Introduction
Background
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KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD). UK Renal Association Commentary available at: BMC Nephrology 2018; 19: 240.
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KDOQI Clinical Practice Guideline for Haemodialysis, 2015.
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KDIGO Clinical Practice Guideline for the Evaluation and Management of CKD, 2012
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KDIGO Clinical Practice Guideline for Glomerulonephritis, 2012
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KDIGO Guideline for the Care of Kidney Transplant Recipients, 2009.
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KDIGO Clinical Practice Guidelines for Nutrition in Chronic Renal Failure, 2008.
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NICE: Intrapartum Care for Women with Existing Medical Conditions or Obstetric Complications and their Babies [NG121], 2019.
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NICE: Urinary Tract Infection (Lower) Antimicrobial Prescribing [NG109], 2018
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NICE: Urinary Tract Infection (Recurrent) Antimicrobial Prescribing [NG112], 2018.
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NICE: Antenatal Care for Uncomplicated Pregnancies [CG62], 2008, updated 2017.
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NICE: Vitamin D supplement use in specific population groups [PH56], 2017
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NICE: Diabetes in Pregnancy: Management from Pre-conception to the Post-partum Period [NG3], 2015.
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NICE: Antenatal and postnatal mental health: clinical management and service guidance [CG192], 2014, updated 2018.
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NICE: Fertility: Assessment and Treatment for People with Fertility Problems, 2013.
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NICE: Weight management before, during and after pregnancy [PH27], 2010 [additional data from 2017 surveillance available at: https://www.nice.org.uk/guidance/ph11/evidence/appendix-a-summary-of-evidence-from-surveillance-pdf-4671107966]
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NICE: Hypertension in Pregnancy: Diagnosis and Management [CG107], 2011 (update awaited 2019).
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UK Renal Association Clinical Practice Guidelines: Undernutrition in Chronic Kidney Disease, June 2019
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RCOG: Thrombosis and Embolism During Pregnancy and the Puerperium, Reducing the Risk [Green-Top Guideline 37a], 2015.
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MBBRACE Confidential Enquiry into Maternal Deaths and Morbidity: lessons learned to inform maternity care (triennial reports)
Aims
Scope
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General practice
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Community and hospital antenatal clinics
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Antenatal, labour and postnatal wards
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Renal out-patients
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Renal wards
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Dialysis units
Structure of care
Medication
Pre-pregnancy care
Pregnancy care
Specific conditions
Search strategy
Summary of clinical practice guidelines
Structure of care
Guideline 1.1
Medication in pregnancy and lactation
Guideline 2.1
Guideline 2.2
Guideline 2.3
Guideline 2.4
Guideline 2.5
Guideline 2.6
Guideline 2.7
Guideline 2.8
Guideline 2.9
Guideline 2.10
Guideline 2.11
Pre-pregnancy care
Contraception
Fertility
Pre-pregnancy counseling and optimization for pregnancy
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stabilising disease activity in advance of pregnancy on minimised doses of pregnancy-appropriate medications (1B).
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optimising blood pressure control (< 140/90 mmHg) on pregnancy-appropriate medications (1B).
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optimising glycaemic control in women with diabetes mellitus (1A) (see section 5.4).
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minimising risk of exposure to teratogenic medications (1C) (see section 2).
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making a treatment plan in the event of hyperemesis or disease exacerbation/relapse during pregnancy (1D).
Pregnancy Care
Assessment of renal function in pregnancy
Antenatal care
Pre-eclampsia prophylaxis
Blood pressure management
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in a woman with non-proteinuric CKD, if she develops new hypertension (systolic BP > 140 mmHg and/or diastolic BP > 90 mmHg) and proteinuria (uPCR > 30 mg/mmol or uACR > 8 mg/mmol) or maternal organ dysfunction after 20 weeks’ gestation (1B).
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in a women with proteinuric CKD if she develops new hypertension (systolic BP > 140 mmHg and/or diastolic BP > 90 mmHg) or maternal organ dysfunction after 20 weeks’ gestation (1B)
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in a women with chronic hypertension and proteinuria, if she develops maternal organ dysfunction after 20 weeks’ gestation (1B).
Venous thromboembolism
Anaemia
Bone health
Renal biopsy
Peripartum care
Postnatal care
Specific conditions
Renal transplantation
Dialysis
Lupus nephritis and vasculitis
Diabetic nephropathy
Urinary Tract Infection (UTI)
Reflux nephropathy and Congenital Abnormalities of the Kidney and Urinary Tract (CAKUT)
Summary of audit measures
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Audit Measure 1: Proportion of UK renal units and obstetric centres with access to a multidisciplinary team (including a consultant obstetrician, consultant nephrologist/expert physician, and expert midwife or midwifery team) to advise and/or manage renal disease in pregnancy.
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Audit Measure 2: Incidence of pregnancies (including spontaneous miscarriage and elective terminations of pregnancy) exposed to mycophenolate mofetil and cyclophosphamide within 6 weeks prior to date of conception.
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Audit Measure 3: Proportion of women of reproductive age with CKD within the first year of transplantation offered safe and effective contraception.
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Audit Measure 4: Proportion of women of reproductive age with CKD within 6 months of a lupus flare offered safe and effective contraception.
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Audit Measure 5: Proportion of women of reproductive age with CKD taking teratogenic medication (mycophenolate mofetil, cyclophosphamide, methotrexate) offered safe and effective contraception.
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Audit Measure 6: Proportion of pregnant women with CKD with quantification of proteinuria before 20 weeks’ gestation.
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Audit Measure 7: Proportion of women with CKD taking prednisolone or calcineurin inhibitors who are screened for gestational diabetes.
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Audit Measure 8: Proportion of pregnant women with CKD offered low dose aspirin (75-150 mg) before 16 weeks’ gestation.
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Audit Measure 9: Proportion of pregnant women with CKD that have a target blood pressure for pregnancy documented in their antenatal record.
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Audit Measure 10: Proportion of women with CKD given non-steroidal anti-inflammatory drugs in the post-partum period.
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Audit Measure 11: Proportion on women with CKD who are breastfeeding their infants (exclusively or mixed feeding) at 6 weeks post-partum.
Summary of research recommendations
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renal disease aetiology and mechanisms of disease progression
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factors influencing outcomes in women with dialysis, transplantation
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optimal schedule of care in pregnancy
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optimal management of hypertension, proteinuria, medications, anaemia, vitamin D concentrations
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impact of kidney donation on pregnancy and renal outcomes
Rationale for Clinical Practice Guidelines
Structure of care
Guideline 1.1
Medication in pregnancy and lactation
Guideline 2.1
Guideline 2.2
Guideline 2.3
Guideline 2.4
Guideline 2.5
Guideline 2.6
Guideline 2.7
Guideline 2.8
Guideline 2.9
Guideline 2.10
Guideline 2.11
Drug | Conception (see Section 3.3) | Pregnancy | Lactation | References | ||
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Overall | Maternal considerations | Fetal considerations | ||||
Antihypertensive drugs (see section 4.4) | ||||||
Labetalol | Safe | Safe | License for pregnancy. Avoid if asthmatic. | No association with congenital abnormalities. Reduced birth weight in unadjusted observational data. Neonatal bradycardia (2%) and hypoglycaemia (5%). | Safe | |
Nifedipine | Safe | Safe | None | No association with congenital abnormalities. | Safe | |
Amlodipine | Safe | Limited data. | None | Limited data. No adverse effects reported. | Safe | |
Methyldopa | Safe | Safe | Avoid in depression or if risk of depression. | No association with congenital abnormalities. | Avoid in all due to risk of postnatal depression. | |
Doxazosin | Safe | Limited data | None | No evidence of harm in animal studies | < 1% maternal dose detected. | [15] |
Hydralazine | Safe | Safe | Risk of hypotension, tachycardia | No association with congenital abnormalities | Safe | [15] |
Beta-blockers | Safe | Limited data on individual drugs | Avoid if asthmatic. Use in pregnancy determined by maternal indication. | No association with congenital abnormalities. Reduced birth weight, clinical significance unclear. Neonatal bradycardia (1%) and hypoglycaemia (3%). | No adverse effects reported | |
Angiotensin converting enzyme inhibitors | No apparent increase in risk with first trimester use when data are corrected for underlying hypertension. Continue until conception if required for nephroprotection. | Unsafe | None | Fetotoxic in second and third trimesters leading to fetal and neonatal renal failure, bone and aortic arch malformations, oligohydramnios, and pulmonary hypoplasia. | Safety data available for captopril and enalapril. | |
Angiotensin receptor antagonists | Insufficient data on exposure in early pregnancy. Discontinue in advance of pregnancy. | Unsafe | None | Fetotoxicity in second and third trimesters comparable to angiotensin converting enzyme inhibitors. | No data. | |
Thiazide diuretics | Insufficient data on exposure in early pregnancy. No evidence of harm. | Unsafe | Reduced plasma volume expansion in pregnancy (n = 10) | No evidence of thrombocytopenia, jaundice, hypokalaemia or hyponatraemia in meta-analysis (n = 5292) but advised to avoid. | Potential suppression of lactation. Avoid. | |
Immunosuppressant drugs (see Section 5.1 and 5.3) | ||||||
Corticosteroids | Safe | Safe | Potential risks: diabetes, hypertension, pre-eclampsia, infection, preterm rupture of membranes. Aim for minimum maintenance dose. | Fetus exposed to < 10% maternal dose due to placental deactivation. No evidence of increase in congenital abnormalities. | Safe. Small amounts in breast milk. Consider timing feeds to 4 h post administration if high dose given (e.g. methylprednisolone induction) and monitor neonate. | |
Hydroxychloroquine | Safe | Safe | Withdrawal may precipitate lupus flare. Indicated throughout pregnancy if patient has a history of lupus nephritis. | Placental transfer. No increase in miscarriage or congenital abnormality. May reduce risk of congenital heart block if maternal anti-SSA and or anti-SSB antibodies. | Safe | |
Azathioprine | Safe | Safe | Recommend check TPMT status before dosing. | Placental transfer. No association with congenital abnormalities. | Safe. Low concentration in breast milk | |
Ciclosporin | Safe | Safe | Monitor pre-dose levels more frequently in pregnancy and immediately post partum. May need higher dose in pregnancy. Avoid medications which interfere with calcineurin inhibitor metabolism (e.g. erythromycin, clarithromycin). Increased risk of gestational diabetes | Placental transfer. No association with congenital abnormalities. | Safe | |
Tacrolimus | Safe | Safe | Monitor pre-dose levels more frequently in pregnancy and immediately post-partum. May need a higher dose in pregnancy. Avoid medications which interfere with calcineurin inhibitor metabolism (e.g. erythromycin, clarithromycin). Increased risk of gestational diabetes | Placental transfer. No association with congenital abnormalities. | Safe | |
Mycophenolate mofetil | Unsafe. Effective contraception during treatment and for 6 weeks after treatment. Ensure disease/transplant stability prior to conception. | Unsafe | None | Placental transfer. Teratogenic causing ear, heart, eye, lip/palate, kidney, and bone abnormalities, tracheoesophageal fistula, congenital diaphragmatic hernia. Increased miscarriage. | Avoid use during lactation due to insufficient data. | |
Cyclophosphamide | Unsafe. Effective contraception during and for 3 months after treatment. Dose- and age-related risk of infertility. | Unsafe | None | Placental transfer. Teratogenic. Congenital abnormalities of the skull, ear, face, limb and visceral organs. Increased risk of miscarriage. | Excreted in breast milk. Discontinue breast-feeding during and for 36 h after treatment. | |
Rituximab | Unclear (limited data available). Treatment decision depends on indication and alternative options. | Unclear (limited data available) | If indicated for severe disease, aim to give dose before, or in early, pregnancy to minimise the risk of neonatal B-cell depletion. | Active placental transfer in 2nd and 3rd trimester. Potential risk of neonatal B-cell depletion. Avoid unless potential benefit to woman outweighs risk. Long term effects unknown. | Unclear (limited data available). Possible excretion of trace amounts but neonatal absorption unlikely. | |
Sirolimus / Everolimus | Unsafe – fetal toxicity in rats. Effective contraception during and for 3 months after treatment. | Unsafe | Impaired wound healing. Proteinuria. | Likely placental transfer. Toxicity in animal studies | Limited data available Avoid. | |
Eculizumab | Unclear (limited data available). Treatment decision depends on indication and alternative options. | Unclear (limited data available) | Morbidity of underlying condition may mean treatment in pregnancy is required. Monitor for increased dosage requirements. | Active placental transfer in 2nd and 3rd trimester. No congenital abnormality reported in 20 infants. Long-term effects unknown. | Limited data available. Possible excretion of trace amounts but neonatal absorption unlikely. | |
Other drugs | ||||||
Aspirin (75–150 mg) (see Section 4.3) | Safe | Safe | Decreases risk of pre-eclampsia in general obstetric population. No evidence of maternal haemorrhagic complications. Insufficient data on optimum dose (i.e. 75 mg versus 150 mg). | No association with congenital abnormalities. | Safe | |
Iron (see Section 4.6) | Safe | Safe | Intravenous preparations may offer better bioavailability in CKD | Safety data available in 2nd and 3rd trimesters but limited data on exposure on the first trimester. Expert consensus is not to withhold IV iron if indicated in the first trimester. | Safe | |
Low-molecular- weight heparin | Safe | Safe | Level of proteinuria which confers a significant risk of VTE in pregnancy is unclear. All pregnant women should be risk assessed for VTE. | No placental transfer. | Safe | |
Erythropoietin (see section 4.6) | Safe | Safe | Monitor blood pressure. | No placental transfer. | Safe | |
Metformin (see Section 5.4) | Safe | Safe | Use contraindicated outside of pregnancy if eGFR < 30 ml/min/1.73m2 (approximates to serum creatinine > 150 μmol/L in pregnancy). | None | Levels in milk are low, infants receive < 0.5% of maternal weight-adjusted dosage. No reported adverse effects. |
Pre-pregnancy care
Contraception
Fertility
Pre-pregnancy counseling and optimization for pregnancy
-
stabilising disease activity in advance of pregnancy on minimised doses of pregnancy-appropriate medications (1B).
-
optimising blood pressure control (< 140/90 mmHg) on pregnancy-appropriate medications (1B).
-
optimising glycaemic control in women with diabetes mellitus (1A) (see section 5.4).
-
minimising risk of exposure to teratogenic medications (1C) (see section 2).
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making a treatment plan in the event of hyperemesis or disease exacerbation/relapse during pregnancy (1D).
Pregnancy Care
Assessment of renal function in pregnancy
Antenatal care
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Advice regarding pregnancy care and delivery, with referral back to the local maternity unit
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Shared maternity care between the Maternal Medicine Centre and the local unit
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Maternal Medicine Centre to lead and deliver maternity care
Pre-eclampsia prophylaxis
Blood pressure management
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in a woman with non-proteinuric CKD, if she develops new hypertension (systolic BP > 140 mmHg and/or diastolic BP > 90 mmHg) and proteinuria (uPCR > 30 mg/mmol or uACR > 8 mg/mmol) or maternal organ dysfunction after 20 weeks’ gestation (1B).
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in a women with proteinuric CKD if she develops new hypertension (systolic BP > 140 mmHg and/or diastolic BP > 90 mmHg) or maternal organ dysfunction after 20 weeks’ gestation (1B)
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in a women with chronic hypertension and proteinuria, if she develops maternal organ dysfunction after 20 weeks’ gestation (1B).
• New proteinuria (uPCR> 30 mg/mmol or ACR > 8 mg/mmol) | |
• AKI (serum creatinine ≥90 μmol/L in a woman with previously normal creatinine concentrations) | |
• Liver involvement (alanine aminotransferase or aspartate aminotransferase > 40 IU/L) with or without right upper quadrant or epigastric pain | |
• Neurological complications (eclampsia, altered mental status, blindness, stroke, clonus, severe headache, persistent visual scotomata) | |
• Hematological complications (platelet count < 150,000/μL, disseminated intravascular coagulation, hemolysis) | |
• Uteroplacental dysfunction (fetal growth restriction, abnormal umbilical artery Doppler wave form analysis, stillbirth |
Venous thromboembolism
Anaemia
Bone health
Renal biopsy
Peripartum care
Postnatal care
Specific conditions
Renal transplantation
Dialysis
Lupus nephritis and vasculitis
Diabetic nephropathy
Urinary Tract Infection (UTI)
Reflux nephropathy and Congenital Abnormalities of the Kidney and Urinary Tract (CAKUT)
Lay Summary
Acknowledgments
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Alison Armitage
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Laura Baines
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Helene Brown
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Sue Carr
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Jemma Hale
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Mary Mather
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Jenny Myers
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Nadia Sarween
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Sarah Winfield