*Vrije Universiteit Brussel and ^&Magdalena Sonora, Mexico

Synonyms: Potter type 2

Definition: A disorder characterized by enlarged, echogenic kidneys with multiple cysts, unilateral or bilateral, probably due to an early obstructive defect.

Prevalence: rare. There is a male predominance (ratio M2.4/F1) but female fetuses are twice as likely to have bilateral multicystic dysplastic kidney disease and associated non-renal abnormalities. They are four times more likely to have an abnormal karyotype[1].

Etiology: unknown

Pathogenesis: The pathogenesis is unknown but a hypothesis is that an early obstructive defect of the developing kidney causes the disorder1. Multicystic dysplastic kidney disease is characterized by architectural disorganization of the kidney. Matsell et al. demonstrated early cystic enlargement of various segments of the nephron at 14 weeks gestation. At later stages the predominant features include cyst enlargement with marked fibromuscular collars, architectural disorganization, and replacement of the interstitium with a disorder of mesenchymal tissue[2]. There is atresia of the ipsilateral ureter.

Sonographic findings: Multicystic dysplastic kidney disease is most common an incidentally finding1.

• The kidney(s) appear(s) enlarged with multiple cysts[3] which are
  • mostly randomly positioned, but sometimes peripheral;
  • variable in size and
  • non-communicating although artifacts may make non-communicating cysts appear as they communicate[4].
  • The parenchym is seen in small islands between the cysts and the outline of the kidney tends to be lost.
  • The size of the kidney is proportional to the size and the number of visible cysts4.
• The contralateral kidney needs to be assessed. The contralateral kidney is mostly normal but multicystic dyplastic kidney disease may occur bilaterally or with contralateral agenesis[5], in which there is no functional kidney tissue left and as such the condition is fatal.
• If detected in the second trimester the cysts will initially increase in size and number of cysts, followed by involutional changes either in utero or postnatal[6].
• Mitchell et al. demonstrated Doppler changes in the peripheral pulmonary arteries in case of multicystic dysplastic kidney disease with pulmonary hypoplasia. The resistance index of the peripheral arteries showed a high resistance pattern. By lack of amniotic fluid lung development is compromised and is incomplete. This results in fewer canaliculi followed by reduced vascularization of the bronchioles and terminal air spaces. The capillary walls are thicker and there is increased resistance. However the permanent changes seen in case of multicystic dysplastic kidney disease seem to give similar waveforms as seen in the temporary changes in case of intra-uterine growth restriction[7].

Cases:

Case 1: 26 years, 26 weeksCase 1: 26 years, 26 weeks

Case 1, 33 weeks

Case 1, 39 weeks

Case 2

There is also a 3.5 MB video clip of the last case.

Differential diagnosis:

• Adult polycystic kidney disease: autosomal dominant chronic disease with late onset but progressive development of cysts resulting in renal failure. Prenatal diagnosis can be made in the third trimester: enlarged and hyper-echogenic kidneys with preservation of the medullary region, with or without multiple cysts, randomly distributed, in association with normal amount of amniotic fluid. The sonographic appearance of the parental kidneys is essential in making the diagnosis: if neither parent displays cysts then autosomal-dominant polycystic dysplastic kidney disease is unlikely4,[8].
• Infantile polycystic kidney disease: autosomal recessive disorder; huge echogenic kidneys but almost no cysts visible and oligo(an)hydramnion. The amount and size of visible cysts will not account for the size of the kidney. Sonographic findings similar to adult polycystic dysplastic kidney disease but often there are more cysts visible and the amount of fluid is higher in the adult disease than in the infantile disease4,8.
• Meckel syndrome (Meckel-Gruber syndrome): rare and lethal condition characterized by occipital cephalocele, post-axial polydactyly and cystic dysplasia of the kidneys. The cysts, initially microscopic, develop, destroy the parenchym and enlarge the organ extremely. Oligohydramnios is often associated[9],[10].
• Trisomy 13: Characteristic features are: holoprosencephaly and facial anomalies; post-axiale hexadactyly; enlarged, hyperechogenic kidneys similar to polycystic kidneys; cardiac defects, echogenic cardiac foci; intra-uterine growth restriction; mild ventriculomegaly, abnormal cisterna magna and cystic hygroma4.
• Asphyxiating thoracic dysplasia (Jeune syndrome): rare autosomal recessive skeletal disorder characterized with a small thorax, short limbs and pelvic abnormalities. Renal abnormalities (cystic hypoplasia) are a significant feature[11].
• Congenital hypernephric nephromegaly with tubular dysgenesis4: inherited renal disorder characterized by oligohydramnios, the Potter phenotype, and enlarged non-functional kidneys.
• Tuberous sclerosis: This syndrome is characterized by fibroangiomatous skin lesions (undetectable prenatally), renal cysts, multiple and bilateral angiofibroma of the kidney (not yet reported prenatally), rhabdomyoma of the heart, mental retardation and epilepsy, “café au lait” spots. The predominant prenatal finding is that of the cardial tumor9,[12]. A minority of patients with tuberous sclerosis have a clinical image of enlarged and polycystic kidneys at birth or shortly thereafter. The kidneys are characterized by variably sized cysts resembling those seen in later life of adult polycystic kidney disease[13].
• Alagille syndrome: autosominal dominant disorder characterized by neonatal jaundice; characteristic facies (broad forehead, pointed mandible, bulbous tip of the nose); posterior embryotoxon and retinal pigmentary changes; “butterfly” vertebrae; peripheral arterial stenosis and pulmonic valvular stenosis. Martin et al described 2 cases of children with Alagille syndrome in whom a unilateral multicystic dysplastic kidney was detected by prenatal ultrasound[14].

Associated anomalies: Associated anomalies can be differentiated into two groups:

• 43.6%[15] - 51%[16] have other urologic associated anomalies: most common contralateral vesico-ureteral reflux16,[17], varying degree of contralateral hydronephrosis secondary to uretero-pelvic junction obstruction or a duplicating collecting system, agenesis of the contralateral kidney, ectopic pelvic kidney1 and ureterocele[18];
• associated non-renal abnormalities: are more common in bilateral multicystic dysplastic kidney disease (80%) and rare in unilateral multicystic dysplastic kidney disease (11%)6. Most commonly associated syndrome is the VATER sequence (vertebral defects, anal atresia, tracheoesopfageal fistula with esophageal atresia, radial and renal dysplasia) 1,18. Other associated anomalies include congenital heart disease18, gastro-intestinal, spinal and cranial abnormalities1. Fanos et al reported a frequency of 1.76% of cystic renal disease in Turner syndrome[19],[20].

Prognosis: Unilateral multicystic dysplastic kidney disease, absence of associated anomalies, normal karyotype and adequate amniotic fluid[21] are reassuring findings 1,5. Bilateral disease or contralateral agenesis is fatal.

Although rare, malignant degeneration of multicystic dysplastic kidney has been demonstrated including Wilms tumor, renal cell carcinomas, mesothelioma and mesoblastic nephroma[22],[23].

Recurrence risk: none4

Management:

The natural history of the disease is unpredictable15 but serial ultrasound examinations demonstrated that multicystic dysplastic kidney disease lesions involute with time6,[24].

A complete neonatal work-up should be performed1,15. Close follow-up with renal ultrasound every 3-4 months is essential during the first year of life23 as well as annual clinical review[25].

Routine removal of the kidney for either diagnostic or prophylactic reasons is not advisable24,25,[26] but surgical exploration is indicated if the diagnosis becomes ambiguous at any point, if there is little compliance regarding follow –up23, in the absence of no involution15 and if complications develop[27].

Some reports demonstrated the use of post-natal percutaneous puncture of the cysts as a diagnostic tool in differentiating hydronephrosis and cystic kidney disease[28],[29],[30].

Reviewers: Graziella Secchi, MD, Carlos Alberto Mejia Escobar, MD

[1] Lazebnik N, Bellinger MF, Ferguson JE, Hogge JS, Hogge WA. Insights into the pathogenesis and natural history of fetuses wiyh multicystic dysplastic kidney disease. Prenat Diagn. 1999;19:418-23

[2] Matsell DG, Bennett T, Armstrong RA, Goodyer P, Han VK. Insulin-like growth factor and IGF binding protein gene expression in multicystic renal dysplasia. J Am Soc Nephrol 1997;8(1):85-94

[3] Rizzo N, Gabrielli S, Pilu G, Perolo A, Cacciari A, Domini R, Bovicelli L. Prenatal diagnosis and obstetrical management of multicystic dysplastic kidney disease. Prenat Diagn 1987 Feb;7(2):109-18

[4] Callen PW. Ultrasonography in Obstetrics and Gynecology. PW Saunders, 4^th edition. Fetal genitourinary tract pp 541-3

[5] Feldenberg LR, Siegel NJ. Clinical course and outcome for children with multicystic dysplastic kidneys. Pediatr Nephrol 2000;14(12):1098-101

[6] Dungan JS, Fernandez MT, Abbitt PL, Thiagarajah S, Howards SS, Hogge WA. Multicystic dysplastic kidney: natural history of prenatally detected cases. Prenat Diagn 1990 Mar;10(3):175-82

[7] Mitchell JM, Roberts AB, Lee A. Doppler waveforms from the pulmonary arterial system in normal fetuses and those with pulmonary hypoplasia. Ultrasound Obstet Gynecol 1998;11:167-172

[8] Mikic AN. Adult polycystic kidney disease. www.thefetus.net/

[9] Benacerraf B. Ultrasound of fetal syndromes. Churchill Livingstone 1998. Meckel-Gruber syndrome. pp 125-7

[10] Silva RS, Jeanty P. Meckel syndrome. www.thefetus.net/.

[11] Tongsong T, Chanprapaph P, Thongpadungroj T. Prenatal sonographic findings associated with asphyxiating thoracic dystrophy (Jeune syndrome). J Ultrasound Med 1999;18:573-6

[12] Jeanty P, Silva SR. Tuberous sclerosis. www.thefetus.net/

[13] OMIM database #600273

[14] Martin SR, Garel L, Alvarez F. Alagille’s syndrome associated with cystic renal disease. Arch Dis Child 1996;74(3):232-4

[15] Kessler OJ, Ziv N, Livne Pm, Merlob P. Involution rate of multicystic renal dysplasia. Pediatrics 1998;102(6):E73

[16] Atiyeh B, Husmann D, Baum M. Contralateral renal abnormalities in multicystic dysplastic kidney disease. J Pediatr 1992;121(1):65-7

[17] Kaneko K, Suzuki Y, Fukuda Y, Yabuta K, Miyano T. Abnormal contralateral kidney in unilateral multicystic dysplastic kidney disease. Pediatr Radiol 1995;25(4):275-7

[18] Blane CE, Ritchey ML, DiPietro MA, Sumida R, Bloom DA. Single system ectopic ureters and ureteroceles associated with dysplastic kidney. Pediatr Radiol 1992;22(3):217-20

[19] Fanos V, Schena S, Dal Moro A, Portuese A, Antoniazzi F. Multicystic kidney dysplasia and Turner syndrome: two cases and a literature review. Pediatr Nephrol 2000;14(8-9):754-7

[20] Herman TE, Siegel MJ. Renal cysts associated with Turner’s syndrome. Pediatr Radiol 1994;24(4):139-40

[21] Estroff JA, Mandell J, Benacerraf BR. Increased renal parenchymal echogenicity in the fetus: importance and clinical outcome. Radiology 1991;181(1):135-9

[22] Hornsy YL, Anderson JH, Oudjhane K, Russo P. Wilmstumor and multicystic dysplastic kidney disease. J Urol 1997;158(6):2256-9

[23] Minevich E, Wacksman J, Phipps L, Lewis AG, Sheldon CA. The importance of accurate diagnosis and early close follow-up in patients with suspected multicystic dysplastic kidney. J Urol 1997;158(3 Pt2):1301-4

[24] al-Khaldi N, Watson AR, Zuccollo J, Twining P, Rose DH. Outcome of antenatally detected cystic dysplastic kidney disease. Arch Dis Child 1994;70(6):520-2

[25] Suthankar S, Warson AR. Unilateral multicystic dysplastic kidney disease: defining the natural history.Anglia Paediatric Nephrourology Group. Acta Paediatr 2000;89(7):811-3

[26] Menster M, Mahan J, Koff S. Multicystic dysplastic kidney. Pediatr Nephrol 1994;8(1):113-5.

[27] Martin JA, Piro C, Sanchis L, Ezzedine H, Aso C, Gosalbez R. Is it necessary to remove polycystic kidneys ? Cir Pediatr 1990 Apr;3(2):53-5

[28] Kullendorf CM, Salmonson EC, Laurin S. Diagnostic cyst ouncture of multicystic kidney in neonates. Acta Radiol 1990;31(3):287-9

[29] Greenfield SP, Salem Y, Seidel FG, Feld LG. Diagnosis and management of the hydronephrotic type of multicystic dysplastic kidney. Use of antegrade pyelography. Child Nephrol Urol 1990;10(1):44-8

[30] Blane CE, DiPietro MA, Bloom DA, Sedman AB. Percutaneous nephrostogram in the newborn with bilateral renal cystic disease. Am J Dis Child 1988;142(12):1349-51

There is also a 3.5 MB video clip of the last case.

Differential diagnosis:

• Adult polycystic kidney disease: autosomal dominant chronic disease with late onset but progressive development of cysts resulting in renal failure. Prenatal diagnosis can be made in the third trimester: enlarged and hyper-echogenic kidneys with preservation of the medullary region, with or without multiple cysts, randomly distributed, in association with normal amount of amniotic fluid. The sonographic appearance of the parental kidneys is essential in making the diagnosis: if neither parent displays cysts then autosomal-dominant polycystic dysplastic kidney disease is unlikely4,[8].
• Infantile polycystic kidney disease: autosomal recessive disorder; huge echogenic kidneys but almost no cysts visible and oligo(an)hydramnion. The amount and size of visible cysts will not account for the size of the kidney. Sonographic findings similar to adult polycystic dysplastic kidney disease but often there are more cysts visible and the amount of fluid is higher in the adult disease than in the infantile disease4,8.
• Meckel syndrome (Meckel-Gruber syndrome): rare and lethal condition characterized by occipital cephalocele, post-axial polydactyly and cystic dysplasia of the kidneys. The cysts, initially microscopic, develop, destroy the parenchym and enlarge the organ extremely. Oligohydramnios is often associated[9],[10].
• Trisomy 13: Characteristic features are: holoprosencephaly and facial anomalies; post-axiale hexadactyly; enlarged, hyperechogenic kidneys similar to polycystic kidneys; cardiac defects, echogenic cardiac foci; intra-uterine growth restriction; mild ventriculomegaly, abnormal cisterna magna and cystic hygroma4.
• Asphyxiating thoracic dysplasia (Jeune syndrome): rare autosomal recessive skeletal disorder characterized with a small thorax, short limbs and pelvic abnormalities. Renal abnormalities (cystic hypoplasia) are a significant feature[11].
• Congenital hypernephric nephromegaly with tubular dysgenesis4: inherited renal disorder characterized by oligohydramnios, the Potter phenotype, and enlarged non-functional kidneys.
• Tuberous sclerosis: This syndrome is characterized by fibroangiomatous skin lesions (undetectable prenatally), renal cysts, multiple and bilateral angiofibroma of the kidney (not yet reported prenatally), rhabdomyoma of the heart, mental retardation and epilepsy, “café au lait” spots. The predominant prenatal finding is that of the cardial tumor9,[12]. A minority of patients with tuberous sclerosis have a clinical image of enlarged and polycystic kidneys at birth or shortly thereafter. The kidneys are characterized by variably sized cysts resembling those seen in later life of adult polycystic kidney disease[13].
• Alagille syndrome: autosominal dominant disorder characterized by neonatal jaundice; characteristic facies (broad forehead, pointed mandible, bulbous tip of the nose); posterior embryotoxon and retinal pigmentary changes; “butterfly” vertebrae; peripheral arterial stenosis and pulmonic valvular stenosis. Martin et al described 2 cases of children with Alagille syndrome in whom a unilateral multicystic dysplastic kidney was detected by prenatal ultrasound[14].

Associated anomalies: Associated anomalies can be differentiated into two groups:

• 43.6%[15] - 51%[16] have other urologic associated anomalies: most common contralateral vesico-ureteral reflux16,[17], varying degree of contralateral hydronephrosis secondary to uretero-pelvic junction obstruction or a duplicating collecting system, agenesis of the contralateral kidney, ectopic pelvic kidney1 and ureterocele[18];
• associated non-renal abnormalities: are more common in bilateral multicystic dysplastic kidney disease (80%) and rare in unilateral multicystic dysplastic kidney disease (11%)6. Most commonly associated syndrome is the VATER sequence (vertebral defects, anal atresia, tracheoesopfageal fistula with esophageal atresia, radial and renal dysplasia) 1,18. Other associated anomalies include congenital heart disease18, gastro-intestinal, spinal and cranial abnormalities1. Fanos et al reported a frequency of 1.76% of cystic renal disease in Turner syndrome[19],[20].

Prognosis: Unilateral multicystic dysplastic kidney disease, absence of associated anomalies, normal karyotype and adequate amniotic fluid[21] are reassuring findings 1,5. Bilateral disease or contralateral agenesis is fatal.

Although rare, malignant degeneration of multicystic dysplastic kidney has been demonstrated including Wilms tumor, renal cell carcinomas, mesothelioma and mesoblastic nephroma[22],[23].

Recurrence risk: none4

Management:

The natural history of the disease is unpredictable15 but serial ultrasound examinations demonstrated that multicystic dysplastic kidney disease lesions involute with time6,[24].

A complete neonatal work-up should be performed1,15. Close follow-up with renal ultrasound every 3-4 months is essential during the first year of life23 as well as annual clinical review[25].

Routine removal of the kidney for either diagnostic or prophylactic reasons is not advisable24,25,[26] but surgical exploration is indicated if the diagnosis becomes ambiguous at any point, if there is little compliance regarding follow –up23, in the absence of no involution15 and if complications develop[27].

Some reports demonstrated the use of post-natal percutaneous puncture of the cysts as a diagnostic tool in differentiating hydronephrosis and cystic kidney disease[28],[29],[30].

Reviewers: Graziella Secchi, MD, Carlos Alberto Mejia Escobar, MD

[1] Lazebnik N, Bellinger MF, Ferguson JE, Hogge JS, Hogge WA. Insights into the pathogenesis and natural history of fetuses wiyh multicystic dysplastic kidney disease. Prenat Diagn. 1999;19:418-23

[2] Matsell DG, Bennett T, Armstrong RA, Goodyer P, Han VK. Insulin-like growth factor and IGF binding protein gene expression in multicystic renal dysplasia. J Am Soc Nephrol 1997;8(1):85-94

[3] Rizzo N, Gabrielli S, Pilu G, Perolo A, Cacciari A, Domini R, Bovicelli L. Prenatal diagnosis and obstetrical management of multicystic dysplastic kidney disease. Prenat Diagn 1987 Feb;7(2):109-18

[4] Callen PW. Ultrasonography in Obstetrics and Gynecology. PW Saunders, 4^th edition. Fetal genitourinary tract pp 541-3

[5] Feldenberg LR, Siegel NJ. Clinical course and outcome for children with multicystic dysplastic kidneys. Pediatr Nephrol 2000;14(12):1098-101

[6] Dungan JS, Fernandez MT, Abbitt PL, Thiagarajah S, Howards SS, Hogge WA. Multicystic dysplastic kidney: natural history of prenatally detected cases. Prenat Diagn 1990 Mar;10(3):175-82

[7] Mitchell JM, Roberts AB, Lee A. Doppler waveforms from the pulmonary arterial system in normal fetuses and those with pulmonary hypoplasia. Ultrasound Obstet Gynecol 1998;11:167-172

[8] Mikic AN. Adult polycystic kidney disease. www.thefetus.net/

[9] Benacerraf B. Ultrasound of fetal syndromes. Churchill Livingstone 1998. Meckel-Gruber syndrome. pp 125-7

[10] Silva RS, Jeanty P. Meckel syndrome. www.thefetus.net/.

[11] Tongsong T, Chanprapaph P, Thongpadungroj T. Prenatal sonographic findings associated with asphyxiating thoracic dystrophy (Jeune syndrome). J Ultrasound Med 1999;18:573-6

[12] Jeanty P, Silva SR. Tuberous sclerosis. www.thefetus.net/

[13] OMIM database #600273

[14] Martin SR, Garel L, Alvarez F. Alagille’s syndrome associated with cystic renal disease. Arch Dis Child 1996;74(3):232-4

[15] Kessler OJ, Ziv N, Livne Pm, Merlob P. Involution rate of multicystic renal dysplasia. Pediatrics 1998;102(6):E73

[16] Atiyeh B, Husmann D, Baum M. Contralateral renal abnormalities in multicystic dysplastic kidney disease. J Pediatr 1992;121(1):65-7

[17] Kaneko K, Suzuki Y, Fukuda Y, Yabuta K, Miyano T. Abnormal contralateral kidney in unilateral multicystic dysplastic kidney disease. Pediatr Radiol 1995;25(4):275-7

[18] Blane CE, Ritchey ML, DiPietro MA, Sumida R, Bloom DA. Single system ectopic ureters and ureteroceles associated with dysplastic kidney. Pediatr Radiol 1992;22(3):217-20

[19] Fanos V, Schena S, Dal Moro A, Portuese A, Antoniazzi F. Multicystic kidney dysplasia and Turner syndrome: two cases and a literature review. Pediatr Nephrol 2000;14(8-9):754-7

[20] Herman TE, Siegel MJ. Renal cysts associated with Turner’s syndrome. Pediatr Radiol 1994;24(4):139-40

[21] Estroff JA, Mandell J, Benacerraf BR. Increased renal parenchymal echogenicity in the fetus: importance and clinical outcome. Radiology 1991;181(1):135-9

[22] Hornsy YL, Anderson JH, Oudjhane K, Russo P. Wilmstumor and multicystic dysplastic kidney disease. J Urol 1997;158(6):2256-9

[23] Minevich E, Wacksman J, Phipps L, Lewis AG, Sheldon CA. The importance of accurate diagnosis and early close follow-up in patients with suspected multicystic dysplastic kidney. J Urol 1997;158(3 Pt2):1301-4

[24] al-Khaldi N, Watson AR, Zuccollo J, Twining P, Rose DH. Outcome of antenatally detected cystic dysplastic kidney disease. Arch Dis Child 1994;70(6):520-2

[25] Suthankar S, Warson AR. Unilateral multicystic dysplastic kidney disease: defining the natural history.Anglia Paediatric Nephrourology Group. Acta Paediatr 2000;89(7):811-3

[26] Menster M, Mahan J, Koff S. Multicystic dysplastic kidney. Pediatr Nephrol 1994;8(1):113-5.

[27] Martin JA, Piro C, Sanchis L, Ezzedine H, Aso C, Gosalbez R. Is it necessary to remove polycystic kidneys ? Cir Pediatr 1990 Apr;3(2):53-5

[28] Kullendorf CM, Salmonson EC, Laurin S. Diagnostic cyst ouncture of multicystic kidney in neonates. Acta Radiol 1990;31(3):287-9

[29] Greenfield SP, Salem Y, Seidel FG, Feld LG. Diagnosis and management of the hydronephrotic type of multicystic dysplastic kidney. Use of antegrade pyelography. Child Nephrol Urol 1990;10(1):44-8

[30] Blane CE, DiPietro MA, Bloom DA, Sedman AB. Percutaneous nephrostogram in the newborn with bilateral renal cystic disease. Am J Dis Child 1988;142(12):1349-51