Dialysis and a plant-based diet to achieve physiologic urea levels for fetal benefit: Normal pregnancy outcome despite chronic kidney disease and hypertension

Introduction

Chronic kidney disease (CKD) increases the risk of adverse maternal and perinatal outcomes. ¹ The first successful pregnancy in a woman receiving haemodialysis (HD) was reported in 1971. ² Since then, a growing body of evidence suggests improved outcomes with intensive dialysis during pregnancy, indicating that physiologic pre-dialysis blood urea is associated with longer durations of pregnancy and a decreased risk of intrauterine growth restriction (IUGR).^3,4

Thresholds for commencing dialysis during pregnancy for fetal indications remain controversial, with protocols varying between institutions and tending to be based on expert opinion rather than evidence-based guidelines. ⁵ In addition to dialysis, evidence suggests that consumption of a plant-based diet is associated with improved fetal outcomes in women with advanced CKD due to a reduction in acidaemia and hyperphospataemia.^6,7

We report a case of a successful pregnancy outcome in a woman with stage 4 CKD who was dialysed from 11 to 31 weeks' gestation for fetal benefit and converted to a plant-based diet.

Case report

A 32-year-old nulliparous woman was referred for Obstetric Medicine opinion at 7 weeks' gestation. At the age of 24 years, she was diagnosed with CKD secondary to underlying vesico-ureteric reflux. In the 3 years preceding pregnancy, her renal function deteriorated from creatinine 117 µmol/l with an estimated glomerular filtration rate (eGFR) 33 ml/min to creatinine 245 µmol/L, eGFR 22 ml/min, likely related to uncontrolled hypertension. In the nephrology outpatient clinic, 1 month prior to pregnancy, blood pressure (BP) was noted to be 174/114 mmHg and methyldopa was commenced. Prior to pregnancy, she was initiating early workup for transplant. The only other significant medical history was a body mass index of 33 kg/m². Medications included vitamin D3, iron supplement, magnesium supplement, vitamin B6, folic acid and coenzyme Q10.

At 7 weeks' gestation, renal function improved to urea 12.6 mmol/l (Figure 1), creatinine 199 µmol/l and BP control to 142/84 mmHg. The woman elected to proceed with the pregnancy following counselling regarding risks of adverse maternal and fetal outcomes, including hypertensive disorders of pregnancy, extreme prematurity, IUGR and permanent deterioration in her renal function. Low-dose aspirin and calcium were commenced for pre-eclampsia prophylaxis. A plan was made for HD to commence for urea >15 mmol/l based on local practice, to reduce the risk of adverse fetal outcomes.

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Figure 1.

Changes in urea concentration throughout pregnancy.

By 10 weeks' gestation urea had increased to 16.3 mmol/l and creatinine to 243 µmol/l. HD was commenced via internal jugular tunneled catheter (Permcath™), 3 days per week, 3 h per session. Urea targets were 10–15 mmol/l pre-HD and <7 mmol/l post-HD in keeping with international guidance. ⁸ BP targets were 120–140/70–90 mmHg measured both at home and on HD. Weekly haemoglobin measurements on HD targeted 110–130 g/l with erythropoietin (Epoetin alfa) administered for Hb <105 g/l based on the World Health Organization definitions of anaemia in pregnancy ⁹ and once-weekly iron sucrose 100 mg.

Obstetric surveillance consisted of four-weekly growth ultrasounds, BP monitoring and regular obstetric medicine and obstetric clinical review. First-trimester screening and anatomy scans were unremarkable and fetal growth was maintained throughout the pregnancy. She commenced verapamil at 15 weeks and labetalol at 26 weeks due to progressive hypertension.

The HD protocol was decreased to 2.5-hour sessions twice per week from 21 weeks' gestation due to a reduction in pre-HD urea. It was noted that at the commencement of dialysis, the woman began a plant-based diet upon advice from her nephrologist although she declined formal dietary prescription. At 31 weeks, HD was ceased due to the stability of renal function and patient request. Urea remained stable with the highest subsequent level noted to be 14.8 mmol/l at 34 weeks' gestation and the patient associated the subsequent improvement in urea levels with better adherence to a plant-based diet.

Labour was induced at 38 weeks, progressing to a vaginal birth of a live baby girl weighing 2730 g on the 15th centile, APGARs 9 and 9 at 1 and 5 min respectively. The birth was complicated by a 1.7 l postpartum haemorrhage requiring an examination under anaesthetic. Day 1 postpartum investigations revealed Hb 63 g/l, creatinine 291 µmol/l and urea 14 mmol/l. The woman was administered intravenous iron polymaltose and subcutaneous Darbepoetin on day 2 postpartum. She was discharged on day 3 with a follow-up arranged with nephrology and obstetric medicine. Renal function had deteriorated to creatinine 327 µmol/l, eGFR 14ml/min and urine protein:creatinine ratio 191 mg/mmol at 3 weeks postpartum. This decline in renal function appears to be permanent with creatinine 326 µmol/l and eGFR 15 ml/min 1-year postpartum. Preconception counselling was recommended prior to future pregnancies.

Discussion

The prevalence of CKD amongst Australian mothers is rising due to multiple factors including increasing rates of diabetes, obesity and advancing maternal age. ¹⁰ Continued advancements in dialysis protocols and complex multidisciplinary obstetric care have resulted in improved live birth rates in women with CKD. This means that pregnancy, although not without considerable risk, is now a more feasible option than previously thought. ¹¹

According to Jesudason et al., women who conceive prior to the commencement of dialysis are likely to achieve better outcomes, require less dialysis, and maintain superior live birth rates. ⁵ In this case, we hypothesise that early initiation of HD contributed to the success of the pregnancy. We also observed that there may have been a relationship between adherence to a plant-based diet and urea reduction, enabling the woman to reduce and eventually cease HD during the pregnancy.

Plant-based diets increase the fibre-to-protein ratio and reduce nitrogenous compounds. ¹² Subsequently, gut bacteria shift from a proteolytic profile to a saccharolytic profile resulting in increased production of short-chain fatty acids and reduced production of uraemic toxins and inflammation. ¹³ However, the association between low protein intake in pregnancy and IUGR should be considered and any dietary modifications made in conjunction with expert dietetic advice.

Family planning is a source of great trepidation for women with CKD, often related to concerns of risk to both their own and their baby's health. ¹⁴ Considering more recent evidence, the way in which women are counselled regarding pregnancy is changing. ¹⁵ Whilst these pregnancies should still be considered high risk and must be managed as part of an experienced multidisciplinary team, perhaps it is time to change our perspective. Kidney transplantation and intensive preconception optimisation offer the greatest chance of a live birth to women with advanced CKD, ¹⁶ but with ongoing improvements in maternal and fetal outcomes for women receiving dialysis, here too lies a realistic hope of a successful pregnancy.^17,18