Contraception and family planning
Third and Fourth degree perineal tear

Chronic kidney disease in pregnancy

Table of content

1. Introduction

2. Stages

3. Pre-pregnancy counselling

4. Effect of chronic renal disease on pregnancy

5. Antenatal care

6. Fetal growth monitoring

7. Intrapartum care

8. Postnatal care

9. Renal transplant

10. Pregnancy and dialysis

11. Gestational proteinuria

12. References


Introduction

Chronic Kidney Disease (CKD) can be associated with adverse maternal and fetal outcomes. The key to achieving optimum outcome in these women depends on effective preconception counselling and management by a multidisciplinary team. CKD is classified into 5 stages based on eGFR.


Stages
  • Stage 1: Normal GFR; GFR >90 but urine findings or structural abnormalities or genetic traits point to kidney disease
  • Stage 2: Mild impairment; GFR 60-89 and other findings point to kidney disease (as for stage 1)
  • Stage 3: Moderate impairment; GFR 30-59
  • GFR 45-59 (stage 3A)
  • GFR 30-44 (stage 3B)
  • Stage 4: Severe impairment: GFR 15-29
  • Stage 5: Established renal failure (ERF): GFR < 15 or on dialysis

Pre-pregnancy counselling

All high-risk women and ideally all women in the moderate risk group must have a pre-conception appointment with a renal physician and obstetrician with special interest in renal disease


Assessment
  • Previous history including previous surgical intervention.
  • Co-morbidities
  • Previous obstetric history
  • Assessment of current functional status (BP, renal function, proteinuria to facilitate provision of information about pregnancy risks)

Optimise condition
  • In all conditions, it is usually advisable to delay conception until the disease and drug regime are stable.
  • Lifestyle modification and folic acid supplementation

Manage medication
  • Determine which drugs can be continued in pregnancy and plans for changing any which cannot be used in pregnancy.

Safe in pregnancy: Ca channel blockers, methyl dopa, hydralazine, labetalol, propranolol, prednisolone, azathioprine, tacrolimus and cyclosporin.

Prednisolone, atenolol, tacrolimus – IUGR risk

Contraindicated in pregnancy: ACE inhibitors (captopril, enalapril), Angiotensin II receptor blockers   (candesartan, losartan) – risk of congenital malformations, renal problems etc but provide renal protection, hence switch over to safer alternatives as early as possible in proteinuric kidney disease.

Mycophenolate mofetil – teratogenic

Sirolimus- limited evidence of safety


Counselling about risk
  • Information should be given to the woman and her family about the risks of pregnancy to her long-term health and CKD.
  • Inform patient about risk of new or worsening hypertension and or proteinuria in pregnancy, preeclampsia, increased risk of gestational diabetes, venous thromboembolism and Caesarean section.
  • Risk of transient or permanent deterioration of background renal function, risk of requiring dialysis, acute transplant rejection and situations where termination of pregnancy is offered should be discussed.
  • Fetal risks including small for gestational age, premature delivery and fetal death in utero. The risks should again be individualised according to her background CKD.
  • Clear explanation of what a pregnancy will entail, risks and outcomes and the intensity of monitoring and the frequency of appointments.
  • Communication with the background renal team including discussion about any alteration of medication.
  • All information should be summarised in a letter to the woman and the team of professionals who care for her. This should include any instructions for when she becomes pregnant e.g. continuing on ACE inhibitor in a heavily proteinuric patient until she gets pregnant and stop it as soon as possible once she has a positive pregnancy test.
  • Clear information on how to access antenatal services rapidly should she get pregnant as often these women need to be seen before a GP/MW referral is received
Effects of chronic renal disease on pregnancy
Renal Diseases Effects
Chronic glomerulonephritis and focal glomerular sclerosis Caution in primigravida as pregnancy might be a flare factor.

If not flared during a prior pregnancy then good chance they will not flare again.

If previous flare in pregnancy, high chance of recurrence

IgA nephropathy Risk of uncontrolled hypertension, flare and nephrotic syndrome
Polycystic kidney disease Autosomal dominant

Risk of preeclampsia, UTI

No adverse long-term effect due to pregnancy

SLE nephritis May manifest for 1st time in pregnancy

Prognosis better if remission >6months preconception

After nephrectomy, solitary/pelvic kidney Maybe associated with other malformations

Dystocia rare with pelvic kidney

Granulomatosis with polyangiitis Proteinuria, hypertension common from early pregnancy.

Often have granulomas in lung, throat, nose

Periarteritis nodosa Fetal prognosis poor, risk of maternal death
Renal artery stenosis Presents as chronic hypertension or recurrent, isolated PET

Antenatal care
  • Pregnancy should be planned and managed by a multidisciplinary team including obstetricians with special interest in maternal medicine, midwives and nephrologists.

The outcome of pregnancy in women with chronic renal disease depends on the following factors:

  • the degree of renal impairment and the rate of decline
  • the presence of chronic hypertension
  • the presence of proteinuria
  • underlying renal pathology.

Antenatal investigation
  • A baseline renal profile, liver function, full blood count, assessment for proteinuria (PCR) should be performed.
  • Normal Serum Creatinine level in pregnancy is <65 umol/l. Creatinine > 70 or Proteinuria < 20 weeks (no UTI) = CKD Kidney function should be assessed regularly by serum creatinine and degree of proteinuria. Frequency of testing should depend on the level of kidney function and progress during pregnancy e.g. every 4weeks in CKD 2, every 2 weeks in CKD 3 and 4.
  • Kidney function should be assessed regularly by serum creatinine and degree of proteinuria. Frequency of testing should depend on the level of kidney function and progress during pregnancy e.g. every 4weeks in CKD 2, every 2 weeks in CKD 3 and 4.
  • Regular MSSU in women with recurrent UTIs and reflux nephropathy and consideration of prophylactic antibiotics.
  • Renal ultrasound in nephropathy secondary to renal stones.
  • Consider uterine artery dopplers at 20–24 weeks.
  • Consider a glucose tolerance test at 26 weeks if taking steroids or tacrolimus

Management
  • Low-dose aspirin (75-150 mg) is recommended from as early as possible in pregnancy until birth of the baby to reduce the risk of pre-eclampsia.
  • Women with nephrotic syndrome, uPCR >200, serum albumin of <20 should receive prophylactic LMWH in pregnancy as well as for 6 weeks postpartum. Consider starting LWMH on a lower PCR level, if there are additional risk factors for VTE.
  • Blood pressure should be monitored regularly.

Aim for – BP of < 140/90 if CKD 1 or normal renal function at booking,

– systolic <130-135 and diastolic 75-85 if CKD 2 or 3

– systolic 130 and diastolic 70-80 if nephrotic, CKD 3b and above and in transplant.

  • Admit to the antenatal ward if severe or worsening hypertension, deteriorating kidney function or proteinuria (differentiation between pre-eclampsia and deterioration of pre-existing renal disease may be extremely difficult. The renal physicians should be involved early).
  • Maternal anaemia in women with renal impairment occurs due to decreased erythropoietin production and shortened red cell survival. This can usually be managed by oral/intravenous iron therapy.
  • IOL is recommended between 37-38 weeks if CKD 3 or more, deterioration in renal function and PCR >50. Early delivery should be considered for obstetric indications such as pre-eclampsia and fetal growth restriction or for rapidly deteriorating maternal renal function.

Fetal growth monitoring
  • Regular scans are recommended every 4 weeks from 26 weeks of gestation onwards to check growth as well as liquor volume.
  • If CKD 3 or more, consider fortnightly scans from 24 weeks
  • If PCR >150, fortnightly scans from 26 weeks.
  • Polyhydramnios may complicate pregnancies where the maternal urea level is greater than 10 µmol/l. This is owing to fetal polyuria due to the osmotic load from the high urea level. Once the urea level is greater than 20–25 µmol/l, there is risk of fetal death.

Intrapartum care
  • Vaginal delivery should be the mode of choice. Lower segment caesarean section should only be performed for obstetric reasons.
  • Continuous electronic fetal monitoring is recommended.
  • If the woman is on 7.5mg of prednisolone or greater daily then intravenous hydrocortisone 100mg should be given in labour 6 hourly until oral medication can be recommenced.
  • There is no contraindication to the use of labour analgesia including epidural. If on LMWH, will need heparin care plan.
  • There should be a careful assessment of fluid balance using an hourly input/output chart and an hourly urometer in high risk cases.
  • An arterial line may be indicated and this should be specified in the anaesthetic care plan.
  • Blood loss should be assessed as accurately as possible.
  • Limitation of second stage is not needed.
  • Ergometrine and syntometrine are often contraindicated due to pre-existing hypertension or preeclampsia

Blood pressure control
  • Magnesium sulphate prophylaxis can be used in severe pre-eclampsia.
  • The loading dose of MgSo4 can remain the same but the maintenance dose may need to be reduced depending on the severity of CKD after discussion with the renal physicians or tertiary unit

Preterm labour
  • Preterm labour is common.
  • The prompt treatment of bacterial vaginal and urinary tract infections, including asymptomatic bacteriuria, can be helpful in prevention of preterm labour.
  • Women with recurrent urinary tract infections should be given antibiotic prophylaxis throughout pregnancy.
  • Atosiban or nifedipine can be used for tocolysis. There is no evidence for the use of atosiban in CKD but renal impairment is unlikely as only small amounts excreted in urine.
  • Steroids for fetal lung maturity is not contraindicated.
  • Magnesium sulphate used for fetal neuroprotection should be used with caution as mentioned above.

Postnatal care
  • All renal medications should be reviewed postpartum, as drugs and doses may need changing.
  • Not contraindicated in breastfeeding: labetalol, β blockers, nifedipine, amlodipine), ACE inhibitors (captopril, enalapril), hydralazine, prednisolone, azathioprine, tacrolimus.
  • Contraindicated in breastfeeding: mycophenolate, cyclosporine
  • Contraindicated in all postnatal women: methyl dopa
  • LMWH should be continued for 6 weeks postpartum in women with significant proteinuria (uPCR >200) and or with additional risk factors for VTE.
  • Women should continue their established care with the nephrology team and be seen at a postnatal combined clinic.
  • Referral to renal clinic should be made for those who had new diagnosis of underlying renal disease in pregnancy.
  • Women should be informed about the risks in future pregnancies and the importance of pre-conception care when planning future pregnancies.
  • Women should be given advice about contraception and how to access services rapidly when they become pregnant.

 Contraception: All types of contraception are generally safe, tolerated, effective with minimal interactions.

  • Emergency contraception is safe in CKD and transplant.
  • LNG-IUS is safe & effective in immunosuppressed
  • Combined OCP 3rd line but not excluded.
  • Depot progestogens can have variable interaction with tacrolimus and cyclosporine.

Renal transplant
  • All pregnant women with renal transplant should be managed at the tertiary unit.
  • Transplant complications (infection, rejection, urological) are more during the first two years post-transplantation and more aggressive immunosuppressive treatment is used during this period. Patients are advised to avoid conception at this time.
  • The miscarriage rate and the incidence of congenital anomalies is similar to the general population.
  • Potential pregnancy complications in kidney transplant recipients include hypertension, PET, FGR (20–40%), preterm delivery (45–60%), increased risk of infections due to immunosuppression and anaemia.
  • Approximately 10–18% of women will have a temporary or permanent deterioration of kidney function
  • Acute rejection in pregnancy occurs in 9–14% of women but the incidence of serious episodes of rejection is 5%, which is similar to the rates observed in non pregnant transplant patients.

The features of acute rejection include:

  • deteriorating renal function
  • fever
  • oliguria
  • graft swelling and tenderness
  • altered echogenicity of renal parenchyma and blurring of corticomedullary junction on ultrasound.
  • Vaginal birth is the safest route of delivery.
  • There is a risk of injury to the transplant kidney during Caesarean section. Hence the location of transplant kidney must be available prior to Caesarean section.
  • Renal transplant surgeon should ideally be present at Caesarean section.

Pregnancy and dialysis
  • Pregnant women on dialysis should be managed at the tertiary centre.
  • Conception is more likely in women with residual renal function and those just beginning dialysis.
  • The incidence of pregnancy is lower in women on peritoneal dialysis than on haemodialysis.
  • Pregnancy outcomes in women receiving dialysis are poor but can be improved with intensive dialysis.
  • Maternal complications include hypertension, hypertensive crisis, pre-eclampsia, anaemia and placental abruption.
  • Spontaneous miscarriage, preterm delivery, premature deaths, polyhydramnios are common.

Gestational proteinuria
  • Definition: New onset proteinuria in the absence of hypertension.
  • The investigations needed include:
  • – MSSU to exclude UTI
  • – PCR to quantify proteinuria
  • – Baseline FBC, U&Es, LFTs, urate, LA, ACA, ANA, LDH and RH factor.
  • – Renal USS
  • Consider LMWH depending on the PCR level and other risk factors for VTE.
  • Risk of preeclampsia, growth restriction and abruption.
  • Monitor BP twice a week, more frequently if high risk of preeclampsia or early onset of proteinuria.
  • Serial growth scans from 26 weeks.
  • Offer delivery at 37+ weeks.
  • Follow up 6 weeks postnatal to ensure proteinuria has cleared and evaluate the need for Renal referral.
  • Renal biopsy may be needed in a small number of these cases.

References
  1. Davison J, Nelson Piercy C, Kehoe S, Baker P (editors). Renal Disease in Pregnancy. Cambridge: Cambridge University Press; 2008.
  2. EBPG Expert Group on Renal Transplantation European best practice guidelines for renal transplantation. Section IV: long‐term management of the transplant recipient. IV.10. Pregnancy in renal transplant recipients Nephrol Dial Transplant 2002 17 Suppl 4 50–55.
  3. Lindheimer MD, et al. Gestation in women with kidney disease: prognosis and management. Baillieres Clin Obstet Gynaecol. 1994.
  4. 4.Guideline on the management of renal disease in pregnancy-Greater Manchester and Eastern Cheshire strategic clinical network