Archives of Gynecology and Obstetrics

, Volume 297, Issue 6, pp 1421–1431 | Cite as

Alport syndrome and pregnancy: a case series and literature review

  • Francesca BruniniEmail author
  • Barbara Zaina
  • Davide Gianfreda
  • Wally Ossola
  • Marisa Giani
  • Luigi Fedele
  • Piergiorgio Messa
  • Gabriella Moroni
Maternal-Fetal Medicine



To assess pregnancy outcome in women with Alport syndrome and the impact of pregnancy on the disease progression.


We describe one of the largest series of pregnancies in Alport syndrome. Seven pregnancies of six women were monitored by a multidisciplinary team of nephrologists and gynecologists. After delivery, patients were followed for at least 3 years. We compare our results with those in the literature.


Pregnancy course was uneventful in the patient with isolated microscopic hematuria. In the other cases, all presenting mild proteinuria at conception, some complications occurred. Proteinuria worsened during the last trimester, reaching nephrotic ranges in five out of six pregnancies and was associated with fluid overload leading to hospitalizations and early delivery. The majority of the newborns had a low birth weight. The two patients with arterial hypertension at conception and twin pregnancy developed pre-eclampsia and renal function deterioration persisted after delivery. The one with pre-pregnancy renal dysfunction reached end-stage renal disease. In the other patients, in which renal function and blood pressure were and remained normal, proteinuria improved after delivery and no signs of disease progression were recorded at last observation.


Our observations suggest that Alport syndrome should be considered a potential risk factor for pregnancy in proteinuric patients due to the development of pre-eclampsia, renal function deterioration, and/or full-blown nephrotic syndrome that results in anasarca, slowing of fetal growth and pre-term delivery. Thus, all women with Alport syndrome should receive pre-conceptional counseling and be kept in close follow-up during pregnancy.


Alport syndrome Pregnancy Fetal and maternal outcome Kidney disease progression Proteinuria 


Author contribution

FB data collection, data analysis, and manuscript writing/editing. BZ clinical assessment of mothers and fetus during pregnancy and patient follow-up. DG data collection. WO clinical assessment of mothers and fetus during pregnancy and patient follow-up. MG patient follow-up at diagnosis. LF paper assessment. PGM paper assessment. GM project development; clinical assessment of mothers and fetus during pregnancy and patient follow-up; data analysis and manuscript writing/editing.


No supplemental funding was provided for this research.

Compliance with ethical standards

Conflict of interest

The authors report no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the IRCCS Ca’ Granda Ospedale Maggiore Policlinico ethics committee-Milano area B- and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

Informed consent

Data were collected retrospectively in an anonymous database without interfering with the best clinical practice at any time during patients’ follow-up. Due to the retrospective nature of the study, neither written nor verbal informed consent was necessary, according to the ethical standards of the institutional Ethics Committee.


  1. 1.
    Savige J, Colville D, Rheault M, Gear S, Lennon R, Lagas S, Finlay M, Flinter F (2016) Alport syndrome in women and girls. Clin J Am Soc Nephrol 11:1713–1720CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Cosgrove D, Liu S (2017) Collagen IV diseases: a focus on the glomerular basement membrane in Alport syndrome. Matrix Biol 57–58:45–54CrossRefPubMedGoogle Scholar
  3. 3.
    Hudson BG, Tryggvason K, Sundaramoorthy M, Neilson EG (2003) Alport’s syndrome, Goodpasture’s syndrome, and type IV collagen. New Engl J Med 348:2543–2556CrossRefPubMedGoogle Scholar
  4. 4.
    Kashtan CE (2001) Alport syndrome and thin basement membrane nephropathy (last updated 2015 Nov 25) gene reviews. University of Washington, SeattleGoogle Scholar
  5. 5.
    Morinière V, Dahan K, Hilbert P, Lison M, Lebbah S, Topa A, Bole-Feysot C, Pruvost S, Nitschke P, Plaisier E, Knebelmann B, Macher MA, Noel LH, Gubler MC, Antignac C, Heidet L (2014) Improving mutation screening in familial hematuric nephropathies through next generation sequencing. J Am Soc Nephrol 25:2740–2751CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Fallerini C, Dosa L, Tita R, Del Prete D, Feriozzi S, Gai G, Clementi M, La Manna A, Miglietti N, Mancini R, Mandrile G, Ghiggeri GM, Piaggio G, Brancati F, Diano L, Frate E, Pinciaroli AR, Giani M, Castorina P, Bresin E, Giachino D, De Marchi M, Mari F, Bruttini M, Renieri A, Ariani F (2014) Unbiased next generation sequencing analysis confirms the existence of autosomal dominant Alport syndrome in a relevant fraction of cases. Clin Genet 86:252–257CrossRefPubMedGoogle Scholar
  7. 7.
    Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer K-O, Flinter F, Pirson Y, Verellen C, Wieslander JR, Persson U, Tryggvason K, Martin P, Hertz JM, Schroder C, Sanak M, Krejcova S, Carvalho MF, Saus J, Antignac C, Smeets H, Gubler MC (2000) X-linked Alport syndrome: natural history in 195 families and genotype- phenotype correlations in males. J Am Soc Nephrol 11:649–657PubMedGoogle Scholar
  8. 8.
    Bekheirnia MR, Reed B, Gregory MC (2010) Genotype-phenotype correlation in X-linked Alport syndrome. J Am Soc Nephrol 21:876–883CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Rheault MN (2012) Women and Alport syndrome. Pediatr Nephrol 27:41–46CrossRefPubMedGoogle Scholar
  10. 10.
    Jais JP, Knebelmann B, Giatras I, De Marchi M, Rizzoni G, Renieri A, Weber M, Gross O, Netzer K-O, Flinter F, Pirson Y, Dahan K, Wieslander JR, Persson U, Tryggvason K, Martin P, Hertz JM, Schroder C, Sanak M, Carvalho MF, Saus J, Antignac C, Smeets H, Gubler MC (2003) X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: a “European Community Alport Syndrome Concerted Action” study. J Am Soc Nephrol 14:2603–2610CrossRefPubMedGoogle Scholar
  11. 11.
    Yefet E, Tovbin D, Nachum Z (2016) Pregnancy outcomes in patients with Alport syndrome. Arch Gynaecol Obstet 293:739–747CrossRefGoogle Scholar
  12. 12.
    Crovetto F, Moroni G, Zaina B, Acaia B, Ossola MW, Fedele L (2013) Pregnancy in women with Alport syndrome. Int Urol Nephrol 45:1223–1227CrossRefPubMedGoogle Scholar
  13. 13.
    Nevis IF, Reitsma A, Dominic A, McDonald S, Thabane L, Akl EA, Hladunewich M, Akbari A, Joseph G, Sia W, Iansavichus AV, Garg AX (2011) Pregnancy outcomes in women with chronic kidney disease: a systematic review. Clin J Am Soc Nephrol 6:2587–2598CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Bramham K, Parnell B, Nelson-Piercy C, Seed PT, Poston L, Chappell LC (2014) Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis. BMJ 348:g2301CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Cabiddu G, Castellino S, Gernone G, Moroni G, Giannattasio M, Gregorini G, Giacchino F, Attini R, Loi V, Limardo M, Gammaro L, Todros T, Piccoli GB (2016) A best practice position statement on pregnancy in chronic kidney disease: the Italian Study Group on kidney and pregnancy. J Nephrol 29:277–303CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Matsuo K, Tudor EL, Baschat AA (2007) Alport syndrome and pregnancy. Obstet Gynecol 109:531–532CrossRefPubMedGoogle Scholar
  17. 17.
    Mehta S, Saifan C, Abdellah M, Choueiry R, Nasr R, El-Sayegh S (2013) Alport’s syndrome in pregnancy. Case Rep Med. PubMedPubMedCentralGoogle Scholar
  18. 18.
    Kitanovska BG, Gerasimovska V, Livrinova V (2016) Two pregnancies with a different outcome in a patient with Alport syndrome. Open Access Maced J Med Sci 4(3):439–442CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Alessi M, Fabris A, Zambon A, Cremasco D, Murar o E, Dosa L (2014) Pregnancy in Alport syndrome: a report of two differently-evolving cases. J Obstet Gynaecol 34(1):98–100CrossRefPubMedGoogle Scholar
  20. 20.
    Nishizawa Y, Takei T, Miyaoka T, Kamei D, Mochizuki T, Nitta K (2016) Alport syndrome and pregnancy: good obstetric and nephrological outcomes in a pregnant woman with homozygous autosomal recessive Alport syndrome. J Obstet Gynaecol Res 42(3):331–335CrossRefPubMedGoogle Scholar
  21. 21.
    Matsubara S, Ueda Y, Takahashi H, Nagai T, Kuwata T, Muto S, Yamaguchi T, Takizawa T, Suzuki M (2009) Pregnancy complicated with Alport syndrome: a good obstetric outcome and failure to diagnose an infant born to a mother with Alport syndrome by umbilical cord immunofluorescence staining. J Obstet Gynaecol Res 35(6):1109–1114CrossRefPubMedGoogle Scholar
  22. 22.
    Matsubara S, Muto S (2012) Good obstetric outcome of consecutive pregnancies in a woman with Alport syndrome. Arch Gynecol Obstet 286:261–262CrossRefPubMedGoogle Scholar
  23. 23.
    Bramham K, Lightstone L (2012) Pre-pregnancy counseling for women with chronic kidney disease. J Nephrol 25(04):450–459CrossRefPubMedGoogle Scholar
  24. 24.
    Helal I, Fick-Brosnahan GM, Reed-Gitomer B, Schrier RW (2012) Glomerular hyperfiltration: definitions, mechanisms and clinical implications. Nat Rev Nephrol 8:293–300CrossRefPubMedGoogle Scholar
  25. 25.
    Sibai BM, Villar MA, Mabie BC (1990) Acute renal failure in hypertensive disorders of pregnancy: pregnancy outcome and remote prognosis in thirty-one consecutive cases. Am J Obstet Gynecol 162:777–783CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Nephrology UnitFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
  2. 2.Department of Obstetrics and GynecologyFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly
  3. 3.Pediatric Nephrology UnitFondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoMilanItaly

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