- Email: [email protected]
Glomerulocystic Kidney: Proposed Etiology and Pathogenesis
0022-534 7/78/1195-0678$02. 00/0
Vol. 119, May Printed in U.SA.
THE JOURNAL OF UROLOGY
Copyright © 1978 by The Williams & Wilkins Co.
Case Reports GLOMERULOCYSTIC KIDNEY: PROPOSED ETIOLOGY AND PATHOGENESIS BILLY SELLERS
AND
JEROME P. RICHIE*
From the Departments ofPediatrics and Urology, Naval Regional Medical Center, San Diego, California
ABSTRACT
Glomerulocystic kidney, an unusual lesion seen only in infancy or early childhood, involves cystic dilatation of Bowman's space without evidence of urinary obstruction. This disease may result from intrarenal medullary obstruction in the third trimester of pregnancy because 1) it is similar to the cystic kidney lesion produced by urethral obstruction, 2) patients with glomerulocystic kidney have no evidence of extrarenal urinary tract obstruction and 3) most patients with glomerulocystic kidney have evidence of inflammation and fibrosis in the renal medulla. A prenatal drug history of prolonged maternal ingestion of phenacetin in an infant with glomerulocystic kidney prompted us to submit a possible etiologic source for the hypothesis of intrarenal obstruction. Polycystic kidney disease occurs in several forms, all of which may be seen in infants. Attempts to classify these entities from pathological, clinical, genetic and radiographic standpoints have been numerous.1-4 The intriguing maternal drug history in a patient with glomerulocystic kidney has prompted us to propose a hypothesis for the etiology and pathogenesis of this unusual disease and to correlate experimental data with clinical and pathological findings in cases reported previously.
Open surgical biopsies of the right kidney and the liver were performed. The kidney had a mottled appearance and contained diffuse microcystic lesions, and several larger cystic lesions measuring up to 7 cm. in diameter (fig. 2, B). The liver appeared to be normal. Convalescence was uneventful. At 13 months old the patient is growing and developing within the 50th percentile and the most recent serum creatinine level was 0.4 mg./100 ml. PATHOLOGICAL FINDINGS
CASE REPORT
The renal biopsy specimen was comprised of outer cortex, including approximately the last 5 generations of nephrons. Cystic dilatation of Bowman's space and rarely the initial portion of the proximal convoluted tubule was the most striking abnormality (fig. 3). The glomerular tufts, although developed fully, manifested regressive and atrophic changes. Tubular hyaline casts extruded occasionally from the proximal tubular lumen into the interstitium, stimulating an interstitial mononuclear inflammatory infiltration. The cytoplasm of the proximal tubular epithelium was vacuolated. The remainder of the nephron and the vessels were normal. lmmunofluorescent stains were negative for IgG, IgA, IgM, fibrinogen and the third component of complement. Electron microscopy was not done. The histologic appearance of the liver was normal.
J. V. L., a 4-month-old black infant, was referred for evaluation of bilaterally enlarged kidneys. He was the product of a 40-week gestation, delivered of a gravida II, para 1, 26year-old mother. In addition to multivitamins the mother took 1 tablet of butalbital, salicylate and phenacetin 4 times a day for migraine headaches approximately 2 days a week during the last half of the pregnancy. The delivery was uncomplicated. Family history was unrevealing for renal disease or malformations. At the time of newborn examination bilateral flank masses were discovered. An excretory urogram (IVP) revealed large kidneys but lack of parental consent precluded further evaluation. The patient grew and developed normally until he was 4 months old, when he was referred for evaluation of the bilateral flank masses. Physical examination was normal except for bilateral flank masses. Serum electrolytes, blood count, urinalysis, serum calcium and phosphorus were normal. Serum creatinine level was 1.0 mg./100 ml. and creatinine clearance was 25 ml./ minute/1.73 M. 2 • A repeat IVP revealed bilateral double renal collecting systems (fig. 1) and a voiding cystourethrogram was normal. Selective renal arteriography demonstrated intrarenal vessels stretched around numerous cortical cysts of varying size (fig. 2, A) and both renal arteries were normal.
DISCUSSION
Ten patients with renal cystic disease involving cysts of Bowman's capsule without evidence of urinary tract obstruction have been reported previously (see table).6-8 The diagnosis was made during infancy except in 1 female subject6 in whom the diagnosis was made when she was 4 years old. Based on morphologic findings Taxy and Filmer proposed the term glomerulocystic kidney for this lesion. 8 The etiology and pathogenesis of glomerulocystic kidney remain unknown but certain conclusions can be reached from morphologic observations. Marked dilatation of Bowman's space associated with retrogressive and atrophic changes in fully developed glomerular tufts suggests strongly that the
Accepted for publication June 10, 1977. Read at annual meeting of A~erican Urological Association, Chicago, Illinois, April 24-28, 1977. * Requests for reprints: Peter Bent Brigham Hospital, 721 Huntington Ave., Boston, Massachusetts 02115. 678
GLOMERULOCYSTIC KIDNEY
679
injurious event occurs late in gestation when nephrogenesis is complete. Nephron induction from metanephric blastema by the ampullary portion of the ureteral bud ends at about 32 to 33 weeks of gestation. Thereafter, only maturation and elongation of existing nephrons occur. The morphologic lesion is similar to type IV cystic kidney caused by urethral obstruction as described by Osathanondh and Potter. 1 In type IV cystic kidney the principal abnormality is cystic dilatation of Bowman's space, primarily in the subcapsular glomeruli. Presumably, the same histologic features could result from other extrarenal mechanisms of obstruction, that is ureteropelvic or ureterovesical stenosis. Only in the latter half of intrauterine life is there sufficient urine production and flow to create enough retrograde pressure to produce retrogressive and atrophic glomerular changes. These changes usually are confined to the subcapsular region, apparently because of the direct alignment of these last formed nephrons to the collecting ducts. The earlier formed nephrons, which are in arcades, are protected by their acute angle of attachment to the collecting duct. Extrarenal obstructive phenom-
ena were excluded carefully in our patient as well as in most of the other 10 cases of glomerulocystic kidney reported in the literature. Intrarenal obstruction during the last 10 weeks of gestation is a possible cause of the glomerular cystic changes in these patients. Specifically, the medulla appears to be the most logical site for this obstruction. Of the 10 previous reports in the literature 9 described pathologic changes in the medulla, consisting of interstitial fibrosis, inflammation, hemorrhage, calcification, tubular epithelial swelling, degeneration and parenchymal atrophy.6-8 In contrast, similar pathologic changes were unnoticed virtually in the cortex. Thus, although the evidence is not conclusive it seems reasonable. to postulate that significant obstruction to urinary flow through the collecting tubules, loops of Henle or both may have resulted from medullary interstitial edema and tubular epithelial swelling. Phenacetin has been implicated in interstitial nephritis and papillary necrosis in adults when taken long enough or in sufficiently large doses. 9 Phenacetin and its major metabolic
Fm. 1. IVP 5 minutes post-injection of contrast medium demonstrates bilateral enlargement with duplicated collecting systems.
Fm. 3. Histologic section of cortex shows subglomerular cysts and dilatation of proximal tubules. H & E, reduced from x125.
Fm. 2. A, selective right renal arteriogram reveals stretching of vessels over multiple cysts. B, gross appearance of kidney with multiple cysts, especially prominent in upper pole.
680
SELLERS AND RICHIE
Clinical findings in patients with glomerulocystic kidney References
Sex
Roos·
Female
Baxter"
Female Female Male
i
'
Female Not stated Not stated Vlachosand Tsakraklidis7
Female
Male Taxyand Filmer" Present case
Female Male
Associated Anomalies
Renal Function
Outcome
Benign hepatic adenoma, patent ductus arteriosus Cleft lip and palate, talipes, congenital heart disease, absent gallbladder, uterus duplex Hypoplastic kidneys
Severe impairment, serum creatinine 2.5 mg./100 ml. Not stated
Died at age 8 mos. of pneumonia Stillborn
Severe impairment implied
Hydrocephalus, enlarged thyroid, ascites, mobile cecum Grosstalipes Not stated Enlarged kidneys
Not stated
Died at age 4 yrs., cause not stated Stillborn
Not stated Not stated Not stated
Congenital heart disease, fetal lobulation Fetal lobulation Subcapsular hepatic cysts, 2 small hepatocellular cysts Double renal collecting systems
breakdown products10 are similar chemically to diphenylamine, a compound used to produce cystic kidney disease in adult rats. 11 Moreover, when fed to pregnant rats during the last 6 days of gestation diphenylamine derivatives produced. polycystic disease in a high percentage of offspring. 12 Data on the placental transmission of phenacetin or its derivatives are not available but the chemical similarity of these compounds to diphenylamine raises the issue of the role of phenacetin in the production of glomerulocystic kidney. One might postulate that the developing fetal kidney is susceptible to the interstitial inflammatory effects of phenacetin derivatives and, furthermore, that the resulting tubular obstruction produced the cystic changes described in our patient. A cystic kidney disease closely resembling that of our patient has been reported in offspring of pregnant rabbits injected with high-dose, long-acting corticosteroids. 13 This type of glomerular cystic lesion also has been seen transiently in newborn rabbits injected soon after birth with corticosteroids. In these rabbits this lesion has been correlated with hypokalemia. 13 The functional impairment in our patient was transient, suggesting that the lesion itself may be transient as in the rabbit model. Glomerulocystic kidney may be produced by a combination of factors, such as environmental toxins or intrauterine viral infections. An autosomal recessive or polygenic mode of inheritance remains possible. Renal function in infantile glomerulocystic kidney is apparently unpredictable from the data available. The patient reported on by Roos showed substantial alteration of renal function together with albuminuria, hematuria and cylindruria. 5 Renal function was said to be normal in the 2 patients reported by Vlachos and Tsakraklidis, although no data were given. 7 Our pati1mt had moderate impairment of renal function at diagnosis with what appeared to be gradual spontaneous resolution during a 5-month period. Although no deaths from renal insufficiency have been reported in patients with glomerulocystic kidney 3 of the 11 known patients were stillborn. 6 It would appear that a wide range of renal functional impairment can occur in patients with glomerulocystic kidney. It remains to be seen if this disorder is permanent. It is likely that the incidence of glomerulocystic kidney is greater than reports in the literature would suggest. Increased awareness of this entity will, undoubtedly, lead to more
Said to be normal Not stated Moderate impairment, serum creatinine 1.0 mg./100 ml. Moderate impairment, serum creatinine 1.0 mg./100 ml., creatinine clearance 25 ml./min./1. 73 M. 2
Died, cause not stated Stillborn Died at age 8 wks. of hemorrhage and liver failure Died at age 40 days of heart disease Died at age 4 yrs. Died at age 9 wks. of anaphylaxis during IVP Alive and thriving at age 13 mos.
definitive diagnosis of the lesion. A better understanding of the etiology and pathogenesis of this disorder depends upon detailed histories of late gestation, which include pertinent information regarding infections and medications, thorough pathological examination of all renal compartments, especially the medulla, and careful followup of known patients. Dr. Jay Bernstein reviewed the histologic sections and confirmed the diagnosis and classification. REFERENCES
1. Osathanondh, V. and Potter, E. L.: Pathogenesis of polycystic kidneys: historical survey. Arch. Path., 77: 459, 1964. 2. Bernstein, J.: Heritable cystic disorders of the kidney. The mythology of polycystic disease. Pediat. Clin. N. Amer., 18: 435, 1971. 3. Blyth, H. and Ockenden, B. G.: Polycystic disease of kidney and liver presenting in childhood. J. Med. Genet., 8: 257, 1971. 4. Lieberman, E., Salinas-Madrigal, L., Gwinn, J. L., Brennan, L. P., Fine, R. N. and Landing, B. H.: Infantile polycystic disease of the kidneys and liver. Clinical, pathological and radiological correlations and comparisons with congenital hepatic fibrosis. Medicine, 50: 277, 1971. 5. Roos, A.: Polycystic kidney: report of a case studied by reconstruction. Amer. J. Dis. Child., 61: 116, 1941 6. Baxter, T. J.: Cysts arising in the renal corpuscle. A microdissection study. Arch. Dis. Child., 40: 455, 1965. 7. Vlachos, J. and Tsakraklidis, V.: Glomerular cysts. An unusual variety of "polycystic kidneys": report of two cases. Amer. J. Dis. Child., 114: 379, 1967. 8. Taxy, J.B. and Filmer, R. B.: Glomerulocystic kidney: report of a case. Arch. Path. Lab. Med., 100: 186, 1976. 9. Larsen, K. and M0ller, C. E.: A renal lesion caused by abuse of phenacetin. Acta Med. Scand., 164: 53, 1959. 10. Brodie, B. B. and Axelrod, J.: The fate of acetophenetidin (phenacetic) in man and methods for the estimation of acetophenetidin and its metabolites in biological material. J. Pharmacol. Exp. Ther., 97: 58, 1949. 11. Woodhouse, M. A., Offer, J. and Darmady, E. M.: Diphenylamine-induced polycystic kidneys compared with human polycystic kidneys. Nephron, 2: 253, 1965. 12. Crocker, J. F. S., Brown, D. M., Borch, R. F. and Vernier, R. L.: Renal cystic disease induced in newborn rats by diphenylamine derivatives. Amer. J. Path., 66: 343, 1972. 13. Vlachos, J. D.: A new experimental model ofpolycystic kidneys. Similarity to a human variety. Amer. J. Dis. Child., 123: 118, 1972.
Vol. 119, May Printed in U.SA.
THE JOURNAL OF UROLOGY
Copyright © 1978 by The Williams & Wilkins Co.
Case Reports GLOMERULOCYSTIC KIDNEY: PROPOSED ETIOLOGY AND PATHOGENESIS BILLY SELLERS
AND
JEROME P. RICHIE*
From the Departments ofPediatrics and Urology, Naval Regional Medical Center, San Diego, California
ABSTRACT
Glomerulocystic kidney, an unusual lesion seen only in infancy or early childhood, involves cystic dilatation of Bowman's space without evidence of urinary obstruction. This disease may result from intrarenal medullary obstruction in the third trimester of pregnancy because 1) it is similar to the cystic kidney lesion produced by urethral obstruction, 2) patients with glomerulocystic kidney have no evidence of extrarenal urinary tract obstruction and 3) most patients with glomerulocystic kidney have evidence of inflammation and fibrosis in the renal medulla. A prenatal drug history of prolonged maternal ingestion of phenacetin in an infant with glomerulocystic kidney prompted us to submit a possible etiologic source for the hypothesis of intrarenal obstruction. Polycystic kidney disease occurs in several forms, all of which may be seen in infants. Attempts to classify these entities from pathological, clinical, genetic and radiographic standpoints have been numerous.1-4 The intriguing maternal drug history in a patient with glomerulocystic kidney has prompted us to propose a hypothesis for the etiology and pathogenesis of this unusual disease and to correlate experimental data with clinical and pathological findings in cases reported previously.
Open surgical biopsies of the right kidney and the liver were performed. The kidney had a mottled appearance and contained diffuse microcystic lesions, and several larger cystic lesions measuring up to 7 cm. in diameter (fig. 2, B). The liver appeared to be normal. Convalescence was uneventful. At 13 months old the patient is growing and developing within the 50th percentile and the most recent serum creatinine level was 0.4 mg./100 ml. PATHOLOGICAL FINDINGS
CASE REPORT
The renal biopsy specimen was comprised of outer cortex, including approximately the last 5 generations of nephrons. Cystic dilatation of Bowman's space and rarely the initial portion of the proximal convoluted tubule was the most striking abnormality (fig. 3). The glomerular tufts, although developed fully, manifested regressive and atrophic changes. Tubular hyaline casts extruded occasionally from the proximal tubular lumen into the interstitium, stimulating an interstitial mononuclear inflammatory infiltration. The cytoplasm of the proximal tubular epithelium was vacuolated. The remainder of the nephron and the vessels were normal. lmmunofluorescent stains were negative for IgG, IgA, IgM, fibrinogen and the third component of complement. Electron microscopy was not done. The histologic appearance of the liver was normal.
J. V. L., a 4-month-old black infant, was referred for evaluation of bilaterally enlarged kidneys. He was the product of a 40-week gestation, delivered of a gravida II, para 1, 26year-old mother. In addition to multivitamins the mother took 1 tablet of butalbital, salicylate and phenacetin 4 times a day for migraine headaches approximately 2 days a week during the last half of the pregnancy. The delivery was uncomplicated. Family history was unrevealing for renal disease or malformations. At the time of newborn examination bilateral flank masses were discovered. An excretory urogram (IVP) revealed large kidneys but lack of parental consent precluded further evaluation. The patient grew and developed normally until he was 4 months old, when he was referred for evaluation of the bilateral flank masses. Physical examination was normal except for bilateral flank masses. Serum electrolytes, blood count, urinalysis, serum calcium and phosphorus were normal. Serum creatinine level was 1.0 mg./100 ml. and creatinine clearance was 25 ml./ minute/1.73 M. 2 • A repeat IVP revealed bilateral double renal collecting systems (fig. 1) and a voiding cystourethrogram was normal. Selective renal arteriography demonstrated intrarenal vessels stretched around numerous cortical cysts of varying size (fig. 2, A) and both renal arteries were normal.
DISCUSSION
Ten patients with renal cystic disease involving cysts of Bowman's capsule without evidence of urinary tract obstruction have been reported previously (see table).6-8 The diagnosis was made during infancy except in 1 female subject6 in whom the diagnosis was made when she was 4 years old. Based on morphologic findings Taxy and Filmer proposed the term glomerulocystic kidney for this lesion. 8 The etiology and pathogenesis of glomerulocystic kidney remain unknown but certain conclusions can be reached from morphologic observations. Marked dilatation of Bowman's space associated with retrogressive and atrophic changes in fully developed glomerular tufts suggests strongly that the
Accepted for publication June 10, 1977. Read at annual meeting of A~erican Urological Association, Chicago, Illinois, April 24-28, 1977. * Requests for reprints: Peter Bent Brigham Hospital, 721 Huntington Ave., Boston, Massachusetts 02115. 678
GLOMERULOCYSTIC KIDNEY
679
injurious event occurs late in gestation when nephrogenesis is complete. Nephron induction from metanephric blastema by the ampullary portion of the ureteral bud ends at about 32 to 33 weeks of gestation. Thereafter, only maturation and elongation of existing nephrons occur. The morphologic lesion is similar to type IV cystic kidney caused by urethral obstruction as described by Osathanondh and Potter. 1 In type IV cystic kidney the principal abnormality is cystic dilatation of Bowman's space, primarily in the subcapsular glomeruli. Presumably, the same histologic features could result from other extrarenal mechanisms of obstruction, that is ureteropelvic or ureterovesical stenosis. Only in the latter half of intrauterine life is there sufficient urine production and flow to create enough retrograde pressure to produce retrogressive and atrophic glomerular changes. These changes usually are confined to the subcapsular region, apparently because of the direct alignment of these last formed nephrons to the collecting ducts. The earlier formed nephrons, which are in arcades, are protected by their acute angle of attachment to the collecting duct. Extrarenal obstructive phenom-
ena were excluded carefully in our patient as well as in most of the other 10 cases of glomerulocystic kidney reported in the literature. Intrarenal obstruction during the last 10 weeks of gestation is a possible cause of the glomerular cystic changes in these patients. Specifically, the medulla appears to be the most logical site for this obstruction. Of the 10 previous reports in the literature 9 described pathologic changes in the medulla, consisting of interstitial fibrosis, inflammation, hemorrhage, calcification, tubular epithelial swelling, degeneration and parenchymal atrophy.6-8 In contrast, similar pathologic changes were unnoticed virtually in the cortex. Thus, although the evidence is not conclusive it seems reasonable. to postulate that significant obstruction to urinary flow through the collecting tubules, loops of Henle or both may have resulted from medullary interstitial edema and tubular epithelial swelling. Phenacetin has been implicated in interstitial nephritis and papillary necrosis in adults when taken long enough or in sufficiently large doses. 9 Phenacetin and its major metabolic
Fm. 1. IVP 5 minutes post-injection of contrast medium demonstrates bilateral enlargement with duplicated collecting systems.
Fm. 3. Histologic section of cortex shows subglomerular cysts and dilatation of proximal tubules. H & E, reduced from x125.
Fm. 2. A, selective right renal arteriogram reveals stretching of vessels over multiple cysts. B, gross appearance of kidney with multiple cysts, especially prominent in upper pole.
680
SELLERS AND RICHIE
Clinical findings in patients with glomerulocystic kidney References
Sex
Roos·
Female
Baxter"
Female Female Male
i
'
Female Not stated Not stated Vlachosand Tsakraklidis7
Female
Male Taxyand Filmer" Present case
Female Male
Associated Anomalies
Renal Function
Outcome
Benign hepatic adenoma, patent ductus arteriosus Cleft lip and palate, talipes, congenital heart disease, absent gallbladder, uterus duplex Hypoplastic kidneys
Severe impairment, serum creatinine 2.5 mg./100 ml. Not stated
Died at age 8 mos. of pneumonia Stillborn
Severe impairment implied
Hydrocephalus, enlarged thyroid, ascites, mobile cecum Grosstalipes Not stated Enlarged kidneys
Not stated
Died at age 4 yrs., cause not stated Stillborn
Not stated Not stated Not stated
Congenital heart disease, fetal lobulation Fetal lobulation Subcapsular hepatic cysts, 2 small hepatocellular cysts Double renal collecting systems
breakdown products10 are similar chemically to diphenylamine, a compound used to produce cystic kidney disease in adult rats. 11 Moreover, when fed to pregnant rats during the last 6 days of gestation diphenylamine derivatives produced. polycystic disease in a high percentage of offspring. 12 Data on the placental transmission of phenacetin or its derivatives are not available but the chemical similarity of these compounds to diphenylamine raises the issue of the role of phenacetin in the production of glomerulocystic kidney. One might postulate that the developing fetal kidney is susceptible to the interstitial inflammatory effects of phenacetin derivatives and, furthermore, that the resulting tubular obstruction produced the cystic changes described in our patient. A cystic kidney disease closely resembling that of our patient has been reported in offspring of pregnant rabbits injected with high-dose, long-acting corticosteroids. 13 This type of glomerular cystic lesion also has been seen transiently in newborn rabbits injected soon after birth with corticosteroids. In these rabbits this lesion has been correlated with hypokalemia. 13 The functional impairment in our patient was transient, suggesting that the lesion itself may be transient as in the rabbit model. Glomerulocystic kidney may be produced by a combination of factors, such as environmental toxins or intrauterine viral infections. An autosomal recessive or polygenic mode of inheritance remains possible. Renal function in infantile glomerulocystic kidney is apparently unpredictable from the data available. The patient reported on by Roos showed substantial alteration of renal function together with albuminuria, hematuria and cylindruria. 5 Renal function was said to be normal in the 2 patients reported by Vlachos and Tsakraklidis, although no data were given. 7 Our pati1mt had moderate impairment of renal function at diagnosis with what appeared to be gradual spontaneous resolution during a 5-month period. Although no deaths from renal insufficiency have been reported in patients with glomerulocystic kidney 3 of the 11 known patients were stillborn. 6 It would appear that a wide range of renal functional impairment can occur in patients with glomerulocystic kidney. It remains to be seen if this disorder is permanent. It is likely that the incidence of glomerulocystic kidney is greater than reports in the literature would suggest. Increased awareness of this entity will, undoubtedly, lead to more
Said to be normal Not stated Moderate impairment, serum creatinine 1.0 mg./100 ml. Moderate impairment, serum creatinine 1.0 mg./100 ml., creatinine clearance 25 ml./min./1. 73 M. 2
Died, cause not stated Stillborn Died at age 8 wks. of hemorrhage and liver failure Died at age 40 days of heart disease Died at age 4 yrs. Died at age 9 wks. of anaphylaxis during IVP Alive and thriving at age 13 mos.
definitive diagnosis of the lesion. A better understanding of the etiology and pathogenesis of this disorder depends upon detailed histories of late gestation, which include pertinent information regarding infections and medications, thorough pathological examination of all renal compartments, especially the medulla, and careful followup of known patients. Dr. Jay Bernstein reviewed the histologic sections and confirmed the diagnosis and classification. REFERENCES
1. Osathanondh, V. and Potter, E. L.: Pathogenesis of polycystic kidneys: historical survey. Arch. Path., 77: 459, 1964. 2. Bernstein, J.: Heritable cystic disorders of the kidney. The mythology of polycystic disease. Pediat. Clin. N. Amer., 18: 435, 1971. 3. Blyth, H. and Ockenden, B. G.: Polycystic disease of kidney and liver presenting in childhood. J. Med. Genet., 8: 257, 1971. 4. Lieberman, E., Salinas-Madrigal, L., Gwinn, J. L., Brennan, L. P., Fine, R. N. and Landing, B. H.: Infantile polycystic disease of the kidneys and liver. Clinical, pathological and radiological correlations and comparisons with congenital hepatic fibrosis. Medicine, 50: 277, 1971. 5. Roos, A.: Polycystic kidney: report of a case studied by reconstruction. Amer. J. Dis. Child., 61: 116, 1941 6. Baxter, T. J.: Cysts arising in the renal corpuscle. A microdissection study. Arch. Dis. Child., 40: 455, 1965. 7. Vlachos, J. and Tsakraklidis, V.: Glomerular cysts. An unusual variety of "polycystic kidneys": report of two cases. Amer. J. Dis. Child., 114: 379, 1967. 8. Taxy, J.B. and Filmer, R. B.: Glomerulocystic kidney: report of a case. Arch. Path. Lab. Med., 100: 186, 1976. 9. Larsen, K. and M0ller, C. E.: A renal lesion caused by abuse of phenacetin. Acta Med. Scand., 164: 53, 1959. 10. Brodie, B. B. and Axelrod, J.: The fate of acetophenetidin (phenacetic) in man and methods for the estimation of acetophenetidin and its metabolites in biological material. J. Pharmacol. Exp. Ther., 97: 58, 1949. 11. Woodhouse, M. A., Offer, J. and Darmady, E. M.: Diphenylamine-induced polycystic kidneys compared with human polycystic kidneys. Nephron, 2: 253, 1965. 12. Crocker, J. F. S., Brown, D. M., Borch, R. F. and Vernier, R. L.: Renal cystic disease induced in newborn rats by diphenylamine derivatives. Amer. J. Path., 66: 343, 1972. 13. Vlachos, J. D.: A new experimental model ofpolycystic kidneys. Similarity to a human variety. Amer. J. Dis. Child., 123: 118, 1972.