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Multicystic Dysplastic Kidney: Is Nephrectomy Still Appropriate?
0022-5347 /38/li!:G5·- 1231-$2.00/0 Voi, 140 1 November
TEE JOURNAL OF UROLOGY
Ccpyr'ght@ 1988 by The Williams &
Printed in U.S.A.
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MULTICYSTIC DYSPLASTIC KIDNEY: NEPHRECTOMY STILL APPROPRIATE? A. C.
D. F. IV:L THOMAS, R. J. ARTHUR
AND
H. C. IRVING
From the Departments of Pediatric Surgery and Radiology, The General Infirmary, and Department of Radiology, St. James's University Hospital, Leeds, England
ABSTRACT
We analyzed 25 cases of multicystic kidney to assess the impact of prenatal diagnosis on the management of this condition. The incidence of unilateral multicystic kidney was 1 in 4,300 live births. Of the 23 children with unilateral rnulticystic kidneys only 3 (13 per cent) had a :readily palpable lesion. These findings suggest that multicystic kidney is a more common renal anomaly than was previously recognized and that the majority of cases remained undiagnosed before the advent of prenatal diagnosis. Ultrasound re-evaluation in 11 children suggests that the natural history of multicystic kidneys is towards spontaneous involution. Two kidneys were not identifiable by followup ultrasound. Hypertension and malignancy complicating multicystic kidney are reported infrequently. The literature on hypertension does not generally support the view that rnulticystic kidney poses a significant risk of hypertension in later childhood or adult lifeo We believe that the routine removal of multicystic kidneys in infancy is no longer appropriate. (J. Ural., part 2, 140: 1231-1234, 1988) Multicystic is a developmental anomaly of the kidney that can be distinguished readily from other forms of cystic renal disease in childhood. The renal parenchyma is replaced by tense noncommunicating cysts and the proximal ureter is atretic or nonpatent. In the days before prenatal ultrasound diagnosis the usual presentation of multicystic kidney was an abdominal mass in the neonatal period. Surgeons generally have opted fo:r nephrectomy, although the precise indications for removing these kidneys have been unclear. We assess the effect of prenatal diagnosis on the presentation of multicystic kidney, estimate the incidence of this condition, document the natural history of multicystic kidneys that have been left in situ and reappraise the indications for nephrectomy. MATERIALS AND METHODS
A total of 25 cases of multicystic kidney presented between August 1982 and July 1987. Of these cases 12 (2 bilateral and 10 ~",,~"~"w' arose in pregnancies managed the 2 large Obstetric Units in Leeds, while 13 neonates (all with unilateral were referred for postnatal evaluation from other hospitals in the Y orkshi:re Region. Both bilateral cases were nosed in utero. One pregnancy was terminated at 22 weeks after the discovery of a bilateral condition associated with oligohydramnios. The kidneys were enlarged and "bright", and contained numerous small parenchymal cysts. The bladder was not noted to fill on ultrasound. In the second case the diagnosis was made late in the pregnancy, which was then allowed to run to term. This infant died of pulmonary hypoplasia at 9 hours after birth. In both cases the diagnosis was confirmed at autopsy. Of the 23 unilateral cases the left kidney was affected in 16 (70 per cent) and the right kidney in 7 (30 per cent). The unilateral group consisted of 13 boys (57 per cent) and 10 girls (43 per cent). We calculated the incidence of multicystic kidney from an analysis of 43,230 pregnancies managed by our own services during the 5-year study period. These units (St. James's University Hospital and The General Infirmary, Leeds) serve a well defined and relatively static population. More than 95 per cent of the pregnancies were scanned
between 17 and 20 weeks of gestation and the current over-all detection rate for fetal uropathic conditions is 1:800 pregnancies. A total of 12 cases of multicystic kidney (2 bilateral and 10 unilateral) was identified, for an incidence of 1:3,600 pregnancieso The 10 unilateral cases arose in 43,175 live births, for an incidence of approximately 1:4,300 live births. In these inborn infants no multicystic kidneys have since been found that were originally missed on prenatal ultrasound. However, it is possible that some multicystic kidneys were undetected and have remained asymptomatic in postnatal life. Conversely, no kidneys that were identified in utero as being multicystic (or grossly hydronephrotic) proved to be normal upon delivery. There is no information on the frequency of false positive findings in pregnancies scanned at other hospitals throughout the region. Literature search. A Medline computerized literature search was done to identify published reports, and assess the incidence of hypertension and malignancy related to multicystic kidney during the 20-year period from 1966 to 1986.
,~u,~acu;
RESULTS
Presentation. Both bilateral cases were detected prenatally as were 18 of the 23 unilateral cases. Of the 5 children with unilateral lesions that were not detected prenatally only 1 presented in the classical fashion with a neonatal abdominal mass. The remaining 4 unilateral multicystic kidneys were discovered during the routine investigations of coexistent abnormalities (esophageal atresia and duodenal atresia) or of unrelated urinary symptoms (voiding disorder with urinary infection and renal failure plus contralateral ureteropelvic junction obstruction). All of these infants were referred from district hospitals outside Leeds. None of the mothers of affected infants had been scanned with ultrasound during pregnancy. Clinical findings. Of the 23 unilateral multicystic kidneys 13 could not be palpated. Ten children had unilateral lesions that were palpable but in 7 the diagnosis had already been made from prenatal ultrasound. It is difficult to estimate how many of the prenatally diagnosed palpable kidneys would have been found on routine postnatal examination if the diagnosis had
1231
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GORDON AND ASSOCIATES
not been made previously in utero. Only 2 of these previously diagnosed lesions were easily palpable and we suspect that the remaining 5 might have been missed on routine neonatal examination. Therefore, it is possible that approximately threequarters of the unilateral multicystic kidneys remained undiagnosed in the days before prenatal ultrasound diagnosis. Morbidity/mortality (25 cases). Urological anomalies included contralateral ureteropelvic junction obstruction (asymptomatic in 1 patient and with renal function in 1), contralateral (asymptomatic) and bilateral (urinary infection) vesicoureteral reflux and voiding disorder (urinary infection). Nonurological anomalies included esophageal and duodenal atresia, ventricular septal defect, epidermolysis bullosa, chromosomal defect (translocation) and pulmonary hypoplasia. The 2 bilateral cases had a fatal outcome (termination of pregnancy and neonatal death). One live born neonate with a unilateral multicystic kidney and multiple coexistent anomalies (duodenal atresia, congenital heart disease and so forth) died of a cause unrelated to the multicystic kidney at 2 weeks after birth. Three infants experienced urological symptoms (urinary infection and renal failure) but in each case this was related to a pathological condition elsewhere in the urinary tract rather than to the multicystic kidney. One of these children whose mother had not been scanned prenatally presented in renal failure when he was 2½ years old. He had a left multicystic kidney and a right hydronephrotic kidney due to ureteropelvic junction obstruction. Pyeloplasty was done but renal function remains poor. There was 1 other case of contralateral ureteropelvic junction obstruction in the series. However, in this instance the diagnosis was made prenatally and the pyeloplasty was done in the neonatal period. This child now is thriving and has a normal plasma creatinine. Diagnosis. All 24 live born neonates had postnatal ultrasound imaging performed by 1 or other of the 2 radiologist authors (R.J.A. or H.C.I.). In 3 cases no functional imaging [excretory urography (IVP) or isotope renography] was performed, that is the 2 neonatal deaths and 1 infant who underwent esophageal and cardiac surgery and whose parents have refused further urological investigation. Three infants referred from district hospitals in the early part of the series had previously undergone an IVP. They have remained totally asymptomatic and the parents have refused any further invasive investigations. However, 18 infants have been investigated by a combination of ultrasound and isotope renography, generally 99"'technetiumdimercapto-succinic acid (99mTc-DMSA). Every case of multicystic kidney was associated with total absence of function, that is O per cent of split differential function. This finding contrasts with our experience of poorly functioning hydronephrotic kidneys in which some uptake of isotope could always be demonstrated.
Management/followup (23 unilateral cases). One neonate with a unilateral multicystic kidney died of unrelated causes and 1 infant has been lost to followup. Of the remaining 21 infants with unilateral lesions 14 were managed conservatively and 7 underwent nephrectomy. Of the latter cases 6 asymptomatic infants underwent prophylactic nephrectomy in the early part of the study, and 1 with a large multicystic kidney and bilateral vesicoureteral reflux also underwent nephrectomy, since it was believed that the abdominal mass might be contributing to the failure to thrive. However, removal of the multicystic kidney was of little benefit and the poor growth has been attributed since to an underlying chromosomal disorder and to urinary infection associated with the vesicoureteral reflux. None of the 7 children who underwent nephrectomy had any significant postoperative complications. Among the 14 children managed nonoperatively symptoms have occurred but without exception these have been related to a coexistent pathological condition rather than the multicystic kidney. None has had hypertension. Eleven children followed for a minimum of 1 year have been re-evaluated with ultrasound (mean followup 15 months). Two multicystic kidneys have shrunk to the point that they can no longer be visualized by ultrasound. In 6 cases there was a decrease in the absolute dimensions of the multicystic kidney with substantial shrinkage of the cysts (see figure). The remaining 3 multicystic kidneys have remained unchanged in absolute dimensions but are relatively smaller in relation to the growing child (see table). DISCUSSION
Current thinking on the management of this condition still is based mainly on observations related to large or symptomatic multicystic kidneys, published before the advent of prenatal ultrasound diagnosis. 1• 2 However, our study suggests that these large or symptomatic cases represent a relatively small proporDimensions of the 6 kidneys that were smaller on followup ultrasound Pt. No. 1 2 3 4 5 6
When Scanned
Kidney Length (cm.)
Kidney Diameter (cm.)
Birth lOmos. lmo. 1 yr. 5 yrs. 5½ yrs. Birth 9mos. Birth 20mos. Birth 16mos.
8 7.7 5 4.5 7.5 6.5 5.5 5.2 7.5 4 5 4
5 4.5 3.5 2.5 6 5 2.5 2.5 5 2 2.5 1.5
No. Cysts 8 4 5 3
4 2 6 3 5 1 3 1
Diameter of Largest Cyst (cm.) 5 4 2.5 2.5 2.5 2 1.8 1.2 4 1.5 2.5 0.5
A, antenatal ultrasound scan shows multicystic kidney in utero. B, neonatal scan shows large cystic kidney. C, scan at 8 months after birth demonstrates small cyst and no identifiable normal kidney.
MULTICYSTIC DYSPLASTIC KIDNEY
tion of the total. In the absence of prenatal diagnosis the majority of multicystic kidneys (at least three-quarters) remain undetected in the neonatal period. Our estimate of the true incidence of multicystic kidney is based on an analysis of only 43,320 pregnancies. Nevertheless, it is likely to be a reasonably accurate figure since our over-all detection rate for fetal uropathy (1:800 pregnancies) approximates the published incidence of renal anomalies derived from large autopsy studies. 3 Certain features of our series (for example the frequency and pattern of coexistent abnormalities) resemble those of previously reported clinically based series.4 Therefore, it seems that small prenatally diagnosed multicystic kidneys are part of the same pathological spectrum as the larger and more clinically obvious lesions. There is to date no evidence to suggest that the relative risks of hypertension or malignant change are related to the size of the multicystic kidney in the neonatal period. The fate of multicystic kidneys that have been left in situ is an aspect of this condition that has not been adequately documented. Our experience with 11 children suggests that the natural history is one of shrinkage and involution. These findings are similar to those of Avni and associates who followed 8 multicystic kidneys with ultrasound for 7 to 30 months. 5 These investigators documented disappearance of cysts and a decrease in the over-all dimensions of the lesions. They also report an interesting case of an infant with a prenatally diagnosed multicystic kidney who was admitted to another hospital for nephrectomy at 3 months after birth. At operation no remaining renal tissue could be identified. The incidence of unilateral renal agenesis in the adult population has been reported variously to be between 1:1,500 and 1:2,000. 6 • 7 It is possible that a significant proportion of these cases are in fact the end result of involution of a multicystic kidney. There is no uniformity of opinion on the role of nephrectomy in the management of multicystic kidney. Surgeons who routinely advise nephrectomy generally do so for one of several reasons: to confirm the diagnosis, to relieve symptoms, because of the potential for malignant change and because of hypertension. To confirm the diagnosis. We believe that to confirm the diagnosis is no longer a valid indication. The sonographic criteria for diagnosis are now well documented. 8 In addition an isotope scan (ideally 99mTc-DMSA) will make the distinction between a nonfunctioning multicystic kidney and a poorly functioning hydronephrotic kidney. 8 A combination of these imaging modalities should enable the diagnosis to be made with a high degree of certainty, removing the need for diagnostic nephrectomy. To relieve symptoms. Pain, hematuria and infection have been reported as complications of multicystic kidneys in later life. 2 The occurrence of hematuria and infection is rather difficult to understand, since the multicystic element usually is isolated from the lower urinary tract by the nonpatent section of ureter. Before symptoms are attributed to a multicystic kidney it clearly is important to exclude a pathological condition elsewhere in the urinary tract. Nevertheless, it would be difficult to argue against the removal of a symptomatic multicystic kidney. We suspect that such cases are rare in relation to the true incidence of the condition and that routine prophylactic nephrectomy is not justified on these grounds. Potential for malignant change. Our computer search of the literature covering the 20-year period from 1966 to 1986 identified 6 reports of malignancy associated with multicystic kidney: nephroblastoma in 2 children 10 months 9 and 4 years old, 10 3 patients with hypernephroma who were 15, 26 and 68 years old, 11- 13 and an embryonal tumor in a 68-year-old adult. 14 The current birth rates for the United Kingdom and the United States are approximately 600,000 and 3,700,000, respectively. Extrapolation from our calculation of the incidence of unilat-
1233
eral multicystic kidney (1:4,300 live births) gives a figure of approximately 1,000 new cases per annum for the United Kingdom and United States, a theoretical total of approximately 20,000 for the period covered by the literature search. While this is obviously a hypothetical figure it may serve nevertheless to put the risks of malignant change and hypertension into context. Hypertension. The undoubted link between hypertension and multicystic kidney is, perhaps, the most commonly cited justification for prophylactic nephrectomy. However, the number of reported cases is surprisingly small. The 20-year literature survey identified a total of only 9 cases. Of these cases 3 had responded to removal of the multicystic kidney while 6 had not. 10 It would be unrealistic to imagine that these 9 reported cases represent the full extent of this complication. Nevertheless, it is clear that multicystic kidney is a relatively common anomaly and if it also is a significant cause of hypertension one might expect this fact to emerge from the published literature on hypertension. This does not seem to be the case. For example Taylor and associates recently reported their experience of 42 children with surgical causes of renal hypertension without a single case of multicystic kidney. 15 Similarly, Hendren and associates encountered no cases of multicystic kidney in their series of 22 children with surgical renal hypertension. 16 The literature on hypertension in adults is more difficult to interpret. At one time the IVP was used widely in the investigation of patients with hypertension. Unfortunately, it is not possible to assess the role of multicystic kidneys by asking what percentage of hypertensive adults have a unilateral nonfunctioning kidney. The IVP cannot reliably distinguish between multicystic kidney and other causes of nonvisualization, for example gross renal scarring, dysplasia, previous renal vein thrombosis, true renal agenesis and so forth. In 1965 Kennedy and associates reviewed the IVPs and other investigations of 750 hypertensive adults. 17 From this total they identified 3 patients with unilateral renal hypoplasia. It is uncertain whether any of these kidneys represented the end result of a shrunken multicystic kidney. More detailed pathological findings were reported in the study of Emmett and associates in 1952. 18 These investigators studied 183 cases of unilateral renal atrophy drawn from an initial study population of 5,000 adults with a variety of renal disorders, including hypertension. They described 6 cases of renal aplasia of which 5 were associated with a nonpatent section of ureter. It seems probable that these 5 kidneys were the remnants of previous multicystic kidneys. One of these 6 cases of renal aplasia was associated with hypertension that did not respond to nephrectomy. The disappointing results of nephrectomy for hypertension in multicystic kidney (only 3 of the 9 reported cases improved) mirror the general experience of nephrectomy for unilateral renal disease. 19 In the case of multicystic kidney there is always the possibility of a specific occult pathological condition, for example renal artery stenosis, in the contralateral kidney. A more general mechanism that is receiving attention is possible hyperfiltration damage to the solitary functioning kidney. Worrying data are beginning to emerge from followup studies of live renal transplant donors. Tapson and associates reported a 38 per cent incidence of hypertension on long-term followup of 75 live donors. 20 Delano and associates evaluated 15 patients (including 13 transplant donors) who had undergone unilateral nephrectomy 9 to 62 years previously. 21 Of the patients 9 (60 per cent) were hypertensive. Interestingly, the patients reported by these authors included a hypertensive 62-year-old man who had undergone removal of a multicystic kidney shortly after birth. There is no doubt that a multicystic kidney can occasionally give rise to renin dependent hypertension. The available evidence suggests, however, that this risk is of a low order in relation to the true incidence of multicystic kidney. Prophylac-
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GORDON AND ASSOCIATES
tic nephrectomy in infancy would be most unlikely to protect individuals against hypertension induced by hyperfiltration damage to the solitary remaining kidney. Indeed, it may be just as important to monitor the blood pressure of individuals who have undergone nephrectomy as those whose multicystic kidney has been left in situ. Therefore, we have abandoned routine prophylactic nephrectomy but will continue to follow these children as part of a larger long-term study. REFERENCES 1. Bloom, D. A. and Brosman, S.: The multicystic kidney. J. Urol., 120: 211, 1978. 2. Ambrose, S. S., Gould, R. A., Trulock, T. S. and Parrott, T. S.: Unilateral multicystic renal disease in adults. J. Urol., 128: 366, 1982. 3. Ashley, D. J. B. and Mostofi, F. K.: Renal agenesis and dysgenesis. J. Urol., 83: 211, 1960. 4. Pathak, I. G. and Williams, D. I.: Multicystic and cystic dysplastic kidneys. Brit. J. Urol., 36: 318, 1964. 5, Avni, E. F., Thoua, Y., Lalmand, B., Didier, F., Droulle, P. and Schulman, C. C.: Multicystic dysplastic kidney: evolving concepts. In utero diagnosis and post-natal follow-up by ultrasound. Ann. Rad., 29: 663, 1986. 6. Campbell, M. F.: Congenital absence of one kidney: unilateral renal agenesis. Ann. Surg., 88: 1039, 1928. 7. Emanuel, B., Nachman, R., Aronson, N. and Weiss, H.: Congenital solitary kidney: a review of 74 cases. J. Urol., 111: 394, 1974. 8. Stuck, K. J., Koff, S. A. and Silver, T. M.: Ultrasonic features of multicystic dysplastic kidney: expanded diagnostic criteria. Radiology, 143: 217, 1982. 9. Raffensperger, J. and Abousleiman, A.: Abdominal masses in children under one year of age. Surgery, 63: 514, 1968. 10. Hartman, G. E., Smolik, L. M. and Shochat, S. J.: The dilemma of
11. 12. 13.
14.
15. 16.
17. 18. 19.
20.
21.
the multicystic dysplastic kidney. Amer. J. Dis. Child., 140: 925, 1986. Birken, G., King, D., Vane, D. and Lloyd, T.: Renal cell carcinoma arising in a multicystic dysplastic kidney. J. Ped. Surg., 20: 619, 1985. Barrett, D. M. and Wineland, R. E.: Renal cell carcinoma in multicystic dysplastic kidney. Urology, 15: 152, 1980. Burgler, W. and Hauri, D.: Vitale Komplikationen bei multizystischer Nierendegeneration (multizystischer Dysplasie). Urol. Int., 38: 251, 1983. Gutter, W. and Hermanek, P.: Maligner Tumor der nierengegend unter dem Bilde der Knollenniere (Nierenblastemcysten). Urol. Int., 4: 164, 1957. Taylor, R. C., Azmy, A. F. and Young, D. G.: Long-term follow-up of surgical renal hypertension. J. Ped. Surg., 22: 228, 1987. Hendren, W. H., Kim, S. H., Herrin, J. T. and Crawford, J. D.: Surgically correctable hypertension of renal origin in childhood. Amer. J. Surg., 143: 432, 1982. Kennedy, A. C., Luke, R. G., Briggs, J. D. and Stirling W. B.: Detection of renovascular hypertension. Lancet, 2: 963, 1965. Emmett, J. L., Alvarez-lerena, J. J. and McDonald, J. R.: Atrophic pyelonephritis versus congenital renal hypoplasia. J.A.M.A., 148: 1470, 1952. Vaughan, E. D., Buhler, F. R. Laragh, J. H., Sealey, J.E., Gavras, H. and Baer, L.: Hypertension and unilateral parenchymal renal disease. Evidence for abnormal vasoconstriction-volume interaction. J.A.M.A., 233: 1177, 1975. Tapson, J. S., Marshall, S. M., Tisdall, S. R., Wilkinson, R., Ward, M. K. and Kerr, D. N. S.: Renal function and blood pressure after donor nephrectomy. Proc. Eur. Dial. Transplant Ass. Eur. Ren. Ass., 21: 580, 1984. Delano, B. G., Lazar, I. L. and Friedman, E. A.: Hypertension, a late consequence of kidney donation. Kidney Int., 23: 168, abstract, 1983.
TEE JOURNAL OF UROLOGY
Ccpyr'ght@ 1988 by The Williams &
Printed in U.S.A.
Co.
MULTICYSTIC DYSPLASTIC KIDNEY: NEPHRECTOMY STILL APPROPRIATE? A. C.
D. F. IV:L THOMAS, R. J. ARTHUR
AND
H. C. IRVING
From the Departments of Pediatric Surgery and Radiology, The General Infirmary, and Department of Radiology, St. James's University Hospital, Leeds, England
ABSTRACT
We analyzed 25 cases of multicystic kidney to assess the impact of prenatal diagnosis on the management of this condition. The incidence of unilateral multicystic kidney was 1 in 4,300 live births. Of the 23 children with unilateral rnulticystic kidneys only 3 (13 per cent) had a :readily palpable lesion. These findings suggest that multicystic kidney is a more common renal anomaly than was previously recognized and that the majority of cases remained undiagnosed before the advent of prenatal diagnosis. Ultrasound re-evaluation in 11 children suggests that the natural history of multicystic kidneys is towards spontaneous involution. Two kidneys were not identifiable by followup ultrasound. Hypertension and malignancy complicating multicystic kidney are reported infrequently. The literature on hypertension does not generally support the view that rnulticystic kidney poses a significant risk of hypertension in later childhood or adult lifeo We believe that the routine removal of multicystic kidneys in infancy is no longer appropriate. (J. Ural., part 2, 140: 1231-1234, 1988) Multicystic is a developmental anomaly of the kidney that can be distinguished readily from other forms of cystic renal disease in childhood. The renal parenchyma is replaced by tense noncommunicating cysts and the proximal ureter is atretic or nonpatent. In the days before prenatal ultrasound diagnosis the usual presentation of multicystic kidney was an abdominal mass in the neonatal period. Surgeons generally have opted fo:r nephrectomy, although the precise indications for removing these kidneys have been unclear. We assess the effect of prenatal diagnosis on the presentation of multicystic kidney, estimate the incidence of this condition, document the natural history of multicystic kidneys that have been left in situ and reappraise the indications for nephrectomy. MATERIALS AND METHODS
A total of 25 cases of multicystic kidney presented between August 1982 and July 1987. Of these cases 12 (2 bilateral and 10 ~",,~"~"w' arose in pregnancies managed the 2 large Obstetric Units in Leeds, while 13 neonates (all with unilateral were referred for postnatal evaluation from other hospitals in the Y orkshi:re Region. Both bilateral cases were nosed in utero. One pregnancy was terminated at 22 weeks after the discovery of a bilateral condition associated with oligohydramnios. The kidneys were enlarged and "bright", and contained numerous small parenchymal cysts. The bladder was not noted to fill on ultrasound. In the second case the diagnosis was made late in the pregnancy, which was then allowed to run to term. This infant died of pulmonary hypoplasia at 9 hours after birth. In both cases the diagnosis was confirmed at autopsy. Of the 23 unilateral cases the left kidney was affected in 16 (70 per cent) and the right kidney in 7 (30 per cent). The unilateral group consisted of 13 boys (57 per cent) and 10 girls (43 per cent). We calculated the incidence of multicystic kidney from an analysis of 43,230 pregnancies managed by our own services during the 5-year study period. These units (St. James's University Hospital and The General Infirmary, Leeds) serve a well defined and relatively static population. More than 95 per cent of the pregnancies were scanned
between 17 and 20 weeks of gestation and the current over-all detection rate for fetal uropathic conditions is 1:800 pregnancies. A total of 12 cases of multicystic kidney (2 bilateral and 10 unilateral) was identified, for an incidence of 1:3,600 pregnancieso The 10 unilateral cases arose in 43,175 live births, for an incidence of approximately 1:4,300 live births. In these inborn infants no multicystic kidneys have since been found that were originally missed on prenatal ultrasound. However, it is possible that some multicystic kidneys were undetected and have remained asymptomatic in postnatal life. Conversely, no kidneys that were identified in utero as being multicystic (or grossly hydronephrotic) proved to be normal upon delivery. There is no information on the frequency of false positive findings in pregnancies scanned at other hospitals throughout the region. Literature search. A Medline computerized literature search was done to identify published reports, and assess the incidence of hypertension and malignancy related to multicystic kidney during the 20-year period from 1966 to 1986.
,~u,~acu;
RESULTS
Presentation. Both bilateral cases were detected prenatally as were 18 of the 23 unilateral cases. Of the 5 children with unilateral lesions that were not detected prenatally only 1 presented in the classical fashion with a neonatal abdominal mass. The remaining 4 unilateral multicystic kidneys were discovered during the routine investigations of coexistent abnormalities (esophageal atresia and duodenal atresia) or of unrelated urinary symptoms (voiding disorder with urinary infection and renal failure plus contralateral ureteropelvic junction obstruction). All of these infants were referred from district hospitals outside Leeds. None of the mothers of affected infants had been scanned with ultrasound during pregnancy. Clinical findings. Of the 23 unilateral multicystic kidneys 13 could not be palpated. Ten children had unilateral lesions that were palpable but in 7 the diagnosis had already been made from prenatal ultrasound. It is difficult to estimate how many of the prenatally diagnosed palpable kidneys would have been found on routine postnatal examination if the diagnosis had
1231
1232
GORDON AND ASSOCIATES
not been made previously in utero. Only 2 of these previously diagnosed lesions were easily palpable and we suspect that the remaining 5 might have been missed on routine neonatal examination. Therefore, it is possible that approximately threequarters of the unilateral multicystic kidneys remained undiagnosed in the days before prenatal ultrasound diagnosis. Morbidity/mortality (25 cases). Urological anomalies included contralateral ureteropelvic junction obstruction (asymptomatic in 1 patient and with renal function in 1), contralateral (asymptomatic) and bilateral (urinary infection) vesicoureteral reflux and voiding disorder (urinary infection). Nonurological anomalies included esophageal and duodenal atresia, ventricular septal defect, epidermolysis bullosa, chromosomal defect (translocation) and pulmonary hypoplasia. The 2 bilateral cases had a fatal outcome (termination of pregnancy and neonatal death). One live born neonate with a unilateral multicystic kidney and multiple coexistent anomalies (duodenal atresia, congenital heart disease and so forth) died of a cause unrelated to the multicystic kidney at 2 weeks after birth. Three infants experienced urological symptoms (urinary infection and renal failure) but in each case this was related to a pathological condition elsewhere in the urinary tract rather than to the multicystic kidney. One of these children whose mother had not been scanned prenatally presented in renal failure when he was 2½ years old. He had a left multicystic kidney and a right hydronephrotic kidney due to ureteropelvic junction obstruction. Pyeloplasty was done but renal function remains poor. There was 1 other case of contralateral ureteropelvic junction obstruction in the series. However, in this instance the diagnosis was made prenatally and the pyeloplasty was done in the neonatal period. This child now is thriving and has a normal plasma creatinine. Diagnosis. All 24 live born neonates had postnatal ultrasound imaging performed by 1 or other of the 2 radiologist authors (R.J.A. or H.C.I.). In 3 cases no functional imaging [excretory urography (IVP) or isotope renography] was performed, that is the 2 neonatal deaths and 1 infant who underwent esophageal and cardiac surgery and whose parents have refused further urological investigation. Three infants referred from district hospitals in the early part of the series had previously undergone an IVP. They have remained totally asymptomatic and the parents have refused any further invasive investigations. However, 18 infants have been investigated by a combination of ultrasound and isotope renography, generally 99"'technetiumdimercapto-succinic acid (99mTc-DMSA). Every case of multicystic kidney was associated with total absence of function, that is O per cent of split differential function. This finding contrasts with our experience of poorly functioning hydronephrotic kidneys in which some uptake of isotope could always be demonstrated.
Management/followup (23 unilateral cases). One neonate with a unilateral multicystic kidney died of unrelated causes and 1 infant has been lost to followup. Of the remaining 21 infants with unilateral lesions 14 were managed conservatively and 7 underwent nephrectomy. Of the latter cases 6 asymptomatic infants underwent prophylactic nephrectomy in the early part of the study, and 1 with a large multicystic kidney and bilateral vesicoureteral reflux also underwent nephrectomy, since it was believed that the abdominal mass might be contributing to the failure to thrive. However, removal of the multicystic kidney was of little benefit and the poor growth has been attributed since to an underlying chromosomal disorder and to urinary infection associated with the vesicoureteral reflux. None of the 7 children who underwent nephrectomy had any significant postoperative complications. Among the 14 children managed nonoperatively symptoms have occurred but without exception these have been related to a coexistent pathological condition rather than the multicystic kidney. None has had hypertension. Eleven children followed for a minimum of 1 year have been re-evaluated with ultrasound (mean followup 15 months). Two multicystic kidneys have shrunk to the point that they can no longer be visualized by ultrasound. In 6 cases there was a decrease in the absolute dimensions of the multicystic kidney with substantial shrinkage of the cysts (see figure). The remaining 3 multicystic kidneys have remained unchanged in absolute dimensions but are relatively smaller in relation to the growing child (see table). DISCUSSION
Current thinking on the management of this condition still is based mainly on observations related to large or symptomatic multicystic kidneys, published before the advent of prenatal ultrasound diagnosis. 1• 2 However, our study suggests that these large or symptomatic cases represent a relatively small proporDimensions of the 6 kidneys that were smaller on followup ultrasound Pt. No. 1 2 3 4 5 6
When Scanned
Kidney Length (cm.)
Kidney Diameter (cm.)
Birth lOmos. lmo. 1 yr. 5 yrs. 5½ yrs. Birth 9mos. Birth 20mos. Birth 16mos.
8 7.7 5 4.5 7.5 6.5 5.5 5.2 7.5 4 5 4
5 4.5 3.5 2.5 6 5 2.5 2.5 5 2 2.5 1.5
No. Cysts 8 4 5 3
4 2 6 3 5 1 3 1
Diameter of Largest Cyst (cm.) 5 4 2.5 2.5 2.5 2 1.8 1.2 4 1.5 2.5 0.5
A, antenatal ultrasound scan shows multicystic kidney in utero. B, neonatal scan shows large cystic kidney. C, scan at 8 months after birth demonstrates small cyst and no identifiable normal kidney.
MULTICYSTIC DYSPLASTIC KIDNEY
tion of the total. In the absence of prenatal diagnosis the majority of multicystic kidneys (at least three-quarters) remain undetected in the neonatal period. Our estimate of the true incidence of multicystic kidney is based on an analysis of only 43,320 pregnancies. Nevertheless, it is likely to be a reasonably accurate figure since our over-all detection rate for fetal uropathy (1:800 pregnancies) approximates the published incidence of renal anomalies derived from large autopsy studies. 3 Certain features of our series (for example the frequency and pattern of coexistent abnormalities) resemble those of previously reported clinically based series.4 Therefore, it seems that small prenatally diagnosed multicystic kidneys are part of the same pathological spectrum as the larger and more clinically obvious lesions. There is to date no evidence to suggest that the relative risks of hypertension or malignant change are related to the size of the multicystic kidney in the neonatal period. The fate of multicystic kidneys that have been left in situ is an aspect of this condition that has not been adequately documented. Our experience with 11 children suggests that the natural history is one of shrinkage and involution. These findings are similar to those of Avni and associates who followed 8 multicystic kidneys with ultrasound for 7 to 30 months. 5 These investigators documented disappearance of cysts and a decrease in the over-all dimensions of the lesions. They also report an interesting case of an infant with a prenatally diagnosed multicystic kidney who was admitted to another hospital for nephrectomy at 3 months after birth. At operation no remaining renal tissue could be identified. The incidence of unilateral renal agenesis in the adult population has been reported variously to be between 1:1,500 and 1:2,000. 6 • 7 It is possible that a significant proportion of these cases are in fact the end result of involution of a multicystic kidney. There is no uniformity of opinion on the role of nephrectomy in the management of multicystic kidney. Surgeons who routinely advise nephrectomy generally do so for one of several reasons: to confirm the diagnosis, to relieve symptoms, because of the potential for malignant change and because of hypertension. To confirm the diagnosis. We believe that to confirm the diagnosis is no longer a valid indication. The sonographic criteria for diagnosis are now well documented. 8 In addition an isotope scan (ideally 99mTc-DMSA) will make the distinction between a nonfunctioning multicystic kidney and a poorly functioning hydronephrotic kidney. 8 A combination of these imaging modalities should enable the diagnosis to be made with a high degree of certainty, removing the need for diagnostic nephrectomy. To relieve symptoms. Pain, hematuria and infection have been reported as complications of multicystic kidneys in later life. 2 The occurrence of hematuria and infection is rather difficult to understand, since the multicystic element usually is isolated from the lower urinary tract by the nonpatent section of ureter. Before symptoms are attributed to a multicystic kidney it clearly is important to exclude a pathological condition elsewhere in the urinary tract. Nevertheless, it would be difficult to argue against the removal of a symptomatic multicystic kidney. We suspect that such cases are rare in relation to the true incidence of the condition and that routine prophylactic nephrectomy is not justified on these grounds. Potential for malignant change. Our computer search of the literature covering the 20-year period from 1966 to 1986 identified 6 reports of malignancy associated with multicystic kidney: nephroblastoma in 2 children 10 months 9 and 4 years old, 10 3 patients with hypernephroma who were 15, 26 and 68 years old, 11- 13 and an embryonal tumor in a 68-year-old adult. 14 The current birth rates for the United Kingdom and the United States are approximately 600,000 and 3,700,000, respectively. Extrapolation from our calculation of the incidence of unilat-
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eral multicystic kidney (1:4,300 live births) gives a figure of approximately 1,000 new cases per annum for the United Kingdom and United States, a theoretical total of approximately 20,000 for the period covered by the literature search. While this is obviously a hypothetical figure it may serve nevertheless to put the risks of malignant change and hypertension into context. Hypertension. The undoubted link between hypertension and multicystic kidney is, perhaps, the most commonly cited justification for prophylactic nephrectomy. However, the number of reported cases is surprisingly small. The 20-year literature survey identified a total of only 9 cases. Of these cases 3 had responded to removal of the multicystic kidney while 6 had not. 10 It would be unrealistic to imagine that these 9 reported cases represent the full extent of this complication. Nevertheless, it is clear that multicystic kidney is a relatively common anomaly and if it also is a significant cause of hypertension one might expect this fact to emerge from the published literature on hypertension. This does not seem to be the case. For example Taylor and associates recently reported their experience of 42 children with surgical causes of renal hypertension without a single case of multicystic kidney. 15 Similarly, Hendren and associates encountered no cases of multicystic kidney in their series of 22 children with surgical renal hypertension. 16 The literature on hypertension in adults is more difficult to interpret. At one time the IVP was used widely in the investigation of patients with hypertension. Unfortunately, it is not possible to assess the role of multicystic kidneys by asking what percentage of hypertensive adults have a unilateral nonfunctioning kidney. The IVP cannot reliably distinguish between multicystic kidney and other causes of nonvisualization, for example gross renal scarring, dysplasia, previous renal vein thrombosis, true renal agenesis and so forth. In 1965 Kennedy and associates reviewed the IVPs and other investigations of 750 hypertensive adults. 17 From this total they identified 3 patients with unilateral renal hypoplasia. It is uncertain whether any of these kidneys represented the end result of a shrunken multicystic kidney. More detailed pathological findings were reported in the study of Emmett and associates in 1952. 18 These investigators studied 183 cases of unilateral renal atrophy drawn from an initial study population of 5,000 adults with a variety of renal disorders, including hypertension. They described 6 cases of renal aplasia of which 5 were associated with a nonpatent section of ureter. It seems probable that these 5 kidneys were the remnants of previous multicystic kidneys. One of these 6 cases of renal aplasia was associated with hypertension that did not respond to nephrectomy. The disappointing results of nephrectomy for hypertension in multicystic kidney (only 3 of the 9 reported cases improved) mirror the general experience of nephrectomy for unilateral renal disease. 19 In the case of multicystic kidney there is always the possibility of a specific occult pathological condition, for example renal artery stenosis, in the contralateral kidney. A more general mechanism that is receiving attention is possible hyperfiltration damage to the solitary functioning kidney. Worrying data are beginning to emerge from followup studies of live renal transplant donors. Tapson and associates reported a 38 per cent incidence of hypertension on long-term followup of 75 live donors. 20 Delano and associates evaluated 15 patients (including 13 transplant donors) who had undergone unilateral nephrectomy 9 to 62 years previously. 21 Of the patients 9 (60 per cent) were hypertensive. Interestingly, the patients reported by these authors included a hypertensive 62-year-old man who had undergone removal of a multicystic kidney shortly after birth. There is no doubt that a multicystic kidney can occasionally give rise to renin dependent hypertension. The available evidence suggests, however, that this risk is of a low order in relation to the true incidence of multicystic kidney. Prophylac-
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tic nephrectomy in infancy would be most unlikely to protect individuals against hypertension induced by hyperfiltration damage to the solitary remaining kidney. Indeed, it may be just as important to monitor the blood pressure of individuals who have undergone nephrectomy as those whose multicystic kidney has been left in situ. Therefore, we have abandoned routine prophylactic nephrectomy but will continue to follow these children as part of a larger long-term study. REFERENCES 1. Bloom, D. A. and Brosman, S.: The multicystic kidney. J. Urol., 120: 211, 1978. 2. Ambrose, S. S., Gould, R. A., Trulock, T. S. and Parrott, T. S.: Unilateral multicystic renal disease in adults. J. Urol., 128: 366, 1982. 3. Ashley, D. J. B. and Mostofi, F. K.: Renal agenesis and dysgenesis. J. Urol., 83: 211, 1960. 4. Pathak, I. G. and Williams, D. I.: Multicystic and cystic dysplastic kidneys. Brit. J. Urol., 36: 318, 1964. 5, Avni, E. F., Thoua, Y., Lalmand, B., Didier, F., Droulle, P. and Schulman, C. C.: Multicystic dysplastic kidney: evolving concepts. In utero diagnosis and post-natal follow-up by ultrasound. Ann. Rad., 29: 663, 1986. 6. Campbell, M. F.: Congenital absence of one kidney: unilateral renal agenesis. Ann. Surg., 88: 1039, 1928. 7. Emanuel, B., Nachman, R., Aronson, N. and Weiss, H.: Congenital solitary kidney: a review of 74 cases. J. Urol., 111: 394, 1974. 8. Stuck, K. J., Koff, S. A. and Silver, T. M.: Ultrasonic features of multicystic dysplastic kidney: expanded diagnostic criteria. Radiology, 143: 217, 1982. 9. Raffensperger, J. and Abousleiman, A.: Abdominal masses in children under one year of age. Surgery, 63: 514, 1968. 10. Hartman, G. E., Smolik, L. M. and Shochat, S. J.: The dilemma of
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the multicystic dysplastic kidney. Amer. J. Dis. Child., 140: 925, 1986. Birken, G., King, D., Vane, D. and Lloyd, T.: Renal cell carcinoma arising in a multicystic dysplastic kidney. J. Ped. Surg., 20: 619, 1985. Barrett, D. M. and Wineland, R. E.: Renal cell carcinoma in multicystic dysplastic kidney. Urology, 15: 152, 1980. Burgler, W. and Hauri, D.: Vitale Komplikationen bei multizystischer Nierendegeneration (multizystischer Dysplasie). Urol. Int., 38: 251, 1983. Gutter, W. and Hermanek, P.: Maligner Tumor der nierengegend unter dem Bilde der Knollenniere (Nierenblastemcysten). Urol. Int., 4: 164, 1957. Taylor, R. C., Azmy, A. F. and Young, D. G.: Long-term follow-up of surgical renal hypertension. J. Ped. Surg., 22: 228, 1987. Hendren, W. H., Kim, S. H., Herrin, J. T. and Crawford, J. D.: Surgically correctable hypertension of renal origin in childhood. Amer. J. Surg., 143: 432, 1982. Kennedy, A. C., Luke, R. G., Briggs, J. D. and Stirling W. B.: Detection of renovascular hypertension. Lancet, 2: 963, 1965. Emmett, J. L., Alvarez-lerena, J. J. and McDonald, J. R.: Atrophic pyelonephritis versus congenital renal hypoplasia. J.A.M.A., 148: 1470, 1952. Vaughan, E. D., Buhler, F. R. Laragh, J. H., Sealey, J.E., Gavras, H. and Baer, L.: Hypertension and unilateral parenchymal renal disease. Evidence for abnormal vasoconstriction-volume interaction. J.A.M.A., 233: 1177, 1975. Tapson, J. S., Marshall, S. M., Tisdall, S. R., Wilkinson, R., Ward, M. K. and Kerr, D. N. S.: Renal function and blood pressure after donor nephrectomy. Proc. Eur. Dial. Transplant Ass. Eur. Ren. Ass., 21: 580, 1984. Delano, B. G., Lazar, I. L. and Friedman, E. A.: Hypertension, a late consequence of kidney donation. Kidney Int., 23: 168, abstract, 1983.