Patterns of Renal Damage in the Management of Vesical Exstrophy

0022-5347 /80/1243-0412$02.00/0 Vol. 124, September Printed in U.S.A.

THE JOURNAL OF UROLOGY

Copyright© 1980 by The Williams & Wilkins Co.

Pediatric Article PATTERNS OF RENAL DAMAGE IN THE MANAGEMENT OF VESICAL EXSTROPHY W.R. TURNER, P. G. RANSLEY

AND

D. I. WILLIAMS

From the Department of Urology, Medical University of South Carolina, Charleston, South Carolina, and The Institute of Urology, London, England

ABSTRACT

We reviewed the patterns of pyelonephritic damage that occurred during surgical management of bladder exstrophy. Renal injury patterns indicate that papillary configuration and obstruction coupled with urinary infection were the primary factors in producing damage. Diversion by the ileal conduit resulted in frequent injury, whereas the colon conduit was associated rarely with renal damage. The incidence of renal injury from bladder closure and continence attempts suggested closure as a reasonable course, especially in view of present continence results. Exstrophy of the bladder is a rare anomaly that lies in a continuum of embryonic defects, ranging from cloacal exstrophy to balanitic epispadias. Exstrophy occurs in 1 patient per 50,000 live births and is twice as common in male subjects. 1 Congenital renal damage in exstrophy patients before surgical correction is quite rare but it is not uncommon postoperatively. 2 Since these renal units drain freely onto the open bladder they usually are not subjected to reflux or obstruction before surgical manipulation and, thus, the upper tracts almost invariably are normal at birth. We herein attempt to delineate the pathogenesis and extent of pyelonephritic changes that often occur in these patients after surgical management. A review of the exstrophy series at our institute was predicated upon the pig research model of Ransley and Risdon. 3 MATERIALS AND METHODS

We have treated > 170 patients with bladder exstrophy. Of these cases 14 were split symphysis variants, having classical musculoskeletal defects of exstrophy but with varying degrees of bladder and skin cover, and the remainder were classic bladder exstrophy cases. The charts and x-rays of all patients were reviewed and 101 cases were found suitable for study, the remaining patients being excluded owing to unavailable x-ray films or hospital records. The excretory urograms (IVPs) of these 101 cases were examined with regard to the incidence and type of renal damage, and the relationship of this damage to surgical management. The average age of the patients at the time of closure or diversion was noted and the followup was calculated in terms of actual length of radiologic surveillance. When we were confident in assigning a causative factor the renal damage was categorized as owing to reflux or obstruction. We categorized renal damage into 3 groups: 1) single caliceal damage, which obviously refers to a renal lesion involving only 1 calix and, since parenchymal scarring usually is not visible in these cases, the term refers to the radiologic caliceal configuration alone; 2) segmental damage, which refers to damage limited to classic renal segments such as the apical segments and 3) multiple segmental damage, which refers to damage involving several classic renal segments and for practical purposes refers to all radiologically visible segments. Patients were Accepted for publication November 30, 1979. 412

divided further into those who underwent urinary diversion as an initial procedure and those who underwent bladder closure attempts. The cases also were evaluated according to sex. Of our 101 patients 37 were judged to have an unsuitable bladder for closure and, thus, underwent initial diversion at an average of 2.5 years. Eight female and 29 male patients were diverted initially, with an average radiological followup of 9 years. Of the 37 patients 31 had an initial IVP that was normal, 1 had an abnormal pyelogram secondary to bilateral ureteral meatal stenosis and the initial films could not be obtained in the remaining 5. The types of diversion performed and the damage suffered were noted (table 1). Ten patients underwent ureterosigmoid diversion, with 5 cases having renal injury: 2 with segmental damage, 2 with multisegmental damage and 1 with bilateral segmental damage. Of these 10 patients 5 were changed subsequently to another type of diversion, either owing to incontinence or ureteral obstruction. Four of these 5 patients were changed to ileal conduits, 3 remaining stable thereafter. One patient was changed to a colon conduit and remains undamaged and stable. The patients who underwent ureterosigmoid diversion were followed radiologically for an average of 15 years and all cases were judged to be owing to obstruction. It is interesting to note that 3 of the patients with obstructive damage had renal stones. Fourteen patients were diverted initially by ileal conduits. Of the 14 patients 7 suffered renal damage and, significantly, only 1 of these damaged patients had unilateral injury. The remaining 6 cases showed bilateral segmental damage in 2 and multisegmental damage was present in the other 4 patients. The average length of followup was 6 years, and it is interesting that only 1 patient followed for <7.6 years sustained renal damage that was ascribable to the ileal conduit. In 2 patients Maydl procedures were done without damage, 1 patient subsequently being converted to a colon conduit and the upper tracts remain normal. In 2 cases bilateral ureterostomy was done and both had severe bilateral obstructive change and were converted to ileal conduits when the damage remained stable. Eight colon conduits were done as an initial procedure and there was no subsequent renal damage in any of these cases. Three further patients were diverted initially by other means and they were converted to colon conduits without damage. However, it must be indicated that the average followup in this group was only 4.4 years.

413

PATTERNS OF RENAL DAMAGE IN MANAGEMENT OF VESICAL EXSTROPHY

A total of 17 patients had ureterosigmoid diversion in all categories of exstrophy management. Of these patients 5 had unilateral renal damage and 1 had bilateral multisegmental damage. Of the patients with unilateral damage 3 suffered segmental damage owing to initial diversion and 1 had damage after closure. A single case of multisegmental damage was obstructive in nature and followed diversion. A total of 38 ileal conduits was done in all classes of exstrophy patients and 5 resulted in unilateral renal damage, while 17 had bilateral damage. Of the 5 patients with unilateral renal damage 3 had segmental injury owing to diversion: 1 was secondary to closure and 2 patients had unilateral multiple segmental damage. In the 17 bilateral cases 5 patients had segmental damage: 2 were damaged by closure and 3 were injured by diversion. The remaining 12 patients had bilateral multisegmental damage. The over-all experience with colon conduits was composed of 17 cases. There were 2 cases of unilateral segmental damage that resulted from bladder closure. Two cases of bilateral damage occurred, 1 of which was after closure and was thought to be owing to reflux. Only 1 case demonstrated renal injury that could be ascribed to factors related to colon diversion. The average length of followup of the patients with colon conduits was 4.4 years. Surgical attempts at bladder closure and continence were made in 60 cases. In this group 44 patients had preoperative IVPs available for review and none was abnormal. In 16 cases the initial films could not be obtained. The cases that were subjected initially to surgical closure and subsequent continence procedures were summarized (table 2). Eighteen female patients underwent surgical reconstruction, with 9 cases demonstrating postoperative renal damage. Of these 9 cases 5 were unilateral and 4 were bilateral. The 1 case of single segmental damage was after a Young-Dees-Leadbetter procedure and was believed to be secondary to reflux. One additional case of segmental damage was ascribed to reflux after closure and in 5 cases damage was thought to be owing to obstruction. In 1 patient the cause of damage could not be defined clearly and 5 damaged segments that occurred after diversion were secondary to obstruction. Information concerning the presence of infection at the time of damage was not available uniformly. Bladder

closure was associated with renal damage in 4 of 11 cases but diversion after closure resulted in injury in 5 of 7 patients. Forty-two male patients underwent surgical closure, 37 with normal preoperative IVPs and in 5 cases the initial films were unavailable. These patients were followed for an average of 6.6 years. Of 42 patients 9 had damage judged to result from the closure procedure. Unilateral damage occurred in 6 of 9 cases, with 2 resulting from reflux. Bilateral damage occurred in 3 patients, the pattern was multisegmental in all but 1 case of segmental injury. Six patients who underwent bladder closure and subsequent diversion had renal damage after diversion, 4 of these being bilateral multisegmental damage. One interesting case demonstrated bilateral segmental damage. Of 14 male patients who remained undiverted 5 had renal damage, 4 with unilateral injury and 1 with bilateral renal scarring. The status of continence did not seem to influence the frequency of renal injury. If one considers the over-all patterns of damage we find that 20 patients had injury of 1 kidney. Three patients in whom closure was attempted had single caliceal damage and 2 were owing to reflux. Over-all, there were 9 cases of single segmental damage, 5 after closure and 4 owing to reflux. Four of the unilateral segmental cases followed diversion. There were 8 cases of unilateral multisegmental damage, 6 of which were owing to obstruction and 1 to reflux. Bilateral renal damage occurred in 22 cases, 7 having at least 1 kidney with segmental damage. In the 7 cases of segmental damage 4 were caused by obstruction after diversion and 3 were owing to closure attempts. Fifteen patients had bilateral multisegmental damage and 8 of these had had continence procedures. Of these units 4 were clearly owing to obstruction. The remaining cases of multisegmental damage were thought to be caused by obstruction but the precise mechanism was uncertain. Four cases did not lend themselves to easy classification because of absent information or unusual features. Of these 4 patients 2 who had ureterosigmoid diversion were undamaged but no further information was available. One male patient had the trigone implanted into a segment of colon that was placed into the sigmoid. This patient subsequently was changed to an ileal conduit and sustained unilateral segmental damage. One

1. Types of diversion performed and damage suffered Bilat. Damage

TABLE

Unilat. Damage Single Caliceal Ureterosigmoid-moidostomy Ilea! conduit Maydl procedure Colon Gersuny procedure Ureterotomy

TABLE

Multiple Segmental Segmental

2 1 0 0 0

0 0 0 0 0 0

Single Caliceal

Segmental

0 0 0 0 0 0

0 2 0 0 0 0

2 0 0 0 0 0

0

Multiple Segmental

1 4

0 0 0 2

Diversion Changed.

Stable

5 0 1 0 1 2

3

5 2 8

1 2

2. Surical closure and subsequent continence procedures in 42 male and 18 female patients Diversion Damage

Closure Damage Unilat. Single Caliceal

Segmenta!

Segmental

Bilat.

Unilat.

Bilat. Multiple Segmenta!

Multiple Segmenta!

Single Caliceal

Multiple Segmenta!

Segmenta!

Multiple Segmenta!

No. Damaged

Male patients Reflux Obstruction Cause Unknown

3

1 1

3

½

½ 1

1

4 1

10

l½

6

4

Female Patients Reflux Obstruction Cause Unknown

2

1 2

11/,

1

414

TURNER, RANSLEY AND WILLIAMS

patient had an ileal conduit with a single segmentally damaged kidney but no further information was available. DISCUSSION

The upper urinary tracts in neonatal bladder exstrophy cases usually are completely normal so that renal dysplasia or intrauterine reflux nephropathy can be eliminated as a cause of any subsequently found pyelonephritic scarring. 2 The ureters drain freely onto the exposed bladder surface and, thus, the renal parenchyma usually is not subjected to the effects of reflux, obstruction or infection until diversion or closure is attempted. This study was done in an attempt to ascertain the types and pathogenesis of renal damage resulting from the surgical management of bladder exstrophy. The fundamental mechanisms affecting the kidneys are urinary obstruction and reflux but the 2 mechanisms are not clearly separable. After initial bladder closure there should be total incontinence of urine, maintaining free urinary exchange, but such a system occasionally may be complicated by an increase in bladder outflow resistance owing to either stenosis or intentional bladder neck reconstruction. The occurrence of bladder outflow obstruction initially may lead to vesicoureteral reflux with a low resting pressure between bladder contractions. However, the small capacity and often fibrotic nature of the closed exstrophic bladder may cause this system to shift urodynamically in the direction of pure urinary obstruction, while in the absence of a ureterovesical junction antireflux mechanism the kidneys will be exposed continuously to a high resting bladder pressure. A similar situation may arise in those patients diverted by an ileal conduit when the progression of stomal stenosis may produce a complex combination of reflux and obstruction. The resulting renal damage may be described loosely as pyelonephritic in nature and, although this term is not strictly applicable to all cases, it seems likely that the basic mechanism of the pyelonephritic scar is operative. Pyelonephritis has been described pathologically as a broad renal parenchymal, wedge-shaped scar associated with retraction of the corresponding papilla. Chronic pyelonephritis is characterized radiologically by caliceal blunting and clubbing, a parenchymal scar overlying an abnormal calix and areas of damage that are interspersed with areas of normal parenchyma. In addition, pyelonephritis is associated frequently with vesicoureteral reflux and occurs most frequently in the renal poles. 4 • 5 The intriguing factor about pyelonephritis is that a sharply defined scar often occurs with normal adjacent parenchyma. Cases of single segmental damage seem to lend themselves to radiologic evaluation owing to the distinct nature of the defect. Cases with multiple segmental pyelonephritic damage are quite difficult to separate radiologically from those that had hydronephrotic damage or obstructive atrophy. Therefore, no effort to distinguish these 2 entities was made. Why then does segmental scarring occur, leaving the adjacent parenchyma undamaged? Certainly, with this series of exstrophy cases one can eliminate the possibility of dysplasia or intrauterine reflux as causes of damage. Hodson and associates presented some convincing evidence that pyelonephritis was secondary to intrarenal reflux6 , and Ransley and Risdon subsequently have presented experimental evidence that the configuration of the renal papilla may be the determining factor in allowing intrarenal reflux to occur.'1 These investigators postulate that intrarenal reflux leads to pyelonephritis when associated with infection. Ransley and Risdon proposed 2 types of papillae: 1) a cone-shaped papilla that has slit-like collecting duct orifices which, because of the cone-shaped configuration, allow the collecting ducts to be subjected to lateral pressure, thus closing the ducts and preventing intrarenal reflux (part A of figure), and 2) a compound papilla that is formed by fusion of the adjoining renal segments (part B of figure).'3 The collecting ducts are wide open, allowing intrarenal reflux and, thus, allowing increased pressure within the renal pelvis and intensifying reflux. Ransley and Risdon have demonstrated this

relationship between papillary configuration and pyelonephritis in piglets in which they produced vesicoureteral reflux on 1 side, while leaving the other side normal.'3 When infection with reflux was introduced pyelonephritis occurred in the areas occupied by compound calices, resulting in the rapid formation of renal scars, at times occurring within 2 to 3 weeks. Sterile reflux resulted in no renal damage and no retardation of kidney growth. Increasing the pressure within the system by banding the urethra resulted in increased damage, suggesting the decompensation of previously normal papillae. These investigators postulated that if the kidney is composed of cone-shaped papillae then no renal damage occurs with vesicoureteral reflux and infection but if compound papillae are present, pyelonephritis and scars will result in the renal segment served by these compound papillae. :i Although in the experience of 1 of us (D. I. W.) new renal scars are seen rarely after the age of 7 years 7 these lesions do occur and Ransley and Risdon have explained this fact. The central portion of a cone-shaped papilla has become scarred and retracted, therefore leading to a configuration similar to the compound papillae, which facilitates intrarenal reflux. Ransley and Risdon have correlated their pig data with human autopsy material. 3 Smellie has reported that 13 per cent of the children with urinary tract infections will have renal parenchymal damage when first seen. 8 This fact, coupled with the comment by Williams that new scars will occur rarely beyond the age of 7 years, suggests that renal damage occurs quite early and the study by Ransley and Risdon would tend to indicate that damage should occur with the first infections. To correlate the types of renal damage in cases of exstrophy with the study by Ransley and Risdon we decided to divide the renal injuries into 3 classes: 1) single caliceal damage, 2) damage limited to 1 renal segment alone and 3) multisegmental damage. It rapidly became apparent that, as noted

FIG. 3

PATTERNS OF RENAL DAMAGE IN MANAGEMENT OF VESICAL EXSTROPHY

previously, kidneys with multisegmental pyelonephritis could not be separated radiologically from hydronephrotic damage. However, the single segmental damage was a clearly defined entity radiologically and fulfilled the gross pathological characteristics of pyelonephritis. Therefore, the occurrence of single areas of change, such as single caliceal damage or segmental scarring, seems most profitable to review since areas of normal parenchyma remained adjacent to these areas of damage. We first evaluated these children with exstrophy, who had undergone closure attempts, by further dividing them into those in whom the damage occurred after closure and those whose injury followed diversion. Closure attempts consisted of an initial procedure closing the bladder and covering it with skin with no attempt to achieve continence. In an attempt to gain continence and prevent reflux a Young-Dees-Leadbetter type of bladder neck revision was done at a later date. Our initial assumption was that typical reflux nephropathy damage would occur after closure but it was found that unilateral, segmental damage occurring in 3 cases after closure was ascribed to obstruction radiologically. The difficulties in defining the urodynamic disturbance in these cases have been discussed. In 2 cases reflux did result in a classical chronic pyelonephritic scar affecting a single segment of previously normal kidneys, a clear demonstration of the occurrence of new pyelonephritic scar formation in an area of previously normal parenchyma. However, when one looks at the total number of damaged diverted cases, one finds 9 incidences of segmental damage, the majority owing to obstruction. Three cases of single caliceal damage were caused by reflux. Thirty-seven patients had bladders that were not suitable for closure and, thus, had initial diversion. As would be expected, unilateral damage was most common in those patients who had ureterosigmoid diversion, since no common stomal problems are present in these cases. The propensity toward bilateral damage in ileal conduits is owing to obstruction and the most common obstruction is stomal stenosis. Three cases of segmental damage occurred in ileal conduit cases and, since stomal stenosis was present, one wonders if we are dealing with renal damage essentially secondary to reflux. As noted previously 7 segmentally damaged cases occurred on 1 side of a bilaterally damaged system, with multisegmental damage on the opposite side. However, the fact that bilateral damage may be multiple, may affect many calices on 1 side and a single segment on the other, suggests variability in the number of susceptible papillae, perhaps associated with different degrees of obstruction at the ureteroileal junction, and may be the reason for this apparently contradictory damage pattern. It is interesting that in 10 patients who were diverted initially by a colon conduit with an antireflux ureterocolonic junction none had renal scarring, although this enthusiasm must be tempered by the fact that they have been followed for only 4.6 years. The ultimate fate of all patients who were diverted was of interest, since these cases represent a common initial diagnosis and a normal upper urinary tract. Seventeen patients underwent ureterosigmoid diversion and were followed for an average of 15 years. During that period 6 of the 17 cases had renal damage, 5 of which were unilateral. Of the 6 patients who were converted to another type of diversion 4 remain stable. These figures agree with those of Wear and Barquin who showed abnormal postoperative pyelograms in 16 of 32 patients after ureterosigmoidostomy 9 and in the series of Williams and associates 42 per cent had clinical pyelonephritis. 10 The injury pattern continued to be unilateral in those series and in ours. Forty-two patients had ileal conduits and segmental damage occurred in 8. Thirty-two patients remained stable, with an average followup of 7.6 years. Seventeen cases showed bilateral renal injury. However, Schwarz and Jeffs have indicated the increasing incidence of renal damage that occurs as ileal conduits are followed during the years. 11 The colon conduits were noted to have the least incidence of damage, with only 1 case of renal injury ascribed

415

to the colon conduit diversion in 17 cases. These patients have been followed for a short period and the original series by Mogg has shown that problems also tend to increase with increasing length of followup in patients with colon conduits. 12 No upper tract damage occurred in the patients who underwent the Madyl procedure. What then were the risks of surgical treatment? If a child underwent initial diversion there was a 27 per cent chance of renal damage. If a continence trial was done the damage from closure alone was 15 per cent but if one includes the patients who subsequently were diverted the total renal damage for initiating closure procedures was 33 per cent. This figure seems quite acceptable when one considers the present series indicating increasing success with achieving continence in the unfortunate children. Also, the data presented would suggest that vigilant observation for obstruction, prevention of reflux and suppression of infection could cause a significant decrease in the amount of renal damage that occurs. We are tempted to surmise that partial obstruction and reflux, when combined with infection, lead to similar patterns of pyelonephritic damage, with the severity of that damage predicated upon the degree of obstruction and, thus, pressure as well as the papillary configuration. It is of particular interest that the damage tends to be mild, that is caliceal or limited segmental, or widespread involving essentially all of the pyelographically visible collecting structures. This abrupt shift in damage patterns tends to substantiate the concepts of papillary incompetence P.'ld the influence of pressure within the refluxing or obstructed units. In view of this concept, perhaps we should view critically our present ideas of reflux management inasmuch as these abnormalities of papilla, in association with pressure and infection, lead to early renal damage. It is apparent that consideration must be given to evaluating children for reflux, not only on the basis of infection but on factors such as family inheritance. REFERENCES 1. Lattimer, J. K. and Smith, M. J. V.: Exstrophy closure: a followup of 170 cases. J. Urol., 95: 356, 1966. 2. Williams, D. I.: Epispadias and exstrophy. In: Paediatric Urology. Edited by D. I. Williams. London: Butterworths & Co., chapt. 20, p. 295, 1972. 3. Ransley, P. G. and Risdon, R. A.: Reflux and renal scarring. Brit. J. Rad., suppl. 14, 1978. 4. Hodson, C. J. and Edwards, D.: Chronic pyelonephritis and ureteric reflux. Radiology, 2: 219, 1960. 5. Ransley, P. G.: Vesicoureteric reflux: continuing surgical dilemma. Urology, 12: 246, 1978. 6. Hodson, C. J., Maling, T. M. J., McManamon, P. J. and Lewis, M. G.: The pathogenesis of reflux nephropathy (chronic atrophic pyelonephritis). Brit. J. Rad., suppl., 13: 1, 1976. 7. Williams, D. I.: Personal communication. 8. Smellie, J.: Do urinary tract infections really matter in children? Proc. Roy. Soc. Med., 65: 513, 1972. 9. Wear, J. B., Jr. and Barquin, 0. P.: Ureterosigmoidostomy. Longterm results. Urology, 1: 192, 1973. 10. Williams, D. F., Burkholder, G. V. and Goodwin, W. E.: Ureterosigmoidostomy: a 15-year experience. J. Urol., 101: 168, 1969. 11. Schwarz, G. R. and Jeffs, R. D.: Ileal conduit urinary diversion in children: computer analyLlis of followup from 2 to 16 years. J. Urol., 114: 285, 1975. 12. Mogg, R. A.: The treatment of neurogenic urinary incontinence using the colonic conduit. Brit. J. Urol., 37: 681, 1965. EDITORIAL COMMENT This retrospective clinical review presents some interesting data and poses some thoughtful questions. It does not answer many questions but it does point out that no matter what the method of treatment for exstrophy there is the distinct possibility of producing renal damage. Therefore, close surveillance for and prompt management of renal