Journal of Nephrology

, Volume 31, Issue 3, pp 361–383 | Cite as

Immunosuppression in pregnant women with renal disease: review of the latest evidence in the biologics era

  • Loredana Colla
  • Davide Diena
  • Maura Rossetti
  • Ana Maria Manzione
  • Luca Marozio
  • Chiara Benedetto
  • Luigi Biancone
Part of the following topical collections:
  1. Obstetric Nephrology


Care of pregnant woman, including fertility and procreation counseling, has become a significant part of the nephrological practice in the last years. In this context, the management of immunosuppression assumes a primary role both for autoimmune diseases and for post-transplant follow up. The present review analyzes the latest evidence on immunosuppressive drugs of current use in nephrology and kidney transplantation. Although the placenta inactivates prednisone and prednisolone, it is advisable to limit the dose to the minimal effective one, to prevent side effects. Azathioprine is generally the immunosuppressive of choice in many high-risk pregnancies in autoimmune diseases because of the safety profile and its steroid-sparing property. In lupus nephropathy, hydroxychloroquine is a current indication in the prevention of flares. Cyclosporine and tacrolimus can also be used as steroid-sparing agents as well as in post-transplant maintenance therapy. Experience on mammalian target of rapamycin inhibitors is limited and its use during pregnancy is still controversial even if initial positive data are emerging. Intravenous immunoglobulins are safe and represent an important option for relapses of lupus and vasculitis. Mycophenolate mofetil and cyclophosphamide are to avoid. An important part is reserved to biologic agents, which are having a huge impact on therapy protocols for several pathologies. Data on the utilization of these molecules during pregnancy, however, are still scant and therefore they do not yet allow a definitive evaluation of their safety profile.


Pregnancy Immunosuppression Glomerulonephritis Kidney transplantation Antibodies Monoclonal 




Compliance with ethical standards

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.


  1. 1.
    (1975) Pregnancy and renal disease. Lancet Lond Engl 2:801–802Google Scholar
  2. 2.
    Smyth A, Radovic M, Garovic VD (2013) Women, kidney disease, and pregnancy. Adv Chronic Kidney Dis 20:402–410. PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Østensen M (2017) The use of biologics in pregnant patients with rheumatic disease. Expert Rev Clin Pharmacol 1–9.
  4. 4.
    Whirledge S, Cidlowski JA (2010) Glucocorticoids, stress, and fertility. Minerva Endocrinol 35:109–125PubMedPubMedCentralGoogle Scholar
  5. 5.
    Jain V, Gordon C (2011) Managing pregnancy in inflammatory rheumatological diseases. Arthritis Res Ther 13:206. PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Grier DG, Halliday HL (2004) Effects of glucocorticoids on fetal and neonatal lung development. Treat Respir Med 3:295–306PubMedCrossRefGoogle Scholar
  7. 7.
    Szweda H, Jóźwik M (2016) Urinary tract infections during pregnancy—an updated overview. Dev Period Med 20:263–272PubMedGoogle Scholar
  8. 8.
    Kiely M, Hemmingway A, O’Callaghan KM (2017) Vitamin D in pregnancy: current perspectives and future directions. Ther Adv Musculoskelet Dis 9:145–154. PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    ACOG Committee on Obstetric Practice (2011) ACOG Committee Opinion No. 495: Vitamin D: screening and supplementation during pregnancy. Obstet Gynecol 118:197–198. CrossRefGoogle Scholar
  10. 10.
    Østensen M, Khamashta M, Lockshin M et al (2006) Anti-inflammatory and immunosuppressive drugs and reproduction. Arthritis Res Ther 8:209. PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Cowchock FS, Reece EA, Balaban D et al (1992) Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment. Am J Obstet Gynecol 166:1318–1323PubMedCrossRefGoogle Scholar
  12. 12.
    Guller S, Kong L, Wozniak R, Lockwood CJ (1995) Reduction of extracellular matrix protein expression in human amnion epithelial cells by glucocorticoids: a potential role in preterm rupture of the fetal membranes. J Clin Endocrinol Metab 80:2244–2250. PubMedCrossRefGoogle Scholar
  13. 13.
    Paramel Jayaprakash T, Wagner EC, van Schalkwyk J et al (2016) High diversity and variability in the vaginal microbiome in women following preterm premature rupture of membranes (PPROM): A prospective cohort Study. PloS One 11:e0166794. PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Levy RA, de Jesús GR, de Jesús NR, Klumb EM (2016) Critical review of the current recommendations for the treatment of systemic inflammatory rheumatic diseases during pregnancy and lactation. Autoimmun Rev 15:955–963. PubMedCrossRefGoogle Scholar
  15. 15.
    Hviid A, Mølgaard-Nielsen D (2011) Corticosteroid use during pregnancy and risk of orofacial clefts. CMAJ Can Med Assoc J (J Assoc Medicale Can) 183:796–804. CrossRefGoogle Scholar
  16. 16.
    Bay Bjørn A-M, Ehrenstein V, Hundborg HH et al (2014) Use of corticosteroids in early pregnancy is not associated with risk of oral clefts and other congenital malformations in offspring. Am J Ther 21:73–80. PubMedCrossRefGoogle Scholar
  17. 17.
    Schmidt PL, Sims ME, Strassner HT et al (1984) Effect of antepartum glucocorticoid administration upon neonatal respiratory distress syndrome and perinatal infection. Am J Obstet Gynecol 148:178–186PubMedCrossRefGoogle Scholar
  18. 18.
    Benediktsson R, Lindsay RS, Noble J et al (1993) Glucocorticoid exposure in utero: new model for adult hypertension. Lancet Lond Engl 341:339–341CrossRefGoogle Scholar
  19. 19.
    Czeizel AE, Tóth M (1998) Birth weight, gestational age and medications during pregnancy. Int J Gynaecol Obstet Off Organ Int Fed Gynaecol Obstet 60:245–249CrossRefGoogle Scholar
  20. 20.
    Scott JR (1977) Fetal growth retardation associated with maternal administration of immunosuppressive drugs. Am J Obstet Gynecol 128:668–676PubMedCrossRefGoogle Scholar
  21. 21.
    Ponticelli C, Moroni G (2015) Immunosuppression in pregnant women with systemic lupus erythematosus. Expert Rev Clin Immunol 11:549–552. PubMedCrossRefGoogle Scholar
  22. 22.
    Adnan MM, Morton J, Hashmi S et al (2016) Anti-GBM disease in pregnancy: acute renal failure resolved after plasma exchange, hemodialysis, and steroids. J Investig Med High Impact Case Rep 4:2324709615624232. PubMedCrossRefGoogle Scholar
  23. 23.
    Kunjal R, Makary R, Poenariu A (2016) Granulomatosis with polyangiitis presenting as pauci-immune crescentic glomerulonephritis in pregnancy. Case Rep Nephrol 2016:1075659. PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Shah S, Verma P (2016) Overview of pregnancy in renal transplant patients. Int J Nephrol 2016:4539342. PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Tendron A, Gouyon J-B, Decramer S (2002) In utero exposure to immunosuppressive drugs: experimental and clinical studies. Pediatr Nephrol Berl Ger 17:121–130CrossRefGoogle Scholar
  26. 26.
    Blom K, Odutayo A, Bramham K, Hladunewich MA (2017) Pregnancy and glomerular disease: a systematic review of the literature with management guidelines. Clin J Am Soc Nephrol CJASN. PubMedCrossRefGoogle Scholar
  27. 27.
    Lockwood CJ, Radunovic N, Nastic D et al (1996) Corticotropin-releasing hormone and related pituitary–adrenal axis hormones in fetal and maternal blood during the second half of pregnancy. J Perinat Med 24:243–251PubMedCrossRefGoogle Scholar
  28. 28.
    Østensen M, Förger F (2009) Management of RA medications in pregnant patients. Nat Rev Rheumatol 5:382–390. PubMedCrossRefGoogle Scholar
  29. 29.
    Moroni G, Doria A, Giglio E et al (2016) Fetal outcome and recommendations of pregnancies in lupus nephritis in the 21st century. A prospective multicenter study. J Autoimmun 74:6–12. PubMedCrossRefGoogle Scholar
  30. 30.
    Wallace DJ, Gudsoorkar VS, Weisman MH, Venuturupalli SR (2012) New insights into mechanisms of therapeutic effects of antimalarial agents in SLE. Nat Rev Rheumatol 8:522–533. PubMedCrossRefGoogle Scholar
  31. 31.
    Leroy C, Rigot J-M, Leroy M et al (2015) Immunosuppressive drugs and fertility. Orphanet J Rare Dis 10:136. PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Costedoat-Chalumeau N, Amoura Z, Aymard G et al (2002) Evidence of transplacental passage of hydroxychloroquine in humans. Arthritis Rheum 46:1123–1124PubMedCrossRefGoogle Scholar
  33. 33.
    Kaplan YC, Ozsarfati J, Nickel C, Koren G (2016) Reproductive outcomes following hydroxychloroquine use for autoimmune diseases: a systematic review and meta-analysis. Br J Clin Pharmacol 81:835–848. PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Klinger G, Morad Y, Westall CA et al (2001) Ocular toxicity and antenatal exposure to chloroquine or hydroxychloroquine for rheumatic diseases. Lancet Lond Engl 358:813–814. CrossRefGoogle Scholar
  35. 35.
    Andreoli L, Bertsias GK, Agmon-Levin N et al (2017) EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis 76:476–485. PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Clowse MEB, Magder L, Witter F, Petri M (2006) Hydroxychloroquine in lupus pregnancy. Arthritis Rheum 54:3640–3647. PubMedCrossRefGoogle Scholar
  37. 37.
    Levy RA, Vilela VS, Cataldo MJ et al (2001) Hydroxychloroquine (HCQ) in lupus pregnancy: double-blind and placebo-controlled study. Lupus 10:401–404. PubMedCrossRefGoogle Scholar
  38. 38.
    Costedoat-Chalumeau N, Amoura Z, Duhaut P et al (2003) Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: a study of 133 cases compared with a control group. Arthritis Rheum 48:3207–3211. PubMedCrossRefGoogle Scholar
  39. 39.
    Izmirly PM, Kim MY, Llanos C et al (2010) Evaluation of the risk of anti-SSA/Ro-SSB/La antibody-associated cardiac manifestations of neonatal lupus in fetuses of mothers with systemic lupus erythematosus exposed to hydroxychloroquine. Ann Rheum Dis 69:1827–1830. PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Sciascia S, Hunt BJ, Talavera-Garcia E et al (2016) The impact of hydroxychloroquine treatment on pregnancy outcome in women with antiphospholipid antibodies. Am J Obstet Gynecol 214:273.e1-273.e8.
  41. 41.
    Mekinian A, Lazzaroni MG, Kuzenko A et al (2015) The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: data from a European multicenter retrospective study. Autoimmun Rev 14:498–502. PubMedCrossRefGoogle Scholar
  42. 42.
    Alstead EM, Ritchie JK, Lennard-Jones JE et al (1990) Safety of azathioprine in pregnancy in inflammatory bowel disease. Gastroenterology 99:443–446PubMedCrossRefGoogle Scholar
  43. 43.
    Dejaco C, Mittermaier C, Reinisch W et al (2001) Azathioprine treatment and male fertility in inflammatory bowel disease. Gastroenterology 121:1048–1053PubMedCrossRefGoogle Scholar
  44. 44.
    Framarino dei Malatesta M (2017) Pregnancy after kidney transplantation. In: Orlando G, Remuzzi G, Williams DF (ed) Kidney transplantation, bioengineering and regeneration. Elsevier, Amsterdam, pp 665–676CrossRefGoogle Scholar
  45. 45.
    Moskovitz DN, Bodian C, Chapman ML et al (2004) The effect on the fetus of medications used to treat pregnant inflammatory bowel-disease patients. Am J Gastroenterol 99:656–661. PubMedCrossRefGoogle Scholar
  46. 46.
    Davison JM, Dellagrammatikas H, Parkin JM (1985) Maternal azathioprine therapy and depressed haemopoiesis in the babies of renal allograft patients. Br J Obstet Gynaecol 92:233–239PubMedCrossRefGoogle Scholar
  47. 47.
    Casanova MJ, Chaparro M, Domènech E et al (2013) Safety of thiopurines and anti-TNF-α drugs during pregnancy in patients with inflammatory bowel disease. Am J Gastroenterol 108:433–440. PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Gisbert JP (2010) Safety of immunomodulators and biologics for the treatment of inflammatory bowel disease during pregnancy and breast-feeding. Inflamm Bowel Dis 16:881–895. PubMedCrossRefGoogle Scholar
  49. 49.
    Cabiddu G, Castellino S, Gernone G et al (2016) A best practice position statement on pregnancy in chronic kidney disease: the Italian Study Group on kidney and pregnancy. J Nephrol 29:277–303. PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Fischer-Betz R, Specker C, Brinks R et al (2013) Low risk of renal flares and negative outcomes in women with lupus nephritis conceiving after switching from mycophenolate mofetil to azathioprine. Rheumatol Oxf Engl 52:1070–1076. CrossRefGoogle Scholar
  51. 51.
    Georgiou GK, Dounousi E, Harissis HV (2016) Calcineurin inhibitors and male fertility after renal transplantation—a review. Andrologia 48:483–490. PubMedCrossRefGoogle Scholar
  52. 52.
    Venkataramanan R, Koneru B, Wang CC et al (1988) Cyclosporine and its metabolites in mother and baby. Transplantation 46:468–469PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    Perales-Puchalt A, Vila Vives JM, López Montes J et al (2012) Pregnancy outcomes after kidney transplantation-immunosuppressive therapy comparison. J Matern Fetal Neonatal Med Off J Eur Assoc Perinat Med Fed Asia Ocean Perinat Soc Int Soc Perinat Obstet 25:1363–1366. CrossRefGoogle Scholar
  54. 54.
    Paziana K, Del Monaco M, Cardonick E et al (2013) Ciclosporin use during pregnancy. Drug Saf 36:279–294. PubMedCrossRefGoogle Scholar
  55. 55.
    Di Paolo S, Schena A, Morrone LF et al (2000) Immunologic evaluation during the first year of life of infants born to cyclosporine-treated female kidney transplant recipients: analysis of lymphocyte subpopulations and immunoglobulin serum levels. Transplantation 69:2049–2054PubMedCrossRefGoogle Scholar
  56. 56.
    Biggioggero M, Borghi MO, Gerosa M et al (2007) Immune function in children born to mothers with autoimmune diseases and exposed in utero to immunosuppressants. Lupus 16:651–656. PubMedCrossRefGoogle Scholar
  57. 57.
    Thomas AG, Burrows L, Knight R et al (1997) The effect of pregnancy on cyclosporine levels in renal allograft patients. Obstet Gynecol 90:916–919PubMedCrossRefGoogle Scholar
  58. 58.
    Hussein MM, Mooij JM, Roujouleh H (1993) Cyclosporine in the treatment of lupus nephritis including two patients treated during pregnancy. Clin Nephrol 40:160–163PubMedGoogle Scholar
  59. 59.
    Østensen M, Lockshin M, Doria A et al (2008) Update on safety during pregnancy of biological agents and some immunosuppressive anti-rheumatic drugs. Rheumatol Oxf Engl 47(Suppl 3):iii28–iii31. CrossRefGoogle Scholar
  60. 60.
    Miyata H, Satouh Y, Mashiko D et al (2015) Sperm calcineurin inhibition prevents mouse fertility with implications for male contraceptive. Science 350:442–445. PubMedCrossRefGoogle Scholar
  61. 61.
    Xu LG, Yang YR, Wang HW et al (2011) Characteristics of male fertility after renal transplantation. Andrologia 43:203–207. PubMedCrossRefGoogle Scholar
  62. 62.
    Vanhove T, Annaert P, Kuypers DRJ (2016) Clinical determinants of calcineurin inhibitor disposition: a mechanistic review. Drug Metab Rev 48:88–112. PubMedCrossRefGoogle Scholar
  63. 63.
    Armenti VT, Constantinescu S, Moritz MJ, Davison JM (2008) Pregnancy after transplantation. Transplant Rev (Orlando) 22:223–240. CrossRefGoogle Scholar
  64. 64.
    Kainz A, Harabacz I, Cowlrick IS et al (2000) Review of the course and outcome of 100 pregnancies in 84 women treated with tacrolimus. Transplantation 70:1718–1721PubMedCrossRefGoogle Scholar
  65. 65.
    Garcia-Donaire JA, Acevedo M, Gutiérrez MJ et al (2005) Tacrolimus as basic immunosuppression in pregnancy after renal transplantation. A single-center experience. Transplant Proc 37:3754–3755. PubMedCrossRefGoogle Scholar
  66. 66.
    Zheng S, Easterling TR, Umans JG et al (2012) Pharmacokinetics of tacrolimus during pregnancy. Ther Drug Monit 34:660–670. PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Kim H, Jeong JC, Yang J et al (2015) The optimal therapy of calcineurin inhibitors for pregnancy in kidney transplantation. Clin Transplant 29:142–148. PubMedCrossRefGoogle Scholar
  68. 68.
    Bramham K, Nelson-Piercy C, Gao H et al (2013) Pregnancy in renal transplant recipients: a UK national cohort study. Clin J Am Soc Nephrol CJASN 8:290–298. PubMedCrossRefGoogle Scholar
  69. 69.
    Jain AB, Shapiro R, Scantlebury VP et al (2004) Pregnancy after kidney and kidney-pancreas transplantation under tacrolimus: a single center’s experience. Transplantation 77:897–902PubMedCrossRefGoogle Scholar
  70. 70.
    Alsuwaida A (2011) Successful management of systemic lupus erythematosus nephritis flare-up during pregnancy with tacrolimus. Mod Rheumatol 21:73–75. PubMedCrossRefGoogle Scholar
  71. 71.
    Webster P, Wardle A, Bramham K et al (2014) Tacrolimus is an effective treatment for lupus nephritis in pregnancy. Lupus 23:1192–1196. PubMedCrossRefGoogle Scholar
  72. 72.
    Midtvedt K, Bergan S, Reisæter AV et al (2017) Exposure to mycophenolate and fatherhood. Transplantation. PubMedCentralCrossRefPubMedGoogle Scholar
  73. 73.
    Mok CC, Chan PT, To CH (2013) Anti-müllerian hormone and ovarian reserve in systemic lupus erythematosus. Arthritis Rheum 65:206–210. PubMedCrossRefGoogle Scholar
  74. 74.
    Hoeltzenbein M, Elefant E, Vial T et al (2012) Teratogenicity of mycophenolate confirmed in a prospective study of the European Network of Teratology Information Services. Am J Med Genet A 158A:588–596. PubMedCrossRefGoogle Scholar
  75. 75.
    Merlob P, Stahl B, Klinger G (2009) Tetrada of the possible mycophenolate mofetil embryopathy: a review. Reprod Toxicol 28:105–108. PubMedCrossRefGoogle Scholar
  76. 76.
    EBPG Expert Group on Renal Transplantation (2002) European best practice guidelines for renal transplantation. Section IV: long-term management of the transplant recipient. IV.10. Pregnancy in renal transplant recipients. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Ren Assoc 17 Suppl 4:50–55Google Scholar
  77. 77.
    Leyder M, Laubach M, Breugelmans M et al (2011) Specific congenital malformations after exposure to cyclophosphamide, epirubicin and 5-fluorouracil during the first trimester of pregnancy. Gynecol Obstet Investig 71:141–144. CrossRefGoogle Scholar
  78. 78.
    Cardonick E, Iacobucci A (2004) Use of chemotherapy during human pregnancy. Lancet Oncol 5:283–291. PubMedCrossRefGoogle Scholar
  79. 79.
    Bermas BL, Hill JA (1995) Effects of immunosuppressive drugs during pregnancy. Arthritis Rheum 38:1722–1732PubMedCrossRefGoogle Scholar
  80. 80.
    Petri M (2003) Immunosuppressive drug use in pregnancy. Autoimmunity 36:51–56PubMedCrossRefGoogle Scholar
  81. 81.
    Lannes G, Elias FR, Cunha B et al (2011) Successful pregnancy after cyclophosphamide therapy for lupus nephritis. Arch Gynecol Obstet 283(Suppl 1):61–65. PubMedCrossRefGoogle Scholar
  82. 82.
    Amant F, Deckers S, Van Calsteren K et al (2010) Breast cancer in pregnancy: recommendations of an international consensus meeting. Eur J Cancer Oxf Engl 1990 46:3158–3168. CrossRefGoogle Scholar
  83. 83.
    Rovira J, Diekmann F, Ramírez-Bajo MJ et al (2012) Sirolimus-associated testicular toxicity: detrimental but reversible. Transplantation 93:874–879. PubMedCrossRefGoogle Scholar
  84. 84.
    Zuber J, Anglicheau D, Elie C et al (2008) Sirolimus may reduce fertility in male renal transplant recipients. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg 8:1471–1479. CrossRefGoogle Scholar
  85. 85.
    Huyghe E, Zairi A, Nohra J et al (2007) Gonadal impact of target of rapamycin inhibitors (sirolimus and everolimus) in male patients: an overview. Transpl Int Off J Eur Soc Organ Transplant 20:305–311. CrossRefGoogle Scholar
  86. 86.
    Wetzstein M, Weestel P-F, Choukroun G (2014) Everolimus and azoospermia, a causal relationship? About one case in a renal transplant patient. Nephrol Ther 10:44–45. PubMedCrossRefGoogle Scholar
  87. 87.
    Braun M, Young J, Reiner CS et al (2012) Low-dose oral sirolimus and the risk of menstrual-cycle disturbances and ovarian cysts: analysis of the randomized controlled SUISSE ADPKD trial. PloS One 7:e45868. PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    Zhang X, Li L, Xu J et al (2013) Rapamycin preserves the follicle pool reserve and prolongs the ovarian lifespan of female rats via modulating mTOR activation and sirtuin expression. Gene 523:82–87. PubMedCrossRefGoogle Scholar
  89. 89.
    Beedie SL, Mahony C, Walker HM et al (2016) Shared mechanism of teratogenicity of anti-angiogenic drugs identified in the chicken embryo model. Sci Rep 6:30038. PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Sifontis NM, Coscia LA, Constantinescu S et al (2006) Pregnancy outcomes in solid organ transplant recipients with exposure to mycophenolate mofetil or sirolimus. Transplantation 82:1698–1702. PubMedCrossRefGoogle Scholar
  91. 91.
    Guardia O, Rial MDC, Casadei D (2006) Pregnancy under sirolimus-based immunosuppression. Transplantation 81:636. PubMedCrossRefGoogle Scholar
  92. 92.
    Veroux M, Corona D, Veroux P (2011) Pregnancy under everolimus-based immunosuppression. Transpl Int Off J Eur Soc Organ Transplant 24:e115-117. CrossRefGoogle Scholar
  93. 93.
    Framarino-dei-Malatesta M, Derme M, Manzia TM et al (2013) Impact of mTOR-I on fertility and pregnancy: state of the art and review of the literature. Expert Rev Clin Immunol 9:781–789. PubMedCrossRefGoogle Scholar
  94. 94.
    Egerup P, Lindschou J, Gluud C et al (2015) The effects of intravenous immunoglobulins in women with recurrent miscarriages: a systematic review of randomised trials with meta-analyses and trial sequential analyses including individual patient data. PloS One 10:e0141588. PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Stiehm ER (2013) Adverse effects of human immunoglobulin therapy. Transfus Med Rev 27:171–178. PubMedCrossRefGoogle Scholar
  96. 96.
    Cherin P, Marie I, Michallet M et al (2016) Management of adverse events in the treatment of patients with immunoglobulin therapy: a review of evidence. Autoimmun Rev 15:71–81. PubMedCrossRefGoogle Scholar
  97. 97.
    Radder CM, Roelen DL, van de Meer-Prins EMW et al (2004) The immunologic profile of infants born after maternal immunoglobulin treatment and intrauterine platelet transfusions for fetal/neonatal alloimmune thrombocytopenia. Am J Obstet Gynecol 191:815–820. PubMedCrossRefGoogle Scholar
  98. 98.
    Croft AP, Smith SW, Carr S et al (2015) Successful outcome of pregnancy in patients with anti-neutrophil cytoplasm antibody-associated small vessel vasculitis. Kidney Int 87:807–811. PubMedCrossRefGoogle Scholar
  99. 99.
    Micheloud D, Nuño L, Rodríguez-Mahou M et al (2006) Efficacy and safety of etanercept, high-dose intravenous gammaglobulin and plasmapheresis combined therapy for lupus diffuse proliferative nephritis complicating pregnancy. Lupus 15:881–885. PubMedCrossRefGoogle Scholar
  100. 100.
    Pagnoux C, Mahendira D, Laskin CA (2013) Fertility and pregnancy in vasculitis. Best Pract Res Clin Rheumatol 27:79–94. PubMedCrossRefGoogle Scholar
  101. 101.
    Katz-Agranov N, Khattri S, Zandman-Goddard G (2015) The role of intravenous immunoglobulins in the treatment of rheumatoid arthritis. Autoimmun Rev 14:651–658. PubMedCrossRefGoogle Scholar
  102. 102.
    Kutzler HL, Ye X, Rochon C, Martin ST (2016) Administration of antithymocyte globulin (rabbit) to treat a severe, mixed rejection episode in a pregnant renal transplant recipient. Pharmacotherapy 36:e18-22. PubMedCrossRefGoogle Scholar
  103. 103.
    Li X, Chen N (2013) Management of crescentic glomerulonephritis: what are the recent advances? Contrib Nephrol 181:229–239. PubMedCrossRefGoogle Scholar
  104. 104.
    Porter C, Armstrong-Fisher S, Kopotsha T et al (2016) Certolizumab pegol does not bind the neonatal Fc receptor (FcRn): consequences for FcRn-mediated in vitro transcytosis and ex vivo human placental transfer. J Reprod Immunol 116:7–12. PubMedCrossRefGoogle Scholar
  105. 105.
    Weiner GJ (2010) Rituximab: mechanism of action. Semin Hematol 47:115–123. PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Grunewald S, Jank A (2015) New systemic agents in dermatology with respect to fertility, pregnancy, and lactation. J Dtsch Dermatol Ges 13:277–289. (quiz 290) PubMedCrossRefGoogle Scholar
  107. 107.
    Lu TY-T, Ng KP, Cambridge G et al (2009) A retrospective 7-year analysis of the use of B cell depletion therapy in systemic lupus erythematosus at University College London Hospital: the first fifty patients. Arthritis Rheum 61:482–487. PubMedCrossRefGoogle Scholar
  108. 108.
    Klink DT, van Elburg RM, Schreurs MWJ, van Well GTJ (2008) Rituximab administration in third trimester of pregnancy suppresses neonatal B-cell development. Clin Dev Immunol 2008:271363. PubMedPubMedCentralCrossRefGoogle Scholar
  109. 109.
    Ojeda-Uribe M, Afif N, Dahan E et al (2013) Exposure to abatacept or rituximab in the first trimester of pregnancy in three women with autoimmune diseases. Clin Rheumatol 32:695–700. PubMedCrossRefGoogle Scholar
  110. 110.
    Chakravarty EF, Murray ER, Kelman A, Farmer P (2011) Pregnancy outcomes after maternal exposure to rituximab. Blood 117:1499–1506. PubMedCrossRefGoogle Scholar
  111. 111.
    Sangle SR, Lutalo PMK, Davies RJ et al (2013) B-cell depletion therapy and pregnancy outcome in severe, refractory systemic autoimmune diseases. J Autoimmun 43:55–59. PubMedCrossRefGoogle Scholar
  112. 112.
    Al-Rabadi L, Ayalon R, Bonegio RG et al (2016) Pregnancy in a patient with primary membranous nephropathy and circulating anti-PLA2R antibodies: a case report. Am J Kidney Dis Off J Natl Kidney Found 67:775–778. CrossRefGoogle Scholar
  113. 113.
    Pendergraft WF, McGrath MM, Murphy AP et al (2013) Fetal outcomes after rituximab exposure in women with autoimmune vasculitis. Ann Rheum Dis 72:2051–2053. PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Götestam Skorpen C, Hoeltzenbein M, Tincani A et al (2016) The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis 75:795–810. PubMedCrossRefGoogle Scholar
  115. 115.
    Hallstensen RF, Bergseth G, Foss S et al (2015) Eculizumab treatment during pregnancy does not affect the complement system activity of the newborn. Immunobiology 220:452–459. PubMedCrossRefGoogle Scholar
  116. 116.
    Kelly RJ, Höchsmann B, Szer J et al (2015) Eculizumab in pregnant patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med 373:1032–1039. PubMedCrossRefGoogle Scholar
  117. 117.
    Ardissino G, Possenti I, Tel F et al (2015) Discontinuation of eculizumab treatment in atypical hemolytic uremic syndrome: an update. Am J Kidney Dis Off J Natl Kidney Found 66:172–173. CrossRefGoogle Scholar
  118. 118.
    Zuber J, Fakhouri F, Roumenina LT et al (2012) Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies. Nat Rev Nephrol 8:643–657. PubMedCrossRefGoogle Scholar
  119. 119.
    Andries G, Karass M, Yandrapalli S et al (2017) Atypical hemolytic uremic syndrome in first trimester pregnancy successfully treated with eculizumab. Exp Hematol Oncol 6:4. PubMedPubMedCentralCrossRefGoogle Scholar
  120. 120.
    Asif A, Nayer A, Haas CS (2016) Atypical hemolytic uremic syndrome in the setting of complement-amplifying conditions: case reports and a review of the evidence for treatment with eculizumab. J Nephrol. PubMedPubMedCentralCrossRefGoogle Scholar
  121. 121.
    Fakhouri F, Roumenina L, Provot F et al (2010) Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am Soc Nephrol JASN 21:859–867. PubMedCrossRefGoogle Scholar
  122. 122.
    Song D, Yu X-J, Wang F-M et al (2015) Overactivation of complement alternative pathway in postpartum atypical hemolytic uremic syndrome patients with renal involvement. Am J Reprod Immunol 1989 74:345–356. PubMedCrossRefGoogle Scholar
  123. 123.
    Vaught AJ, Gavriilaki E, Hueppchen N et al (2016) Direct evidence of complement activation in HELLP syndrome: a link to atypical hemolytic uremic syndrome. Exp Hematol 44:390–398. PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Servais A, Devillard N, Frémeaux-Bacchi V et al (2016) Atypical haemolytic uraemic syndrome and pregnancy: outcome with ongoing eculizumab. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Ren Assoc 31:2122–2130. CrossRefGoogle Scholar
  125. 125.
    De Castro I, Easterling TR, Bansal N, Jefferson JA (2017) Nephrotic syndrome in pregnancy poses risks with both maternal and fetal complications. Kidney Int. PubMedCrossRefGoogle Scholar
  126. 126.
    Gustavsen A, Skattum L, Bergseth G et al (2017) Effect on mother and child of eculizumab given before caesarean section in a patient with severe antiphospholipid syndrome: a case report. Medicine (Baltimore) 96:e6338. CrossRefGoogle Scholar
  127. 127.
    Ling J, Koren G (2016) Challenges in vaccinating infants born to mothers taking immunoglobulin biologicals during pregnancy. Expert Rev Vaccines 15:239–256. PubMedCrossRefGoogle Scholar
  128. 128.
    Kumar M, Ray L, Vemuri S, Simon TA (2015) Pregnancy outcomes following exposure to abatacept during pregnancy. Semin Arthritis Rheum 45:351–356. PubMedCrossRefGoogle Scholar
  129. 129.
    Choi J, Aubert O, Vo A et al (2017) Assessment of tocilizumab (anti-interleukin-6 receptor monoclonal) as a potential treatment for chronic antibody-mediated rejection and transplant glomerulopathy in HLA-sensitized renal allograft recipients. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. CrossRefGoogle Scholar
  130. 130.
    Sakurai T, Takai R, Bürgin H et al (2012) The effects of interleukin-6 signal blockade on fertility, embryo-fetal development, and immunization in vivo. Birth Defects Res B Dev Reprod Toxicol 95:304–317. PubMedCrossRefGoogle Scholar
  131. 131.
    Hoeltzenbein M, Beck E, Rajwanshi R et al (2016) Tocilizumab use in pregnancy: analysis of a global safety database including data from clinical trials and post-marketing data. Semin Arthritis Rheum 46:238–245. PubMedCrossRefGoogle Scholar
  132. 132.
    Danve A, Perry L, Deodhar A (2014) Use of belimumab throughout pregnancy to treat active systemic lupus erythematosus: a case report. Semin Arthritis Rheum 44:195–197. PubMedCrossRefGoogle Scholar
  133. 133.
    Flint J, Panchal S, Hurrell A et al (2016) BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatol Oxf Engl 55:1693–1697. CrossRefGoogle Scholar
  134. 134.
    Kane SV, Acquah LA (2009) Placental transport of immunoglobulins: a clinical review for gastroenterologists who prescribe therapeutic monoclonal antibodies to women during conception and pregnancy. Am J Gastroenterol 104:228–233. PubMedCrossRefGoogle Scholar
  135. 135.
    Hyrich KL, Verstappen SMM (2014) Biologic therapies and pregnancy: the story so far. Rheumatol Oxf Engl 53:1377–1385. CrossRefGoogle Scholar

Copyright information

© Italian Society of Nephrology 2018

Authors and Affiliations

  • Loredana Colla
    • 1
  • Davide Diena
    • 1
  • Maura Rossetti
    • 1
  • Ana Maria Manzione
    • 1
  • Luca Marozio
    • 2
  • Chiara Benedetto
    • 2
  • Luigi Biancone
    • 1
  1. 1.Nephrology, Dialysis and Renal Transplant Division, Department of Medical Sciences, “Città della Salute e della Scienza di Torino” University HospitalUniversità degli Studi di TorinoTurinItaly
  2. 2.Obstetrics and Gynecology 1, Department of Surgical Sciences, Sant’Anna University HospitalUniversity of TurinTurinItaly

Personalised recommendations