Vol. 113. 1\/fay
THE JOURNAL OF UROLOGY
Printed in U.8.A.
Copyright © 1975 by The Williams & 'Nilkins Co.
FAMILY STUDY OF VESICOURETERAL REFLUX HUGH C. BREDIN,* PATRICIA WINCHESTER, JOHN H. MCGOVERN
AND
MARK DEGNAN
From the Department of Surgery (Urology), James Buchanan Brady Foundation of New York Hospital and the Departments of Radiology and Pediatrics, Cornell University Medical College and The New York Hospital-Cameli Medical Center, New York, New York
ABSTRACT
A retrospective analysis of 242 families revealed that the incidence of reflux among siblings of children with reflux was 2.2 per cent. In a prospective study of 24 families, 8 of 50 siblings (16 per cent) had reflux. Although the incidence of reflux in the prospective study is surprisingly high infection was absent in all affected siblings in whom cultures were obtained and in only 2 siblings (4 per cent) was surgical correction necessary. RETROSPECTIVE ANALYSIS
Several series have been reported on the familial occurrence of reflux. 1- 5 We have cared for families in which reflux was present in 2 or more siblings, some of whom had end stage renal disease prior to
The case histories were reviewed of 262 children between 1 month and 16 years old, seen between 1959 and 1971 with a diagnosis of vesicoureteral
Findings and therapy for 8 affected siblings among 50 siblings studied prospectively for reflux Family Size
Affected Sibling -Age-Sex
Urologic Symptoms
Urine Culture
Cystogram Rt. Kid./ Lt. Kid.*
DS-126 70 61 DS-129 81 55
7
CS-13-F RS-11-F
None None
Sterile Sterile
V/30 -/15
Normal Normal
None None
LH-128 14 86
3
PH-2-F
None
Sterile
VI-
Normal
None
AC-127 83 81
3
CC-16-F JC-13-F
None None
Not done Sterile
15/V -/30
Not done Normal
None Lt. Paquin reim-
RJ-126 29 90
8
CJ-4-F PJ-8-F
None Enuresis
Sterile Sterile
-IV 15/-
Normal Caliceal fullness
MJ-3-M
Enuresis
Sterile
-/V
Normal
None Rt. Paquin reimplantation None
PropositusHospital No.
IVP
Treatment
plantation
* 15-reflux at 15 cm. water intravesical pressure, 30-reflux at 30 cm. water intravesical pressure, V-reflux at voiding pressure.
reflux. There were 208 girls and 54 boys. In each patient diagnosis of reflux had been established voiding cystography using previously techniques. 6 - 7 Cases of reflux with posterior urethral valves and neurogenic bladder were not included since it was believed that reflux in these situations was associated with anomalies that should be considered separately. In 13 cases the family size was not recorded. In the remaining 249 children from 242 families the family size had been recorded. Since the patients in this series are a select population, mainly referral, we considered that when 2 or more siblings in a family had reflux the first sibling to be detected should be counted as a propositus. Therefore, we had 242
the detection of reflux. These factors prompted us to review the charts of our patients with reflux to determine the incidence of the abnormality among siblings. In selected families, siblings were evaluated prospectively for the early detection and treatment of asymptomatic reflux. Accepted for publication July 26, 1974. * Current address: Depal'tment of Urology, The Massachusetts General Hospital, Boston, Massachusetts 02114. 1 Stephens, F. D., Joske, R. A. and Simmons, R. T.: Megaureter with vesico-ureteric reflux in twins. Aust. New Zeal. J. Surg., 24: 192, 1955. 2 Tobenkin, M. I.: Hereditary vesicoureteral reflux. South. Med. J ., 57: 139, 1964. 'Mulcahy, J. J., Kelalis, P. P., Stickler, G. B. and Burke, E. C.: Familial vesicoureteral reflux. J. Ural., 104: 762, 1970. 'Burger, R.H.: Familial and hereditary vesicoureteral reflux. J .A.M.A., 216: 680, 1971. 5 Schmidt, J. D., Hawtrey, C. E., Flocks, R. H. and • Culp, D. A.: Vesicoureteral reflux: an inherited lesion. J.A.M.A., 220: 821, 1972.
'McGovern, J. H., Marshall, V. F. and Paquin, J., Jr.: Vesicoureteral regurgitation in children. J. 83: 122, 1960. 7 Woodrow, S. I., Marshall, V. F. and Evans, J. A.: A newly assembled cystoscopic table with televisionfluoroscopy and cine-fluoroscopy. J. Urol., 99: 829, 1968. 623
-'"-· er., t-.:i
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t:c :.:,. t,:J
i:::,
z ~
i:::,
> 00
00
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~
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A, IVP and B, voiding cystourethrogram of 6-year-old boy (R. J., 126 29 90) with bilateral vesicoureteral reflux and hydronephrosis. C, cystourethrograms at 15 cm. and D, at voiding pressures of 8-year-old female sibling of R. J. demonstrates right vesicoureteral reflux with paraureteral diverticulum.
FAMILY STUDY OF VESICOURETERAL REFLUX
with 461 siblings (224 boys, 200 girls and 37 siblings in whom the sex was not recorded). Ten of these siblings were found to have vesicoureteral reflux on voiding cystography, an incidence of 2.2 per cent. An additional 4 siblings who were born after the time that the propositus was ascertained had reflux but were not included in calculating familial incidence since this was a retrospective analysis and we did not attempt to trace families in the series. Of the 10 affected siblings, 7 had urological symptoms, 8 had significant bacteriuria and 8 under went ureteral reimplantation by the Paquin technique. 8 PROSPECTIVE STUDY
The parents of children with documented vesicoureteral reflux admitted to the pediatric urological service between December 1971 and May 1973 were asked to consider evaluation of the remaining siblings by voiding cystography to establish the presence or absence of reflux. Twenty-four families consented to evaluation. Since not all families of children with reflux admitted during that period participated, we are obliged to regard the families that were studied as a select population. Although initially we had planned to study siblings of both sexes, as we proceeded we noted a lower incidence of reflux among male siblings and decided to discontinue evaluation of male siblings unless there was a specific indication. The 24 families studied had 60 siblings (24 male and 36 female), not including the propositus. In 5 families double propositi were present. In 50 siblings (15 male and 35 female) cystograms were performed. The siblings were between 1 and 21 years old. Of the 50 siblings 41 were asymptomatic and 9 had urological symptoms (5 enuresis, 3 prior urinary tract infection and 1 dysuria). Eight siblings (1 male and 7 female) were affected with reflux, an incidence of 16 per cent. The table summarizes the findings in each of the affected siblings. Although the incidence of reflux seems to be high, in only 1 instance (P. J.) was the upper tract dilated and in none of the children studied by excretory urography (IVP) was renal scarring present. Urine for culture was obtained in 6 of the 8 8 Paquin, A. J., Jr.: Ureterovesical anastomosis: the description and evaluation of a technique. J. Urol., 82: 573, 1959.
625
affected siblings and was sterile in all cases. In only 2 siblings was ureteral reimplantation performed: J. C. had urinary tract infection with bacteriuria approximately a year after the discovery of reflux and P. J. had a well defined paraureteral diverticulum with associated reflux and enuresis (see figure). DISCUSSION
The incidence of vesicoureteral reflux among siblings of children with documented vesicoureteral reflux as demonstrated by our retrospective study was low (2.2 per cent). Most affected siblmgs were discovered because of urologic symptoms and repeated infections and the majority required surgical correction. It is indeed possible that many more siblings may have been affected with reflux i;rut did not present to om iustitutiau or that saJTie had asymptomatic reflux or sterile reflux that was not d1scoverea-:-Therefore, an incidence of 2.2p er eent is a minimal estimate.,_ With a prospective study on what must be regaroed as a select population the incidence a£ reflux amon siblin s 1 high. ince the incidence of reflux in the general population has not been determined it is not possible to judge the significance of the figures we have obtained and conclude that reflux is hereditary. In comparison to those in the retrospective analysis the affected siblings discovered in the prospective evaluations had a lesser degree of reflux in terms of symptoms, infection, renal deterioration and, in particular, the need for surgical correction lnd_eecl, in only 2 of the 8 affected siblings prospectively discovered was an operation considered necessary and in both of these urologic symptoms occurred prior to the decision to operate. With this rather low yield of siblings with reflux who needed an operation (4 per cent) we hesitate to recommend routine screening of siblings by cystography. .- An additiol'.lal noteworthy observation from-the .m:_ofi;ective evaluation was the absence of infection in all affected siblings from whom cultures were ootained This £il'.lding again refutes the popular hypothesis that the cause of reflux is urinary i~ction and supports the concept of sterile reflux. 9 r--9 Hutch, J. A. and Smith, D.R.: Sterile reflux: report of 24 cases. Urol. Int., 24: 460, 1969.
THE JOURNAL OF UROLOGY
Printed in U.8.A.
Copyright © 1975 by The Williams & 'Nilkins Co.
FAMILY STUDY OF VESICOURETERAL REFLUX HUGH C. BREDIN,* PATRICIA WINCHESTER, JOHN H. MCGOVERN
AND
MARK DEGNAN
From the Department of Surgery (Urology), James Buchanan Brady Foundation of New York Hospital and the Departments of Radiology and Pediatrics, Cornell University Medical College and The New York Hospital-Cameli Medical Center, New York, New York
ABSTRACT
A retrospective analysis of 242 families revealed that the incidence of reflux among siblings of children with reflux was 2.2 per cent. In a prospective study of 24 families, 8 of 50 siblings (16 per cent) had reflux. Although the incidence of reflux in the prospective study is surprisingly high infection was absent in all affected siblings in whom cultures were obtained and in only 2 siblings (4 per cent) was surgical correction necessary. RETROSPECTIVE ANALYSIS
Several series have been reported on the familial occurrence of reflux. 1- 5 We have cared for families in which reflux was present in 2 or more siblings, some of whom had end stage renal disease prior to
The case histories were reviewed of 262 children between 1 month and 16 years old, seen between 1959 and 1971 with a diagnosis of vesicoureteral
Findings and therapy for 8 affected siblings among 50 siblings studied prospectively for reflux Family Size
Affected Sibling -Age-Sex
Urologic Symptoms
Urine Culture
Cystogram Rt. Kid./ Lt. Kid.*
DS-126 70 61 DS-129 81 55
7
CS-13-F RS-11-F
None None
Sterile Sterile
V/30 -/15
Normal Normal
None None
LH-128 14 86
3
PH-2-F
None
Sterile
VI-
Normal
None
AC-127 83 81
3
CC-16-F JC-13-F
None None
Not done Sterile
15/V -/30
Not done Normal
None Lt. Paquin reim-
RJ-126 29 90
8
CJ-4-F PJ-8-F
None Enuresis
Sterile Sterile
-IV 15/-
Normal Caliceal fullness
MJ-3-M
Enuresis
Sterile
-/V
Normal
None Rt. Paquin reimplantation None
PropositusHospital No.
IVP
Treatment
plantation
* 15-reflux at 15 cm. water intravesical pressure, 30-reflux at 30 cm. water intravesical pressure, V-reflux at voiding pressure.
reflux. There were 208 girls and 54 boys. In each patient diagnosis of reflux had been established voiding cystography using previously techniques. 6 - 7 Cases of reflux with posterior urethral valves and neurogenic bladder were not included since it was believed that reflux in these situations was associated with anomalies that should be considered separately. In 13 cases the family size was not recorded. In the remaining 249 children from 242 families the family size had been recorded. Since the patients in this series are a select population, mainly referral, we considered that when 2 or more siblings in a family had reflux the first sibling to be detected should be counted as a propositus. Therefore, we had 242
the detection of reflux. These factors prompted us to review the charts of our patients with reflux to determine the incidence of the abnormality among siblings. In selected families, siblings were evaluated prospectively for the early detection and treatment of asymptomatic reflux. Accepted for publication July 26, 1974. * Current address: Depal'tment of Urology, The Massachusetts General Hospital, Boston, Massachusetts 02114. 1 Stephens, F. D., Joske, R. A. and Simmons, R. T.: Megaureter with vesico-ureteric reflux in twins. Aust. New Zeal. J. Surg., 24: 192, 1955. 2 Tobenkin, M. I.: Hereditary vesicoureteral reflux. South. Med. J ., 57: 139, 1964. 'Mulcahy, J. J., Kelalis, P. P., Stickler, G. B. and Burke, E. C.: Familial vesicoureteral reflux. J. Ural., 104: 762, 1970. 'Burger, R.H.: Familial and hereditary vesicoureteral reflux. J .A.M.A., 216: 680, 1971. 5 Schmidt, J. D., Hawtrey, C. E., Flocks, R. H. and • Culp, D. A.: Vesicoureteral reflux: an inherited lesion. J.A.M.A., 220: 821, 1972.
'McGovern, J. H., Marshall, V. F. and Paquin, J., Jr.: Vesicoureteral regurgitation in children. J. 83: 122, 1960. 7 Woodrow, S. I., Marshall, V. F. and Evans, J. A.: A newly assembled cystoscopic table with televisionfluoroscopy and cine-fluoroscopy. J. Urol., 99: 829, 1968. 623
-'"-· er., t-.:i
,i:,..
t:c :.:,. t,:J
i:::,
z ~
i:::,
> 00
00
0
~
00
A, IVP and B, voiding cystourethrogram of 6-year-old boy (R. J., 126 29 90) with bilateral vesicoureteral reflux and hydronephrosis. C, cystourethrograms at 15 cm. and D, at voiding pressures of 8-year-old female sibling of R. J. demonstrates right vesicoureteral reflux with paraureteral diverticulum.
FAMILY STUDY OF VESICOURETERAL REFLUX
with 461 siblings (224 boys, 200 girls and 37 siblings in whom the sex was not recorded). Ten of these siblings were found to have vesicoureteral reflux on voiding cystography, an incidence of 2.2 per cent. An additional 4 siblings who were born after the time that the propositus was ascertained had reflux but were not included in calculating familial incidence since this was a retrospective analysis and we did not attempt to trace families in the series. Of the 10 affected siblings, 7 had urological symptoms, 8 had significant bacteriuria and 8 under went ureteral reimplantation by the Paquin technique. 8 PROSPECTIVE STUDY
The parents of children with documented vesicoureteral reflux admitted to the pediatric urological service between December 1971 and May 1973 were asked to consider evaluation of the remaining siblings by voiding cystography to establish the presence or absence of reflux. Twenty-four families consented to evaluation. Since not all families of children with reflux admitted during that period participated, we are obliged to regard the families that were studied as a select population. Although initially we had planned to study siblings of both sexes, as we proceeded we noted a lower incidence of reflux among male siblings and decided to discontinue evaluation of male siblings unless there was a specific indication. The 24 families studied had 60 siblings (24 male and 36 female), not including the propositus. In 5 families double propositi were present. In 50 siblings (15 male and 35 female) cystograms were performed. The siblings were between 1 and 21 years old. Of the 50 siblings 41 were asymptomatic and 9 had urological symptoms (5 enuresis, 3 prior urinary tract infection and 1 dysuria). Eight siblings (1 male and 7 female) were affected with reflux, an incidence of 16 per cent. The table summarizes the findings in each of the affected siblings. Although the incidence of reflux seems to be high, in only 1 instance (P. J.) was the upper tract dilated and in none of the children studied by excretory urography (IVP) was renal scarring present. Urine for culture was obtained in 6 of the 8 8 Paquin, A. J., Jr.: Ureterovesical anastomosis: the description and evaluation of a technique. J. Urol., 82: 573, 1959.
625
affected siblings and was sterile in all cases. In only 2 siblings was ureteral reimplantation performed: J. C. had urinary tract infection with bacteriuria approximately a year after the discovery of reflux and P. J. had a well defined paraureteral diverticulum with associated reflux and enuresis (see figure). DISCUSSION
The incidence of vesicoureteral reflux among siblings of children with documented vesicoureteral reflux as demonstrated by our retrospective study was low (2.2 per cent). Most affected siblmgs were discovered because of urologic symptoms and repeated infections and the majority required surgical correction. It is indeed possible that many more siblings may have been affected with reflux i;rut did not present to om iustitutiau or that saJTie had asymptomatic reflux or sterile reflux that was not d1scoverea-:-Therefore, an incidence of 2.2p er eent is a minimal estimate.,_ With a prospective study on what must be regaroed as a select population the incidence a£ reflux amon siblin s 1 high. ince the incidence of reflux in the general population has not been determined it is not possible to judge the significance of the figures we have obtained and conclude that reflux is hereditary. In comparison to those in the retrospective analysis the affected siblings discovered in the prospective evaluations had a lesser degree of reflux in terms of symptoms, infection, renal deterioration and, in particular, the need for surgical correction lnd_eecl, in only 2 of the 8 affected siblings prospectively discovered was an operation considered necessary and in both of these urologic symptoms occurred prior to the decision to operate. With this rather low yield of siblings with reflux who needed an operation (4 per cent) we hesitate to recommend routine screening of siblings by cystography. .- An additiol'.lal noteworthy observation from-the .m:_ofi;ective evaluation was the absence of infection in all affected siblings from whom cultures were ootained This £il'.lding again refutes the popular hypothesis that the cause of reflux is urinary i~ction and supports the concept of sterile reflux. 9 r--9 Hutch, J. A. and Smith, D.R.: Sterile reflux: report of 24 cases. Urol. Int., 24: 460, 1969.
