natural history of recurrent bacteriuria in school girls, N Engl J Med 282:1443, 1970. 24. Willscher MK, Bauer SB, Zammuto PJ, and Retik AB: Renal growth and urinary infection following antireflux surgery in infants and children, J Urol 115:722, 1976.
TheJournalofPEDIATRICS
743
Infection of the urinary tract after anti-reflux surgery Two hundred twenty-three children who underwent anti-reflux surgery were evaluated Pyelonephritic scarring was more apt to occur with greater degrees" of reflux. Postoperative infection was principally confined to the bladder and occurred primarily in females. The beneficial effect of anti-reflux surgery is discussed
Max K. Willscher, M.D., Stuart B. Bauer, M.D., Peter J. Zammuto, M.S., and Alan B. Retik, M.D.,* Boston, Mass.
R E F L U X is commonly associated with urinary infection and pyelonephritis.' There has been speculation concerning the effect successful antireflux surgery has on the incidence of recurrent urinary infection and the progression of pyelonepfiritic scarring? ~ Herein we describe the effect of anti-reflux surgery on these clinical manifestations in a large number of children. VESICOURETERAL
MATERIALS AND METHODS Anti-reflux surgery was performed on 223 children-48 males and 175 females-at the Boston Floating Hospital for Infants and Children between 1967 and 1973. The children were followed for periods ranging from six months to seven years. The study excluded those children with other associated anatomic abnormalities; e.g., p0ster!or urethral valves, ectopic ureterocele, primary megaureter, and neurogenic bladder dysfunction. The great majority of children were referred to us because of recurrent urinary infection. The presence of pyelonephritis" and/or hydronephrosis, grade of reflux, and ureteral orifice position and configuration 7 were determined during the initial evaluation. The children, who ranged in age from six months to 14 years, underwent surgery for one or more of the following reasons~: (1) recurrence of infection despite the use of antibiotics; (2) From the Department of Urology, Boston Floating Hospital for Infants and Children, Boston, Mass. 02111. *Reprint address." 171 Harrison Ave., Boston, Mass. 02111.
persistent reflux with a basic anatomic abnormality at the ureteral orifice; or (3) severe reflux with pyelonephritis. Average age at the time of surgery was 3.4 years. A modified Politano-Leadbetter procedure was performed in most children." Foilowing surgery, each child received maintenance therapy with an appropriate anti'biotic for four to six months. A postoperative excretory urogram was obtained at six weeks, again at four months along with a voiding cystourethrogram, and repeated yearly thereafter. Subsequent voiding cystourethrograms were obtained when indicated. Urine was cultured at monthly intervals during the first postoperative year and periodical!y thereafter. Preoperative reflux was graded according to degree TM (Fig. 1). Grade I, lower ureteral filling; Grade IIa, total reflux without calyceal distention; Grade IIb, ureteral and pelvic filling with mild calyceal blunting; Grade llI, marked distention of the pelvis, calyces and ureter; Grade IV, massive reflux associated with severe hydroureteronephrosis. RESULTS Of the 223 patients who underwent anti-reflux surgery, 104 had unilateral reimplantation and 119 had bilateral surgery. Thirty-nine patients had a complete duplication of the collecting system--27 unilateral and 12 bilateral. In concurrence with Dwoskin and Perlmutter," pyelonephritic scarring occurred more often with greater degrees of reflux (P = 0.01) (Fig. 2). The severity of reflux and the presence of pye!onephritis were found to be independent of age and sex, and unrelated to the existence of a duplicate system.
Vol. 89, No. 5, pp. 743-746
744
Willscher et al.
The Journal of Pediatrics November 1976
PYELONEPHRITIC
SCARRING
VS GRADE OF REFLUX ( :542 URETERS ) 100ZO')
wV_. rr __ .~ ~
75-
r
,o, o
w i-->z Bm (..)-1Crl-Ld
5025-
1
2A GRADE
2B
3
4
OF REFLUX
Fig. 2. Pyelonephritic scarring is more likely with greater degrees of reflux.
COMPLICATIONS OF ANTI-REFLUX SURGERY PERSISTENT REFLUX
Ipsilateral
Contralateral
Fig. 1. The grades of reflux as described in the text and labeled according to degree.
Following surgery, ureteral obstruction occurred in four patients (1.2%). Transient postoperative reflux was observed on the operated (ipsilateral) side in ten of the 342 ureters (3%), but spontaneously subsided in each case within one year. In 104 unilateral operations, 17 patients (16%) developed reflux on the nonoperated (contralateral) side. Within one year, this reflux stopped in all but two children, each of whom had demonstrated transient preoperative reflux (Fig. 3). Postoperative infection occurred in 21% of the patients (Fig. 3). There were only two boys in this group, each of whom clinically had Cystitis. The majority of postoperative infections occurred in girls (45 of the 175 females), and clinically all but three (1.7%) were confined to the bladder. No patient with transient or persistent postoperative reflux developed an infection. The presence of a duplicate system did not influence the rate of postoperative infection. One-third of all postoperative infections occurred in the first six months while the child was still receiving antibiotics (Fig. 4). The later occurring infections were in those' children not taking antibiotics. With each infection there is less chance for development of a subsequent infection (Fig. 4). The incidence of postoperative infection was
.2Oo)
(
[ 342 Ureters
104 Unilateral Operations
POSTOP INFECTIONS - 2 1 %
o 1.7%
48 Males
175 Females
Fig. 3. No ipsilateral reflux occurred in 342 operated ureters. Contralateral reflux developed in two patients following unilateral surgery. Postoperative infection was rare in males, more common in females, and usually confined to the bladder.
neither related to the preoperative presence of pyelonephritis nor hydronephrosis (Fig. 5). Interestingly, one-third of all patients with greater than Grade IIa reflux had normal excretory urograms~ In addition, greater degrees of preoperative reflux did not predispose the patient to a higher incidence of postoperative infection (Fig. 5).
Volume 89 Number 5
Urinary infection after anti-reflux surgery
POST OPERATIVE INFECTIONS IN 4 5 FEMALES ( TIME OF FIRST INFECTION ) 20
Z
INFECTIONS
_-J '15 ..,r
IN 45 FEMALES
( COMPARISON TO PRE-OPERATIVE
I,,-
UROGRAM
[]INFECTIONS
~_ t0oz uJ
ILl
II.. O
POST OPERATIVE
74 5
[]
NO INFECTIONS
75-
h Q
t0-
50-
re" z
W m
:Ig
w u
5
"
w o_
z
0.5
i
YEARS
2
5
25-
Normal
>5
T.VP
POST OPERATIVE
Pyelone )hritis Hydronephrosis
(COMPARISON TO PRE-OPERATIVE REFLUX )
( DISTRIBUTION )
50
Ioo llJ
z 4O n," d
oc
~"
5o
~-
n- 2 0
(x.
[]
INFECTIONS
[]
NO INFECTIONS
75
DO
50
Z bJ
[a= 0
n~
"'
ILl
25
:E "~ Z
I0 i
2A GRADE
2
3
4
5
NUMBER OF INFECTIONS
Fig. 4. Most infections occurred early in the postoperative period, with recurrences being less frequent with each reinfection. Less than one quarter had more than one infection. DISCUSSION The association of pyelonephritic scarring, as seen by excretory urography and infection, with vesicoureteral reflux is well known. There is recent evidence to suggest that even subclinical infections in infants followed prospectively will produce progressive renal scarring despite subsequent cessation of reflux? 1 Although the argument has been advanced that infection is necessary for pyelonephritic scarring to occur in the kidney with reflux, it is apparent that reflux alone can be a major factor in the development of parenchymal damage. It has been shown that pyelonephritic scarring occurs most frequently in those areas of the kidney where there are patent papillary ducts without check valves to prevent intrarenal reflux. '~ 1:~In this manner, the "water h a m m e r " effect of persistent reflux is said to reach and damage the k i d n e y ? ' ~:' With time, intrarenal reflux may result in pyelonephritic scarring in some children. 1~ Similarly, we have demonstrated that pyelonephritic scarring is most closely associated with the degree of reflux and not with other preoperative clinical factors.
2B
5
4
OF REFLUX
Fig. 5. Comparison of preoperative excretory urogram and voiding cystogram to the occurrence of postoperative infection. Postoperative infection was not dependent on radiographic appearance or grade of reflux.
The postoperative rate of infection in this series is 21% which conforms to the generally reported figure, l; ~" These children rarely developed pyelonephritis, with 98% of infections clinically confined to the bladder. Following an episode of pyelonephritis, a renal scar (as visualized by excretory urography) may take up to two years to become maximally evident? ~ Therefore, successful anti-reflux surgery may not halt the initial progression of renal scarring, -'~ but will protect the kidney against future parenchymal reinfection. Boys rarely developed a postoperative infection presumably because of the protective effect of the longer male urethra. The greater n u m b e r of postoperative infections in girls most likely represents anatomic and physiologic factors peculiar to the female lower urinary tract, rather than to the presence of old pyelonephritis. Thus, successful antireflux surgery returns these female children to that group of patients who get recurrent bladder infection for reasons other than reflux. A b n o r m a l perineal flora may play a role in producing recurrent infection in these children TM ~-~ Neither the severity of reflux nor the radiologic
746
Willscher et al.
evidence of preoperative pyelonephritis predisposes the patient to postoperative infection. Postoperative recurrences tend to be less f r e q u e n t t h e longer the child r e m a i n s free o f infection. W i t h each reinfection, a child is less likely to develop another. 23 Finally, successful anti-reflux surgery m a y h a v e a beneficial effect on the growing kidney. We have f o u n d a statistically significant renal growth spurt in some children, following correction of reflux5 ~ By preventing recurrent infection, the d a m a g e d kidney m a y be able to recuperate from prior n e p h r o n loss by c o m p e n s a t o r y h y p e r t r o p h y o f existing p a r e n c h y m a . REFERENCES
1. Scott JES, and Stansfeld JM: Ureteric reflux and kidney scarring in children, Arch Dis Child 43:468, 1968. 2. Bailey RR: Relationship of vesicoureteric reflux to urinary tract infection and chronic pyelonephritis-reflux nephropathy, Clin Nephrol 1:132, 1973. 3. Blank E: Caliectasis and renal scars in children, J Urol 110:255, 1973. 4. Hodson CJ, and Craven JD: The radiology of obstructive atrophy of the kidney, Clin Radiot 17:355, 1966. 5. Rolleston GL, Shannon FT, and Utley WL: Relationship of infantile vesicoureteric reflux to renal damage, Br Med J 1:460, 1970. 6. Hodson CJ: The radiologic diagnosis of pyelonephritis, Proc R. Soc Med 52:669, 1959. 7. Lyon RP, Marshal S, and Tanagho EA: The ureteral orifice: Its configuration and competency, J Urol 102:504, 1969. 8. Retik AB: Urinary reflux in children: An approach to management, Hosp Prac 9:125, 1974. 9. Politano VA, and Leadbetter WF: An operative technique for correction of vesicoureteral reflux, J Urol 79:932, 1958.
The Journal of Pediatrics November t976
10. Dwoskin JY, and Perlmutter AD: Vesicoureteral reflux in -children: A computerized review, J Urol 109:888, 1973. 11. Randolph MF, Morris KE, and Gould BS: The first urinary tract infection in the female infant, J PEDIATR 86:342, 1975. 12. Ransley PG, and Risdon RA: Renal papillae and intrarenal reflux in the pig, Lancet 2:1114, 1974. 13. Ransley PG, and Risdon RA: Renal papillary morphology in infants and young children (in press). 14. Editorial: V.P.R. + I.R.R. = C.P.N.? Lancet 2:1120, 1974. 15. Evans EJ: Urinary reflux in chronic pyelonephritis, Lancet 2:t259, 1974. 16. Rolleston GL, Maling TMJ, and Hodson CJ: Intrarenal reflux in the scarred kidney, Arch Dis Child 49:531, 1974. 17. Hendren WH: Ureteral reimplantation in children, J Pediatr Surg 3:649, 1968. 18. Williams DI, and Eckstein HB: Surgical treatment of reflux in children, Br J Urol 37:13~ 1965. 19. Filly R, Friedland GW, Govan DE, and Fair WR: Development and progression of clubbing and scarring in children with recurrent urinary tract infections, Radiology 113:145, 1974. 20. Govan DE, and Palmer JM: Urinary tract infections in children: The influence of successful anti-reflux operations and morbidity from infection, Pediatrics 44:677, 1969. 21. Leadbetter (3, and Slavin S: Pediatric urinary tract infection: Significance of vaginal bacteria, Urology 3:58l, 1974. 22. Stamey TA, and Sexton CC: Role of vaginal colonization with enterobacteriacae in recurrent urinary infections, J Urol 113:214, 1975. 23. Kunin CM: The natural history of recurrent bacteriuria in school girls, N Engl J Med 282:1443, 1970. 24. Willscher MK, Bauer SB, Zammuto PJ, and Retik AB: Renal growth and urinary infection following antireflux surgery in infants and children, J Urol 115:722, 1976.
