HYPERTENSION AS A COMPLICATION OF MULTICYSTIC DYSPLASTIC KIDNEY KENNETH W. ANGERMEIER, ROBERT KAY M.D. HOWARD LEVIN, M.D.
M.D.
From the Section of Pediatric Urology, Department of Urology, and Department of Pathology, Cleveland Clinic Foundation, Cleveland, Ohio
ABSTRACTThe detection of multicystic dysplastic kidney in utero using prenatal ultrasound is becoming a more frequent occurrence. An accurate diagnosis of multicystic dysplastic kidney usually can be made radiographically, and therefore the main indication for surgery in the asymptomatic patient may bc the potential risk of complications developing later in life. We report hyperten.sion as a complication of multicystic dysplastic kidney and review the literature.
With the increasing application of prenatal ultrasound, the detection in utero of renal pathology. specifically hydronephrosis and multicystic kidney, is becoming a more frequent occurrence. ‘.e In the past, multicystic kidney was typicallv detected after birth by the presence of an abdominal mass, or in rare cases by complications directly, arising from the multicystic kidney. In utero detection, however, has raised several cluestions regarding the management of these patients, as many have nonpalpable masses which are asymptomatic. If the mass eft’ect poses no problem, the only reasons to remove the multicystic kidney in the newborn wrould be to confirm the diagnosis and differentiate it from ureteropelvic junction obstruction, or to obviate any potential complications. With the use of ultrasonography and radionuclide renal scans, the diagnosis of multicsystic kidney is usually clear,“.4 and surgical exploration to confirm the diagnosis is rarely required. Therefore, the main indication for ,surgery’ may be the risk of multicystic kidney in creating pathologic conditions later in life. Reported complications of multicystic kidney Irave included hypertension,” 7 malignancy,7 I2 l’ain. I3 and possibly infection.12 Recent experience with a case of hypertension in a patient with multicvstic kidney raises questions regarding its potential risk and clinical significance in these patients.
Case Report Case 1 This patient was the product of an uncomplicated full-term pregnancy. Prenatal rlltrasound at thirty-six weeks’ gestation revealed multiple cysts of variable size in the area of the left kidney. The right kidney was normal. Shortly after birth the patient underwent a repeat renal ultrasound followed by a diethylene triamine pentaacetic acid (DTPA) radionuclide renal scan which revealed no function on the left and a diagnosis of multicystic kidney, wras made. The patient was followed up nonoperatively, and at age five months hypertension developed with systolic blood pressures ranging from 126 to 142 mm Hg on multiple determinations. He vvas treated with prazosin, 1 mg twice daily with excellent blood pressure control. The patient was referred to our institution at age seven months. at which time repeat ultrasound and renal scan were again consistent with multicystic kidney. An intravenous pyelogram (IVP) revealed nonvisualization of the left kidney with a normal right kidney and collecting system. The patient subsecluently underwent a left nephrectomy without complication. The specimen consisted of a 4.i x B.‘i x 1.7 cm multicystic red-pink mass (Fig. 1). The lower 4 cm of ureter were patent, but the upper 2 cm contained no lumen. No renal pelvis was
FIGURE 1. Case 1. Gross specimen dysplastic kidney.
of multicystic
identified. The multicystic structure contained both solid and cystic areas. The solid areas were comprised of lobules of fibrous tissue, dysplastic tubules, mostly immature glomeruli and immature cartilage (Fig. 2). The dysplastic tubules were lined by flattened to columnar epithelium and surrounded by a mantle of mesenchymal tissue. Occasional dilated tubules contained eosinophilic material with dystrophic calcification. Admixed with the solid tissue were cysts of varying size lined by a single layer of flattened to cuboidal epithelium and generally surrounded by collagenized mesenchymal tissue. The patient was discharged on the third postoperative day with systolic blood pressures ranging from 90 to 103 mm Hg without medication. At age twenty-eight months the patient’s blood pressure was 94/62 mm Hg without medication. Comment Multicystic dysplasia is the most common form of cystic renal disease in children. A recent review has estimated the incidence of unilateral multicystic kidney disease to be approximately
56
FIGURE 2. Case 1. Photomicrographs: (A) solid area of multicystic dysplastic kidney showing cartilage (C), small renal tubules (T), immatu,re glome&us (G), and dysplastic tubule (arrow). (B) Section of solid area showing mature nephrons (left) and dysplastic tubules mantled by connective tissue (arrows). Hematorylin and eosin, original magnilfications x 111.
l/4,300 live births.14 The most common clinical presentation of a multicystic kidney in infants in the past has been as an asymptomatic abdominal mass.r5 More recently, however, it is being discovered with increasing frequency by prenatal ultrasound,1,2 which raises questions regarding how these small, nonpalpable asymptomatic lesions should be managed. In the past treatment of a multicystic kidney was surgical removal, primarily for verification of the diagnosis and less often for a symptomatic lesion. Recent advances in radiologic techniques, however, have significantly improved our ability to accurately diagnose multicystic kidney. Stuck, Koff, and Silver3 have defined several ultrasound criteria for diagnosing
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multicystic kidney and distinguishing it from hydronephrosis. Using these criteria they were able to make an accurate diagnosis in 93 percent of a series of 15 patients with multicystic kidney. They also suggested a radionuclide renal scan in the evaluation, which in combination with the ultrasound findings can reliably diagnose multicystic kidney in most cases.” Because of the improved diagnostic capabilities, low reported complication rate, and the finding that many multicystic kidneys may regress or undergo complete resorption over time,‘4.*6~17 there has been a recent trend toward conservative management of these patients.‘5.16.18.1g As this nonoperative approach increases in popularity, it is important to continue to document the natural history and complications of multicystic kidney. Hypertension as a result of a multicystic kidnev has been reported in several previous cases. Ambrose ef aZ.,‘” in a review of the literature, identified 4 cases of hypertension in adults that were thought to be secondary to a multicystic kidney. In each case the blood pressure was not significantly altered by nephrectomy. There have been 3 previously reported cases of hypertension which did resolve after removal of a multicystic kidney? 7 The ages of these patients were three weeks, six years, and twenty-one years. In 1 case peripheral plasma renin activity was measured and found to be elevated.fi The plasma renin subsequently returned to normal after nephrectomy. and the authors postulated that the elevated renin activity may have resulted from decreased renal blood flow to the more differentiated nephron units identified histologically. Our case is similar to the aforementioned cases in that significant hypertension requiring medication was present in a child with a multicystic kidney, which promptlv resolved after nephrectomy.” We also identified interspersed areas of more differentiated nephron units histologically in the surgical specimen, which would be consistent with a reninmediated etiology of the hypertension although plasma renins were not measured. Conclusion We have presented a case of hypertension as a complication of multicystic kidney which completely resolved after nephrectomy was performed. As noted previously causally related cases of hypertension as a result of multicystic kidne?, have been infrequently reported to date. Pain and malignancy are two additional com-
plications of multicystic kidney which have been reported in a small number of cases.7 13 These potential risks have prompted much discussion regarding the management of these patients. If the size of the mass causes difficulty, the diagnosis is in question, an associated complication exists, or the patient undergoes laparotomy for another reason, nephrectomy should be performed. If, however, the patient is asymptomatic, a decision must be made regarding nephrectomy versus a nonoperative approach. With a nonoperative approach one must take into consideration the ease of followup and patient’s compliance, and decide on the frequency and duration of follow-up. Previous recommendations on the length of observation have varied from through puberty’” to lifelong monitoring. l2 With the prevalence of multicystic kidney in the general population and the very low reported complication rate to date, we believe it is reasonable to manage these patients conservatively with serial ultrasound examinations if follow-up is reliable. If the kidney. remains large without evidence of regression, nephrectomy should then be considered. Hopefully, more information on these issues will become available as patients are followed nonoperatively and further complications are reported. Addendum Since the submission of this article, we have seen and treated a twelve-year-old boy with significant hypertension who was found to have a multicystic dysplastic kidney. After an uncomplicated nephrectomy, his hypertension resolved, and his blood pressure has remained normal without medication during follow-up. One Clinic Center 9500 Euclid Avenue Cleveland. Ohio 44195-5041 (DR. KAY) References I, 1,~ TC. and Blake S: Prenatal fetal abdominal ultrasonography and diagnosis, Radiology 124: 175 (1977!. 2. Hadlock IT, d al: Snnography of fetal urinarv tract anrmxlies. AJR 137: 261 (1981). 3. Stuck KJ. Koff SA, and Silver ‘Wl: Ultrasonic features of multicystic dysplastic kidney: expanded diagnostics criteria. Radiology 143: 217 (1982). 4. Beretsky I, I,ankin DH, Rusoff JH, and l’helan L: Sonographic differentiation hetween the multicystic dysplastic kidnq and the ureteropclvic junction obstruction in utero using highresolution real-time scanners employing di@al detection. J Clin Ultrasound 12: 429 (1984).
5. Javadpour N, et al: Hypertension in a child caused by a multicystic kidney, J Urol 104: 918 (1970). 6. Chen Y, Stapleton FB, Roy S, and Noe HN: Neonatal hypertension from a unilateral multicystic dysplastic kidney, J Urol133: 664 (1985). 7. Burgler W, and Jauri D: Vitale Komplikationen bei multizystischier nierendegeneration (multizystischer dysplastic), Urol lnt 38: 251 (1983). 8. Barrett DM, and Wineland RE: Renal cell carcinoma in multicystic dysplastic kidney, Urology 15: 152 (1980). 9. Birken G, King D, Vane D, and Lloyd T: Renal cell carcinoma arising in a multicystic dysplastic kidney, J Pediatr Surg 20: 619 (1985). 10. Shirai M, Kitagawa T, Nakata H, and Urano Y: Renal cell carcinoma originating from dysplastic kidney, Acta Path01 Jpn 36: 1263 (1986). 11. Raffensperger J, and Abousleiman A: Abdominal masses in children under one year of age, Surgery 63: 514 (1968). 12. Hartmann GE, Smolik LM, and Shochat SJ: The dilemma of the multicystic dysplastic kidney, Am J Dis Child 140: 925 (1986).
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13. Ambrose SS, Gould RA, Trulock TS, and Parrott TS: Unilateral multicystic renal disease in adults, J Urol 128: 366 (1982). 14. Gordon AC, Thomas DFM, Arthur RJ, and Irving HC: Multicystic dysplastic kidney: is nephrectomy still appropriate? J Urol 140: 1231 (1988). 15. Walker D, Fennel1 R, Garin E, and Richard G: Spectrum of multicystic renal dysplasia, Urology 11: 433 (1978). 16. Avni EF, and Schulman CC: Multicystic dysplastic kidney: natural history from in utero diagnosis and postnatal follow-up, J Urol 138: 1420 (9187). 17. Pedicelli G, Jequier S, Bowen A, and Boisvert J: Multicystic dysplastic kidneys: spontaneous regression demonstrated with US, Radiology 160: 23 (1986). 18. Bloom DA, and Brosnan S: The multicystic kidney, J Urol 120: 211 (1978). 19. Stanisic TH: Review of “The dilemma of the multicystic dysplastic kidney,” Editorial, Am J Dis Child 140: 865 (1986). 20. de Swiet M, Fayers P, and Shinebourne EA: Systolic blood pressure in a population of infants in the first year of life: the Brompton study, Pediatrics 65: 1028 (1980).
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1
M.D.
From the Section of Pediatric Urology, Department of Urology, and Department of Pathology, Cleveland Clinic Foundation, Cleveland, Ohio
ABSTRACTThe detection of multicystic dysplastic kidney in utero using prenatal ultrasound is becoming a more frequent occurrence. An accurate diagnosis of multicystic dysplastic kidney usually can be made radiographically, and therefore the main indication for surgery in the asymptomatic patient may bc the potential risk of complications developing later in life. We report hyperten.sion as a complication of multicystic dysplastic kidney and review the literature.
With the increasing application of prenatal ultrasound, the detection in utero of renal pathology. specifically hydronephrosis and multicystic kidney, is becoming a more frequent occurrence. ‘.e In the past, multicystic kidney was typicallv detected after birth by the presence of an abdominal mass, or in rare cases by complications directly, arising from the multicystic kidney. In utero detection, however, has raised several cluestions regarding the management of these patients, as many have nonpalpable masses which are asymptomatic. If the mass eft’ect poses no problem, the only reasons to remove the multicystic kidney in the newborn wrould be to confirm the diagnosis and differentiate it from ureteropelvic junction obstruction, or to obviate any potential complications. With the use of ultrasonography and radionuclide renal scans, the diagnosis of multicsystic kidney is usually clear,“.4 and surgical exploration to confirm the diagnosis is rarely required. Therefore, the main indication for ,surgery’ may be the risk of multicystic kidney in creating pathologic conditions later in life. Reported complications of multicystic kidney Irave included hypertension,” 7 malignancy,7 I2 l’ain. I3 and possibly infection.12 Recent experience with a case of hypertension in a patient with multicvstic kidney raises questions regarding its potential risk and clinical significance in these patients.
Case Report Case 1 This patient was the product of an uncomplicated full-term pregnancy. Prenatal rlltrasound at thirty-six weeks’ gestation revealed multiple cysts of variable size in the area of the left kidney. The right kidney was normal. Shortly after birth the patient underwent a repeat renal ultrasound followed by a diethylene triamine pentaacetic acid (DTPA) radionuclide renal scan which revealed no function on the left and a diagnosis of multicystic kidney, wras made. The patient was followed up nonoperatively, and at age five months hypertension developed with systolic blood pressures ranging from 126 to 142 mm Hg on multiple determinations. He vvas treated with prazosin, 1 mg twice daily with excellent blood pressure control. The patient was referred to our institution at age seven months. at which time repeat ultrasound and renal scan were again consistent with multicystic kidney. An intravenous pyelogram (IVP) revealed nonvisualization of the left kidney with a normal right kidney and collecting system. The patient subsecluently underwent a left nephrectomy without complication. The specimen consisted of a 4.i x B.‘i x 1.7 cm multicystic red-pink mass (Fig. 1). The lower 4 cm of ureter were patent, but the upper 2 cm contained no lumen. No renal pelvis was
FIGURE 1. Case 1. Gross specimen dysplastic kidney.
of multicystic
identified. The multicystic structure contained both solid and cystic areas. The solid areas were comprised of lobules of fibrous tissue, dysplastic tubules, mostly immature glomeruli and immature cartilage (Fig. 2). The dysplastic tubules were lined by flattened to columnar epithelium and surrounded by a mantle of mesenchymal tissue. Occasional dilated tubules contained eosinophilic material with dystrophic calcification. Admixed with the solid tissue were cysts of varying size lined by a single layer of flattened to cuboidal epithelium and generally surrounded by collagenized mesenchymal tissue. The patient was discharged on the third postoperative day with systolic blood pressures ranging from 90 to 103 mm Hg without medication. At age twenty-eight months the patient’s blood pressure was 94/62 mm Hg without medication. Comment Multicystic dysplasia is the most common form of cystic renal disease in children. A recent review has estimated the incidence of unilateral multicystic kidney disease to be approximately
56
FIGURE 2. Case 1. Photomicrographs: (A) solid area of multicystic dysplastic kidney showing cartilage (C), small renal tubules (T), immatu,re glome&us (G), and dysplastic tubule (arrow). (B) Section of solid area showing mature nephrons (left) and dysplastic tubules mantled by connective tissue (arrows). Hematorylin and eosin, original magnilfications x 111.
l/4,300 live births.14 The most common clinical presentation of a multicystic kidney in infants in the past has been as an asymptomatic abdominal mass.r5 More recently, however, it is being discovered with increasing frequency by prenatal ultrasound,1,2 which raises questions regarding how these small, nonpalpable asymptomatic lesions should be managed. In the past treatment of a multicystic kidney was surgical removal, primarily for verification of the diagnosis and less often for a symptomatic lesion. Recent advances in radiologic techniques, however, have significantly improved our ability to accurately diagnose multicystic kidney. Stuck, Koff, and Silver3 have defined several ultrasound criteria for diagnosing
UROLOGY
/ JANUARY 1992
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VOI,UME
XXXIX, NUMBER
1
multicystic kidney and distinguishing it from hydronephrosis. Using these criteria they were able to make an accurate diagnosis in 93 percent of a series of 15 patients with multicystic kidney. They also suggested a radionuclide renal scan in the evaluation, which in combination with the ultrasound findings can reliably diagnose multicystic kidney in most cases.” Because of the improved diagnostic capabilities, low reported complication rate, and the finding that many multicystic kidneys may regress or undergo complete resorption over time,‘4.*6~17 there has been a recent trend toward conservative management of these patients.‘5.16.18.1g As this nonoperative approach increases in popularity, it is important to continue to document the natural history and complications of multicystic kidney. Hypertension as a result of a multicystic kidnev has been reported in several previous cases. Ambrose ef aZ.,‘” in a review of the literature, identified 4 cases of hypertension in adults that were thought to be secondary to a multicystic kidney. In each case the blood pressure was not significantly altered by nephrectomy. There have been 3 previously reported cases of hypertension which did resolve after removal of a multicystic kidney? 7 The ages of these patients were three weeks, six years, and twenty-one years. In 1 case peripheral plasma renin activity was measured and found to be elevated.fi The plasma renin subsequently returned to normal after nephrectomy. and the authors postulated that the elevated renin activity may have resulted from decreased renal blood flow to the more differentiated nephron units identified histologically. Our case is similar to the aforementioned cases in that significant hypertension requiring medication was present in a child with a multicystic kidney, which promptlv resolved after nephrectomy.” We also identified interspersed areas of more differentiated nephron units histologically in the surgical specimen, which would be consistent with a reninmediated etiology of the hypertension although plasma renins were not measured. Conclusion We have presented a case of hypertension as a complication of multicystic kidney which completely resolved after nephrectomy was performed. As noted previously causally related cases of hypertension as a result of multicystic kidne?, have been infrequently reported to date. Pain and malignancy are two additional com-
plications of multicystic kidney which have been reported in a small number of cases.7 13 These potential risks have prompted much discussion regarding the management of these patients. If the size of the mass causes difficulty, the diagnosis is in question, an associated complication exists, or the patient undergoes laparotomy for another reason, nephrectomy should be performed. If, however, the patient is asymptomatic, a decision must be made regarding nephrectomy versus a nonoperative approach. With a nonoperative approach one must take into consideration the ease of followup and patient’s compliance, and decide on the frequency and duration of follow-up. Previous recommendations on the length of observation have varied from through puberty’” to lifelong monitoring. l2 With the prevalence of multicystic kidney in the general population and the very low reported complication rate to date, we believe it is reasonable to manage these patients conservatively with serial ultrasound examinations if follow-up is reliable. If the kidney. remains large without evidence of regression, nephrectomy should then be considered. Hopefully, more information on these issues will become available as patients are followed nonoperatively and further complications are reported. Addendum Since the submission of this article, we have seen and treated a twelve-year-old boy with significant hypertension who was found to have a multicystic dysplastic kidney. After an uncomplicated nephrectomy, his hypertension resolved, and his blood pressure has remained normal without medication during follow-up. One Clinic Center 9500 Euclid Avenue Cleveland. Ohio 44195-5041 (DR. KAY) References I, 1,~ TC. and Blake S: Prenatal fetal abdominal ultrasonography and diagnosis, Radiology 124: 175 (1977!. 2. Hadlock IT, d al: Snnography of fetal urinarv tract anrmxlies. AJR 137: 261 (1981). 3. Stuck KJ. Koff SA, and Silver ‘Wl: Ultrasonic features of multicystic dysplastic kidney: expanded diagnostics criteria. Radiology 143: 217 (1982). 4. Beretsky I, I,ankin DH, Rusoff JH, and l’helan L: Sonographic differentiation hetween the multicystic dysplastic kidnq and the ureteropclvic junction obstruction in utero using highresolution real-time scanners employing di@al detection. J Clin Ultrasound 12: 429 (1984).
5. Javadpour N, et al: Hypertension in a child caused by a multicystic kidney, J Urol 104: 918 (1970). 6. Chen Y, Stapleton FB, Roy S, and Noe HN: Neonatal hypertension from a unilateral multicystic dysplastic kidney, J Urol133: 664 (1985). 7. Burgler W, and Jauri D: Vitale Komplikationen bei multizystischier nierendegeneration (multizystischer dysplastic), Urol lnt 38: 251 (1983). 8. Barrett DM, and Wineland RE: Renal cell carcinoma in multicystic dysplastic kidney, Urology 15: 152 (1980). 9. Birken G, King D, Vane D, and Lloyd T: Renal cell carcinoma arising in a multicystic dysplastic kidney, J Pediatr Surg 20: 619 (1985). 10. Shirai M, Kitagawa T, Nakata H, and Urano Y: Renal cell carcinoma originating from dysplastic kidney, Acta Path01 Jpn 36: 1263 (1986). 11. Raffensperger J, and Abousleiman A: Abdominal masses in children under one year of age, Surgery 63: 514 (1968). 12. Hartmann GE, Smolik LM, and Shochat SJ: The dilemma of the multicystic dysplastic kidney, Am J Dis Child 140: 925 (1986).
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13. Ambrose SS, Gould RA, Trulock TS, and Parrott TS: Unilateral multicystic renal disease in adults, J Urol 128: 366 (1982). 14. Gordon AC, Thomas DFM, Arthur RJ, and Irving HC: Multicystic dysplastic kidney: is nephrectomy still appropriate? J Urol 140: 1231 (1988). 15. Walker D, Fennel1 R, Garin E, and Richard G: Spectrum of multicystic renal dysplasia, Urology 11: 433 (1978). 16. Avni EF, and Schulman CC: Multicystic dysplastic kidney: natural history from in utero diagnosis and postnatal follow-up, J Urol 138: 1420 (9187). 17. Pedicelli G, Jequier S, Bowen A, and Boisvert J: Multicystic dysplastic kidneys: spontaneous regression demonstrated with US, Radiology 160: 23 (1986). 18. Bloom DA, and Brosnan S: The multicystic kidney, J Urol 120: 211 (1978). 19. Stanisic TH: Review of “The dilemma of the multicystic dysplastic kidney,” Editorial, Am J Dis Child 140: 865 (1986). 20. de Swiet M, Fayers P, and Shinebourne EA: Systolic blood pressure in a population of infants in the first year of life: the Brompton study, Pediatrics 65: 1028 (1980).
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