Clinical practice guideline on pregnancy and renal disease

New Clinical practice guideline on pregnancy and renal disease have been released which have been published in BMC Nephrology.This guidance covers the care of women with CKD (including renal transplant recipients) who are planning a pregnancy, pregnant, or in the post-partum period. It also covers contraception and fertility for women with CKD.

Although Chronic kidney disease is not a barrier to reproduction in most women, the risk of adverse pregnancy outcomes is increased in women with CKD including pre-eclampsia, fetal growth restriction, preterm delivery and accelerated loss of maternal renal function. CKD impacts on communication, decision-making, and the surveillance and management of women before, during, and after pregnancy.

Following are the major recommendations:

1. Structure of care

• We recommend multidisciplinary teams (including a consultant obstetrician, consultant nephrologist/expert physician, and expert midwife or midwifery team) are 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 (1D).

2. Medication in pregnancy and lactation

• We recommend that low dose aspirin, low molecular weight heparin, labetalol, nifedipine, methyldopa, prednisolone, azathioprine, ciclosporin, tacrolimus and hydroxychloroquine are safe for use in pregnancy


• We recommend concentrations of calcineurin inhibitors (tacrolimus, ciclosporin) are checked throughout pregnancy and immediately postpartum, as blood concentrations may change


• We recommend that medications which interfere with calcineurin inhibitor metabolism (e.g. erythromycin, clarithromycin) are avoided in pregnant and post-partum women taking tacrolimus or ciclosporin whenever possible


• We recommend mycophenolate mofetil, methotrexate and cyclophosphamide are not taken in pregnancy as they are teratogenic


• We recommend mycophenolate mofetil is 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


• We recommend that, when other treatment options exist, rituximab is avoided in pregnancy due to the risk of neonatal B cell depletion and unknown long-term outcomes


• We recommend sirolimus and everolimus are avoided in pregnancy due to insufficient safety data


• We suggest the benefits of eculizumab in pregnancy for organ threatening disease are likely to outweigh the risk


• We recommend metformin can be used in pregnancy for women with a pre-pregnancy eGFR>30mls/min/1.73m2 and stable renal function during pregnancy


• We recommend immunosuppressive treatment is not increased routinely in the peripartum period and that dose changes are based on clinical indications and blood concentrations


• We recommend women can breastfeed whilst taking prednisolone, hydroxychloroquine, azathioprine, ciclosporin, tacrolimus, enalapril, captopril, amlodipine, nifedipine, labetalol, atenolol and low molecular weight heparin

3. Pre-pregnancy care

Contraception

• We recommend advice on safe and effective contraception is offered to all women of reproductive age with CKD


• We recommend safe and effective contraception is offered to women of reproductive age who are taking teratogenic medication, have active glomerulonephritis, are within one year of renal transplantation or acute graft rejection, and for any woman who does not wish to conceive


• We recommend that the progesterone only-pill, a progesterone subdermal implant, and the progesterone intra-uterine system are safe and effective for women with CKD


• We recommend that progesterone-only emergency contraception is safe for women with CKD

Fertility

• We suggest fertility preservation is considered for women of reproductive age who require treatment with cyclophosphamide


• We suggest women who have had previous treatment with cyclophosphamide have early investigation of infertility


• We recommend women with CKD are referred for pre-pregnancy counselling before receiving assisted reproduction


• We recommend single-embryo transfer is performed to reduce risk of complications associated with multifetal pregnancies in women with CKD

Pre-pregnancy counseling and optimization for pregnancy

• We suggest women with CKD considering pregnancy are offered pre-pregnancy counselling by a multidisciplinary team including a consultant obstetrician and nephrologist or expert physician


• We recommend women with CKD are advised there is an increased risk of complications in pregnancy including pre-eclampsia, preterm birth, fetal growth restriction, and neonatal unit (NNU) admission, and that they are more likely to require caesarean delivery


• We recommend women with known or suspected inheritable renal diseases are offered genetic counselling including inheritance risk, prognosis, and intervention options including pre-implantation genetic diagnosis


• We recommend pre-pregnancy counselling 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 (< 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
  
  
  
  


• We recommend women with CKD who are taking angiotensin-converting enzyme inhibitors 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


• We recommend angiotensin receptor antagonists are discontinued in advance of pregnancy


• We suggest women with CKD stages 4 and 5 contemplating pregnancy are offered pre-dialysis education

4. Pregnancy Care

Assessment of renal function in pregnancy

• We recommend renal function in pregnancy is assessed using serum creatinine concentrations as estimated GFR (eGFR) is not valid for use in pregnancy


• We recommend women with CKD have formal quantification of proteinuria in pregnancy


• We recommend quantification of proteinuria is undertaken by protein:creatinine ratio (uPCR) or albumin:creatinine ratio (uACR). Twenty-four hour urine collection for quantification of protein is not required

Antenatal care

• We suggest pregnant women with CKD who have not had pre-pregnancy counselling by the MDT are referred to the MDT and receive the same counselling and optimisation as for women attending pre-pregnancy


• We recommend pregnant women with CKD receive routine antenatal care, in addition to specialist input


• We recommend pregnant women with CKD be referred for assessment by a consultant obstetrician


• We recommend pregnant women with CKD have access to usual trisomy screening with specialist interpretation of high-risk results


• We recommend women with CKD exposed to teratogenic drugs in the first trimester are referred to a specialist fetal medicine unit


• We recommend pregnant women with CKD have scans to assess fetal growth and wellbeing in the third trimester


• We recommend pregnant women taking prednisolone and/or calcineurin inhibitors are screened for gestational diabetes

Pre-eclampsia prophylaxis

• We recommend women with CKD are offered low-dose aspirin (75-150 mg) in pregnancy to reduce the risk of pre-eclampsia


• We suggest kidney donors are offered low dose aspirin (75 mg–150 mg) to reduce the risk of pre-eclampsia

Blood pressure management

• We recommend that the target blood pressure during pregnancy for women with CKD is 135/85 mmHg or less, which should be documented in the woman’s healthcare record


• We suggest antihypertensive treatment in women with CKD is continued in pregnancy unless systolic blood pressure is consistently < 110 mmHg systolic, or diastolic blood is pressure consistently < 70 mmHg diastolic BP, or there is symptomatic hypotension


• We recommend labetalol, nifedipine and methyldopa can be used to treat hypertension in pregnancy


• We recommend angiotensin-converting enzyme inhibitors, angiotensin receptor antagonists and diuretics are not used to treat hypertension in pregnancy


• We recommend a diagnosis of superimposed preeclampsia is considered:
  
  
  
  • 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
  
  
  • in 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
  
  
  • in a women with chronic hypertension and proteinuria, if she develops maternal organ dysfunction after 20 weeks’ gestation
  
  
  
  


• We suggest in women with chronic hypertension and proteinuria that the development of sustained severe hypertension (systolic BP > 160 mmHg and/or diastolic BP > 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 (2D).


• We suggest a role for angiogenic markers (PlGF±sFlt-1) is considered as an adjunct to diagnose superimposed pre-eclampsia, dependent upon on-going research in women with CKD


• We recommend that women with nephrotic-range proteinuria (uPCR> 300 mg/mmol or ACR > 250 mg/mmol) be offered thromboprophylaxis with low molecular weight heparin in pregnancy and the post-partum period unless there is a specific contraindication including risk of labour or active bleeding


• We suggest that 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

• We recommend pregnant women with CKD are given parenteral iron if indicated


• We recommend erythropoietin stimulating agents are given if indicated in pregnancy


• We recommend women with CKD who are vitamin D deficient be given vitamin D supplementation in pregnancy


• We recommend calcimimetics are discontinued in pregnancy


• We recommend non-calcium based phosphate binders are discontinued in pregnancy

Renal biopsy

• We recommend if a histological diagnosis will change management in pregnancy then renal biopsy can be performed in the first and early second trimester of pregnancy

Peripartum care

• We recommend women with CKD receive routine peripartum care, with additional specialist input


• We recommend women with CKD have observations taken and documented during any hospital admission. This includes temperature, heart rate, blood pressure, respiratory rate, and oxygen saturation. An early warning score should be calculated and actioned appropriately


• We recommend additional assessment for women with an elevated early warning score, for women considered to be high-risk, and for any women in whom there is any clinical concern. This includes examination of jugular venous pressure, lung auscultation and urine output monitoring (in-dwelling catheter not usually required) in addition to routine parameters


• We recommend women with CKD at risk of volume depletion or volume overload are highlighted by the MDT in advance of delivery


• We recommend that fluid balance is managed with the aim of maintaining normal fluid volume, avoiding dehydration and pulmonary oedema, with input from clinicians with expertise in fluid balance and renal disease


• We recommend all clinicians are aware of the increased risk of pulmonary oedema in women with CKD and pre-eclampsia


• We recommend the timing of birth for women with CKD is determined by obstetric indications, with consideration of renal factors including deteriorating renal function, symptomatic hypoalbuminaemia, pulmonary oedema, and refractory hypertension

Postnatal care

• We recommend that non-steroidal anti-inflammatories should not be given


• We recommend women with CKD have a planned early postpartum renal review


• We recommend that women with CKD are prescribed medications that are compatible with breastfeeding whenever possible


• We recommend that women with CKD are offered safe and effective contraception post-partum and receive updated pre-pregnancy counselling before future pregnancies

5. Specific conditions

Renal transplantation

• We recommend women with renal transplants wait until their kidney function is stable on medications that are safe in pregnancy before conceiving, which is usually more than one year after transplantation


• We recommend that plans for delivery in a woman with a renal transplant are discussed with the local surgical transplant team


• We recommend that mode of delivery in women with renal transplants is based on obstetric indications and maternal preference


• We recommend that caesarean delivery in a woman with a renal transplant patient is performed by the most senior obstetrician available, ideally a consultant


• We recommend that women with kidney-pancreas transplants, kidney-liver transplants, and dual kidney transplants are managed during pregnancy and delivery by a multidisciplinary team including transplant physicians and surgeons, at a transplant centre

Dialysis

Women receiving maintenance dialysis before pregnancy

• We recommend women established on dialysis prior to pregnancy receive pre-pregnancy counselling including the options of postponing pregnancy until transplantation (when feasible) and the need for long frequent dialysis prior to and during pregnancy


• We recommend women established on haemodialysis prior to pregnancy receive long, frequent haemodialysis either in-centre or at home to improve pregnancy outcomes


• We suggest women receiving haemodialysis during pregnancy have dialysis dose prescribed accounting for residual renal function, aiming for pre-dialysis urea < 12.5 mmol/l


• We recommend women established on peritoneal dialysis prior to pregnancy should convert to haemodialysis during pregnancy

Initiating dialysis during pregnancy

• We suggest haemodialysis should be initiated in pregnancy when the maternal urea concentration is 17-20 mmol/L and the risks of preterm delivery outweigh those of dialysis initiation. Gestation, renal function trajectory, fluid balance, biochemical parameters, blood pressure and uraemic symptoms should be considered in addition to maternal urea concentration

Lupus nephritis and vasculitis

• We recommend that women with lupus or vasculitis should be advised to wait until their disease is quiescent for at least 6 months before conceiving


• We recommend that all women with lupus should be advised to take hydroxychloroquine in pregnancy unless it is contraindicated


• We recommend that women with lupus be monitored for disease activity during pregnancy


• We recommend that women who are positive for anti-Ro (SSA) or anti-La (SSB) antibodies be referred for fetal echocardiography in the second trimester


• We recommend women with antiphospholipid syndrome and a history of a confirmed thromboembolic event or previous adverse obstetric outcome (excluding recurrent early fetal loss) receive low molecular weight heparin in pregnancy and for six weeks postpartum


• We recommend that steroids, azathioprine, calcineurin inhibitors, intravenous immunoglobulin and plasma exchange can be used to treat lupus in pregnancy

Diabetic nephropathy

• We recommend that women with diabetic nephropathy have the optimisation of blood glucose, blood pressure and proteinuria prior to conception


• We recommend that women with diabetic nephropathy continue angiotensin-converting enzyme inhibitors until conception, with regular pregnancy testing during attempts to conceive


• We recommend that 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 (UTI)

• We suggest women with reflux nephropathy, congenital anomalies of the kidneys and urinary tract (CAKUT), women with CKD taking immunosuppression, and women with a history of recurrent UTI should be offered antibiotic prophylaxis during pregnancy after a single UTI in pregnancy, including asymptomatic bacteriuria


• We recommend pre-pregnancy UTI prophylaxis be continued in pregnancy using agents known to be safe

Reflux nephropathy and Congenital Abnormalities of the Kidney and Urinary Tract (CAKUT)

• We recommend women with previous bladder surgery (re-implantation of the ureter, bladder reconstruction, all complex paediatric urology) should be discussed during pregnancy with a urologist with expertise in bladder reconstruction to evaluate options for delivery


• We recommend that antenatally detected abnormalities in the fetal kidneys and/or urinary tract should be discussed with fetal medicine and paediatric nephrology specialists to determine appropriate neonatal management


• We recommend that children with antenatally detected abnormalities in the fetal kidneys and/or urinary tract should have specialist follow up if features of urinary tract infection are identified