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Summary for primary care

Clinical Practice Guideline on Pregnancy and Renal Disease

Overview

This Guidelines summary covers recommendations on caring for women with chronic kidney disease (CKD) who are planning a pregnancy, pregnant, or in the postpartum period. It also covers contraception and fertility for women with CKD. Acute kidney injury and renal stone disease are not covered.

For a complete set of recommendations, refer to the full guideline.

Structure of Care

  • Multidisciplinary teams (MDTs; including a consultant obstetrician, consultant nephrologist/expert physician, and expert midwife or midwifery team) should be established to offer advice and care for women with CKD who are pregnant or planning a pregnancy. All healthcare professionals caring for women with CKD should be able to access this MDT.

Medication in Pregnancy and Lactation

  • Low-dose aspirin, low molecular weight heparin, labetalol, nifedipine, methyldopa, prednisolone, azathioprine, ciclosporin, tacrolimus, and hydroxychloroquine are safe for use in pregnancy
  • Concentrations of calcineurin inhibitors (tacrolimus, ciclosporin) should be checked throughout pregnancy and immediately postpartum, as blood concentrations may change
  • Medications that interfere with calcineurin inhibitor metabolism (for example, erythromycin, clarithromycin) should be avoided in pregnant and postpartum women taking tacrolimus or ciclosporin whenever possible
  • Mycophenolate mofetil, methotrexate, and cyclophosphamide should not be taken in pregnancy as they are teratogenic
  • Mycophenolate mofetil should be stopped before pregnancy, as use in pregnancy is associated with an increased risk of spontaneous miscarriage and fetal abnormality. A 3-month interval is advised before conception to allow conversion to a pregnancy-safe alternative and ensure stable disease/kidney function
  • When other treatment options exist, rituximab should be avoided in pregnancy due to the risk of neonatal B cell depletion and unknown long-term outcomes
  • Sirolimus and everolimus should be avoided in pregnancy due to insufficient safety data
  • The benefits of eculizumab in pregnancy for organ-threatening disease are likely to outweigh risk
  • Metformin can be used in pregnancy for women with a pre-pregnancy estimated glomerular filtration rate (eGFR) greater than 30 ml/min/1.73 m2 and stable renal function during pregnancy
  • Immunosuppressive treatment should not be increased routinely in the peripartum period and dose changes should be based on clinical indications and blood concentrations
  • Women can breastfeed while taking prednisolone, hydroxychloroquine, azathioprine, ciclosporin, tacrolimus, enalapril, captopril, amlodipine, nifedipine, labetalol, atenolol, and low molecular weight heparin.

Pre-pregnancy Care

Contraception

  • Advice on safe and effective contraception should be offered to all women of reproductive age with CKD
  • Safe and effective contraception should be offered to women of reproductive age who are taking teratogenic medication, have active glomerulonephritis, are within 1 year of renal transplantation or acute graft rejection, and for any woman who does not wish to conceive
  • The progesterone-only pill, a progesterone subdermal implant, and the progesterone intrauterine system are safe and effective for women with CKD
  • Progesterone-only emergency contraception is safe for women with CKD.

Fertility

  • Fertility preservation should be considered for women of reproductive age who require treatment with cyclophosphamide
  • Women who have had previous treatment with cyclophosphamide should have early investigation of infertility
  • Women with CKD should be referred for pre-pregnancy counselling before receiving assisted reproduction
  • Single-embryo transfer should be performed to reduce risk of complications associated with multifetal pregnancies in women with CKD.

Pre-pregnancy Counselling and Optimisation for Pregnancy

  • Women with CKD considering pregnancy should be offered pre-pregnancy counselling by an MDT, including a consultant obstetrician and nephrologist or expert physician
  • Women with CKD should be advised that there is an increased risk of complications in pregnancy, including pre-eclampsia, preterm birth, fetal growth restriction, and neonatal unit admission, and that they are more likely to require caesarean delivery
  • Women with known or suspected inheritable renal diseases should be offered genetic counselling, including inheritance risk, prognosis, and intervention options including pre-implantation genetic diagnosis
  • Pre-pregnancy counselling is recommended for the optimisation of maternal and neonatal outcomes in women with CKD, which may include:
    • stabilising disease activity in advance of pregnancy on minimised doses of pregnancy-appropriate medications
    • optimising blood pressure control (less than 140/90 mmHg) on pregnancy-appropriate medications
    • optimising glycaemic control in women with diabetes mellitus
    • minimising risk of exposure to teratogenic medications
    • making a treatment plan in the event of hyperemesis or disease exacerbation/relapse during pregnancy
  • Women with CKD who are taking angiotensin-converting enzyme (ACE) inhibitors should have a plan for discontinuation/conversion guided by the strength of indication for renin–angiotensin blockade and the likelihood of pregnancy confirmation in the first trimester
  • Angiotensin receptor antagonists should be discontinued in advance of pregnancy
  • Women with CKD stages 4 and 5 contemplating pregnancy should be offered pre-dialysis education.

Pregnancy Care

Assessment of Renal Function in Pregnancy

  • Renal function in pregnancy should be assessed using serum creatinine concentrations, as eGFR is not valid for use in pregnancy
  • Women with CKD should have formal quantification of proteinuria in pregnancy
  • Quantification of proteinuria should be undertaken by protein:creatinine ratio (uPCR) or albumin:creatinine ratio (uACR). 24-hour urine collection for quantification of protein is not required.

Antenatal Care

  • Pregnant women with CKD who have not had pre-pregnancy counselling by the MDT should be referred to the MDT and receive the same counselling and optimisation as for women attending pre-pregnancy
  • Pregnant women with CKD should receive routine antenatal care, in addition to specialist input
  • Pregnant women with CKD should be referred for assessment by a consultant obstetrician
  • Pregnant women with CKD should have access to usual trisomy screening with specialist interpretation of high-risk results
  • Women with CKD exposed to teratogenic drugs in the first trimester should be referred to a specialist fetal medicine unit
  • Pregnant women with CKD should have scans to assess fetal growth and wellbeing in the third trimester
  • Pregnant women taking prednisolone and/or calcineurin inhibitors should be screened for gestational diabetes.

Pre-eclampsia Prophylaxis

  • Women with CKD should be offered low-dose aspirin (75–150 mg) in pregnancy to reduce the risk of pre-eclampsia
  • Kidney donors should be offered low-dose aspirin (75–150 mg) to reduce the risk of pre-eclampsia.

Blood Pressure Management

  • The target blood pressure (BP) during pregnancy for women with CKD should be 135/85 mmHg or less, which should be documented in the woman’s healthcare record
  • Antihypertensive treatment in women with CKD should be continued in pregnancy unless systolic BP is consistently less than 110 mmHg, or diastolic BP is consistently less than 70 mmHg, or there is symptomatic hypotension
  • Labetalol, nifedipine, and methyldopa can be used to treat hypertension in pregnancy
  • ACE inhibitors, angiotensin receptor antagonists, and diuretics should not be used to treat hypertension in pregnancy
  • A diagnosis of superimposed pre-eclampsia should be considered:
    • in a woman with non-proteinuric CKD, if she develops new hypertension (systolic BP greater than 140 mmHg and/or diastolic BP greater than 90 mmHg) and proteinuria (uPCR greater than 30 mg/mmol or uACR greater than 8 mg/mmol) or maternal organ dysfunction after 20 weeks’ gestation
    • in a woman with proteinuric CKD, if she develops new hypertension (systolic BP greater than 140 mmHg and/or diastolic BP greater than 90 mmHg) or maternal organ dysfunction after 20 weeks’ gestation
    • in a woman with chronic hypertension and proteinuria, if she develops maternal organ dysfunction after 20 weeks’ gestation
  • In women with chronic hypertension and proteinuria, the development of sustained severe hypertension (systolic BP greater than 160 mmHg and/or diastolic BP greater than 110 mmHg or doubling of antihypertensive agents) and/or a substantial rise in proteinuria (doubling of uPCR or uACR compared to early pregnancy) should prompt clinical assessment for superimposed pre-eclampsia
  • A role for angiogenic markers (PlGF±sFlt-1) could be considered as an adjunct to diagnose superimposed pre-eclampsia, dependent upon ongoing research in women with CKD.

Venous Thromboembolism

  • Women with nephrotic-range proteinuria (uPCR greater than 300 mg/mmol or uACR greater than 250 mg/mmol) should be offered thromboprophylaxis with low molecular weight heparin in pregnancy and the postpartum period unless there is a specific contraindication, including risk of labour or active bleeding
  • Non-nephrotic-range proteinuria in pregnancy is a risk factor for thrombosis, and thromboprophylaxis with low molecular weight heparin should be considered in the presence of additional risk factors.

Anaemia

  • Pregnant women with CKD should be given parenteral iron if indicated
  • Erythropoietin-stimulating agents should be given if indicated in pregnancy.

Bone Health

  • Women with CKD who are vitamin D deficient should be given vitamin D supplementation in pregnancy
  • Calcimimetics should be discontinued in pregnancy
  • Non-calcium-based phosphate binders should be discontinued in pregnancy.
For recommendations on renal biopsy and peripartum care, refer to the full guideline.

Postnatal Care

  • Non-steroidal anti-inflammatories should not be given
  • Women with CKD should:
    • have a planned early postpartum renal review
    • be prescribed medications that are compatible with breastfeeding whenever possible
    • be offered safe and effective contraception post-partum, and receive updated pre-pregnancy counselling before future pregnancies. 

Specific Conditions

Lupus Nephritis and Vasculitis

  • Women with lupus or vasculitis should be advised to wait until their disease is quiescent for at least 6 months before conceiving
  • All women with lupus should be advised to take hydroxychloroquine in pregnancy unless it is contraindicated
  • Women with lupus should be monitored for disease activity during pregnancy
  • Women who are positive for anti-Ro (SSA) or anti-La (SSB) antibodies should be referred for fetal echocardiography in the second trimester
  • Women with antiphospholipid syndrome and a history of a confirmed thromboembolic event or previous adverse obstetric outcome (excluding recurrent early fetal loss) should receive low molecular weight heparin in pregnancy and for 6 weeks postpartum
  • Steroids, azathioprine, calcineurin inhibitors, intravenous immunoglobulin, and plasma exchange can be used to treat lupus in pregnancy.

Diabetic Nephropathy

  • Women with diabetic nephropathy should have optimisation of blood glucose, blood pressure, and proteinuria prior to conception
  • Women with diabetic nephropathy should continue ACE inhibitors until conception, with regular pregnancy testing during attempts to conceive
  • The schedule of care, surveillance, and management of women with diabetic nephropathy should be untaken according to national guidelines for diabetes in pregnancy, in addition to specialist monitoring of renal disease in pregnancy.

Urinary Tract Infection

  • Women with reflux nephropathy, congenital anomalies of the kidneys and urinary tract, women with CKD taking immunosuppression, and women with a history of recurrent urinary tract infection (UTI) should be offered antibiotic prophylaxis during pregnancy after a single UTI in pregnancy, including asymptomatic bacteriuria
  • Pre-pregnancy UTI prophylaxis should be continued in pregnancy using agents known to be safe.

For recommendations on renal transplantation, dialysis, reflux nephropathy, and congenital abnormalities of the kidney and urinary tract, refer to the full guideline.


References


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