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Increased Physical Growth After Successful Antireflux Operation
0022-5347 /79/1224-0523$02.00/0 Vol. 122, October
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1979 by The Williams & Wilkins Co.
Pediatric Articles INCREASED PHYSICAL GROWTH AFTER SUCCESSFUL ANTIREFLUX OPERATION RAYMOND W. MERRELL
AND
JOSEPH J. MOW AD
ABSTRACT
Gross vesicoureteral reflux with infection can retard renal growth. Resumption of renal growth or even accelerated growth has been reported after successful surgical repair of reflux in chil~en. No published reports examining the effect on ph)'.sical_ growth are ~vailabl_e. ~he p_reoperative 3:nd postoperative physical growth curves were exammed m 35 consecutive pediatric patients undergo~ng ureteroneocystostomy for reflux. The significant (average 81 per cent) increase in the postoperative physical growth percentile is presented and discussed. Renal growth arrest has been noted secondary to vesicoureteral reflux and a normal renal growth rate or even an accelerated growth rate has been reported after successful surgical correction of reflux. 1- 3 However, the published reports do not examine the effect of reflux on physical growth. Herein we examine the relationship of physical growth and surgically corrected vesicoureteral reflux.
RESULTS
The birth length distribution of the study group was the same as the normal population and the birth weights were slightly lower. The postoperative growth percentiles also followed the general population. The preoperative growth percentiles were significantly lower than normal. The average birth length percentile for the group was 46 per cent. This decreased to an average 27th percentile preoperatively and returned to the 49th percentile after ureteroneocystostomy (fig. 1). Therefore, the group experienced an average 40 per cent decrease in height percentile between birth and the preoperative period, and an average of 81 per cent increase in height percentile followed reimplantation. This represents a statistically significant decrease preoperatively (p <0.01) and increase postoperatively (p <0.01) (figs. 2 and 3). The corresponding average percentiles for the body weight were 32 per cent at birth, 36 per cent preoperatively and 55 per cent postoperatively. The group experienced an average 51 per cent increase in body weight postoperatively. The postoperative weight increase is significant (p = 0.02) (figs. 4 and 5). The 16 children with bilateral reflux had a slightly lower average preoperative growth percentile (20 per cent) but they were undistinguishable from the entire group during the birth or postoperative periods. The 1 child with reflux into a solitary kidney had one of the most dramatic courses, decreasing fr~m the 97th birth length percentile to less than the 3rd percentile preoperatively, and rebounding to the 60th percentile after reimplantation. There were 3 technical failures in the 35 children, a failure rate of 8.6 per cent. Two patients had postoperative ureteral stenosis and 1 had persistent reflux. None of these 3 failures had increased physical growth postoperatively and all 3 maintained their low preoperative growth percentile. The patient with persistent reflux had a subsequent successful reimplant and has demonstrated increased growth. The parents of the 2 children with postoperative ureteral stenosis have refused reoperation to date.
MATERIALS AND METHODS
From 1962 through 1976, 167 children presented with vesicoureteral reflux. Of these patients 35 (21 per cent) were treated by ureteroneocystostomy. With the grading system of Dwoskin and Perlmutter4 all patients undergoing ureteral reimplant had grade II, III or IV reflux. In grade IV reflux an operation was done soon after the diagnosis was made. Indications for operation in grades II and III reflux included progressive renal scarring, renal growth arrest or breakthrough infection while on antimicrobial therapy. Height and weight measurements on these patients in the immediate postoperative period and during the initial followup period were readily available from the hospital charts. Measurements at birth as well as supplemental preoperative and postoperative measurements were obtained from questionnaires sent to the children's parents and primary physicians. Physical growth percentiles were determined for each child using standard growth charts prepared by the National Center for Health Statistics. 5 Growth percentiles at birth, preoperatively and on at least 3 separate occasions postoperatively were determined. All patients were followed a minimum of 18 months and a maximum of 10 years postoperatively. At the time of operation all patients had normal blood urea nitrogen, creatinine and hematocrit, and all had had documented urinary tract infection on at least 2 separate occasions preoperatively. The children had negative urine cultures at the time of operation. Of these patients 16 had bilateral reflux, 18 had unilateral reflux and 1 had reflux into a congenital solitary kidney. There were 7 boys (20 per cent) and 28 girls (80 per cent). All patients were white. The average age at operation was 5. 7 years, with a range of 10 months to 9.5 years.
DISCUSSION
Accepted for publication December 22, 1978. Read at annual meeting of Mid-Atlantic Section, American Urological Association, White Sulphur Springs, West Virginia, October 29November 1, 1978.
523
The growth retardation we observed in children with gross vesicoureteral reflux is an interesting aspect of this abnormality. Although these patients were not azotemic the well studied phenomenon of growth retardation in children with chronic renal failure may offer some clues to the etiology of slowed
524
MERRELL AND MOW AD
AVERAGE HEIGHTS AND WEIGHTS OF STUDY GROUP 60
50
DHeight 40 I-
zUJ u Q::
fflweight 30
UJ
Cl.
20
10
BIRTH
PRE-OP
POST-OP
FIG. 1
BIRTH
LENGTH
Z 15
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Expected Normal
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Group
I
() 10 LL
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5
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0 -20
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BIRTH
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:E
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40-60
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INCREASED PHYSICAL GROWTH AFTER SUCCESSFUL ANTIREFLUX OPERATION
A PRE OPERATIVE HEIGHT Expected Normal
D
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Expected Normal
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MERRELL AND MOWAD
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growth in children with gross reflux. Several factors have been examined in the children with chronic renal failure and correlated with retarded physical growth. Possible etiologic factors included renal osteodystrophy, chronic urinary tract infection, protein loss secondary to nephrosis, negative caloric balance, possible hormonal changes, chronic acidosis, azotemia, anemia and loss of renal concentrating ability. 6-B Several of these possible factors can be eliminated easily when discussing the present series of patients with vesicoureteral reflux. No patient had changes compatible with renal rickets, significant proteinuria, acidosis, azotemia or significant anemia. West and Smith showed that chronic urinary tract infection alone does not retard physical growth. 7 They did find that decreased renal concentrating ability was present in most renal patients with growth retardation and that an inadequate caloric intake was a factor in almost all of these children. Simmons and associates demonstrated that decreased caloric intake was the single most important factor in growth retardation among pediatric renal failure patients and demonstrated increased growth on adequate dietary supplements.8 Growth hormone levels are unchanged in patients with renal failure 6 but somatomedin (sulfation factor), a newly recognized factor in linear growth, has been found to be low in children with renal failure and to return to normal after successful transplantation. 9 Walker and associates have shown that the glomerular filtration rate is not substantially reduced until an advanced degree
of hydronephrosis is evident in cases of vesicoureteral reflux. 10 They and others 11 demonstrated that reflux produces a decrease in the renal concentrating ability that is corrected after successful ureteral reimplantation. However, this etiology would not account for the slowed somatic growth in children with unilateral reflux in whom 1 kidney would retain concentrating ability. None of our patients was in renal failure but both groups may have some aspects in common, including possible decreased concentrating ability, negative caloric balance, recurrent infection and possible hormonal factors. These possible etiologic factors in the observed growth retardation require further specific study.
Department of Urology, Geisinger Medical Center, Danville, Pennsylvania 17821. (R. W. M.) REFERENCES 1. Willscher, M. K., Bauer, S. B., Zammuto, P. J. and Retik, A. B.:
Renal growth and urinary infection following antireflux surgery in infants and children. J. Urol., 115: 722, 1976. 2. McRae, C. U., Shannon, F. T. and Utley, W. L. F.: Effect on renal growth of reirnplantation of refluxing ureters. Lancet, 1: 1310, 1974. 3. Scott, J. E. S. and Stansfeld, J. M.: Treatment of vesico-ureteric reflux in children. Arch. Dis. Child., 43: 323, 1968. 4. Dwoskin, J. Y. and Perlmutter, A. D.: Vesicoureteral reflux in children; a computerized review. J. Urol., 109: 888, 1973.
INCREASED PHYSICAL GROWTH AFTER SUCCESSFUL ANTIREFLUX OPERATION
5. National Center for Health Statistics: NCHS growth charts, 1976. Monthly vital statistics report. Rockville, Maryland: Health Resources Administrations, vol. 25, No. 3, suppl. (HRA) 76-1120, June 1976. 6. Piel, C. F. and Roof, B. S.: Skeletal growth disturbances in renal disease. In: Pediatric Nephrology. Edited by M. I. Rubin and T. M. Barratt. Baltimore: The Williams & Wilkins Co., chapt. 32, p. 740. 1975. 7. West, C. D. and Smith, W. C.: An attempt to elucidate the cause of growth retardation in renal disease. Amer. J. Dis. Child., 91: 460, 1956. 8. Simmons, J, M., Wilson, C. J., Potter, D. E. and Holliday, M. A.: Relation of calorie deficiency to growth failure in children on hemodialysis and the growth response to calorie supplementation. New Engl. J, Med., 285: 653, 1971. 9. Saenger, P., Wiedemann, E., Korth-Schultz, S., Lewy, J.E., Riggio, R. R., Rubin, A. L., Stenzel, K. H., Schwartz, E. and New, M. I.:
527
Role of somatomedin and renal function in growth after renal transplantation (abstr). Ped. Res., 7: 183, 1973. 10. Walker, D., Richard, G., Dobson, D. and Finlayson, B.: Maximum urine concentration: early means of identifying patients with reflux who may require surgery. Urology, 1: 343, 1973. 11. Uehling, D. T. and Wear, J. B., Jr.: Concentrating ability after antireflux operation. J. Urol., 116: 83, 1976.
EDITORIAL COMMENT
It has been my impression for years that there seems to be a general improvement in the well being of a child after an antireflux operation. The authors' simple correlation of growth patterns now suggests this to be a fact. This preliminary needs to be confirmed with other groups of patients along further elucidation into the causative factors. J. W. D.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1979 by The Williams & Wilkins Co.
Pediatric Articles INCREASED PHYSICAL GROWTH AFTER SUCCESSFUL ANTIREFLUX OPERATION RAYMOND W. MERRELL
AND
JOSEPH J. MOW AD
ABSTRACT
Gross vesicoureteral reflux with infection can retard renal growth. Resumption of renal growth or even accelerated growth has been reported after successful surgical repair of reflux in chil~en. No published reports examining the effect on ph)'.sical_ growth are ~vailabl_e. ~he p_reoperative 3:nd postoperative physical growth curves were exammed m 35 consecutive pediatric patients undergo~ng ureteroneocystostomy for reflux. The significant (average 81 per cent) increase in the postoperative physical growth percentile is presented and discussed. Renal growth arrest has been noted secondary to vesicoureteral reflux and a normal renal growth rate or even an accelerated growth rate has been reported after successful surgical correction of reflux. 1- 3 However, the published reports do not examine the effect of reflux on physical growth. Herein we examine the relationship of physical growth and surgically corrected vesicoureteral reflux.
RESULTS
The birth length distribution of the study group was the same as the normal population and the birth weights were slightly lower. The postoperative growth percentiles also followed the general population. The preoperative growth percentiles were significantly lower than normal. The average birth length percentile for the group was 46 per cent. This decreased to an average 27th percentile preoperatively and returned to the 49th percentile after ureteroneocystostomy (fig. 1). Therefore, the group experienced an average 40 per cent decrease in height percentile between birth and the preoperative period, and an average of 81 per cent increase in height percentile followed reimplantation. This represents a statistically significant decrease preoperatively (p <0.01) and increase postoperatively (p <0.01) (figs. 2 and 3). The corresponding average percentiles for the body weight were 32 per cent at birth, 36 per cent preoperatively and 55 per cent postoperatively. The group experienced an average 51 per cent increase in body weight postoperatively. The postoperative weight increase is significant (p = 0.02) (figs. 4 and 5). The 16 children with bilateral reflux had a slightly lower average preoperative growth percentile (20 per cent) but they were undistinguishable from the entire group during the birth or postoperative periods. The 1 child with reflux into a solitary kidney had one of the most dramatic courses, decreasing fr~m the 97th birth length percentile to less than the 3rd percentile preoperatively, and rebounding to the 60th percentile after reimplantation. There were 3 technical failures in the 35 children, a failure rate of 8.6 per cent. Two patients had postoperative ureteral stenosis and 1 had persistent reflux. None of these 3 failures had increased physical growth postoperatively and all 3 maintained their low preoperative growth percentile. The patient with persistent reflux had a subsequent successful reimplant and has demonstrated increased growth. The parents of the 2 children with postoperative ureteral stenosis have refused reoperation to date.
MATERIALS AND METHODS
From 1962 through 1976, 167 children presented with vesicoureteral reflux. Of these patients 35 (21 per cent) were treated by ureteroneocystostomy. With the grading system of Dwoskin and Perlmutter4 all patients undergoing ureteral reimplant had grade II, III or IV reflux. In grade IV reflux an operation was done soon after the diagnosis was made. Indications for operation in grades II and III reflux included progressive renal scarring, renal growth arrest or breakthrough infection while on antimicrobial therapy. Height and weight measurements on these patients in the immediate postoperative period and during the initial followup period were readily available from the hospital charts. Measurements at birth as well as supplemental preoperative and postoperative measurements were obtained from questionnaires sent to the children's parents and primary physicians. Physical growth percentiles were determined for each child using standard growth charts prepared by the National Center for Health Statistics. 5 Growth percentiles at birth, preoperatively and on at least 3 separate occasions postoperatively were determined. All patients were followed a minimum of 18 months and a maximum of 10 years postoperatively. At the time of operation all patients had normal blood urea nitrogen, creatinine and hematocrit, and all had had documented urinary tract infection on at least 2 separate occasions preoperatively. The children had negative urine cultures at the time of operation. Of these patients 16 had bilateral reflux, 18 had unilateral reflux and 1 had reflux into a congenital solitary kidney. There were 7 boys (20 per cent) and 28 girls (80 per cent). All patients were white. The average age at operation was 5. 7 years, with a range of 10 months to 9.5 years.
DISCUSSION
Accepted for publication December 22, 1978. Read at annual meeting of Mid-Atlantic Section, American Urological Association, White Sulphur Springs, West Virginia, October 29November 1, 1978.
523
The growth retardation we observed in children with gross vesicoureteral reflux is an interesting aspect of this abnormality. Although these patients were not azotemic the well studied phenomenon of growth retardation in children with chronic renal failure may offer some clues to the etiology of slowed
524
MERRELL AND MOW AD
AVERAGE HEIGHTS AND WEIGHTS OF STUDY GROUP 60
50
DHeight 40 I-
zUJ u Q::
fflweight 30
UJ
Cl.
20
10
BIRTH
PRE-OP
POST-OP
FIG. 1
BIRTH
LENGTH
Z 15
1:=J
UJ
0:::
Expected Normal
lxxx:>I Study
Cl _.J
Group
I
() 10 LL
0 0::: UJ
co
5
~
:J
z
0 -20
HEIGHT PERCENTILE FIG. 2
BIRTH
WEIGHT . - , Expected L__J Normal
Z 15 UJ
a::
0
!>006<1
_J
Study Group
:E
(.) 10
u. 0
a:: w
al ~
:)
z
5
I
0-20
20- 40
40-60
60- 80
WEIGHT PERCENTILE FIG. 3
80-100
INCREASED PHYSICAL GROWTH AFTER SUCCESSFUL ANTIREFLUX OPERATION
A PRE OPERATIVE HEIGHT Expected Normal
D
Z 15
LU
a::
C
l~I Study Group
...J
:I:
(.)10 LL
0
a::
LU
al ~
5
::::,
z
0 0 -20
20-40
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HEIGHT PERCENTILE
B POST-OPERATIVE HEIGHT 215
Expected Normal
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D
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~ Study Group
5:
U10 LL
0
0:::
LU 5
al ~
::::,
z
0 - 20
20 - 40
40 - 60
60 - 80
HEIGHT PERCENTILE FIG. 4
I
80 - 100
525
526
MERRELL AND MOWAD
PREOPERATIVE WEIGHT
A ~
15
Expected Normal
0:::
D
::::! :::c
l'ltV'.ll Study Group
0
() 10
u.
0
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60 -80
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WEIGHT PERCENTILE
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WEIGHT
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0
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5
Expect ed Normal
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Study Group
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~
-
0
ffi OJ
D
r,
-
-
m
0-20
I
20-40
.
ii:
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40-60
60- 80
80-100
WEIGHT PERCENTILE Fm. 5
growth in children with gross reflux. Several factors have been examined in the children with chronic renal failure and correlated with retarded physical growth. Possible etiologic factors included renal osteodystrophy, chronic urinary tract infection, protein loss secondary to nephrosis, negative caloric balance, possible hormonal changes, chronic acidosis, azotemia, anemia and loss of renal concentrating ability. 6-B Several of these possible factors can be eliminated easily when discussing the present series of patients with vesicoureteral reflux. No patient had changes compatible with renal rickets, significant proteinuria, acidosis, azotemia or significant anemia. West and Smith showed that chronic urinary tract infection alone does not retard physical growth. 7 They did find that decreased renal concentrating ability was present in most renal patients with growth retardation and that an inadequate caloric intake was a factor in almost all of these children. Simmons and associates demonstrated that decreased caloric intake was the single most important factor in growth retardation among pediatric renal failure patients and demonstrated increased growth on adequate dietary supplements.8 Growth hormone levels are unchanged in patients with renal failure 6 but somatomedin (sulfation factor), a newly recognized factor in linear growth, has been found to be low in children with renal failure and to return to normal after successful transplantation. 9 Walker and associates have shown that the glomerular filtration rate is not substantially reduced until an advanced degree
of hydronephrosis is evident in cases of vesicoureteral reflux. 10 They and others 11 demonstrated that reflux produces a decrease in the renal concentrating ability that is corrected after successful ureteral reimplantation. However, this etiology would not account for the slowed somatic growth in children with unilateral reflux in whom 1 kidney would retain concentrating ability. None of our patients was in renal failure but both groups may have some aspects in common, including possible decreased concentrating ability, negative caloric balance, recurrent infection and possible hormonal factors. These possible etiologic factors in the observed growth retardation require further specific study.
Department of Urology, Geisinger Medical Center, Danville, Pennsylvania 17821. (R. W. M.) REFERENCES 1. Willscher, M. K., Bauer, S. B., Zammuto, P. J. and Retik, A. B.:
Renal growth and urinary infection following antireflux surgery in infants and children. J. Urol., 115: 722, 1976. 2. McRae, C. U., Shannon, F. T. and Utley, W. L. F.: Effect on renal growth of reirnplantation of refluxing ureters. Lancet, 1: 1310, 1974. 3. Scott, J. E. S. and Stansfeld, J. M.: Treatment of vesico-ureteric reflux in children. Arch. Dis. Child., 43: 323, 1968. 4. Dwoskin, J. Y. and Perlmutter, A. D.: Vesicoureteral reflux in children; a computerized review. J. Urol., 109: 888, 1973.
INCREASED PHYSICAL GROWTH AFTER SUCCESSFUL ANTIREFLUX OPERATION
5. National Center for Health Statistics: NCHS growth charts, 1976. Monthly vital statistics report. Rockville, Maryland: Health Resources Administrations, vol. 25, No. 3, suppl. (HRA) 76-1120, June 1976. 6. Piel, C. F. and Roof, B. S.: Skeletal growth disturbances in renal disease. In: Pediatric Nephrology. Edited by M. I. Rubin and T. M. Barratt. Baltimore: The Williams & Wilkins Co., chapt. 32, p. 740. 1975. 7. West, C. D. and Smith, W. C.: An attempt to elucidate the cause of growth retardation in renal disease. Amer. J. Dis. Child., 91: 460, 1956. 8. Simmons, J, M., Wilson, C. J., Potter, D. E. and Holliday, M. A.: Relation of calorie deficiency to growth failure in children on hemodialysis and the growth response to calorie supplementation. New Engl. J, Med., 285: 653, 1971. 9. Saenger, P., Wiedemann, E., Korth-Schultz, S., Lewy, J.E., Riggio, R. R., Rubin, A. L., Stenzel, K. H., Schwartz, E. and New, M. I.:
527
Role of somatomedin and renal function in growth after renal transplantation (abstr). Ped. Res., 7: 183, 1973. 10. Walker, D., Richard, G., Dobson, D. and Finlayson, B.: Maximum urine concentration: early means of identifying patients with reflux who may require surgery. Urology, 1: 343, 1973. 11. Uehling, D. T. and Wear, J. B., Jr.: Concentrating ability after antireflux operation. J. Urol., 116: 83, 1976.
EDITORIAL COMMENT
It has been my impression for years that there seems to be a general improvement in the well being of a child after an antireflux operation. The authors' simple correlation of growth patterns now suggests this to be a fact. This preliminary needs to be confirmed with other groups of patients along further elucidation into the causative factors. J. W. D.