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Reproductive health and pregnancy in women with chronic kidney disease

Key Points

  • 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

Abstract

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.

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Figure 1: Endocrine effects of chronic kidney disease on the hypothalamic–pituitary–ovarian axis.
Figure 2: Physiological changes in the renal system in pregnancy.
Figure 3: Adverse pregnancy outcomes according to chronic kidney disease stage.

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Acknowledgements

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.

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K.W., C.N.P. and K.B. contributed equally to the conception, design, drafting and revision of this article.

Corresponding authors

Correspondence to Kate S. Wiles or Catherine Nelson-Piercy.

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The authors declare no competing financial interests.

PowerPoint slides

Glossary

Amenorrhoea

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.

Progestogen

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.

Ribonucleoproteins

Protein–RNA complexes.

Endocardial fibroelastosis

A disease of the endocardium characterized by collagen deposition, endocardial thickening and ventricular hypertrophy.

Macrosomia

A large-for-gestational-age infant.

Hyperparathyroidism

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.

Microtia

A congenital abnormality in which the pinna (external ear) is underdeveloped.

Micrognathia

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.

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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

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