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Renal tubular dysgenesis

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Abstract

Renal tubular dysgenesis (RTD) is a severe foetal disorder characterised by the absence or poor development of proximal tubules, early onset and persistent anuria (leading to oligohydramnios and the Potter sequence) and ossification defects of the skull. In most cases, early death occurs from pulmonary hypoplasia, anuria and refractory arterial hypotension. RTD may be acquired during foetal development or inherited as an autosomal recessive disease. Inherited RTD is genetically heterogeneous and linked to mutations in the genes encoding the major components of the renin–angiotensin system (RAS): angiotensinogen, renin, angiotensin-converting enzyme or angiotensin II receptor type 1. Mutations result in either the absence of production or lack of efficacy of angiotensin II. Secondary RTD has been observed in various situations, particularly in the donor twin of severe twin-to-twin transfusion syndrome, in foetuses affected with congenital haemochromatosis or in foetuses exposed to RAS blockers. All cases result in renal hypoperfusion. These examples illustrate the importance of a functional RAS in the maintenance of blood pressure and renal blood flow for humans during foetal life. The diagnosis of RTD in an anuric foetus with normal renal sonography results is important for the management of the foetus or neonate. Depending on the genetic or secondary cause of the disease, such findings can lead to genetic counselling or the prevention of recurrence in subsequent pregnancies.

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References

  1. Allanson JE, Pantzar JT, MacLeod PM (1983) Possible new autosomal recessive syndrome with unusual renal histopathological changes. Am J Med Genet 16:57–60

    Article  PubMed  CAS  Google Scholar 

  2. Allanson JE, Hunter AGW, Mettler GS, Jimenez C (1992) Renal tubular dysgenesis: a not uncommon autosomal recessive syndrome: a review. Am J Med Genet 43:811–814

    Article  PubMed  CAS  Google Scholar 

  3. Voland JR, Hawkins EP, Wells TR, Saunders B, Jones M, Benirschke K (1985) Congenital hypernephronic nephromegaly with tubular dysgenesis: a distinctive inherited renal anomaly. Pediatr Pathol 4:231–245

    Article  PubMed  CAS  Google Scholar 

  4. Schwartz BR, Lage JM, Pober BR, Driscoll SG (1986) Isolated congenital renal tubular immaturity in siblings. Hum Pathol 17:1259–1263

    Article  PubMed  CAS  Google Scholar 

  5. Swinford AE, Bernstein J, Toriello HV, Higgins JV (1989) Renal tubular dysgenesis: delayed onset of oligohydramnios. Am J Med Genet 32:127–132

    Article  PubMed  CAS  Google Scholar 

  6. Ariel I, Wells TR, Landing BH, Sagi M, Bar-Oz B, Ron N, Rosenmann E (1995) Familial renal tubular dysgenesis: a disorder not isolated to proximal tubules. Pediatr Pathol Lab Med 15:915–922

    Article  PubMed  CAS  Google Scholar 

  7. Querfeld U, Ortmann M, Vierzig A, Roth B (1996) Renal tubular dysgenesis: a report of two cases. J Perinatol 16:498–500

    PubMed  CAS  Google Scholar 

  8. Kumar D, Moss G, Primhak R, Coombs R (1997) Congenital renal tubular dysplasia and skull ossification defects similar to teratogenic effects of angiotensin-converting enzyme (ACE) inhibitors. J Med Genet 34:541–545

    Article  PubMed  CAS  Google Scholar 

  9. Kriegsmann J, Coerdt W, Kommos SF, Beetz R, Hallermann C, Müntefering H (2000) Renal tubular dysgenesis (RTD). An important cause of the oligo-hydramnion-sequence. Report of 3 cases and review of the literature. Pathol Res Pract 196:861–865

    Article  PubMed  CAS  Google Scholar 

  10. Ramalho C, Matias A, Brandão O, Montenegro N (2007) Renal tubular dysgenesis: report of two cases in a non-consanguineous couple and review of the literature. Fetal Diagn Ther 22:10–13

    Article  PubMed  CAS  Google Scholar 

  11. Amar B, Gargouri A, Makni S, Kammoun H, Trigui L, Hentati Hmida N, Gubler MC, Regaieg R, Boudawara T, Rekik A (2007) Autosomal recessive renal tubular dysgenesis: morphologic and genetic study of 2 cases. Arch Pediatr 14:1088–1091

    Article  PubMed  Google Scholar 

  12. Gribouval O, Gonzales M, Neuhaus T, Aziza J, Bieth E, Laurent N, Bouton JM, Feuillet F, Makni S, Ben Amar H, Laube G, Delezoide AL, Bouvier R, Dijoud F, Ollagnon-Roman E, Roume J, Joubert N, Antignac C, Gubler MC (2005) Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Nat Genet 37:964–968

    Article  PubMed  CAS  Google Scholar 

  13. Gribouval O, Morinière V, Pawtowski A, Arrondel C, Sallinen SL, Saloranta C, Clericuzio C, Viot G, Tantau J, Blesson S, Cloarec S, Machet MC, Chitayat D, Thauvin C, Laurent N, Sampson JR, Bernstein JA, Clemenson A, Prieur F, Daniel L, Levy-Mozziconacci A, Lachlan K, Alessandri JL, Cartault F, Rivière JP, Picard N, Baumann C, Delezoide AL, Belar Ortega M, Chassaing N, Labrune P, Yu S, Firth H, Wellesley D, Bitzan M, Alfares A, Braverman N, Krogh L, Tolmie J, Gaspar H, Doray B, Majore S, Bonneau D, Triau S, Loirat C, David A, Bartholdi D, Peleg A, Brackman D, Stone R, DeBerardinis R, Corvol P, Michaud A, Antignac C, Gubler MC (2012) Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis. Hum Mutat 33:316–326

    Article  PubMed  CAS  Google Scholar 

  14. Seyle H (1948) Transformation of the kidney into an exclusively endocrine organ. Nature 158:131

    Article  Google Scholar 

  15. Marcussen N (1991) Atubular glomeruli in renal artery stenosis. Lab Invest 65:558–565

    PubMed  CAS  Google Scholar 

  16. Kim SY, Kong HG, Kim EK, Choi JH, Choi Y, Cheong HI (2012) Survival over 2 years of autosomal renal tubular dysgenesis. Clin Kidney J 5:56–58

    Article  Google Scholar 

  17. John U, Benz K, Hübler A, Patzer L, Zenker M, Amann K (2012) Oligohydramnios associated with sonographically normal kidneys. Urology 79:1155–1157

    Article  PubMed  Google Scholar 

  18. Uematsu M, Sakamoto O, Nishio T, Ohura T, Matsuda T, Inagaki T, Abe T, Okamura K, Kondo Y, Tsuchiya S (2007) A case surviving for over a year of renal tubular dysgenesis with compound heterozygous angiotensinogen gene mutations. Am J Med Genet A 140:2355–2360

    Google Scholar 

  19. Bacchetta J, Dijoud F, Bouvier R, Putet G, Gubler MC, Cochat P (2007) Renal Tubular dysgenesis and mutation in the renin gene. Arch Pediatr 14:1084–1087

    Article  PubMed  CAS  Google Scholar 

  20. Zingg-Schenk A, Bachetta J, Corvol P, Michaud A, Stallmach T, Cochat P, Gribouval O, Gubler M-C, Neuhaus TJ (2008) Inherited renal tubular dysgenesis: the first patients surviving the neonatal period. Eur J Paediatr 167:311–316

    Article  Google Scholar 

  21. Schreiber R, Gubler MC, Gribouval O, Shalev H, Landau D (2010) Inherited renal tubular dysgenesis may not be universally fatal. Pediatr Nephrol 25:2531–2534

    Article  PubMed  Google Scholar 

  22. Uematsu M, Sakamoto O, Ohura T, Shimizu N, Satomura K, Tsuchiya S (2009) A further case of renal tubular dysgenesis surviving the perinatal period. Eur J Pediatr 168:207–209

    Article  PubMed  Google Scholar 

  23. Barr M, Cohen MM (1999) ACE inhibitor fetopathy and hypocalvaria. The kidney–skull connection. Teratology 44:485–495

    Article  Google Scholar 

  24. Lacoste M, Cai Y, Guicharnaud L, Mounier F, Dumez Y, Bouvier R, Dijoud F, Gonzales M, Chatten J, Delezoide AL, Daniel L, Joubert M, Laurent N, Aziza J, Sellami T, Amar HB, Jarnet C, Frances AM, Daïkha-Dahmane F, Coulomb A, Neuhaus TJ, Foliguet B, Chenal P, Marcorelles P, Gasc J-M, Corvol P, Gubler M-C (2006) Renal tubular dysgenesis, a not uncommon autosomal recessive disorder leading to oligohydramnios: role of the renin-angiotensin system. J Am Soc Nephrol 17:2253–2263

    Article  PubMed  CAS  Google Scholar 

  25. Zivná M, Hůlková H, Matignon M, Hodanová K, Vylet’al P, Kalbácová M, Baresová V, Sikora J, Blazková H, Zivný J, Ivánek R, Stránecký V, Sovová J, Claes K, Lerut E, Fryns JP, Hart PS, Hart TC, Adams JN, Pawtowski A, Clemessy M, Gasc JM, Gübler MC, Antignac C, Elleder M, Kapp K, Grimbert P, Bleyer AJ, Kmoch S (2009) Dominant renin gene mutations associated with early-onset hyperuricemia, anemia, and chronic renal failure. Am J Hum Genet 85:204–213

    Article  PubMed  Google Scholar 

  26. Beck BB, Trachtman H, Gitman M, Miller I, Sayer JA, Pannes A, Baasner A, Hildebrandt F, Wolf MT (2011) Autosomal dominant mutation in the signal peptide of renin in a kindred with anemia, hyperuricemia, and CKD. Am J Kidney Dis 58:821–825

    Article  PubMed  CAS  Google Scholar 

  27. Michaud A, Bur D, Gribouval O, Iturrioz X, Clemessy M, Gasc JM, Gubler MC, Corvol P (2011) Loss-of-function point mutations associated with renal tubular dysgenesis provide insights about renin function and cellular trafficking. Hum Mol Genet 20:301–311

    Article  PubMed  CAS  Google Scholar 

  28. Genest DR, Lage JM (1991) Absence of normal-appearing proximal tubules in the fetal and neonatal kidney: prevalence and significance. Hum Pathol 22:147–153

    Article  PubMed  CAS  Google Scholar 

  29. Hegde S, Wright C, Shenoy M, Moghal NE, Coulthard MG (2007) Renovascular hypertension commencing during fetal life. Arch Dis Child Fetal Neonatal Ed 92:F301–F304

    Article  PubMed  Google Scholar 

  30. Barr M, Sedman AB, Heidelberger KP (1998) Renal tubular dysgenesis in twins. Pediatr Nephrol 12:408–413

    Article  PubMed  Google Scholar 

  31. Oberg KC, Pestaner JP, Bielamowicz L, Hawkins EP (1999) Renal tubular dysgenesis in twin-to-twin transfusion syndrome. Pediatr Dev Pathol 2:25–32

    Article  PubMed  CAS  Google Scholar 

  32. Mahieu-Caputo D, Dommergues M, Delezoide AL, Lacoste M, Cai Y, Narcy F, Jolly D, Gonzales M, Dumez Y, Gubler MC (2000) Twin to twin transfusion syndrome. Role of the fetal renin–angiotensin system. Am J Pathol 156:629–636

    Article  PubMed  CAS  Google Scholar 

  33. Mahieu-Caputo D, Salomon LJ, Le Bidois J, Fermont L, Brunhes A, Jouvet P, Dumez Y, Dommergues M (2003) Fetal hypertension: an insight into the pathogenesis of the twin–twin transfusion syndrome. Prenat Diagn 23:640–645

    Article  PubMed  CAS  Google Scholar 

  34. Mahieu-Caputo D, Meulemans A, Martinovic J, Gubler MC, Delezoide AL, Muller F, Madelenat P, Fisk NM, Dommergues M (2005) Paradoxic activation of the renin-angiotensin system in twin-twin transfusion syndrome: an explanation for cardiovascular disturbances in the recipient. Pediatr Res 58:685–688

    Article  PubMed  Google Scholar 

  35. Whitington PF (2007) Neonatal hemochromatosis: a congenital alloimmune hepatitis. Semin Liver Dis 27:243–250

    Article  PubMed  CAS  Google Scholar 

  36. Collardeau-Frachon S, Heissat S, Bouvier R, Fabre M, Baruteau J, Broue P, Cordier MP, Debray D, Debiec H, Ronco P, Guigonis V (2012) French retrospective multicentric study of neonatal haemochromatosis: importance of autopsy and of auto-immune maternal manifestations. Pediatr Dev Pathol 15:450–470

    Article  PubMed  CAS  Google Scholar 

  37. Bale PM, Kan AE, Dorney SFA (1994) Renal proximal tubular dysgenesis associated with severe neonatal hemosiderotic liver disease. Pediatr Pathol 14:479–489

    Article  PubMed  CAS  Google Scholar 

  38. Johal JS, Thorp JW, Oyer CE (1998) Neonatal hemochromatosis, renal tubular dysgenesis, and hypocalvaria in a neonate. Pediatr Dev Pathol 1:433–437

    Article  PubMed  CAS  Google Scholar 

  39. Morris S, Akima S, Dahlstrom JE, Ellwood D, Kent A, Falk MC (2004) Renal tubular dysgenesis and neonatal hemochromatosis without pulmonary hypoplasia. Pediatr Nephrol 19:341–344

    Article  PubMed  Google Scholar 

  40. Bonilla SF, Melin-Aldana H, Whitington PF (2010) Relationship of proximal renal tubular dysgenesis and fetal liver injury in neonatal hemochromatosis. Pediatr Res 67:188–193

    Article  PubMed  CAS  Google Scholar 

  41. Guignard JP, Gouyon JB, John EG (1991) Vasoactive factors in the immature kidney. Pediatr Nephrol 5:443–446

    Article  PubMed  CAS  Google Scholar 

  42. Cunniff C, Lyons-Jones K, Phillipson J, Benischke K, Short S, Wujek J (1990) Oligohydramnios sequence and renal tubular malformation associated with maternal enalapril use. Am J Obstet Gynecol 162:187–189

    Article  PubMed  CAS  Google Scholar 

  43. Pryde PG, Seman AB, Nugent CE, Barr M Jr (1993) Angiotensin-converting enzyme inhibitor fetopathy. J Am Soc Nephrol 3:1575–1582

    PubMed  CAS  Google Scholar 

  44. Martinovic J, Benachi A, Laurent N, Daïkha-Dahmane F, Gubler MC (2001) Fetal toxic effects of angiotensin II receptor antagonists. Report of three additional cases. Lancet 358:241–242

    Article  PubMed  CAS  Google Scholar 

  45. Daïkha-Dahmane F, Levy-Beff E, Jugie M, Lenclen R (2006) Foetal kidney maldevelopment in maternal use of angiotensin II type I receptor antagonists. Pediatr Nephrol 21:729–732

    Article  PubMed  Google Scholar 

  46. Neves S, Santos R, Gomes C, Correia AJ (2010) Fetopathy associated with exposure to angiotensin converting enzyme inhibitors. Acta Med Port 23:697–700

    PubMed  Google Scholar 

  47. Spaggiari E, Heidet L, Grange G, Guimiot F, Dreux S, Delezoide AL, Renin-Angiotensin System Blockers Study Group, Muller F (2012) Prognosis and outcome of pregnancies exposed to renin–angiotensin system blockers. Prenat Diagn 32:1–6

    Article  Google Scholar 

  48. Cooper WO, Hernandez-Diaz S, Arbogast PG, Dudley JA, Dyer S, Gideon PS, Hall K, Ray WA (2006) Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med 354:2443–2451

    Article  PubMed  CAS  Google Scholar 

  49. Bullo M, Tschumi S, Bucher BS, Bianchetti MG, Simonetti GD (2012) Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists: a systematic review. Hypertension 60:444–450

    Article  PubMed  CAS  Google Scholar 

  50. Guron G, Mölne J, Swerkersson S, Friberg P, Hansson S (2006) A 14-year-old girl with renal abnormalities after brief intrauterine exposure to enalapril during late gestation. Nephrol Dial Transplant 21:522–525

    Article  PubMed  Google Scholar 

  51. Laube GF, Kemper MJ, Schubiger G, Neuhaus TJ (2007) Angiotensin-converting enzyme inhibitor fetopathy: long-term outcome. Arch Dis Child Fetal Neonatal Ed 92:F402–F403

    Article  PubMed  Google Scholar 

  52. Schindera C, Huber BM, Nelle M, Utsch B, Tschumi S, Gerull R (2012) Early development of arterial hypertension in an infant with valsartan nephropathy. J Neonatal Biol 1:1–2

    Article  Google Scholar 

  53. Deva M, Kara T (2012) ACE inhibitor fetopathy: a case series and survey of opinion amongst New Zealand paediatricians, obstetricians, neonatologists, and nephrologists. N Z Med J 125:51–61

    PubMed  Google Scholar 

  54. Schutz S, Le Moullec JM, Corvol P, Gasc JM (1996) Early expression of all components of the renin–angiotensin–system in human development. Am J Pathol 149:2067–2079

    PubMed  CAS  Google Scholar 

  55. Gubler MC, Antignac C (2010) Renin-angiotensin system in kidney development: renal tubular dysgenesis. Kidney Int 77:400–406

    Article  PubMed  CAS  Google Scholar 

  56. Corvol P, Michaud A, Gribouval O, Gubler MC (2008) Can we live without a functional renin-angiotensin system? Clin Exp Pharmacol Physiol 35:431–433

    Article  PubMed  CAS  Google Scholar 

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  1. INSERM, U983, 149 rue de Sèvres, 75743, Paris cedex 15, France

    Marie-Claire Gubler

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Correspondence to Marie-Claire Gubler.

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1. a, d

2. a

3. a

4. b, c

5. b, c

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Gubler, MC. Renal tubular dysgenesis. Pediatr Nephrol 29, 51–59 (2014). https://doi.org/10.1007/s00467-013-2480-1

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