0022-5347/78/1121-0211$02.00/0 Vol. 120, August
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright © 1978 by The Williams & Wilkins Co.
Pediatric Articles THE MULTICYSTIC KIDNEY DAVID A. BLOOM
AND
STANLEY BROSMAN
From the Department of Surgery, Division of Urology, University of California School of Medicine, Los Angeles, California
ABSTRACT
When an abdominal mass is found in a newborn it is likely to be a multicystic kidney. This asymptomatic mass is diagnosed in 60 per cent of the children within the first year of life. Two forms can be identified: 1) the large multicystic kidney, tending to have a normal contralateral kidney, and 2) the small multicystic kidney, which has a high incidence of contralateral renal anomalies and other congenital anomalies. The use of sonography has improved the diagnostic accuracy of this condition, B-mode sonography being superior to the A-mode technique. In a survey of 136 urologists selected because of their pediatric experience 75 per cent believed that an accurate diagnosis could be made non-operatively. However, 25 per cent reported an unexpected operative finding on at least 1 occasion, usually hydronephrosis. Hypertension, infection and manifestations of pressure attributed to the multicystic kidney were reported by 35 per cent of the respondents. Surgical exploration with removal of the abnormal kidney was considered mandatory by 56 per cent of the respondents, while 44 per cent believed that today an operation is no longer requiredstatistics that represent a change in attitude toward this condition. However, the ability to diagnose this condition accurately needs to be proved before this non-surgical approach can be adapted for each child. Moreover, if a child with this condition does not undergo an operation the parents should be advised of the possibility of problems stemming from the continued presence of the multicystic kidney in later years. HISTORIC CONSIDERATIONS
In 1836 Cruveilhier described an unusual appearing cystic kidney found at autopsy on a 3-year-old boy. 1 As a descriptive pathologist Cruveilhier published the Anatomie Pathologique du Corps Humain (fig. 1). In 6 volumes encompassing more than 200 colored plates he noted such entities as acoustic neuroma, Medusa's head and fibrocystic disease of the breast. Buried in this unindexed collection was the multicystic kidney (fig. 2), which Cruveilhier described as containing no trace of normal parenchyma and which he believed to be congenital. One hundred years elapsed before this lesion was described in the English literature. In 1936 Schwartz discovered an unusual unilateral multicystic kidney in an infant found to have an asymptomatic abdominal mass when he was 4 months old. 2 An excretory urogram (IVP) demonstrated non-visualization on the left side and cystoscopy revealed an absent left ureteral orifice. At exploration the left kidney was described as multicystic, the cysts varying from the size of a pea to that of a hen's egg, held together by connective tissue. There was a small grape-like nubbin of renal parenchyma. The right kidney was normal although somewhat large. Schwartz considered this lesion to be substantially different from the more commonly recognized polycystic kidney. In 1949 Ravitch and Sanford reported on 4 patients and discussed 6 others previously described. 3 Spence reviewed this condition in 19554 and discussed 4 of his patients as well as an additional 15 cases reported earlier. The 4 patients described by Spence were female subjects who ranged from 3 months to Accepted for publication September 9, 1977.
70 years old and displayed most of the spectrum ofmulticystic kidney. The youngest patient had an asymptomatic left abdominal mass that proved to be a multicystic kidney with an atretic ureter. Only a few remnants of atrophic renal tissue could be identified. A 4-year-old child with azotemia had a multicystic kidney on the right side and a ureteropelvic junction stenosis with hydronephrosis on the left side. The multicystic kidney was removed and the contralateral side was repaired successfully. A 21-year-old woman who presented with right flank pain was found to have shell-like calcifications in the right upper quadrant of the abdomen but there was no urographic visualization of the right kidney. Removal of this multicystic kidney relieved the symptoms. A 70-year-old woman with a history of recurrent urinary tract infections was shown to have ring-like calcifications and a functionless right kidney with an atretic ureter. A multicystic kidney was removed uneventfully, although the reason for the infections was not clear. Exploration in these patients was believed necessary to establish a diagnosis and, particularly, to rule out a neoplasm. It also was clear from the patients described by Spence that the multicystic kidney could cause problems later in life. By 1965 it had become apparent that the multicystic kidney was not an uncommon lesion. In that year Griscom reviewed 117 neonates who had abdominal masses and found that the single most common cause was a multicystic kidney. 5 Renal lesions accounted for more than half of the neonatal abdominal masses, while instances of multicystic and hydronephrotic kidneys were responsible for 40 per cent of the total. In this series the multicystic kidney was slightly more common than the hydronephrotic kidney. 211
212
BLOOM AND BROSMAN
Fm. 1. A, Cruveilhier toward end of life (1793-1874). B, descriptive anatomy of human body
Fm. 3. Multicystic kidney, typical gross appearance Fm. 2. Cruveilhier's multicystic kidney PATHOGENESIS AND HISTOPATHOLOGY
Renal cystic disease exists as a spectrum that can vary in composition from kidneys that are only small nubbins of solid and cystic tissue to those that consist entirely of large cysts. Potter believes that the abnormalities are caused by environmental factors affecting ampullary function and are not genetically transmitted. 6 Normally, the ureteral bud begins its first ampullary branching before 8 to 10 weeks of fetal life. The final structure of the kidney depends on its stage of development at the time of the injury and the effect of the injury on ampullary function. Two types of cystic kidneys tend to occur. If the terminal portions of the first few ampullary divisions enlarge, the kidneys are composed of cysts of variable size and may be normal or larger than normal. This is the situation in the Potter IIA classification (fig. 3). Failure of early ampullary branching leads to the small cystic kidney known as the dysgenetic, dysplastic or aplastic kidney. This is the Potter IIB abnormality. There are variations between these extremes. Some kidneys may have segmental cystic disease or multilocular cysts, representing another form of incomplete ampullary development. Moreover, cystic disease may accompany other renal anomalies, such as the horseshoe kidney. The microscopic appearance of the multicystic kidney is
characterized by the absence of normal tubular or glomerular structures. There is a great variability in the number and size of the cysts, thickness of the cyst walls, presence or absence of cartilage, amount of connective tissue, blood vessels and nerves, and number of primitive tubules that are present. Areas of erythropoiesis may be found. The ureter usually is affected and is always abnormal whenever the entire kidney is cystic. The ureter may be dilated throughout its length or segmented with intervening areas of atresia. There may be free communication with a few residual tubules or no communication at all. CLINICAL ASPECTS
Multicystic kidneys usually are discovered as asymptomatic abdominal masses in newborns or infants. This lesion may be the most commonly occurring abdominal mass in the newborn5 and is certainly at least as common as hydronephrosis. 7 Those born with bilateral multicystic kidneys have the characteristic facies described by Potter and renal function may be absent or depressed. This situation is incompatible with survival although 1 patient in the series of Williams lived as long as 17 days after birth despite bilateral multicystic kidneys. 8 Wise and Schirmer described a case in which a newborn had severe respiratory distress caused by a multicystic kidney9 but such symptoms are extremely unusual. In a
review of 68 ""'"""""" Cendron and associates found that foe diagnosis was made in 60 per cent of the children before were 1 year old and in 80 per cent before they were 2. 10 They distinguished between 2 forms of cystic kidney, 1 of which is large, weighing as much or more than a normal kidney, and the other type is small and hypoplastic. This distinction, which conforms with the Potter classifications HA and IIB, is sig11ificant because patients with the large cystic kidney (HA) tend to have a normal contralateral kidney, whereas those with the small cystic kidney (HE) are likely to suffer from contralateral renal anomalies and other associated congenital defects. Greene and associates reviewed the records of 27 patients with multicystic kidneys, 12 of whom had significant contralateral disease such as ureteropelvic junction obstruction or horseshoe kidneys. 11 Eight newborns who had bilateral multicystic kidneys died shortly after birth. A third of the patients in this series had associated contralateral renal disorders but no distinction was made between those with large and those with small cystic kidneys. Greene and associates commented that nephrectomy was not necessary if the diagnosis of multicystic kidney would be ascertained positively. In 1970 Schroder and associates reviewed 11 patients managed at our hospital and an additional 89 patients reported in the literature. 12 They found that a significant number with multicystic kidney had associated non-renal congenital malformations. When the diagnosis was clear and there were no symptoms they favored a non-operative approach. They concluded that hydronephrosis and Wilms tumor usually could be distinguished nonoperatively. However, when a child had associated anomalies that required operation the rnulticystic kidney was removed. DIAGNOSTIC METHODS
Radiologic diagnosis of multicystic kidney can be highly accurate. Kyaw described radiologic features of the multicystic kidney: 1) unilateral non-functioning kidney on IVP with flank mass or shell-like calcifications on scout and lateral films, 2) absent or atretic proximal ureter on retrograde pyelogram-visualized ureter may have sacculation or pseudodiverticula and 3) absent or hypoplastic renal artery, no collateral arterial supply and no nephrogram phase on aortogram, and distilled these into a triad, using IVPs, retrograde studies and angiography. 13 The IVP may reveal a flank mass, a non-visualizing kidney and shell-like calcifications. Often, lucencies corresponding to the cysts can be identified. The retrograde pyelogram may demonstrate an atretic ureter. In the visualized portion of the ureter there may be multiple sacculations or pseudodiverticula, The angiogram may indicate an absent or hypoplastic renal artery vvith no nephrogram phase and no collateral arterial supply. In the neonate an angiogram can be performed conveniently through the umbilical vessels. O'Connor and Neuhauser identified rnulticystic means of total opacificatin using dose (3 to 4 ml./kg. diatrizoate meglumine). An appearance radiopaque rims surrounding radiolucent areas of uneven size and shape is characteristic. Leonidas and associates suggested that rim opacification reflected vascularization and not function of the tissue. 15 Multicystic kidneys usually are nonfunctional in radiographic terms. However, Young and associates discovered that there can be opacification and puddling of contrast material in films that are delayed. 16 For this effect to occur there must be a lesser degree of dysplasia with at least 15 per cent of the tissue matrix consisting of well differentiated parenchyma. Warshawsky and associates concurred that there can be some degree of function in the multicystic kidney. 17 Even Schwartz described a small nubbin ofparenchyma in the multicystic kidney he discussed in 1936. 2 Sonography recently has added a new dimension of accuracy to the diagnosis of multicystic kidney. Hunig and Kinser elucidated the advantages of B-mode over A-mode techniques
in the of renal 1r1asses. 18 Bearman and associates showed that kidneys have a distinct ultrasonographic pattern using the B-mode, 19 which permits differentiation from hydronephrotic kidneys on the basis of pathognomonic echo patterns. The hydronephrotic kidney has irregular, centrally clumped, pelviocaliceal echoes and the multicystic kidney has multiple linearly arranged echoes from the cyst septa. These authors had 1 patient with renal vein thrombosis in whom a cystic pattern emerged owing to central hemorrhage and necrosis that can simulate the sonographic pattern of cysts. More experience will be necessary before the diagnostic accuracy of ultrasonography can be determined. Like most tests, its accuracy is dependent upon the skill of the examiner performing and evaluating the study. ~"/4"CLVWL~
SURVEY OF PEDIATRIC UROLOGISTS
To determine prevailing attitudes toward the need for an operation in patients with multicystic kidneys a survey was conducted among a selected group of 250 urologists who treat a substantial number of children. The questions dealt with nomenclature, diagnosis and management of the multicystic kidney, and 136 responses were received (see table). Although Schwartz originally called this condition unilateral multicystic kidney a variety of other descriptive and often confusing terms has been used- 86 per cent of the respondents favored a term that included the word multicystic but the most popular was simply multicystic kidney. Clinical findings associated with multicystic kidney as reported by 35 per cent of the responding pediatric urologists included hypertension, infection and manifestations of pressure. The most helpful diagnostic tools were considered to be the IVP, ultrasonography and retrograde pyelog:rnphy. Transillumination, cyst Results of multicystic survey %
V\Thich term do you prefer? Multicystic kidney Congenital multicystic kidney Unilateral multicystic kidney Dysplastic kidney Clinical findings attributed to rnu!ticystic kidney (48 of 136) Enlargement Hypertension Infection Pressure Malignancy Pain Which diagnostic procedures have been most helpful? IVP Ultrasound Retrograde pyelogram Ti·ansillumination Angiograms Can you diagnose multicystic kidney vlithou~ exploration? Yes No Do you need to explore multicystic kidneys? Yes Do you need to remove multicystic kidneys? Yes
39 25
21 12
18 15 14 13
80 62 46
34 10 75
25 56 65
Were you ever surprised by your operative findings? (34 of 136 No. respondents- 25%) Respondents Hydronephrosis 17 Wilms tumor 3 Dysplasia (non-cystic) 2 Hamartoma 1 Duplication 1 Renal vein thrombosis l Unlisted 9 Operative complications (14 of 136 respondents-10%) Wound dehiscence 2 Bowel obstruction 2 Renal failure 1 Wound infection 2 Death 2 Ileus 1 Unlisted 3 Removal of good kidney 1
214
BLOOM AND BROSMAN
puncture, tomography and computer scans were used less frequently. Among the respondents 75 per cent believed that they could make accurate diagnoses of multicystic kidney nonoperatively. However, when exploring for an anticipated multicystic kidney, 25 per cent reported at least 1 instance in which there was an unexpected operative finding. The most frequent cause of surprise was a hydronephrotic kidney, which was found by half of the respondents. On the other hand, Wilms tumor was discovered in only 3 instances. Operative complications were noted by 10 per cent, including wound dehiscence, infection, prolonged ileus and 2 deaths. One urologist mentioned that he knew of 2 additional operative deaths in patients with whom he was not involved personally. In conclusion, 56 per cent of the respondents deemed diagnostic exploration necessary, while 46 per cent believed such operation was no longer mandatory. However, 65 per cent expressed the opinion that excision of the multicystic kidney was necessary eventually. COULD A MALIGNANCY BE OVERLOOKED?
Before a non-operative approach is considered in treating patients with multicystic kidneys the risk of missing a malignancy must be weighed. Nephroblastoma, a lesion that is likely to be overlooked, can be coincident with a cystic kidney or it can assume a polycystic configuration itself. Moreover, hemorrhage and necrosis of a tumor can produce a pseudocyst. Uson and associates described 2 cases of Wilms tumor associated with cystic renal disease. 20 Neither case would have satisfied any of the radiological criteria for multicystic kidney and both involved kidneys that functioned normally on an IVP with the malignancy presenting as a filling defect. Christ reported a case of a diffusely cystic Wilms tumor in a 10month-old girl but this kidney also visualized well on pyelography. 21 Some form of renal function in terms of an IVP or scan would be expected in cystic renal malignancies, although Datnow and Daniel made the unnerving discovery of a polycystic nephroblastoma in a 7-month-old boy with non-visualization of the involved kidney on an IVP. 22 Angiography in this patient demonstrated a hypovascular mass but no mention was made of the size of the renal artery or function on renal scan. Raffensperger and Abousleiman studied abdominal masses in children less than 1 year old and reported a Wilms tumor arising in the periphery of a multicystic kidney in a 10month-old child. 23 Although cystic renal malignancies are rare and none has been described in neonates, it is prudent to be wary when considering a non-operative approach to multicystic kidneys. The malignant potential of any dysgenetic tissues, such as nodular renal blastomas, also must be considered. 24 These are nests of primitive undifferentiated cells from which glomeruli and tubules develop. However, this type of cell is not seen in the normal term infant. 25 Nephroblastomas are thought to arise from the same renal blastoma cells, although their exact relationship to Wilms tumor is unclear. Rous and associates recently discussed a patient in whom a nephroblastoma was believed to arise from areas of nodular renal blastoma. 26 The patient described by Raffensperger and Abousleiman also could represent such an event. 2:i Because areas of nodular renal blastoma have been found in multicystic kidneys a theoretical argument exists for their removal.
related to a multicystic kidney. 27 However, the practice of measuring the blood pressure in infants and children has been largely ignored until recently and, thus, it is possible that other instances of hypertension related to multicystic kidney may have been missed. 28 In his reply to our questionnaire Ambrose related his experience with 20 adults who had symptoms referable to multicystic kidneys. 29 Ten complained of regional pain, 3 had a mass, 3 suffered urinary tract infections, 2 had hematuria and 2 were hypertensive. Nevertheless, neither of the hypertensive patients was cured by nephrectomy. Ambrose located 1 patient in the German literature who had a renal carcinoma in a multicystic kidney when he was 68 years old. :io A final aspect of the liability of a multicystic kidney is the predisposition of the contralateral kidney toward anomalous . development. This situation may be particularly true with the Potter IIB variety. Pathak and Williams argue strongly that "The whole urinary tract must be fully investigated and treatment to the contralateral kidney should be regarded as of greater importance than nephrectomy for the cystic kidney".'ll It is clear that a multicystic kidney can be symptomatic, particularly later in life, in terms of pain, pressure and infection. The relation to hypertension is not resolved, although there may be an association. The predisposition to malignancy remains another undefined possibility. CONCLUSION
Cruveilhier described the first multicystic kidney in 1836. On the basis of a survey of pediatric urologists the preferred name for this lesion is multicystic kidney. Complete urologic evaluation is necessary to identify abnormalities in the contralateral kidney and ureter. The small cystic kidney is more likely to be associated with a contralateral abnormality than is the large cystic kidney. The prognosis is good if there are no other anomalies either within the urinary tract or elsewhere in the body. Diagnosis of a multicystic kidney can usually be established by IVP (flank mass, non-visualizing kidney, shelllike calcifications), retrograde pyelogram and B-mode ultrasound. However, it has yet to be proved that non-operative diagnosis can be established with certainty. In most cases, when the diagnosis is clear and the patient is asymptomatic, nephrectomy may not be necessary in the neonatal period. However, because the multicystic kidney may be symptomatic in later life and until its relationship to hypertension and possible malignant degeneration is established, elective nephrectomy should be considered after the neonatal period. When there is any doubt about the diagnosis of a multicystic kidney or when there are any related symptoms an operation is mandatory. EDITORIAL COMMENT The authors have compiled a comprehensive review, incorporating our current knowledge and opinions on a clinical entity important to those doing pediatric urology. As newer diagnostic methods come along the management of these lesions becomes potentially more complex. Nevertheless, I predict the equation mass plus surgeon equals operation will hold indefinitely. Harry M. Spence 4105 Live Oak Street Dallas, Texas
THE LIABILITY OF A MULTICYSTIC KIDNEY
Clinical symptoms owing to multicystic kidneys are not uncommon. Pain, infection and encroachment on adjacent viscera are well recognized. Indeed, 31 per cent of the responding urologists had encountered patients with symptoms attributed to a multicystic kidney. In about a third of these cases infection and hypertension were listed as symptoms. The literature contains only 1 clear-cut example of hypertension
REFERENCES
1. Cruveilhier, J.: Anatomie Pathologique du Corps Humain.
Paris: J. B. Bailliere Libraire, 1836. 2. Schwartz, J.: An unusual unilateral multicystic kidney in an infant. J. Urol., 35: 259, 1936. 3. Ravitch, M. M. and Sanford, M. C.: Unilateral multicystic kidney in infants. Pediatrics, 4: 769, 1949. 4. Spence, H. M.: Congenital unilateral multicystic kidney: an
IvfULTICYS1'1C KID:NEY
5. 6. 7. 8. 9. 10. 11.
12. 13. 14. 15. 16. 17.
entity to be distinguished from polycystic kidney disease and other cystic disorders. J. Urol., 74: 693, 1955. Griscom, N. T.: The roentgenology of neonatal abdominal masses. Amer. J. Roentgen., 93: 447, 1965. Potter, E. L.: Normal and Abnormal Development of the Kidney Chicago: Yearbook Medical Publishers, 1972. Emanuel, B. and White, H.: Intravenous pyelography in the differential diagnosis of renal masses in the neonatal period. Clin. Pediat., 7: 529, 1968. Williams, D. I.: Multicystic and dysplastic kidneys. Trans. Amer. Ass. Genitourin. Surg., 56: 88, 1964. Wise, H. A., II and Schirmer, H. K. A.: An unusual cause of respiratory distress in a newborn.J. Urol., 108: 792, 1972. Cendron, J., Gubler, J. P., Valayer, J. and Kiriakos, S.: Dysplasie Multicystique du rein chez l'enfant. J. d'Urol. Nephrol., 79: 773, 1973. Greene, L. F., Feinzaig, W. and Dahlin, D. C.: Multicystic dysplasia of the kidney: with special reference to the contralateral kidney. J. Urol., 105: 482, 1971. Schroder, F. H., Fiedler, U. and Goodwin, W. E.: Die multizystische Dysplasie der Niere-ein kleinisches Syndrom. Z. Urol. Nephrol., 63: 631, 1970. Kyaw, M. M.: The radiological diagnosis of congenital multicystic kidney. Radiological triad. Clin. Radiol., 25: 45, 1974. O'Connor, J. F. and Neuhauser, E. B.: Total body opacification in conventional and high dose intravenous urography in infancy. Amer. J. Roentgen., 90: 63, 1963. Leonidas, J. C., Strauss, L. and Krasna, I. H.: Roentgen diagnosis of rnulticystic renal dysplasia in infancy by high doseurography. J. Urol., 108: 963, 1972. Young, L. W., Wood, B. P., Spohr, C. H. and Panner, B.: Delayed excretory urographic opacification, a puddling effect, in multicystic renal dysplasia. Ann. Radio!., 17: 391, 1974. Warshawsky, A. B., Miller, K. E. and Kaplan, G. W.: Urographic visualization of multicystic kidneys. J. Urol., 117: 94,
215
rnn 180 Hiinig, R. and Kinser, J.: Ultrasonic diagnosis ofWilms tumorso Amer. J. Roentgen., 117: 119, 1973. 19. Bearman, S. B., Hine, P. L. and Sanders, R. C.: Multicystic kidney: a sonographic pattern. Radiology, 118: 685, 1976. 20. Uson, A. C., Del Rosario, C. and Melicow, M. M.: Wilms tumor in association with cystic renal disease: report of two cases. J. Urol., 83: 262, 1960. 21. Christ, M. L.: Polycystic nephroblastoma. J. Urol., 98: 570, 1967. 22. Datnow, B. and Daniel, W.W., Jr.: Polycystic nephroblastoma. J.A.M.A., 236: 2528, 1976. 23. Raffensperger, J. and Abousleiman, A.: Abdominal masses in children under one year of age. Surgery, 63: 514, 1968. 24. Bove, K. E., Kaffler, H. and McAdams, A. J.: Nodular renal blastema. Definition and possible significance. Cancer, 24: 323, 1969. 25. Potter, E. L.: Pathology of the Fetus and Infant, 2nd ed. Chicago: Yearbook Medical Publishers, p. 199, 1961. 26. Rous, S. N., Bailie, M. D., Kaufman, D. B., Raddy, T. B. and Mattson, J. C.: Nodular renal blastema, nephroblastomatosis, and Wilms' tumor. Different points on the same disease spectrum? Urology, 8: 599, 1976. 27. Javadpour, N., Chelouhy, E., Moncada, L., Rosenthal, I. M. and Bush, I. M.: Hypertension in a child caused by a multicystic kidney. J. Urol., 104: 918, 1970. 28. Pazdral, P. T., Lieberman, H. M., Pazdral, W. E., Neuman, C. G. and Lieberman, E.: Awareness of pediatric hypertension. Measuring blood pressure. J.A.M.A., 235: 2320, 1976. 29. Ambrose, S.: Unilateral multicystic renal disease in adults. Personal communication. 30. Giitter, W. and Hermanek, P.: Maligner Tumor der Nierengegend Unter dem Bilde der Knollenniere (Nierenblastemcysten). Urol. Int., 4: 164, 1957 .. 31. Pathak, I. G. and Williams, D. I.: Multicystic and cystic dysplastic kidneys. Brit. J. Urol., 36: 318, 1964.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright © 1978 by The Williams & Wilkins Co.
Pediatric Articles THE MULTICYSTIC KIDNEY DAVID A. BLOOM
AND
STANLEY BROSMAN
From the Department of Surgery, Division of Urology, University of California School of Medicine, Los Angeles, California
ABSTRACT
When an abdominal mass is found in a newborn it is likely to be a multicystic kidney. This asymptomatic mass is diagnosed in 60 per cent of the children within the first year of life. Two forms can be identified: 1) the large multicystic kidney, tending to have a normal contralateral kidney, and 2) the small multicystic kidney, which has a high incidence of contralateral renal anomalies and other congenital anomalies. The use of sonography has improved the diagnostic accuracy of this condition, B-mode sonography being superior to the A-mode technique. In a survey of 136 urologists selected because of their pediatric experience 75 per cent believed that an accurate diagnosis could be made non-operatively. However, 25 per cent reported an unexpected operative finding on at least 1 occasion, usually hydronephrosis. Hypertension, infection and manifestations of pressure attributed to the multicystic kidney were reported by 35 per cent of the respondents. Surgical exploration with removal of the abnormal kidney was considered mandatory by 56 per cent of the respondents, while 44 per cent believed that today an operation is no longer requiredstatistics that represent a change in attitude toward this condition. However, the ability to diagnose this condition accurately needs to be proved before this non-surgical approach can be adapted for each child. Moreover, if a child with this condition does not undergo an operation the parents should be advised of the possibility of problems stemming from the continued presence of the multicystic kidney in later years. HISTORIC CONSIDERATIONS
In 1836 Cruveilhier described an unusual appearing cystic kidney found at autopsy on a 3-year-old boy. 1 As a descriptive pathologist Cruveilhier published the Anatomie Pathologique du Corps Humain (fig. 1). In 6 volumes encompassing more than 200 colored plates he noted such entities as acoustic neuroma, Medusa's head and fibrocystic disease of the breast. Buried in this unindexed collection was the multicystic kidney (fig. 2), which Cruveilhier described as containing no trace of normal parenchyma and which he believed to be congenital. One hundred years elapsed before this lesion was described in the English literature. In 1936 Schwartz discovered an unusual unilateral multicystic kidney in an infant found to have an asymptomatic abdominal mass when he was 4 months old. 2 An excretory urogram (IVP) demonstrated non-visualization on the left side and cystoscopy revealed an absent left ureteral orifice. At exploration the left kidney was described as multicystic, the cysts varying from the size of a pea to that of a hen's egg, held together by connective tissue. There was a small grape-like nubbin of renal parenchyma. The right kidney was normal although somewhat large. Schwartz considered this lesion to be substantially different from the more commonly recognized polycystic kidney. In 1949 Ravitch and Sanford reported on 4 patients and discussed 6 others previously described. 3 Spence reviewed this condition in 19554 and discussed 4 of his patients as well as an additional 15 cases reported earlier. The 4 patients described by Spence were female subjects who ranged from 3 months to Accepted for publication September 9, 1977.
70 years old and displayed most of the spectrum ofmulticystic kidney. The youngest patient had an asymptomatic left abdominal mass that proved to be a multicystic kidney with an atretic ureter. Only a few remnants of atrophic renal tissue could be identified. A 4-year-old child with azotemia had a multicystic kidney on the right side and a ureteropelvic junction stenosis with hydronephrosis on the left side. The multicystic kidney was removed and the contralateral side was repaired successfully. A 21-year-old woman who presented with right flank pain was found to have shell-like calcifications in the right upper quadrant of the abdomen but there was no urographic visualization of the right kidney. Removal of this multicystic kidney relieved the symptoms. A 70-year-old woman with a history of recurrent urinary tract infections was shown to have ring-like calcifications and a functionless right kidney with an atretic ureter. A multicystic kidney was removed uneventfully, although the reason for the infections was not clear. Exploration in these patients was believed necessary to establish a diagnosis and, particularly, to rule out a neoplasm. It also was clear from the patients described by Spence that the multicystic kidney could cause problems later in life. By 1965 it had become apparent that the multicystic kidney was not an uncommon lesion. In that year Griscom reviewed 117 neonates who had abdominal masses and found that the single most common cause was a multicystic kidney. 5 Renal lesions accounted for more than half of the neonatal abdominal masses, while instances of multicystic and hydronephrotic kidneys were responsible for 40 per cent of the total. In this series the multicystic kidney was slightly more common than the hydronephrotic kidney. 211
212
BLOOM AND BROSMAN
Fm. 1. A, Cruveilhier toward end of life (1793-1874). B, descriptive anatomy of human body
Fm. 3. Multicystic kidney, typical gross appearance Fm. 2. Cruveilhier's multicystic kidney PATHOGENESIS AND HISTOPATHOLOGY
Renal cystic disease exists as a spectrum that can vary in composition from kidneys that are only small nubbins of solid and cystic tissue to those that consist entirely of large cysts. Potter believes that the abnormalities are caused by environmental factors affecting ampullary function and are not genetically transmitted. 6 Normally, the ureteral bud begins its first ampullary branching before 8 to 10 weeks of fetal life. The final structure of the kidney depends on its stage of development at the time of the injury and the effect of the injury on ampullary function. Two types of cystic kidneys tend to occur. If the terminal portions of the first few ampullary divisions enlarge, the kidneys are composed of cysts of variable size and may be normal or larger than normal. This is the situation in the Potter IIA classification (fig. 3). Failure of early ampullary branching leads to the small cystic kidney known as the dysgenetic, dysplastic or aplastic kidney. This is the Potter IIB abnormality. There are variations between these extremes. Some kidneys may have segmental cystic disease or multilocular cysts, representing another form of incomplete ampullary development. Moreover, cystic disease may accompany other renal anomalies, such as the horseshoe kidney. The microscopic appearance of the multicystic kidney is
characterized by the absence of normal tubular or glomerular structures. There is a great variability in the number and size of the cysts, thickness of the cyst walls, presence or absence of cartilage, amount of connective tissue, blood vessels and nerves, and number of primitive tubules that are present. Areas of erythropoiesis may be found. The ureter usually is affected and is always abnormal whenever the entire kidney is cystic. The ureter may be dilated throughout its length or segmented with intervening areas of atresia. There may be free communication with a few residual tubules or no communication at all. CLINICAL ASPECTS
Multicystic kidneys usually are discovered as asymptomatic abdominal masses in newborns or infants. This lesion may be the most commonly occurring abdominal mass in the newborn5 and is certainly at least as common as hydronephrosis. 7 Those born with bilateral multicystic kidneys have the characteristic facies described by Potter and renal function may be absent or depressed. This situation is incompatible with survival although 1 patient in the series of Williams lived as long as 17 days after birth despite bilateral multicystic kidneys. 8 Wise and Schirmer described a case in which a newborn had severe respiratory distress caused by a multicystic kidney9 but such symptoms are extremely unusual. In a
review of 68 ""'"""""" Cendron and associates found that foe diagnosis was made in 60 per cent of the children before were 1 year old and in 80 per cent before they were 2. 10 They distinguished between 2 forms of cystic kidney, 1 of which is large, weighing as much or more than a normal kidney, and the other type is small and hypoplastic. This distinction, which conforms with the Potter classifications HA and IIB, is sig11ificant because patients with the large cystic kidney (HA) tend to have a normal contralateral kidney, whereas those with the small cystic kidney (HE) are likely to suffer from contralateral renal anomalies and other associated congenital defects. Greene and associates reviewed the records of 27 patients with multicystic kidneys, 12 of whom had significant contralateral disease such as ureteropelvic junction obstruction or horseshoe kidneys. 11 Eight newborns who had bilateral multicystic kidneys died shortly after birth. A third of the patients in this series had associated contralateral renal disorders but no distinction was made between those with large and those with small cystic kidneys. Greene and associates commented that nephrectomy was not necessary if the diagnosis of multicystic kidney would be ascertained positively. In 1970 Schroder and associates reviewed 11 patients managed at our hospital and an additional 89 patients reported in the literature. 12 They found that a significant number with multicystic kidney had associated non-renal congenital malformations. When the diagnosis was clear and there were no symptoms they favored a non-operative approach. They concluded that hydronephrosis and Wilms tumor usually could be distinguished nonoperatively. However, when a child had associated anomalies that required operation the rnulticystic kidney was removed. DIAGNOSTIC METHODS
Radiologic diagnosis of multicystic kidney can be highly accurate. Kyaw described radiologic features of the multicystic kidney: 1) unilateral non-functioning kidney on IVP with flank mass or shell-like calcifications on scout and lateral films, 2) absent or atretic proximal ureter on retrograde pyelogram-visualized ureter may have sacculation or pseudodiverticula and 3) absent or hypoplastic renal artery, no collateral arterial supply and no nephrogram phase on aortogram, and distilled these into a triad, using IVPs, retrograde studies and angiography. 13 The IVP may reveal a flank mass, a non-visualizing kidney and shell-like calcifications. Often, lucencies corresponding to the cysts can be identified. The retrograde pyelogram may demonstrate an atretic ureter. In the visualized portion of the ureter there may be multiple sacculations or pseudodiverticula, The angiogram may indicate an absent or hypoplastic renal artery vvith no nephrogram phase and no collateral arterial supply. In the neonate an angiogram can be performed conveniently through the umbilical vessels. O'Connor and Neuhauser identified rnulticystic means of total opacificatin using dose (3 to 4 ml./kg. diatrizoate meglumine). An appearance radiopaque rims surrounding radiolucent areas of uneven size and shape is characteristic. Leonidas and associates suggested that rim opacification reflected vascularization and not function of the tissue. 15 Multicystic kidneys usually are nonfunctional in radiographic terms. However, Young and associates discovered that there can be opacification and puddling of contrast material in films that are delayed. 16 For this effect to occur there must be a lesser degree of dysplasia with at least 15 per cent of the tissue matrix consisting of well differentiated parenchyma. Warshawsky and associates concurred that there can be some degree of function in the multicystic kidney. 17 Even Schwartz described a small nubbin ofparenchyma in the multicystic kidney he discussed in 1936. 2 Sonography recently has added a new dimension of accuracy to the diagnosis of multicystic kidney. Hunig and Kinser elucidated the advantages of B-mode over A-mode techniques
in the of renal 1r1asses. 18 Bearman and associates showed that kidneys have a distinct ultrasonographic pattern using the B-mode, 19 which permits differentiation from hydronephrotic kidneys on the basis of pathognomonic echo patterns. The hydronephrotic kidney has irregular, centrally clumped, pelviocaliceal echoes and the multicystic kidney has multiple linearly arranged echoes from the cyst septa. These authors had 1 patient with renal vein thrombosis in whom a cystic pattern emerged owing to central hemorrhage and necrosis that can simulate the sonographic pattern of cysts. More experience will be necessary before the diagnostic accuracy of ultrasonography can be determined. Like most tests, its accuracy is dependent upon the skill of the examiner performing and evaluating the study. ~"/4"CLVWL~
SURVEY OF PEDIATRIC UROLOGISTS
To determine prevailing attitudes toward the need for an operation in patients with multicystic kidneys a survey was conducted among a selected group of 250 urologists who treat a substantial number of children. The questions dealt with nomenclature, diagnosis and management of the multicystic kidney, and 136 responses were received (see table). Although Schwartz originally called this condition unilateral multicystic kidney a variety of other descriptive and often confusing terms has been used- 86 per cent of the respondents favored a term that included the word multicystic but the most popular was simply multicystic kidney. Clinical findings associated with multicystic kidney as reported by 35 per cent of the responding pediatric urologists included hypertension, infection and manifestations of pressure. The most helpful diagnostic tools were considered to be the IVP, ultrasonography and retrograde pyelog:rnphy. Transillumination, cyst Results of multicystic survey %
V\Thich term do you prefer? Multicystic kidney Congenital multicystic kidney Unilateral multicystic kidney Dysplastic kidney Clinical findings attributed to rnu!ticystic kidney (48 of 136) Enlargement Hypertension Infection Pressure Malignancy Pain Which diagnostic procedures have been most helpful? IVP Ultrasound Retrograde pyelogram Ti·ansillumination Angiograms Can you diagnose multicystic kidney vlithou~ exploration? Yes No Do you need to explore multicystic kidneys? Yes Do you need to remove multicystic kidneys? Yes
39 25
21 12
18 15 14 13
80 62 46
34 10 75
25 56 65
Were you ever surprised by your operative findings? (34 of 136 No. respondents- 25%) Respondents Hydronephrosis 17 Wilms tumor 3 Dysplasia (non-cystic) 2 Hamartoma 1 Duplication 1 Renal vein thrombosis l Unlisted 9 Operative complications (14 of 136 respondents-10%) Wound dehiscence 2 Bowel obstruction 2 Renal failure 1 Wound infection 2 Death 2 Ileus 1 Unlisted 3 Removal of good kidney 1
214
BLOOM AND BROSMAN
puncture, tomography and computer scans were used less frequently. Among the respondents 75 per cent believed that they could make accurate diagnoses of multicystic kidney nonoperatively. However, when exploring for an anticipated multicystic kidney, 25 per cent reported at least 1 instance in which there was an unexpected operative finding. The most frequent cause of surprise was a hydronephrotic kidney, which was found by half of the respondents. On the other hand, Wilms tumor was discovered in only 3 instances. Operative complications were noted by 10 per cent, including wound dehiscence, infection, prolonged ileus and 2 deaths. One urologist mentioned that he knew of 2 additional operative deaths in patients with whom he was not involved personally. In conclusion, 56 per cent of the respondents deemed diagnostic exploration necessary, while 46 per cent believed such operation was no longer mandatory. However, 65 per cent expressed the opinion that excision of the multicystic kidney was necessary eventually. COULD A MALIGNANCY BE OVERLOOKED?
Before a non-operative approach is considered in treating patients with multicystic kidneys the risk of missing a malignancy must be weighed. Nephroblastoma, a lesion that is likely to be overlooked, can be coincident with a cystic kidney or it can assume a polycystic configuration itself. Moreover, hemorrhage and necrosis of a tumor can produce a pseudocyst. Uson and associates described 2 cases of Wilms tumor associated with cystic renal disease. 20 Neither case would have satisfied any of the radiological criteria for multicystic kidney and both involved kidneys that functioned normally on an IVP with the malignancy presenting as a filling defect. Christ reported a case of a diffusely cystic Wilms tumor in a 10month-old girl but this kidney also visualized well on pyelography. 21 Some form of renal function in terms of an IVP or scan would be expected in cystic renal malignancies, although Datnow and Daniel made the unnerving discovery of a polycystic nephroblastoma in a 7-month-old boy with non-visualization of the involved kidney on an IVP. 22 Angiography in this patient demonstrated a hypovascular mass but no mention was made of the size of the renal artery or function on renal scan. Raffensperger and Abousleiman studied abdominal masses in children less than 1 year old and reported a Wilms tumor arising in the periphery of a multicystic kidney in a 10month-old child. 23 Although cystic renal malignancies are rare and none has been described in neonates, it is prudent to be wary when considering a non-operative approach to multicystic kidneys. The malignant potential of any dysgenetic tissues, such as nodular renal blastomas, also must be considered. 24 These are nests of primitive undifferentiated cells from which glomeruli and tubules develop. However, this type of cell is not seen in the normal term infant. 25 Nephroblastomas are thought to arise from the same renal blastoma cells, although their exact relationship to Wilms tumor is unclear. Rous and associates recently discussed a patient in whom a nephroblastoma was believed to arise from areas of nodular renal blastoma. 26 The patient described by Raffensperger and Abousleiman also could represent such an event. 2:i Because areas of nodular renal blastoma have been found in multicystic kidneys a theoretical argument exists for their removal.
related to a multicystic kidney. 27 However, the practice of measuring the blood pressure in infants and children has been largely ignored until recently and, thus, it is possible that other instances of hypertension related to multicystic kidney may have been missed. 28 In his reply to our questionnaire Ambrose related his experience with 20 adults who had symptoms referable to multicystic kidneys. 29 Ten complained of regional pain, 3 had a mass, 3 suffered urinary tract infections, 2 had hematuria and 2 were hypertensive. Nevertheless, neither of the hypertensive patients was cured by nephrectomy. Ambrose located 1 patient in the German literature who had a renal carcinoma in a multicystic kidney when he was 68 years old. :io A final aspect of the liability of a multicystic kidney is the predisposition of the contralateral kidney toward anomalous . development. This situation may be particularly true with the Potter IIB variety. Pathak and Williams argue strongly that "The whole urinary tract must be fully investigated and treatment to the contralateral kidney should be regarded as of greater importance than nephrectomy for the cystic kidney".'ll It is clear that a multicystic kidney can be symptomatic, particularly later in life, in terms of pain, pressure and infection. The relation to hypertension is not resolved, although there may be an association. The predisposition to malignancy remains another undefined possibility. CONCLUSION
Cruveilhier described the first multicystic kidney in 1836. On the basis of a survey of pediatric urologists the preferred name for this lesion is multicystic kidney. Complete urologic evaluation is necessary to identify abnormalities in the contralateral kidney and ureter. The small cystic kidney is more likely to be associated with a contralateral abnormality than is the large cystic kidney. The prognosis is good if there are no other anomalies either within the urinary tract or elsewhere in the body. Diagnosis of a multicystic kidney can usually be established by IVP (flank mass, non-visualizing kidney, shelllike calcifications), retrograde pyelogram and B-mode ultrasound. However, it has yet to be proved that non-operative diagnosis can be established with certainty. In most cases, when the diagnosis is clear and the patient is asymptomatic, nephrectomy may not be necessary in the neonatal period. However, because the multicystic kidney may be symptomatic in later life and until its relationship to hypertension and possible malignant degeneration is established, elective nephrectomy should be considered after the neonatal period. When there is any doubt about the diagnosis of a multicystic kidney or when there are any related symptoms an operation is mandatory. EDITORIAL COMMENT The authors have compiled a comprehensive review, incorporating our current knowledge and opinions on a clinical entity important to those doing pediatric urology. As newer diagnostic methods come along the management of these lesions becomes potentially more complex. Nevertheless, I predict the equation mass plus surgeon equals operation will hold indefinitely. Harry M. Spence 4105 Live Oak Street Dallas, Texas
THE LIABILITY OF A MULTICYSTIC KIDNEY
Clinical symptoms owing to multicystic kidneys are not uncommon. Pain, infection and encroachment on adjacent viscera are well recognized. Indeed, 31 per cent of the responding urologists had encountered patients with symptoms attributed to a multicystic kidney. In about a third of these cases infection and hypertension were listed as symptoms. The literature contains only 1 clear-cut example of hypertension
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Paris: J. B. Bailliere Libraire, 1836. 2. Schwartz, J.: An unusual unilateral multicystic kidney in an infant. J. Urol., 35: 259, 1936. 3. Ravitch, M. M. and Sanford, M. C.: Unilateral multicystic kidney in infants. Pediatrics, 4: 769, 1949. 4. Spence, H. M.: Congenital unilateral multicystic kidney: an
IvfULTICYS1'1C KID:NEY
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rnn 180 Hiinig, R. and Kinser, J.: Ultrasonic diagnosis ofWilms tumorso Amer. J. Roentgen., 117: 119, 1973. 19. Bearman, S. B., Hine, P. L. and Sanders, R. C.: Multicystic kidney: a sonographic pattern. Radiology, 118: 685, 1976. 20. Uson, A. C., Del Rosario, C. and Melicow, M. M.: Wilms tumor in association with cystic renal disease: report of two cases. J. Urol., 83: 262, 1960. 21. Christ, M. L.: Polycystic nephroblastoma. J. Urol., 98: 570, 1967. 22. Datnow, B. and Daniel, W.W., Jr.: Polycystic nephroblastoma. J.A.M.A., 236: 2528, 1976. 23. Raffensperger, J. and Abousleiman, A.: Abdominal masses in children under one year of age. Surgery, 63: 514, 1968. 24. Bove, K. E., Kaffler, H. and McAdams, A. J.: Nodular renal blastema. Definition and possible significance. Cancer, 24: 323, 1969. 25. Potter, E. L.: Pathology of the Fetus and Infant, 2nd ed. Chicago: Yearbook Medical Publishers, p. 199, 1961. 26. Rous, S. N., Bailie, M. D., Kaufman, D. B., Raddy, T. B. and Mattson, J. C.: Nodular renal blastema, nephroblastomatosis, and Wilms' tumor. Different points on the same disease spectrum? Urology, 8: 599, 1976. 27. Javadpour, N., Chelouhy, E., Moncada, L., Rosenthal, I. M. and Bush, I. M.: Hypertension in a child caused by a multicystic kidney. J. Urol., 104: 918, 1970. 28. Pazdral, P. T., Lieberman, H. M., Pazdral, W. E., Neuman, C. G. and Lieberman, E.: Awareness of pediatric hypertension. Measuring blood pressure. J.A.M.A., 235: 2320, 1976. 29. Ambrose, S.: Unilateral multicystic renal disease in adults. Personal communication. 30. Giitter, W. and Hermanek, P.: Maligner Tumor der Nierengegend Unter dem Bilde der Knollenniere (Nierenblastemcysten). Urol. Int., 4: 164, 1957 .. 31. Pathak, I. G. and Williams, D. I.: Multicystic and cystic dysplastic kidneys. Brit. J. Urol., 36: 318, 1964.
