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Medullary sponge kidney
T h e J o u r n a l o[ P E D I A T R I C S
901
Medullary sponge kidney Two cases in young infants
Medullary sponge kidneys are characterized by the cystic dilatation o[ collecting tubules in the renal medulla. T h e cortex is generally normal. No symptoms are present unless there is injection or lithiasis. The abnormality appears to be an intrinsic enlargement o[ collecting tubules related to hamartomatous polycystic kidneys. I t has only recently been recognized and most cases have been described in adults. T w o examples in young in[ants are reported.
Edith L. Potter, M.D., Ph.D.,* and Vitoon Osathanondh, M.D., M.S. ** CHICAGO,
ILL.
M E D U L L A R Y sponge kidney is a term applied to those kidneys in which localized or generalized cystic dilatation of collecting tubules in the renal medulla, especially in the papillae, is the outstanding abnormality. In the majority of documented cases the diagnosis has been made by x-ray examination of patients with symptoms of hematuria, pyuria, or lithiasis. It has been observed most often in the fourth decade and more than twice as often in men as in women. It has generally been considered a congenital malformation and a variant of polycystic
From the Department o[ Obstetrics and Gynecology, The University o[ Chicago and Chicago Lying-in Hospital, Chicago, lU. Support [or this work was provided by United States Public Health Service Grant [or Medical 9Research RG-3166. ~Address, De#artment o] Obstetrics and Gynecology, Chicago Lying-ln Hospital, 5841 Maryland Avenue, Chicago 37, Ill. "• Medical Board o[ New York Postdoctoral Fellow in Pathology, ]rom Sirlra) Medical School, Bangkok, Thailand.
kidneys; however, no cases intermediate between sponge kidneys and polycystic kidneys have been described. If this is a congenital malformation, it should be found in any large series of autopsies on infants and, consequently, a search was made among the 12,000 autposies on fetuses and infants under 1 year of age that have been performed at the Chicago Lying-in Hospital. This revealed only 2 cases where dilatation of the medullary portions of collecting tubules was the outstanding abnormality. In most cases where collecting tubules are cystic there were also varying degrees of cortical dysplasia which eliminates them from the condition under discussion.
CASE 1 This autopsy was performed in another hospital and the protocol and tissues were sent to the Chicago Lying-in Hospital for microscopic examination and final review. The child was female, aged 7 months, 8 days. The clinical diagnosis was Mongolism and probable congenital heart
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disease. The gross postmortem examination revealed abnormalities only in heart and kidneys. The heart was enlarged and had an interventricular septal defect and a patent ductus arteriosus. Both kidneys were moderately enlarged and had a barely visible diffuse dilatation of tubules irt some papillae; this was especially marked in the left kidney. In the right there were a few groups of small subscapsular cysts measuring 1 to 4 mm. in diameter. O n microscopic examination changes were found only in localized portions of medulla and cortex. In the left kidney changes were most marked in the medulla, in the right they were most marked in the cortex, but both zones were involved to some extent in both kidneys. Some of the renal pyramids were normal while others were moderately enlarged as a result of a marked, fairly uniform increase in diameter of collecting tubules and a slight diffuse increase in intertubular connective tissue (Fig. 1). In a few papillae only scattered tubules were abnormal. The outlines of all involved tubules were irregular, were lined by high cuboidal epithelium, and communicated freely with the renal pelvis. In the cortex peripheral to the abnormal pyramids a few of the collecting tubules in the medullary rays were slightly dilated, a few of the nephrons had localized areas of dilatation producing minute cysts, Bowman's capsules were occasionally dilated, and capillary tufts were spread out over part of the surface instead of being in one clump as in the normal glomerulus. Similar changes although of lesser degree were present in the cortex peripheral to the normal pyramids. The right kidney had only a slight medullary abnormality consisting of a few scattered small round cavities produced by local dilatation of collecting tubules. Cortical changes were more severe than in the left kidney and everywhere under the capsule were occasional small cysts caused by enlargement of Bowman's spaces and local dilatation of secretory tubules. Most of those that had been visible grossly were in wedge-shaped groups, the largest of the cysts being closest to the capsule. A dense layer of connective tissue closely encircled a few of the larger cysts but in the region of the smaller cysts the connective tissue increase was more diffuse. Located in the connective tissue between cysts were dysplastic structures similar to those found in many polycystic kidneys including rudimentary tubules without lumens, abnormal glomeruli, and local hypercellularity of connective tissue.
June 1963
Fig. 1. Case 1. Papilla composed entirely of cystic tubules with a few subcapsular cysts. CASE
2
A mature white female infant weighing 3,785 Gm. was delivered by low forceps after an uneventful pregnancy. The mother was gravida iii, the first 2 pregnancies having terminated in abortions. Examination immediately after birth revealed no abnormalities except a webbed neck and edema of the lower extremities. The child was in satisfactory condition at birth and continued so until the seventh day when the temperature fell, she became cyanotic, and, breathed irregularly. She became rapidly worse and died about 1 hour after onset of symptoms. The folds of skin at the back of the neck and edema of the lower exetremities had led to a tentative clinical diagnosis of ovarian agenesis, but the cause of death was not apparent. Autopsy was limited to thorax and abdomen. Significant changes were found only in ovaries, heart, and kidneys. The ovaries were the threadlike structures without definite ova as characteristically found in ovarian agenesls, although the fallopian tubes, uterine corpus, cervix, and vagina were normal. The heart was symmetrically enlarged to 1 ~ times the normal size but otherwise all chambers and
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great vessels were normal. The endocardium of both ventricles was thickened by an increase in connective and elastic tissue characteristic of fibroelastosis. This extended to the chordae tendinae, many of which were also calcified. The kidneys were slightly large as a result of mild increase in size of the pelvis and medullary portions. The lining of the pelves was moderately thickened and more opaque than normal. No cysts were grossly visible. The microscopic appearance was similar to that of Case 1 except that the changes were somewhat more mild. In some papillae most tubules were enlarged (Fig. 2). The walls were smooth and more regular than in the preceding case, but there was no flattening of epitheliaI celIs or other evidence of stretching due to obstruction and no increase in connective tissue. In some papillae only scattered tubules were enlarged and in some all tubules were normal. Cortical changes were less marked than in Case 1 and no cysts were grossly visible. However, in the medullary rays there were occasional groups of cystic collecting tubules and under the capsule a few cysts that had resulted from dilatation of secretory tubules or Bowman's capsules. Changes were of the same variety and degree in both kidneys.
Fig. 2. Case 2. Papilla with many cystic tubules.
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COMMENT
F o r m a n y years cysts l i m i t e d largely to the m e d u l l a r y p o r t i o n of the k i d n e y have been known to occur but they have received little a t t e n t i o n until recently. I n 1939 L e n a r d u z z i la called a t t e n t i o n to such cysts a n d a t t r i b u t e d t h e m to a developm e n t a l arrest. I n 1945 S m i t h a n d G r a h a m ~~ described a n 8-year-old child w i t h cysts h o n e y c o m b i n g the m e d u l l a r y p o r t i o n of the kidney who died of renal insufficiency complicated by severe a n e m i a a n d h y p e r p a r a thyroidism. T h e cortex was v e r y thin a n d showed severe changes, especially g l o m e r u l a r fibrosis, w h i c h was explained as a result of i n t r a r e n a l h y d r o n e p h r o s i s following increased i n t r a t u b u l a r pressure caused b y the e x p a n d i n g m e d u l l a r y cysts. PowelP 7 in 1949 r e c o r d e d small m e d u l l a r y cysts a n d dilated collecting tubules in the kidney of a 20-yearold m a n who h a d h a d h e m a t u r i a a n d renal colic. T h e cortex was n o r m a l b u t the collecting tubules were described as enlarged, b r a n c h e d , a n d often completely d i l a t e d even to their calyceat outlets. Some, on the other had, seemed n o t to be canalized. H e was unable to find a similar case in the l i t e r a t u r e a n d t h o u g h t he was describing a n e w form of t u b u l a r m a l f o r m a t i o n . I n the same y e a r Cacchi a n d R i c c i a described 5 cases u n d e r the designation of sponge k i d n e y in which m e d u l l a r y cysts were visible on x-ray. This appears to have been the first use of this term a n d it seems to have s t i m u l a t e d considerable interest especially a m o n g roentgenologists. I n the next few years m a n y case reports a n d descriptions of x - r a y s were p u b lished in I t a l y and France. I n the U n i t e d States V e r m o o t e n ~1 a n d M u l v a n e y a n d Collins 2~ listed single cases of m e d u l l a r y cysts, a n d Hogness a n d Burnell n (1954) r e p o r t e d 4 cases similar to the one described b y Smith a n d G r a h a m . T h e first general discussions in English of sponge kidney came in 1959 from E k s t r 6 m and his co-workers" a n d L i n d v a l l 2~ in Sweden, a n d Rubin, Ross, a n d T u r n e r "s in England. Since then extensive reviews h a v e been published in the U n i t e d States b y Abeshouse a n d Abeshouse 1 a n d M u r p h y , Palubinskas a n d S m i t h y a
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The condition, as generally described by the roentgenologists, consists of multiple localized cavities adjacent to the renal calyces which are better visualized on intravenous urography than on retrograde pyelograms. The cavities are of various sizes and shapes and have been likened to fans, grapes, flowers, mosaics, and so on. Pressure applied to the ureter is said to increase their size; this would indicate a communication with the renal pelvis. Only Neuhaus 24 has insisted that they may be visible in retrograde pyelograms while invisible on intravenous urography. Lithiasis, attributed to infection, is also often present. Other conditions that must be differentiated on x-ray are renal tuberculosis, papillary necrosis or abscesses, calyceal cysts and diverticulae, cysts secondary to acute or chronic pyelonephritis, nephrocalcinosis and tubular stasis. Some authors, especially De Sienna and GuareschP have thought that m a n y cases formerly considered as calyceal diverticulae or nephrocalcinosis should be designated sponge kidneys. Since nephrocatcinosis is a nonspecific term indicating only that calcium salts are deposited in the kidney, Batestra and Delpino 2 have suggested that to be certain of the diagnosis of sponge kidney as opposed to nephrocalcinosis, the involvement should be limited to a part of one kidney or to those in which lithiasis is absent if both kidneys are affected. There has been some question as to whether the sponge kidney should be considered a definite entity but with the exception of a few authors such as Fey, 7 who have expressed some doubt, the roentgenologists are fairly well agreed that it should. Petkovic's 26 summary of the condition has been widely quoted and the features he described have been accepted as characteristic. These include a nonprogressive bilateral involvement of all pyramids, the dilated tubules giving an x-ray appearance of a bunch of flowers, a normal cortex, and good renal function. It has also been generally agreed that the cystic~ tubules per se produce no symptoms and that symptoms arise only from infection or lithiasis; that although one or
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both of the latter are almost always present when the diagnosis is made, they are secondary and not etiologic. Some of these concepts have been challenged. Ekstr6m and Lindvall in reporting cases from the Karolinska Sjukkuset included several with unilateral involvement and some in which only 1 pyramid was affected. In none was the cortex thin and in several the kidney was enlarged. They also thought that the x-ray appearance was not always like a "bunch of flowers" and ineluded cases that showed fine or coarse striations that appeared to be dilated collecting tubules passing from tip to base of papillae. Other cavities were rounded and cystlike and varied from those hardly visible to those the size of a pea. Darget and Ballanger 4 questioned whether lack of change is necessarily a characteristic because 1 case they observed showed marked improvement after several months on a tuberculosis regimen, and Neuhaus reported a case in which an earlier examination had failed to reveal medullary abnormality. Hickle, 1~ Fey, Pelot ~ and others have objected to designating the cavities as cysts saying that cysts do not have an outlet and would not be expected to fill with any kind of injection media. It seems evident from a careful perusal of the literature that the cases included under the term medullary sponge kidney vary considerably and that the principle requirement for the x-ray diagnosis is tile demonstration of multiple areas in the medullary portion of the kidney that fill with contrast media and are ordinarily better demonstrated by intravenous urography than retrograde pyelograms. Histologic studies of kidneys whose main abnormality has been cystic dilatation of medullary tubules have been far fewer than the x-ray studies. As would be expected, the kidneys described have varied widely. Some have exhibited fairly uniform dilatation of tubules, m a n y of which communicated freely with the pelvis as in the cases of Powell 2~ and Giinther2 Mulvaney and Collins 22 could pass a probe from the renal pelvis into m a n y of the cavities in their case. In some in-
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stances, especially one observed by Giinther, the collecting tubules were fairly uniformly ectatic and separated by thickened connective tissue septa having an appearance much like that in our first case. In some cases the majority of the collecting tubules appeared normal and only occasional round or oval cystic spaces which had no visible communciation with the pelvis were scattered throughout the medulla. Where photographs of the gross appearance have been published, cavities varying from a few millimeters to a centimeter or more have usually been present throughout the medulla and extension toward the capsule has often caused considerable thinning of the cortex. Although the statement is generally made that the cortex is normal and Abeshouse and Abeshouse 1 have insisted that any cysts in the cortex are secondary to pyelonephritis and are not part of the intrinsic renal disturbance, most of the photomicrographs that include renal cortex show at least occasional cystic structures that do not appear to be a result of pyelonephritis. The one case of Smith and Graham a~ and the four cases of Hogness and BurnelP 1 are generally not included in discussions of sponge kidney in spite of the fact that the lesions in the medulla appear to be as marked as in any described. This may be because of the accompanying glomerular sclerosis and atrophy (which were attributed to pressure from enlarging medullary cysts) or because no x-rays were made. However, if one were to include as sponge kidneys only those in which the cortex is entirely normal except for infection, most of the kidneys studied histologically would be excluded. It is a question of how much cortical change can exist and still warrant a diagnosis of this condition. The tendency on the part of most reviewers seems to have been to include those with markedly dilated or cystic collecting tubules associated with nephrons t h a t were normal except for changes secondary to infection. In our opinion the case of Smith and Graham and those of Hogness and Burnell should be included. If this condition is a congenital malforma-
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tion, it should be found occasionally in infants and children. The only references to its occurrence in children under 10 are extremely vague. Ekstr6m mentioned that Ricci said Cabanne observed the condition in a fetus and Lenarduzzi 14 documented that he saw a 3-day-old who died of a renal malformation which included hydronephrosis, calyceal dilatation, and parenchymal compression as well as being a sponge kidney. One case that has been included in some reviews is in a paper by Sanchez-Lucas 29 on polycystic kidneys. His case, however, appears to have been a typical polycsytic kidney of the hamartomatous type in which all collecting tubules were dilated. This variety has occasionally been designated sponge kidney, especially by the French. It is possible that Cabanne's case was of the same type. Gayet s refered to a diagnosis made in a 7-year-old child by Professor Cibert but gave no further information. Josserand, Annius, and Mugniery 12 described a typical x-ray picture in a child of 10 years without symptoms other than polyuria. The eases of Smith and Graham in an 8-year-old child and Hogness and Burnell in one of 15 years both showed multiple medullary cysts but had such marked degenerative changes in the cortex that they are generally not included as medullary sponge kidneys. The pathogenesis of sponge kidney has almost without exception been considered a derangement of embryonic development related to polycystic kidneys. Most authors have described Kampmeier's theory of the etiology of polycystic kidneys as a probable cause. Vermooten attributed the dilatation to irritation from deposits of uric acid crystals. According to Kampmeier's 13 theory renal cysts result from enlargement of vestigeal nephrons that never attach to collecting tubules or after a period of attachment detach and never reattach. We do not think Kampmeier was correct in his deductions, but even if he were, sponge kidneys could not be explained on this basis inasmuch as it is collecting tubules and not nephrons that are primarily involved in sponge kidneys. According to Vermooten's al theory the
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deposit of uric acid is responsible for obstruction and dilatation, but the frequency of uric acid deposits and the rarity of diffuse cystic dilatation of tubules renders an association between the two highly unlikely. From a careful perusal of the literature and investigation of 2 cases observed at the Chicago Lying-in Hospital, it seems to us that the dilatation of tubules found in socalled medullary sponge kidney is a form of congenital dysplasia of renal development related to the hamartomatous variety of polycystic kidneys. In a fully developed state hamartomatous kidneys are found only in the newborn period. The majority of collecting tubules are greatly widened and elongated and the cortex appears almost as abnormal as the medulla. Such kidneys have been designated as sponge kidneys by some investigators and by others as hamartomas, polycystic kidneys of the newborn, and so on. On first inspection they seem to be in sharp contrast to the medullary sponge kidney under discussion where the changes, when generalized, are most marked in the papillae and when localized are visible as scattered cysts limited to the medulla. In hamartomatous kidneys development of nephrons is generally normal and the only abnormality is a great increase in size of collecting tubules. The changes are uniform throughout both kidneys and we have never seen peritubular fibrosis or cysts of Bowman's spaces. It does seem possible, however, that in some instances the hamartomatous changes might be limited to the tubules in the papillae and that the medullary sponge kidney might be mild or localized form of the generalized variety that is well recognized in the newborn. If true medullary sponge kidney is to be interpreted as a localized form of the newborn hamartomatous variety, then our 2 cases, and probably m a n y reported by other authors, should perhaps, be considered a mixed variety in which the predominant change is in medullary tubules but in which minor changes characteristic of the dysplastic polycystic kidney are present in the cortex.
Under any circumstances medullary sponge kidney can be considered a form of polycystic kidney in which cystic dilatation of the medullary portions of the tubules is the outstanding feature. The coexistence of mild cystic dilatation of cortical tubules or cortical changes secondary to infection or other disturbance would be compatible with the diagnosis. Such a definition would inelude the cases of Smith and Hogness and Burnell since cysts were not found in the cortex. It would seem that neither complete absence of cysts in the cortex nor a lack of change with the passage of time should be required for a diagnosis. Infection is reputedly present in at least 80 per cent of cases and occasional microscopic cortical cysts are to be expected whenever collecting tubules are severely involved. I t is also almost inconceivable that cavities should remain completely static from birth to old age. If they were to completely disappear or to suddenly show great increase in size, it could be assumed that the diagnosis had been in error, but moderate changes might well be found. The fact that the prognosis is said to be excellent may be true of the entirely uncomplicated cases, but secondary changes m a y be severe, and the fact that x-rays show cysts only in the renal papillae does not ensure normal renal function. SUMMARY
Medullary sponge kidney is a term applied when all or part of the collecting tubules in the medulla are dilated to cystic proportions but tubules in the cortex are normal. Such cysts do not interfere with renal function but predispose to infection and lithiasis. A diagnosis of cystic tubules can be made by x-ray, especially excretory urography, but the condition of tile rest of the kidney must be determined by laboratory tests or histologic examination. It appears to be a congenital malformation characterized by an intrinsic enlargement of the proximal portions of the collecting tubules and as such is a dysplasia related to polycystic kidneys. Two cases in infants are described.
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REFERENCES 1. Abeshouse, B, S., and Abeshouse, G. A.: Sponge kidney. A review of the literature and report of 5 cases, J. Urol. 84: 252, 1960. 2. Balestra, G., and Delpino, B.: In tema di rene a spugna e di nefrocalcinosi, Radiol. med. 42: 745, 1956. 3. Cacchi, R., and Ricci, V.: Sur une rare maladie Kystique multiple des pyramides rdnales le "rein en 6ponge," J. Urol. m6d. chit. 55: 497, 1949. 4. Darget, R., and Ballanger, R.: Sur un cas de rein "en @onge," J. Urol. m6d. chit. 60: 409, 1953. 5. Di Sieno, A., and Guareschi, B.: I1 rene a spugna midollare con calcolosi multipla endocavitaria ed i suoi possibili rapporti con la nefrocalcinosi, Radiol. med. 42: 167, 1956. 6. EkstrSm, F., Engefeldt, B., Lagergren, L., and Lindvall, N.: Medullary sponge kidney, Stockholm, 1959, Almquist-Wiksel (monograph ) 7. Fey, M.: Discussion to Hickel, R., 8. Gayet, R.: Discussion to Hickel, R.: Un cas de "rein de 6ponge," J. Urol. m6d. chir. 59: 409, 1953. 9. Giinther, G. W.: Die Markcysten der Niere, Z. Urol. 43: 29, I950. 10. Hickel, R.: U n cas de "rein en ~ponge," J. Urol. m6d. chir. 59: 408, 1953~ 11. Hogness, J. R., Burnell, J. M.: Medullary cysts of the kidney, A. M. A. Arch. int. Med. 93: 355, 1954. 12. Josserand, P., Annius, R., and Mugniery, L.: Le rein 6ponge, Pfdiatrie 7: 31, 1952. 13. Kampmeier, O. F.: A hitherto unrecognized mode of origin of congenital renal cysts, Surg. Gynee. Obst. 36: 208, 1923. 14. Lenarduzzi, G.: Reperto pielografico poco comune (dilatazione della vie urlnaire intrarenali), Radiol. med. 26: 346, 1939. 15. Lenarduzzi, G.: Un altro caso di dilatazione delle vie urinarie preprelviche, Radiol. reed. 26: 884, 1939.
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16. Lenarduzzi, G.: Sul rene a spugna, Radiol. med. 35: 992, 1949. 17. Lenarduzzi, G.: La forma circoscritta di rene spugna, Radiol. reed. 37: 776, 1951. 18. Lenarduzzi, G.: Evoluzione del rene a spugna, Radiol. reed. 38" 57, 1952. 19. Lenarduzzi, G.: Rene a spugna parcellare, Radiol. reed. 38: 1084, 1952. 20. Lindvall, N.: Roentgenologic diagnosis of medullary sponge kidney, Acta, radiol. 51" 193, 1959. 21. Lhez, M. A.: Le rein en 6ponge (douze observations), J. Urol. m6d. chir. 60: 575, 1954. 22. Mulvaney, W. P., and Collins, W. J.: Cystic disease of the renal pyramids, J. Urol. 75: 776, 1956. 23. Murphy, W. K., Palubinskas, A. J., and Smith, D. R., Sponge kidney: Report of seven cases, J. Urol. 85: 866, 1961. 24. Neuhaus, W.: Multiple Zysten der Tubuli recti, Fortschr. Oeb. R6ntgenstrahlen 84: 108, 1956. 25. Pelot, G.: Discussion to Lhez, A.: Le rein en 6ponge, J. Urol. todd. chit. 60: 587, 1954. 26. Petkovic, S.: Contribution ~t l'4tude de la maladie kystique des pyramides r6nales, J. Urol, m6d. chir. 58: 425, 1952. 27. PoweII, R. E.: An unusual congenital deformity of the kidney, Canad. M. A. J. 60: 48, 1949. 28. Rubin, E. L., Ross, J. C., and Turner, D. P. B.: Cystic disease of the renal pyramids ("sponge kidney"), J. Fac. Radiologists I0: 134, 1959. 29. Sanchez-Lucas, J. G.: Morphogenese de rein Polykystique, Semaine H6p. Paris 71: 2793, 1951. 30. Smith, C. H., and Graham, J. B.: Congenital medullary cysts of the kidney with severe refractory anemia, Am. J. Dis. Child. 69: 369, 1945. 31. Vermooten, V.: Congenital cystic dilatation of the renal collecting tubules, Yale J. Biol. Med. 23: 450, 1951.
901
Medullary sponge kidney Two cases in young infants
Medullary sponge kidneys are characterized by the cystic dilatation o[ collecting tubules in the renal medulla. T h e cortex is generally normal. No symptoms are present unless there is injection or lithiasis. The abnormality appears to be an intrinsic enlargement o[ collecting tubules related to hamartomatous polycystic kidneys. I t has only recently been recognized and most cases have been described in adults. T w o examples in young in[ants are reported.
Edith L. Potter, M.D., Ph.D.,* and Vitoon Osathanondh, M.D., M.S. ** CHICAGO,
ILL.
M E D U L L A R Y sponge kidney is a term applied to those kidneys in which localized or generalized cystic dilatation of collecting tubules in the renal medulla, especially in the papillae, is the outstanding abnormality. In the majority of documented cases the diagnosis has been made by x-ray examination of patients with symptoms of hematuria, pyuria, or lithiasis. It has been observed most often in the fourth decade and more than twice as often in men as in women. It has generally been considered a congenital malformation and a variant of polycystic
From the Department o[ Obstetrics and Gynecology, The University o[ Chicago and Chicago Lying-in Hospital, Chicago, lU. Support [or this work was provided by United States Public Health Service Grant [or Medical 9Research RG-3166. ~Address, De#artment o] Obstetrics and Gynecology, Chicago Lying-ln Hospital, 5841 Maryland Avenue, Chicago 37, Ill. "• Medical Board o[ New York Postdoctoral Fellow in Pathology, ]rom Sirlra) Medical School, Bangkok, Thailand.
kidneys; however, no cases intermediate between sponge kidneys and polycystic kidneys have been described. If this is a congenital malformation, it should be found in any large series of autopsies on infants and, consequently, a search was made among the 12,000 autposies on fetuses and infants under 1 year of age that have been performed at the Chicago Lying-in Hospital. This revealed only 2 cases where dilatation of the medullary portions of collecting tubules was the outstanding abnormality. In most cases where collecting tubules are cystic there were also varying degrees of cortical dysplasia which eliminates them from the condition under discussion.
CASE 1 This autopsy was performed in another hospital and the protocol and tissues were sent to the Chicago Lying-in Hospital for microscopic examination and final review. The child was female, aged 7 months, 8 days. The clinical diagnosis was Mongolism and probable congenital heart
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disease. The gross postmortem examination revealed abnormalities only in heart and kidneys. The heart was enlarged and had an interventricular septal defect and a patent ductus arteriosus. Both kidneys were moderately enlarged and had a barely visible diffuse dilatation of tubules irt some papillae; this was especially marked in the left kidney. In the right there were a few groups of small subscapsular cysts measuring 1 to 4 mm. in diameter. O n microscopic examination changes were found only in localized portions of medulla and cortex. In the left kidney changes were most marked in the medulla, in the right they were most marked in the cortex, but both zones were involved to some extent in both kidneys. Some of the renal pyramids were normal while others were moderately enlarged as a result of a marked, fairly uniform increase in diameter of collecting tubules and a slight diffuse increase in intertubular connective tissue (Fig. 1). In a few papillae only scattered tubules were abnormal. The outlines of all involved tubules were irregular, were lined by high cuboidal epithelium, and communicated freely with the renal pelvis. In the cortex peripheral to the abnormal pyramids a few of the collecting tubules in the medullary rays were slightly dilated, a few of the nephrons had localized areas of dilatation producing minute cysts, Bowman's capsules were occasionally dilated, and capillary tufts were spread out over part of the surface instead of being in one clump as in the normal glomerulus. Similar changes although of lesser degree were present in the cortex peripheral to the normal pyramids. The right kidney had only a slight medullary abnormality consisting of a few scattered small round cavities produced by local dilatation of collecting tubules. Cortical changes were more severe than in the left kidney and everywhere under the capsule were occasional small cysts caused by enlargement of Bowman's spaces and local dilatation of secretory tubules. Most of those that had been visible grossly were in wedge-shaped groups, the largest of the cysts being closest to the capsule. A dense layer of connective tissue closely encircled a few of the larger cysts but in the region of the smaller cysts the connective tissue increase was more diffuse. Located in the connective tissue between cysts were dysplastic structures similar to those found in many polycystic kidneys including rudimentary tubules without lumens, abnormal glomeruli, and local hypercellularity of connective tissue.
June 1963
Fig. 1. Case 1. Papilla composed entirely of cystic tubules with a few subcapsular cysts. CASE
2
A mature white female infant weighing 3,785 Gm. was delivered by low forceps after an uneventful pregnancy. The mother was gravida iii, the first 2 pregnancies having terminated in abortions. Examination immediately after birth revealed no abnormalities except a webbed neck and edema of the lower extremities. The child was in satisfactory condition at birth and continued so until the seventh day when the temperature fell, she became cyanotic, and, breathed irregularly. She became rapidly worse and died about 1 hour after onset of symptoms. The folds of skin at the back of the neck and edema of the lower exetremities had led to a tentative clinical diagnosis of ovarian agenesis, but the cause of death was not apparent. Autopsy was limited to thorax and abdomen. Significant changes were found only in ovaries, heart, and kidneys. The ovaries were the threadlike structures without definite ova as characteristically found in ovarian agenesls, although the fallopian tubes, uterine corpus, cervix, and vagina were normal. The heart was symmetrically enlarged to 1 ~ times the normal size but otherwise all chambers and
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great vessels were normal. The endocardium of both ventricles was thickened by an increase in connective and elastic tissue characteristic of fibroelastosis. This extended to the chordae tendinae, many of which were also calcified. The kidneys were slightly large as a result of mild increase in size of the pelvis and medullary portions. The lining of the pelves was moderately thickened and more opaque than normal. No cysts were grossly visible. The microscopic appearance was similar to that of Case 1 except that the changes were somewhat more mild. In some papillae most tubules were enlarged (Fig. 2). The walls were smooth and more regular than in the preceding case, but there was no flattening of epitheliaI celIs or other evidence of stretching due to obstruction and no increase in connective tissue. In some papillae only scattered tubules were enlarged and in some all tubules were normal. Cortical changes were less marked than in Case 1 and no cysts were grossly visible. However, in the medullary rays there were occasional groups of cystic collecting tubules and under the capsule a few cysts that had resulted from dilatation of secretory tubules or Bowman's capsules. Changes were of the same variety and degree in both kidneys.
Fig. 2. Case 2. Papilla with many cystic tubules.
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COMMENT
F o r m a n y years cysts l i m i t e d largely to the m e d u l l a r y p o r t i o n of the k i d n e y have been known to occur but they have received little a t t e n t i o n until recently. I n 1939 L e n a r d u z z i la called a t t e n t i o n to such cysts a n d a t t r i b u t e d t h e m to a developm e n t a l arrest. I n 1945 S m i t h a n d G r a h a m ~~ described a n 8-year-old child w i t h cysts h o n e y c o m b i n g the m e d u l l a r y p o r t i o n of the kidney who died of renal insufficiency complicated by severe a n e m i a a n d h y p e r p a r a thyroidism. T h e cortex was v e r y thin a n d showed severe changes, especially g l o m e r u l a r fibrosis, w h i c h was explained as a result of i n t r a r e n a l h y d r o n e p h r o s i s following increased i n t r a t u b u l a r pressure caused b y the e x p a n d i n g m e d u l l a r y cysts. PowelP 7 in 1949 r e c o r d e d small m e d u l l a r y cysts a n d dilated collecting tubules in the kidney of a 20-yearold m a n who h a d h a d h e m a t u r i a a n d renal colic. T h e cortex was n o r m a l b u t the collecting tubules were described as enlarged, b r a n c h e d , a n d often completely d i l a t e d even to their calyceat outlets. Some, on the other had, seemed n o t to be canalized. H e was unable to find a similar case in the l i t e r a t u r e a n d t h o u g h t he was describing a n e w form of t u b u l a r m a l f o r m a t i o n . I n the same y e a r Cacchi a n d R i c c i a described 5 cases u n d e r the designation of sponge k i d n e y in which m e d u l l a r y cysts were visible on x-ray. This appears to have been the first use of this term a n d it seems to have s t i m u l a t e d considerable interest especially a m o n g roentgenologists. I n the next few years m a n y case reports a n d descriptions of x - r a y s were p u b lished in I t a l y and France. I n the U n i t e d States V e r m o o t e n ~1 a n d M u l v a n e y a n d Collins 2~ listed single cases of m e d u l l a r y cysts, a n d Hogness a n d Burnell n (1954) r e p o r t e d 4 cases similar to the one described b y Smith a n d G r a h a m . T h e first general discussions in English of sponge kidney came in 1959 from E k s t r 6 m and his co-workers" a n d L i n d v a l l 2~ in Sweden, a n d Rubin, Ross, a n d T u r n e r "s in England. Since then extensive reviews h a v e been published in the U n i t e d States b y Abeshouse a n d Abeshouse 1 a n d M u r p h y , Palubinskas a n d S m i t h y a
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The condition, as generally described by the roentgenologists, consists of multiple localized cavities adjacent to the renal calyces which are better visualized on intravenous urography than on retrograde pyelograms. The cavities are of various sizes and shapes and have been likened to fans, grapes, flowers, mosaics, and so on. Pressure applied to the ureter is said to increase their size; this would indicate a communication with the renal pelvis. Only Neuhaus 24 has insisted that they may be visible in retrograde pyelograms while invisible on intravenous urography. Lithiasis, attributed to infection, is also often present. Other conditions that must be differentiated on x-ray are renal tuberculosis, papillary necrosis or abscesses, calyceal cysts and diverticulae, cysts secondary to acute or chronic pyelonephritis, nephrocalcinosis and tubular stasis. Some authors, especially De Sienna and GuareschP have thought that m a n y cases formerly considered as calyceal diverticulae or nephrocalcinosis should be designated sponge kidneys. Since nephrocatcinosis is a nonspecific term indicating only that calcium salts are deposited in the kidney, Batestra and Delpino 2 have suggested that to be certain of the diagnosis of sponge kidney as opposed to nephrocalcinosis, the involvement should be limited to a part of one kidney or to those in which lithiasis is absent if both kidneys are affected. There has been some question as to whether the sponge kidney should be considered a definite entity but with the exception of a few authors such as Fey, 7 who have expressed some doubt, the roentgenologists are fairly well agreed that it should. Petkovic's 26 summary of the condition has been widely quoted and the features he described have been accepted as characteristic. These include a nonprogressive bilateral involvement of all pyramids, the dilated tubules giving an x-ray appearance of a bunch of flowers, a normal cortex, and good renal function. It has also been generally agreed that the cystic~ tubules per se produce no symptoms and that symptoms arise only from infection or lithiasis; that although one or
June 1963
both of the latter are almost always present when the diagnosis is made, they are secondary and not etiologic. Some of these concepts have been challenged. Ekstr6m and Lindvall in reporting cases from the Karolinska Sjukkuset included several with unilateral involvement and some in which only 1 pyramid was affected. In none was the cortex thin and in several the kidney was enlarged. They also thought that the x-ray appearance was not always like a "bunch of flowers" and ineluded cases that showed fine or coarse striations that appeared to be dilated collecting tubules passing from tip to base of papillae. Other cavities were rounded and cystlike and varied from those hardly visible to those the size of a pea. Darget and Ballanger 4 questioned whether lack of change is necessarily a characteristic because 1 case they observed showed marked improvement after several months on a tuberculosis regimen, and Neuhaus reported a case in which an earlier examination had failed to reveal medullary abnormality. Hickle, 1~ Fey, Pelot ~ and others have objected to designating the cavities as cysts saying that cysts do not have an outlet and would not be expected to fill with any kind of injection media. It seems evident from a careful perusal of the literature that the cases included under the term medullary sponge kidney vary considerably and that the principle requirement for the x-ray diagnosis is tile demonstration of multiple areas in the medullary portion of the kidney that fill with contrast media and are ordinarily better demonstrated by intravenous urography than retrograde pyelograms. Histologic studies of kidneys whose main abnormality has been cystic dilatation of medullary tubules have been far fewer than the x-ray studies. As would be expected, the kidneys described have varied widely. Some have exhibited fairly uniform dilatation of tubules, m a n y of which communicated freely with the pelvis as in the cases of Powell 2~ and Giinther2 Mulvaney and Collins 22 could pass a probe from the renal pelvis into m a n y of the cavities in their case. In some in-
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stances, especially one observed by Giinther, the collecting tubules were fairly uniformly ectatic and separated by thickened connective tissue septa having an appearance much like that in our first case. In some cases the majority of the collecting tubules appeared normal and only occasional round or oval cystic spaces which had no visible communciation with the pelvis were scattered throughout the medulla. Where photographs of the gross appearance have been published, cavities varying from a few millimeters to a centimeter or more have usually been present throughout the medulla and extension toward the capsule has often caused considerable thinning of the cortex. Although the statement is generally made that the cortex is normal and Abeshouse and Abeshouse 1 have insisted that any cysts in the cortex are secondary to pyelonephritis and are not part of the intrinsic renal disturbance, most of the photomicrographs that include renal cortex show at least occasional cystic structures that do not appear to be a result of pyelonephritis. The one case of Smith and Graham a~ and the four cases of Hogness and BurnelP 1 are generally not included in discussions of sponge kidney in spite of the fact that the lesions in the medulla appear to be as marked as in any described. This may be because of the accompanying glomerular sclerosis and atrophy (which were attributed to pressure from enlarging medullary cysts) or because no x-rays were made. However, if one were to include as sponge kidneys only those in which the cortex is entirely normal except for infection, most of the kidneys studied histologically would be excluded. It is a question of how much cortical change can exist and still warrant a diagnosis of this condition. The tendency on the part of most reviewers seems to have been to include those with markedly dilated or cystic collecting tubules associated with nephrons t h a t were normal except for changes secondary to infection. In our opinion the case of Smith and Graham and those of Hogness and Burnell should be included. If this condition is a congenital malforma-
Medullary sponge kidney
905
tion, it should be found occasionally in infants and children. The only references to its occurrence in children under 10 are extremely vague. Ekstr6m mentioned that Ricci said Cabanne observed the condition in a fetus and Lenarduzzi 14 documented that he saw a 3-day-old who died of a renal malformation which included hydronephrosis, calyceal dilatation, and parenchymal compression as well as being a sponge kidney. One case that has been included in some reviews is in a paper by Sanchez-Lucas 29 on polycystic kidneys. His case, however, appears to have been a typical polycsytic kidney of the hamartomatous type in which all collecting tubules were dilated. This variety has occasionally been designated sponge kidney, especially by the French. It is possible that Cabanne's case was of the same type. Gayet s refered to a diagnosis made in a 7-year-old child by Professor Cibert but gave no further information. Josserand, Annius, and Mugniery 12 described a typical x-ray picture in a child of 10 years without symptoms other than polyuria. The eases of Smith and Graham in an 8-year-old child and Hogness and Burnell in one of 15 years both showed multiple medullary cysts but had such marked degenerative changes in the cortex that they are generally not included as medullary sponge kidneys. The pathogenesis of sponge kidney has almost without exception been considered a derangement of embryonic development related to polycystic kidneys. Most authors have described Kampmeier's theory of the etiology of polycystic kidneys as a probable cause. Vermooten attributed the dilatation to irritation from deposits of uric acid crystals. According to Kampmeier's 13 theory renal cysts result from enlargement of vestigeal nephrons that never attach to collecting tubules or after a period of attachment detach and never reattach. We do not think Kampmeier was correct in his deductions, but even if he were, sponge kidneys could not be explained on this basis inasmuch as it is collecting tubules and not nephrons that are primarily involved in sponge kidneys. According to Vermooten's al theory the
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Potter and Osathanondh
deposit of uric acid is responsible for obstruction and dilatation, but the frequency of uric acid deposits and the rarity of diffuse cystic dilatation of tubules renders an association between the two highly unlikely. From a careful perusal of the literature and investigation of 2 cases observed at the Chicago Lying-in Hospital, it seems to us that the dilatation of tubules found in socalled medullary sponge kidney is a form of congenital dysplasia of renal development related to the hamartomatous variety of polycystic kidneys. In a fully developed state hamartomatous kidneys are found only in the newborn period. The majority of collecting tubules are greatly widened and elongated and the cortex appears almost as abnormal as the medulla. Such kidneys have been designated as sponge kidneys by some investigators and by others as hamartomas, polycystic kidneys of the newborn, and so on. On first inspection they seem to be in sharp contrast to the medullary sponge kidney under discussion where the changes, when generalized, are most marked in the papillae and when localized are visible as scattered cysts limited to the medulla. In hamartomatous kidneys development of nephrons is generally normal and the only abnormality is a great increase in size of collecting tubules. The changes are uniform throughout both kidneys and we have never seen peritubular fibrosis or cysts of Bowman's spaces. It does seem possible, however, that in some instances the hamartomatous changes might be limited to the tubules in the papillae and that the medullary sponge kidney might be mild or localized form of the generalized variety that is well recognized in the newborn. If true medullary sponge kidney is to be interpreted as a localized form of the newborn hamartomatous variety, then our 2 cases, and probably m a n y reported by other authors, should perhaps, be considered a mixed variety in which the predominant change is in medullary tubules but in which minor changes characteristic of the dysplastic polycystic kidney are present in the cortex.
Under any circumstances medullary sponge kidney can be considered a form of polycystic kidney in which cystic dilatation of the medullary portions of the tubules is the outstanding feature. The coexistence of mild cystic dilatation of cortical tubules or cortical changes secondary to infection or other disturbance would be compatible with the diagnosis. Such a definition would inelude the cases of Smith and Hogness and Burnell since cysts were not found in the cortex. It would seem that neither complete absence of cysts in the cortex nor a lack of change with the passage of time should be required for a diagnosis. Infection is reputedly present in at least 80 per cent of cases and occasional microscopic cortical cysts are to be expected whenever collecting tubules are severely involved. I t is also almost inconceivable that cavities should remain completely static from birth to old age. If they were to completely disappear or to suddenly show great increase in size, it could be assumed that the diagnosis had been in error, but moderate changes might well be found. The fact that the prognosis is said to be excellent may be true of the entirely uncomplicated cases, but secondary changes m a y be severe, and the fact that x-rays show cysts only in the renal papillae does not ensure normal renal function. SUMMARY
Medullary sponge kidney is a term applied when all or part of the collecting tubules in the medulla are dilated to cystic proportions but tubules in the cortex are normal. Such cysts do not interfere with renal function but predispose to infection and lithiasis. A diagnosis of cystic tubules can be made by x-ray, especially excretory urography, but the condition of tile rest of the kidney must be determined by laboratory tests or histologic examination. It appears to be a congenital malformation characterized by an intrinsic enlargement of the proximal portions of the collecting tubules and as such is a dysplasia related to polycystic kidneys. Two cases in infants are described.
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REFERENCES 1. Abeshouse, B, S., and Abeshouse, G. A.: Sponge kidney. A review of the literature and report of 5 cases, J. Urol. 84: 252, 1960. 2. Balestra, G., and Delpino, B.: In tema di rene a spugna e di nefrocalcinosi, Radiol. med. 42: 745, 1956. 3. Cacchi, R., and Ricci, V.: Sur une rare maladie Kystique multiple des pyramides rdnales le "rein en 6ponge," J. Urol. m6d. chit. 55: 497, 1949. 4. Darget, R., and Ballanger, R.: Sur un cas de rein "en @onge," J. Urol. m6d. chit. 60: 409, 1953. 5. Di Sieno, A., and Guareschi, B.: I1 rene a spugna midollare con calcolosi multipla endocavitaria ed i suoi possibili rapporti con la nefrocalcinosi, Radiol. med. 42: 167, 1956. 6. EkstrSm, F., Engefeldt, B., Lagergren, L., and Lindvall, N.: Medullary sponge kidney, Stockholm, 1959, Almquist-Wiksel (monograph ) 7. Fey, M.: Discussion to Hickel, R., 8. Gayet, R.: Discussion to Hickel, R.: Un cas de "rein de 6ponge," J. Urol. m6d. chir. 59: 409, 1953. 9. Giinther, G. W.: Die Markcysten der Niere, Z. Urol. 43: 29, I950. 10. Hickel, R.: U n cas de "rein en ~ponge," J. Urol. m6d. chir. 59: 408, 1953~ 11. Hogness, J. R., Burnell, J. M.: Medullary cysts of the kidney, A. M. A. Arch. int. Med. 93: 355, 1954. 12. Josserand, P., Annius, R., and Mugniery, L.: Le rein 6ponge, Pfdiatrie 7: 31, 1952. 13. Kampmeier, O. F.: A hitherto unrecognized mode of origin of congenital renal cysts, Surg. Gynee. Obst. 36: 208, 1923. 14. Lenarduzzi, G.: Reperto pielografico poco comune (dilatazione della vie urlnaire intrarenali), Radiol. med. 26: 346, 1939. 15. Lenarduzzi, G.: Un altro caso di dilatazione delle vie urinarie preprelviche, Radiol. reed. 26: 884, 1939.
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16. Lenarduzzi, G.: Sul rene a spugna, Radiol. med. 35: 992, 1949. 17. Lenarduzzi, G.: La forma circoscritta di rene spugna, Radiol. reed. 37: 776, 1951. 18. Lenarduzzi, G.: Evoluzione del rene a spugna, Radiol. reed. 38" 57, 1952. 19. Lenarduzzi, G.: Rene a spugna parcellare, Radiol. reed. 38: 1084, 1952. 20. Lindvall, N.: Roentgenologic diagnosis of medullary sponge kidney, Acta, radiol. 51" 193, 1959. 21. Lhez, M. A.: Le rein en 6ponge (douze observations), J. Urol. m6d. chir. 60: 575, 1954. 22. Mulvaney, W. P., and Collins, W. J.: Cystic disease of the renal pyramids, J. Urol. 75: 776, 1956. 23. Murphy, W. K., Palubinskas, A. J., and Smith, D. R., Sponge kidney: Report of seven cases, J. Urol. 85: 866, 1961. 24. Neuhaus, W.: Multiple Zysten der Tubuli recti, Fortschr. Oeb. R6ntgenstrahlen 84: 108, 1956. 25. Pelot, G.: Discussion to Lhez, A.: Le rein en 6ponge, J. Urol. todd. chit. 60: 587, 1954. 26. Petkovic, S.: Contribution ~t l'4tude de la maladie kystique des pyramides r6nales, J. Urol, m6d. chir. 58: 425, 1952. 27. PoweII, R. E.: An unusual congenital deformity of the kidney, Canad. M. A. J. 60: 48, 1949. 28. Rubin, E. L., Ross, J. C., and Turner, D. P. B.: Cystic disease of the renal pyramids ("sponge kidney"), J. Fac. Radiologists I0: 134, 1959. 29. Sanchez-Lucas, J. G.: Morphogenese de rein Polykystique, Semaine H6p. Paris 71: 2793, 1951. 30. Smith, C. H., and Graham, J. B.: Congenital medullary cysts of the kidney with severe refractory anemia, Am. J. Dis. Child. 69: 369, 1945. 31. Vermooten, V.: Congenital cystic dilatation of the renal collecting tubules, Yale J. Biol. Med. 23: 450, 1951.