Although chronic kidney disease (CKD) adversely affects fertility, pregnancies can occur at all stages of CKD severity
Safe and effective contraception should be made available for all women with CKD who do not wish to conceive and those who take teratogenic medications
CKD increases the risk of adverse pregnancy outcomes, including pre-eclampsia, fetal growth restriction, preterm delivery and post-partum loss of maternal renal function
Pre-pregnancy hypertension and proteinuria in CKD complicate the diagnosis of superimposed pre-eclampsia, which could be improved through vasoactive biomarkers as well as placental and fetal Doppler ultrasound
Although data on the use of many drugs in pregnancy are limited, low-dose aspirin, low-molecular-weight heparin, labetalol, nifedipine, prednisolone, hydroxychloroquine, azathioprine, ciclosporin and tacrolimus are considered safe during pregnancy and breastfeeding
Chronic kidney disease (CKD) is associated with reduced fertility and an increased risk of adverse pregnancy outcomes. Rates of pre-eclampsia, fetal growth restriction and preterm delivery increase incrementally with the severity of CKD and proteinuria. Pre-pregnancy counselling can facilitate informed decision-making. Safe and effective contraception is required for women who wish to delay or avoid pregnancy. Pregnancy planning for women who wish to conceive involves appropriate substitution of known teratogens — including mycophenolate mofetil, angiotensin blockers and cyclophosphamide — and can aid optimization of disease control. However, pregnancy, which can occur in women with any stage of CKD, can exacerbate comorbidities such as anaemia, vitamin D deficiency and hypertension. Increased haemodialysis provision is associated with improved pregnancy outcomes for women on dialysis. Diagnosis of pre-eclampsia in women with CKD is complicated in patients with pre-existing hypertension and proteinuria but can be improved by the use of vasoactive biomarkers as well as placental and fetal Doppler ultrasound. Pregnancy data for newer drugs used in CKD are limited as pregnancy and CKD are common exclusion criteria for drug and intervention trials. Although prospective data may be available for older drugs, the use of most drugs in pregnancy is based on retrospective data and expert consensus.
Subscribe to Journal
Get full journal access for 1 year
only $4.92 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Piccoli, G. B. et al. Pregnancy and chronic kidney disease: a challenge in all CKD stages. Clin. J. Am. Soc. Nephrol. 5, 844–855 (2010).
Bramham, K. et al. Pregnancy in renal transplant recipients: a UK national cohort study. Clin. J. Am. Soc. Nephrol. 8, 290–298 (2013).
Piccoli, G. B. et al. Outcomes of pregnancies after kidney transplantation: lessons learned from CKD. A comparison of transplanted, nontransplanted chronic kidney disease patients and low-risk pregnancies: a multicenter nationwide analysis. Transplantation 101, 2536–2544 (2017).
Webster, P., Lightstone, L., McKay, D. B. & Josephson, M. A. Pregnancy in chronic kidney disease and kidney transplantation. Kidney Int. 91, 1047–1056 (2017).
Hladunewich, M. A., Melamad, N. & Bramham, K. Pregnancy across the spectrum of chronic kidney disease. Kidney Int. 89, 995–1007 (2016).
Knight, M., Kurinczuk, J. J., Tuffnell, D. & Brocklehurst, P. The UK Obstetric Surveillance System for rare disorders of pregnancy. BJOG 112, 263–265 (2005).
[No authors listed.] Statistical bulletin: conceptions in England and Wales 2015. Office for National Statistics https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/conceptionandfertilityrates/bulletins/conceptionstatistics/2015#main-points (2017).
Piccoli, G. B. et al. The children of dialysis: live-born babies from on-dialysis mothers in Italy — an epidemiological perspective comparing dialysis, kidney transplantation and the overall population. Nephrol. Dial. Transplant. 29, 1578–1586 (2014).
Basok, E. K. et al. Assessment of female sexual function and quality of life in predialysis, peritoneal dialysis, hemodialysis, and renal transplant patients. Int. Urol. Nephrol. 41, 473–481 (2009).
Finkelstein, F. O., Shirani, S., Wuerth, D. & Finkelstein, S. H. Therapy insight: sexual dysfunction in patients with chronic kidney disease. Nat. Clin. Pract. Nephrol. 3, 200–207 (2007).
Steele, T. E. et al. Sexual experience of the chronic peritoneal dialysis patient. J. Am. Soc. Nephrol. 7, 1165–1168 (1996).
Solak, Y. et al. Effects of sildenafil and vardenafil treatments on sleep quality and depression in hemodialysis patients with erectile dysfunction. Int.J. Impot. Res. 23, 27–31 (2011).
Holley, J. L., Schmidt, R. J., Bender, F. H., Dumler, F. & Schiff, M. Gynecologic and reproductive issues in women on dialysis. Am. J. Kidney Dis. 29, 685–690 (1997).
Lim, V. S., Henriquez, C., Sievertsen, G. & Frohman, L. A. Ovarian function in chronic renal failure: Evidence suggesting hypothalamic anovulation. Ann. Intern. Med. 93, 21–27 (1980).
Wang, G. C. et al. Measurements of serum pituitary-gonadal hormones and investigation of sexual and reproductive functions in kidney transplant recipients. Int. J. Nephrol. 2010, 612126 (2010).
Palmer, B. F. & Clegg, D. J. Gonadal dysfunction in chronic kidney disease. Rev. Endocr. Metab. Disord. 18, 17–30 (2017).
Holley, J. L. & Schmidt, R. J. Changes in fertility and hormone replacement therapy in kidney disease. Adv. Chron. Kidney Dis. 20, 240–245 (2013).
Yavuz, D., Topçu, G., Ozene, r C., Akalin, S. & Sirikçi, O. Macroprolactin does not contribute to elevated levels of prolactin in patients on renal replacement therapy. Clin. Endocrinol. 63, 520–524 (2005).
Weinhandl, E. D., Liu, J., Gilbertson, D. T., Arneson, T. J. & Collins, A. J. Survival in daily home hemodialysis and matched thrice-weekly in-center hemodialysis patients. J. Am. Soc. Nephrol. 23, 895–904 (2012).
Rocco, M. V. et al. The effects of frequent nocturnal home hemodialysis: the frequent hemodialysis network nocturnal trial. Kidney Int. 80, 1080–1091 (2011).
Finkelstein, F. O. et al. At-home short daily hemodialysis improves the long-term health-related quality of life. Kidney Int. 82, 561–569 (2012).
van Eps, C. et al. Changes in serum prolactin, sex hormones and thyroid function with alternate nightly nocturnal home haemodialysis. Nephrology 17, 42–47 (2012).
Hladunewich, M. & Schatell, D. Intensive dialysis and pregnancy. Hemodial. Int. 20, 339–348 (2016).
Barua, M. et al. Successful pregnancies on nocturnal home hemodialysis. Clin. J. Am. Soc. Nephrol. 3, 392–396 (2008).
Meistrich, M. L., Wilson, G., Brown, B. W., da Cunha, M. F. & Lipshultz, L. I. Impact of cyclophosphamide on long-term reduction in sperm count in men treated with combination chemotherapy for ewing and soft tissue sarcomas. Cancer 70, 2703–2712 (1992).
Boumpas, D. T. et al. Risk for sustained amenorrhea in patients with systemic lupus erythematosus receiving intermittent pulse cyclophosphamide therapy. Ann. Intern. Med. 119, 366–369 (1993).
Ioannidis, J. P., Katsifis, G. E., Tzioufas, A. G. & Moutsopoulos, H. M. Predictors of sustained amenorrhea from pulsed intravenous cyclophosphamide in premenopausal women with systemic lupus erythematosus. J. Rheumatol. 29, 2129–2135 (2002).
Bellver, J. & Pellicer, A. Ovarian stimulation for ovulation induction and in vitro fertilization in patients with systemic lupus erythematosus and antiphospholipid syndrome. Fertil. Steril. 92, 1803–1810 (2009).
Elizur, S. E. et al. Fertility preservation treatment for young women with autoimmune diseases facing treatment with gonadotoxic agents. Rheumatology 47, 506–1509 (2008).
Somers, E. C., Marder, W., Christman, G. M., Ognenovski, V. & McCune, W. J. Use of a gonadotropin-releasing hormone analog for protection against premature ovarian failure during cyclophosphamide therapy in women with severe lupus. Arthritis Rheum. 52, 2761–2767 (2005).
Moore, H. C. et al. Goserelin for ovarian protection during breast-cancer adjuvant chemotherapy. N. Engl. J. Med. 372, 923–932 (2015).
Lambertini, M. et al. Ovarian suppression with triptorelin during adjuvant breast cancer chemotherapy and long-term ovarian function, pregnancies, and disease-free survival: a randomized clinical trial. JAMA 314, 2632–2640 (2015).
Lambertini, M. et al. Ovarian suppression using luteinizing hormone-releasing hormone agonists during chemotherapy to preserve ovarian function and fertility of breast cancer patients: a meta-analysis of randomized studies. Ann. Oncol. 26, 2408–2419 (2015).
Shah, P. S. et al. Intention to become pregnant and low birth weight and preterm birth: a systematic review. Maternal Child Health J. 15, 205–216 (2009).
Yildirim, Y. & Uslu, A. Pregnancy in patients with previous successful renal transplantation. Int. J. Gynaecol. Obstet. 90, 198–202 (2005).
Trussell, J. Contraceptive failure in the United States. Contraception 83, 397–404 (2011).
Korver, T. et al. Maintenance of ovulation inhibition with the 75-microg desogestrel-only contraceptive pill (Cerazette) after scheduled 12-h delays in tablet intake. Contraception 71, 8–13 (2005).
Estes, C. M. & Westhoff, C. Contraception for the transplant patient. Semin. Perinatol. 31, 372–377 (2007).
Krajewski, C. M., Geetha, D. & Gomez-Lobo, V. Contraceptive options for women with a history of solid-organ transplantation. Transplantation 95, 1183–1186 (2013).
Morrison, C. S. et al. Is the intrauterine device appropriate contraception for HIV-1 infected women? BJOG 108, 784–790 (2001).
Ramhendar, T. & Byrne, P. Use of the levonorgestrel-releasing intrauterine system in renal transplant recipients: a retrospective case review. Contraception 86, 288–289 (2012).
Brynhildsen, J. Combined hormonal contraceptives: prescribing patterns, compliance, and benefits versus risks. Ther. Adv. Drug Saf. 5, 201–213 (2014).
Davison, J. M. & Dunlop, W. Renal hemodynamics and tubular function in normal human pregnancy. Kidney Int. 18, 152–161 (1980).
Helal, I., Fick-Brosnahan, G. M., Reed-Gitomer, B. & Schrier, R. W. Glomerular hyperfiltration: definitions, mechanisms and clinical implications. Nat. Rev. Nephrol. 8, 293–300 (2012).
Roberts, M., Lindheimer, M. D. & Davison, J. M. Altered glomerular permselectivity to neutral dextrans and heteroporous membrane modelling in human pregnancy. Am. J. Physiol. 270, F338–F343 (1996).
Milne, J. E. C., Lindheimer, M. D. & Davison, J. M. Glomerular heteroporous membrane modeling in third trimester and postpartum before and during amino acid infusion. Am. J. Physiol. Renal Physiol. 282, F170–F175 (2002).
Conrad, K. P. & Davison, J. M. The renal circulation in normal pregnancy and preeclampsia: is there a place for relaxin? Am. J. Physiol. Renal Physiol. 306, F1121–F1135 (2014).
Novak, J. et al. Relaxin is essential for renal vasodilation during pregnancy in conscious rats. J. Clin. Invest. 107, 1469–1475 (2001).
Jeyabalan, A. et al. Essential role for vascular gelatinase activity in relaxin-induced renal vasodilation, hyperfiltration, and reduced myogenic reactivity of small arteries. Circ. Res. 93, 1249–1257 (2003).
Cadnapaphornchai, M. A. et al. Chronic NOS inhibition reverses systemic vasodilation and glomerular hyperfiltration in pregnancy. Am. J. Physiol. Renal Physiol. 280, F592–F598 (2001).
Conrad, K. P. & Baker, V. L. Corpus luteal contribution to maternal pregnancy physiology and outcomes in assisted reproductive technologies. Am. J. Physiol. Regul. Integr. Comp. Physiol. 304, R69–R72 (2013).
Odutayo, A. & Hladunewich, M. Obstetric nephrology: renal hemodynamic and metabolic physiology in normal pregnancy. Clin. J. Am. Soc. Nephrol. 7, 2073–2080 (2012).
Smith, M. C., Moran, P., Ward, M. K. & Davison, J. M. Assessment of glomerular filtration rate during pregnancy using the MDRD formula. BJOG 115, 109–112 (2008).
Alper, A. B. et al. Performance of estimated glomerular filtration rate prediction equations in preeclamptic patients. Am. J. Perinatol. 28, 425–430 (2010).
Kristensen, K. et al. Temporal changes of the plasma levels of cystatin C, beta-trace protein, beta2-microglobulin, urate and creatinine during pregnancy indicate continuous alterations in the renal filtration process. Scand. J. Clin. Lab Invest. 67, 612–618 (2007).
Kristensen, K., Strevens, H., Lindström, V. & Grubb, A. Wide-Swensson, D. Increased plasma levels of beta2-microglobulin, cystatin C and beta-trace protein in term pregnancy are not due to utero-placental production. Scand. J. Clin. Lab Invest. 68, 649–653 (2008).
Strevens, H., Wide-Swensson, D., Torffvit, O. & Grubb, A. Serum cystatin C for assessment of glomerular filtration rate in pregnant and non-pregnant women. Indications of altered filtration process in pregnancy. Scand. J. Clin. Lab Invest. 62, 141–147 (2002).
Bramham, K., Makanjuola, D., Hussein, W., Cafful, D. & Shehata, H. Serum cystatin is not a marker of glomerular filtration rate in pregnancy. Obstet. Med. 2, 121–122 (2009).
Larsson, A., Palm, M., Hansson, L. O. & Axelsson, O. Cystatin C and modification of diet in renal disease (MDRD) estimated glomerular filtration rate differ during normal pregnancy. Acta Obstet. Gynecol. Scand. 89, 939–944 (2010).
Piccoli, G. B. et al. Risk of adverse pregnancy outcomes in women with CKD. J. Am. Soc. Nephrol. 26, 2011–2022 (2015).
Gambaro, G. et al. Increased urinary excretion of glycosaminoglycans in pregnancy and in diabetes mellitus: a protective factor against nephrolithiasis. Nephron 50, 62–63 (1988).
Butler, E. L., Cox, S. M., Eberts, E. G. & Cunningham, F. G. Symptomatic nephrolithiasis complicating pregnancy. Obstet. Gynecol. 96, 753–756 (2000).
Williams, K. P. & Galerneau, F. The role of serum uric acid as a prognostic indicator of the severity of maternal and fetal complications in hypertensive pregnancies. J. Obstet. Gynaecol. Can. 24, 628–632 (2002).
Verdonk, K., Visser, W., Van Den Meiracker, A. H. & Danser, A. H. The renin-angiotensin-aldosterone system in pre-eclampsia: the delicate balance between good and bad. Clin. Sci. 126, 537–544 (2014).
Davison, J. M. & Lindheimer, M. D. Volume homeostasis and osmoregulation in human pregnancy. Baillieres Clin. Endocrinol. Metab. 3, 451–472 (1989).
[No authors listed.] Pregnancy and renal disease. Lancet 306, 801–802 (1975).
Tong, A., Brown, M. A., Winkelmayer, W. C., Craig, J. C. & Jesudason, S. Perspectives on pregnancy in women with CKD: a semistructured interview study. Am. J. Kidney Dis. 66, 951–961 (2015).
Tong, A., Jesudason, S., Craig, J. C. & Winkelmayer, W. C. Perspectives on pregnancy in women with chronic kidney disease: systematic review of qualitative studies. Nephrol. Dial. Transplant. 30, 652–661 (2015).
Knight, M. et al. Saving Lives, Improving Mothers' Care — Surveillance of maternal deaths in the UK 2012–2014 and lessons learned to inform maternity care from the UK and Ireland Confidential Enquiries into Maternal Deaths and Morbidity 2009–2014. (National Perinatal Epidemiology Unit, University of Oxford, 2016).
Wiles, K. S. et al. Pre-pregnancy counselling in chronic kidney disease: a retrospective analysis of nine years' experience. BMC Nephrol. 16, 28 (2015).
Kendrick, J. et al. Kidney disease and maternal and fetal outcomes in pregnancy. Am. J. Kidney Dis. 66, 55–59 (2015).
Zhang, J. J. et al. A systematic review and meta-analysis of outcomes of pregnancy in CKD and CKD outcomes in pregnancy. Clin. J. Am. Soc. Nephrol. 10, 1964–1978 (2015).
Moroni, G. et al. Fetal outcome and recommendations of pregnancies in lupus nephritis in the 21st century. A prospective multicenter study. J. Autoimmun. 74, 6–12 (2016).
Piccoli, G. B. et al. Maternal-foetal outcomes in pregnant women with glomerulonephritides. Are all glomerulonephritides alike in pregnancy? J. Autoimmun. 79, 91–98 (2017).
Chapman, A. B., Johnson, A. M. & Gabow, P. A. Pregnancy outcome and its relationship to progression of renal failure in autosomal dominant polycystic kidney disease. J. Am. Soc. Nephrol. 5, 1178–1185 (1994).
Jones, D. C. & Hayslett, J. P. Outcome of pregnancy in women with moderate or severe renal insufficiency. N. Engl. J. Med. 335, 226–232 (1996).
Imbasciati, E. et al. Pregnancy in CKD stages 3 to 5: fetal and maternal outcomes. Am. J. Kidney Diseases. 49, 753–762 (2007).
Bramham, K. et al. Diagnostic and predictive biomarkers for pre-eclampsia in patients with established hypertension and chronic kidney disease. Kidney Int. 89, 874–885 (2016).
Willey, C. J. et al. Prevalence of autosomal dominant polycystic kidney disease in the European Union. Nephrol. Dial. Transplant. 32, 1356–1363 (2017).
Wu, M. et al. Pregnancy outcomes in autosomal dominant polycystic kidney disease: a case-control study. J. Matern. Fetal Neonatal Med. 29, 807–812 (2016).
Jung, J. H. et al. Successful pregnancy in a patient with autosomal dominant polycystic kidney disease on long-term hemodialysis. J. Kor. Med. Sci. 29, 301–304 (2014).
Swift, O., Vilar, E., Rahman, B., Side, L. & Gale, D. P. Attitudes in patients with autosomal dominant polycystic kidney disease toward prenatal diagnosis and preimplantation genetic diagnosis. Genet. Test. Mol. Biomarkers 20, 741–746 (2016).
Blom, K., Odutayo, A., Bramham, K. & Hladunewich, M. A. Pregnancy and glomerular disease: a systematic review of the literature with management guidelines. Clin. J. Am. Soc. Nephrol. 12, 1862–1872 (2017).
Jungers, P. et al. Chronic kidney disease and pregnancy. Adv. Nephrol. Necker Hosp. 15, 103–141 (1986).
Abe, S., et al. The influence of antecedent renal disease on pregnancy. Am. J. Obstet. Gynecol. 153, 508–514 (1985).
Packham, D., Whitworth, J. A., Fairley, K. F. & Kincaid-Smith, P. Histological features of IgA glomerulonephritis as predictors of pregnancy outcome. Clin. Nephrol. 30, 22–26 (1988).
Limardo, M. et al. Pregnancy and progression of IgA nephropathy: results of an Italian multicenter study. Am. J. Kidney Dis. 56, 506–512 (2010).
Hoover, P. J. & Costenbader, K. H. Insights into the epidemiology and management of lupus nephritis from the US rheumatologist's perspective. Kidney Int. 90, 487–492 (2016).
Imbasciati, E. et al. Pregnancy in women with pre-existing lupus nephritis: predictors of fetal and maternal outcome. Nephrol. Dial. Transplant. 24, 519–525 (2009).
Bramham, K. et al. Pregnancy outcomes in systemic lupus erythematosus with and without previous nephritis. J. Rheumatol. 38, 1906–1913 (2011).
Smyth, A. et al. A systematic review and meta-analysis of pregnancy outcomes in patients with systemic lupus erythematosus and lupus nephritis. Clin. J. Am. Soc. Nephrol. 5, 2060–2068 (2010).
Chakravarty, E. F. et al. Factors that predict prematurity and preeclampsia in pregnancies that are complicated by systemic lupus erythematosus. Am. J. Obstet. Gynecol. 192, 1897–1904 (2005).
Buyon, J. P. et al. Predictors of pregnancy outcomes in patients with lupus: a cohort study. Ann. Intern. Med. 163, 153–163 (2015).
Moroni, G. et al. Maternal outcome in pregnant women with lupus nephritis: a prospective multicenter study. J. Autoimmun. 74, 194–200 (2016).
Royal College of Obstetricians and Gynaecologists. Reducing the risk of venous thromboembolism in pregnancy and the puerperium. Green Top Guideline 37a https://www.rcog.org.uk/globalassets/documents/guidelines/gtg-37a.pdf (2015).
Cimaz, R., Spence, D. L., Hornberger, L. & Silverman, E. D. Incidence and spectrum of neonatal lupus erythematosus: a prospective study of infants born to mothers with anti-Ro autoantibodies. J. Pediatr. 142, 678–683 (2003).
Andreoli, L. et al. 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. 6, 476–485 (2017).
Izmirly, P. M. et al. Maternal use of hydroxychloroquine is associated with a reduced risk of recurrent anti-SSA/Ro-antibody-associated cardiac manifestations of neonatal lupus. Circulation 126, 76–82 (2012).
Klemetti, M. M. et al. Obstetric and perinatal outcome in type 1 diabetes patients with diabetic nephropathy during 1988–2011. Diabetologia 58, 678–686 (2015).
Piccoli, G. B. et al. Type 1 diabetes, diabetic nephropathy, and pregnancy: a systematic review and meta-study. Rev. Diabet. Stud. 10, 6–26 (2013).
Bell, R., Glinianaia, S. V., Tennant, P. W., Bilous, R. W. & Rankin, J. Peri-conception hyperglycaemia and nephropathy are associated with risk of congenital anomaly in women with pre-existing diabetes: a population-based cohort study. Diabetologia 55, 936–947 (2012).
Hod, M. et al. Diabetic nephropathy and pregnancy: the effect of ACE inhibitors prior to pregnancy on fetomaternal outcome. Nephrol. Dialysis Transplant. 10, 2328–2333 (1995).
Bar, J. et al. Pregnancy outcome in patients with insulin dependent diabetes mellitus and diabetic nephropathy treated with ACE inhibitors before pregnancy. J. Pediatr. Endocrinol. Metab. 12, 659–666 (1999).
Nielsen, L. R., Damm, P. & Mathiesen, E. R. Improved pregnancy outcome in type 1 diabetic women with microalbuminuria or diabetic nephropathy: effect of intensified antihypertensive therapy? Diabetes Care. 32, 38–44 (2009).
Bramham, K. Diabetic nephropathy and pregnancy. Semin. Nephrol. 37, 362–369 (2017).
World Health Organization. WHO recommendations on antenatal care for a positive pregnancy experience. http://apps.who.int/iris/bitstream/10665/250796/1/9789241549912-eng.pdf?ua=1 (2016).
Pavord, S. et al. UK guidelines on the management of iron deficiency in pregnancy. Br. J. Haematol. 156, 588–600 (2012).
Steer, P., Alam, M. A., Wadsworth, J. & Welch, A. Relation between maternal haemoglobin concentration and birth weight in different ethnic groups. BMJ 310, 489–491 (1995).
McMullin, M. F., White, R., Lappin, T., Reeves, J. & MacKenzie, G. Haemoglobin during pregnancy: relationship to erythropoietin and haematinic status. Eur. J. Haematol. 71, 44–50 (2003).
Sienas, L., Wong, T., Collins, R. & Smith, J. Contemporary uses of erythropoietin in pregnancy: a literature review. Obstet. Gynecol. Surv. 68, 594–602 (2013).
Sanchez-Gonzalez, L. R. et al. Efficacy and safety of adjuvant recombinant human erythropoietin and ferrous sulfate as treatment for iron deficiency anemia during the third trimester of pregnancy. Eur. J. Obstet. Gynecol. Reprod. Biol. 205, 32–36 (2016).
de Benoist, B., McLean, E., Egll, I. & Cogswell, M. Worldwide prevalence of anaemia 1993–2005. WHO Global Database on Anaemia (World Health Organization, 2008).
Gaweda, A. E. Markers of iron status in chronic kidney disease. Hemodial. Int. 21 (Suppl. 1), S21–27 (2017).
Albaramki, J., Hodson, E. M., Craig, J. C. & Webster, A. C. Parenteral versus oral iron therapy for adults and children with chronic kidney disease. Cochrane Database Syst Rev. 1, CD007857 (2012).
Tariq, N., Ayub, R., Khan, W. U., Ijaz, S. & Alam, A. Y. Parenteral iron therapy in the treatment of iron deficiency anemia during pregnancy: a randomized controlled trial. J. Coll. Physicians Surg. Pak. 25, 193–197 (2015).
Kriplani, A. et al. Intravenous iron sucrose therapy for moderate to severe anaemia in pregnancy. Indian J. Med. Res. 138, 78–82 (2013).
Al, R. A. et al. Intravenous versus oral iron for treatment of anemia in pregnancy: a randomized trial. Obstet. Gynecol. 106, 1335–1340 (2005).
al-Momen, A. K. et al. Intravenous iron sucrose complex in the treatment of iron deficiency anemia during pregnancy. Eur. J. Obstet. Gynecol. Reprod. Biol. 69, 121–124 (1996).
Moll, R. &. Davis, B. Iron, vitamin B12 and folate. Clin. Sci. 45, 198–203 (2017).
Maxwell, P. H. & Eckardt, K. U. HIF prolyl hydroxylase inhibitors for the treatment of renal anaemia and beyond. Nat. Rev. Nephrol. 12, 157–168 (2016).
Royal College of Obstetricians and Gynaecologists. Vitamin D in Pregnancy. Scientific Impact Paper Number 43 https://www.rcog.org.uk/globalassets/documents/guidelines/scientific-impact-papers/vitamin_d_sip43_june14.pdf (2014).
De-Regil, L. M., Palacios, C., Lombardo, L. K. & Peña-Rosas, J. P. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst. Rev. 2, CD008873 (2016).
Palacios, C., De-Regil, L. M., Lombardo, L. K. & Peña-Rosas, J. P. Vitamin D supplementation during pregnancy: updated meta-analysis on maternal outcomes. J. Steroid Biochem. Mol. Biol. 164, 148–155 (2016).
World Health Organization. Vitamin D supplementation in pregnancy. http://www.who.int/nutrition/publications/micronutrients/guidelines/vit_d_supp_pregnant_women/en/ (2012).
Tamblyn, J. A. et al. Dysregulation of maternal and placental vitamin D metabolism in preeclampsia. Placenta 50, 70–77 (2017).
Turner, M., Barré, P. E., Benjamin, A., Goltzman, D. & Gascon-Barré, M. Does the maternal kidney contribute to the increased circulating 1,25-dihydroxyvitamin D concentrations during pregnancy? Miner. Electrolyte Metab. 14, 246–252 (1988).
Hewison, M., Zehnder, D., Chakraverty, R. & Adams, J. S. Vitamin D and barrier function: a novel role for extra-renal 1 alpha-hydroxylase. Mol. Cell Endocrinol. 215, 31–38 (2004).
Bramham, K. et al. Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis. BMJ 348, g2301 (2014).
Magee, L. A. et al. Less-tight versus tight control of hypertension in pregnancy. N. Engl. J. Med. 372, 407–417 (2015).
Bramham, K., Hall, M., Lightstone, L. & Nelson-Piercy, C. Renal Disease in Pregnancy 2nd edn (Cambridge Univ. Press, in press).
Li, D. K., Yang, C., Andrade, S., Tavares, V. & Ferber, J. R. Maternal exposure to angiotensin converting enzyme inhibitors in the first trimester and risk of malformations in offspring: a retrospective cohort study. BMJ 343, d5931 (2011).
Bateman, B. T. et al. Angiotensin-converting enzyme inhibitors and the risk of congenital malformations. Obstet. Gynecol. 129, 174–184 (2017).
US National Library of Medicine. Drugs and Lactation Database (LactMed). TOXNET https://toxnet.nlm.nih.gov/newtoxnet/lactmed.htm (2017).
Nice, F. J. et al. Medications and breast-feeding: a guide for pharmacists, pharmacy technicians, and other healthcare professionals part II. J. Pharmacy Technol. 20, 85–95 (2004).
Benediktsson, R., Calder, A. A., Edwards, C. R. & Seckl, J. R. Placental 11 beta-hydroxysteroid dehydrogenase: a key regulator of fetal glucocorticoid exposure. Clin. Endocrinol. 46, 161–166 (1997).
van Runnard Heimel, P. J., Schobben, A. F., Huisjes, A. J., Franx, A. & Bruinse, H. W. The transplacental passage of prednisolone in pregnancies complicated by early-onset HELLP syndrome. Placenta 26, 842–845 (2005).
Laskin, C. A. et al. Prednisone and aspirin in women with autoantibodies and unexplained recurrent fetal loss. N. Engl. J. Med. 337, 148–153 (1997).
Park-Wyllie, L. et al. Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies. Teratology 62, 385–392 (2000).
Carmichael, S. L. et al. Maternal corticosteroid use and orofacial clefts. Am. J. Obstet. Gynecol. 197, 585.e1–585.e7 (2007).
Källén, B. Maternal drug use and infant cleft lip/palate with special reference to corticoids. Cleft Palate Craniofac. J. 40, 624–628 (2003).
Czeizel, A. E. & Rockenbauer, M. Population-based case-control study of teratogenic potential of corticosteroids. Teratology 56, 335–340 (1997).
Tata, L. J. et al. Effect of maternal asthma, exacerbations and asthma medication use on congenital malformations in offspring: a UK population-based study. Thorax 63, 981–987 (2008).
Hviid, A. & Mølgaard-Nielsen, D. Corticosteroid use during pregnancy and risk of orofacial clefts. CMAJ 183, 796–804 (2011).
Norwood, F. et al. Myasthenia in pregnancy: best practice guidelines from a UK multispecialty working group. J. Neurol. Neurosurg. Psychiatry 85, 538–543 (2014).
Francella, A. et al. The safety of 6-mercaptopurine for childbearing patients with inflammatory bowel disease: a retrospective cohort study. Gastroenterology 124, 9–17 (2003).
lint, J. et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology 55, 1693–1697 (2016).
Götestam Skorpen, C. et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann. Rheum. Dis. 75, 795–810 (2016).
Ostensen, M. et al. Pregnancy and reproduction in autoimmune rheumatic diseases. Rheumatology 50, 657–664 (2011).
Sau, A. et al. Azathioprine and breastfeeding: is it safe? BJOG 114, 498–501 (2007).
Sifontis, N. M. et al. Pregnancy outcomes in solid organ transplant recipients with exposure to mycophenolate mofetil or sirolimus. Transplantation 82, 1698–1702 (2006).
Perez-Aytes, A. et al. In utero exposure to mycophenolate mofetil: a characteristic phenotype? Am. J. Med. Genet. A 146A, 1–7 (2008).
Bar Oz, B., Hackman, R., Einarson, T. & Koren, G. Pregnancy outcome after cyclosporine therapy during pregnancy: a meta-analysis. Transplantation 71, 1051–1055 (2001).
Kainz, A., Harabacz, I., Cowlrick, I. S., Gadgil, S. D. & Hagiwara, D. Review of the course and outcome of 100 pregnancies in 84 women treated with tacrolimus. Transplantation. 70, 1718–1721 (2000).
Chakkera, H. A., Kudva, Y. & Kaplan, B. Calcineurin inhibitors: pharmacologic mechanisms impacting both insulin resistance and insulin secretion leading to glucose dysregulation and diabetes mellitus. Clin. Pharmacol. Ther. 101, 114–120 (2017).
Zheng, S. et al. Pharmacokinetics of tacrolimus during pregnancy. Ther. Drug Monit. 34, 660–670 (2012).
Bramham, K., Chusney, G., Lee, J., Lightstone, L. & Nelson-Piercy, C. Breastfeeding and tacrolimus: serial monitoring in breast-fed and bottle-fed infants. Clin. J. Am. Soc. Nephrol. 8, 563–567 (2013).
Wallace, D. J., Gudsoorkar, V. S., Weisman, M. H. & Venuturupalli, S. R. New insights into mechanisms of therapeutic effects of antimalarial agents in SLE. Nat. Rev. Rheumatol. 8, 522–533 (2012).
Kaplan, Y. C., Ozsarfati, J., Nickel, C. & Koren, G. Reproductive outcomes following hydroxychloroquine use for autoimmune diseases: a systematic review and meta-analysis. Br. J. Clin. Pharmacol. 81, 835–848 (2016).
Clowse, M. E., Magder, L., Witter, F. & Petri, M. Hydroxychloroquine in lupus pregnancy. Arthritis Rheum. 54, 3640–3647 (2006).
Marmor, M. F., Kellner, U., Lai, T. Y., Melles, R. B. & Mieler, W. F. American Academy of Ophthalmology recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology 123, 1386–1394 (2016).
Zemlickis, D. et al. Fetal outcome after in utero exposure to cancer chemotherapy. Arch. Intern. Med. 152, 573–576 (1992).
United States Food and Drug Administration. Rituxan final labeling text https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/103705s5311lbl.pdf (2010).
Chakravarty, E. F., Murray, E. R., Kelman, A. & Farmer, P. Pregnancy outcomes after maternal exposure to rituximab. Blood 117, 1499–1506 (2011).
Bruel, A. et al. Hemolytic uremic syndrome in pregnancy and postpartum. Clin. J. Am. Soc. Nephrol. https://doi.org/10.2215/CJN.00280117(2017).
Kelly, R. J. et al. Eculizumab in pregnant patients with paroxysmal nocturnal hemoglobinuria. N. Engl. J. Med. 373, 1032–1039 (2015).
National Institute for Health and Care Excellence. Hypertension in pregnancy: the management of hypertensive disorders in pregnancy. (RCOG Press, 2011).
Henderson, J. T. et al. Low-dose aspirin for the prevention of morbidity and mortality from preeclampsia: a systematic evidence review for the U. S. Preventive Services Task Force. Ann. Intern. Med. 160, 695–703 (2014).
Rolnik, D. L. et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N. Engl. J. Med. 377, 613–622 (2017).
Poon, L. C. et al. Aspirin for evidence-based preeclampsia prevention trial: effect of aspirin in prevention of preterm preeclampsia in subgroups of women according to their characteristics and medical and obstetrical history. Am. J. Obstet. Gynecol. 217, 585.e1–585.e5 (2017).
Datta, P., Rewers-Felkins, K., Kallem, R. R., Baker, T. & Hale, T. W. Transfer of low dose aspirin into human milk. J. Hum. Lact. 33, 296–299 (2017).
Edling, K. L. et al. A pregnant dilemma: primary hyperparathyroidism due to parathyromatosis in pregnancy. Endocr. Pract. 20, e14–e17 (2014).
Nadarasa, K. et al. The use of cinacalcet in pregnancy to treat a complex case of parathyroid carcinoma. Endocrinol. Diabetes Metab. Case Rep. 2014, 140056 (2014).
Hoeltzenbein, M., Stieler, K., Panse, M., Wacker, E. & Schaefer, C. Allopurinol use during pregnancy — outcome of 31 prospectively ascertained cases and a phenotype possibly indicative for teratogenicity. PLoS ONE 8, e66637 (2013).
Indraratna, P. L., Virk, S., Gurram, D. & Day, R. O. Use of colchicine in pregnancy: a systematic review and meta-analysis. Rheumatology https://doi.org/10.1093/rheumatology/kex353 (2017).
Piccoli, G. B. et al. Pregnancy in dialysis patients in the new millennium: a systematic review and meta-regression analysis correlating dialysis schedules and pregnancy outcomes. Nephrol. Dial. Transplant. 31, 1915–1934 (2016).
Hou, S. H. Frequency and outcome of pregnancy in women on dialysis. Am. J. Kidney Dis. 23, 60–63 (1994).
Hladunewich, M. A. et al. Intensive hemodialysis associates with improved pregnancy outcomes: a Canadian and United States cohort comparison. J. Am. Soc. Nephrol. 25, 1103–1109 (2014).
Asamiya, Y. et al. The importance of low blood urea nitrogen levels in pregnant patients undergoing hemodialysis to optimize birth weight and gestational age. Kidney Int. 75, 1217–1222 (2009).
Piccoli, G. B. et al. Pre-eclampsia or chronic kidney disease? The flow hypothesis. Nephrol. Dial. Transplant. 28, 1199–1206 (2013).
Agrawal, S., Cerdeira, A., S., Redman, C. & Vatish, M. Meta-analysis and systematic review to assess the role of soluble fms-like tyrosine recpetor kinase and placental growth factor ratio in prediction of preeclampsia: the SaPPhirE study. Hypertension https://doi.org/10.1161/HYPERTENSIONAHA.117.10182 (2017).
Chappell, L. C. et al. Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study. Circulation 128, 2121–2131 (2013).
Kim, M. Y. et al. Angiogenic factor imbalance early in pregnancy predicts adverse outcomes in patients with lupus and antiphospholipid antibodies: results of the PROMISSE study. Am. J. Obstet. Gynecol. 214, 108.e1–108.e14 (2016).
Akbari, A. et al. Circulating angiogenic factors in a pregnant woman on intensive hemodialysis: a case report. Can. J. Kidney Health Dis. 3, 7 (2016).
Thadhani, R. et al. Removal of soluble fms-like tyrosine kinase-1 by dextran sulfate apheresis in preeclampsia. J. Am. Soc. Nephrol. 27, 903–913 (2016).
Williams, D. & Davison, J. Chronic kidney disease in pregnancy. BMJ 336, 211 (2008).
The authors acknowledge the US National Institute for Health Research (NIHR) Rare Diseases Translational Research Collaboration as well as the Biomedical Research Centre at Guy's and St. Thomas' UK National Health Service (NHS) Foundation Trust and King's College London for funding K.W. under the terms of a doctoral research fellowship. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the UK Department of Health.
The authors declare no competing financial interests.
The absence of menstruation.
- Ovarian stimulation
The use of drugs to stimulate oocyte development in the ovary before retrieval for artificial reproductive techniques.
- Natural-cycle oocyte retrieval
Oocyte retrieval from the ovary following a normal menstrual cycle, without the use of stimulatory drugs.
- 'Mini pill'
An oral contraceptive pill that contains a synthetic progestogen (no oestrogen).
- Intrauterine device
(IUD). A small birth control device that is inserted into the uterus to prevent pregnancy. May contain a slow-releasing progestogen (for example, Mirena) or offer contraception without hormonal release (copper coil).
- Subdermal implant
A small device inserted under the skin. The contraceptive implant delivers an effective dose of a synthetic progestogen, providing long-acting, reversible contraception.
A synthetic form of progesterone.
- 'Combined pill'
Contraceptive pill containing a synthetic oestrogen and progestogen.
- Transdermal patch
Contraceptive patch that delivers synthetic oestrogen and progestogen through the skin.
- Vaginal ring
A soft plastic ring worn inside the vagina that provides contraception via the release of synthetic oestrogen and progestogen.
- Corpus luteum
The remnants of the ovarian follicle after ovulation.
- Pre-implantation genetic diagnosis
(PGD). Examination of the genetic profile of a gamete or embryo before implantation.
- Endocardial fibroelastosis
A disease of the endocardium characterized by collagen deposition, endocardial thickening and ventricular hypertrophy.
A large-for-gestational-age infant.
Increase in parathyroid hormone levels, which can be primary due to pathology within the parathyroid gland or secondary due to hypocalcaemia or hyperphosphataemia (both of which can be caused by CKD).
- Supratherapeutic dosing
Administering a drug dose that is higher than that needed to achieve therapeutic effects.
- Diaphragmatic hernia
Congenital defect in the diaphragm that allows movement of abdominal viscera into the chest.
A congenital abnormality in which the pinna (external ear) is underdeveloped.
A congenital abnormality in which the jaw is underdeveloped.
- Doppler ultrasound
The use of sound waves to detect movement. This technique is used in pregnancy to examine the vascular waveform in uterine and umbilical arteries to predict or diagnose pathology.
About this article
Cite this article
Wiles, K., Nelson-Piercy, C. & Bramham, K. Reproductive health and pregnancy in women with chronic kidney disease. Nat Rev Nephrol 14, 165–184 (2018). https://doi.org/10.1038/nrneph.2017.187
Low-dose aspirin for the prevention of severe preeclampsia in patients with chronic kidney disease: a retrospective study
Journal of Nephrology (2021)
The fertility willingness and acceptability of preimplantation genetic testing in Chinese patients with autosomal dominant polycystic kidney disease
BMC Nephrology (2020)
Kidney function, blood pressure and proteinuria were associated with pregnancy outcomes of pregnant women with chronic kidney disease: a single-center, retrospective study in the Asian population
Clinical and Experimental Nephrology (2020)
Contraception in chronic kidney disease: a best practice position statement by the Kidney and Pregnancy Group of the Italian Society of Nephrology
Journal of Nephrology (2020)
Successful pregnancy after in vitro fertilization in an ABO-incompatible kidney transplant recipient receiving rituximab: a case report
BMC Nephrology (2019)