Success of Pregnancy in a Patient on High-Volume Hemodiafiltration with Citrate-Acidified Dialysate

Although pregnancy in dialysis patients is rare, recent reports in the literature have shown improvement in pregnancy outcome in this population. Increasing doses of dialysis have led to improvement in fetal prognosis, but recommendations are still lacking, and there are few documented reports of pregnant woman on high-volume online hemodiafiltration. Here, we report the first successful pregnancy in a 28-year-old patient on daily high-volume online post-dilution hemodiafiltration with a citrate dialysate. At 37 weeks and 1 day, she delivered a healthy 2.3 kg baby that did not require neonatal intensive care. This case report suggests that hemodiafiltration with a dialysate acidified with citrate is safe in pregnancy. Further reports and a registry are necessary to confirm that high-volume online hemodiafiltration with a citrate dialysate should be the preferred dialysis modality in pregnant women.

© 2023 The Author(s). Published by S. Karger AG, Basel

Introduction

Fifty years after the first report of a successful pregnancy in a dialysis-dependent patient by Confortini et al. [1], pregnancy outcome in dialysis displays an improving trend, with an approximate 25% fetal survival gain per decade [2]. In 2014, a Canadian and American cohort study compared 22 pregnancies on nocturnal hemodialysis as an intensive dialysis modality to 70 pregnancies from the American Registry for Pregnancy in Hemodialysis Patients. The study found a dose response between dialysis intensity and pregnancy outcomes. Live birth rates were 48% in women who had weekly dialysis >20 h compared to 85% for women who had weekly dialysis >36 h per week (p = 0.02). Fetuses born to women who had more intensive dialysis had longer gestational age and higher infant birth weight [3]. A meta-analysis in 2016 of 681 pregnancies showed an inverse relationship between hours of dialysis per week in hemodialysis and preterm birth, as well as low birth weight [4]. In 2018, a French study identified 100 pregnancies in 84 women on hemodialysis and reported an overall fetal survival of 78%, comparable to fetal prognosis in the transplanted population. But these pregnancies remain at high risk [5].

Dialysis dose appears to be the cornerstone of these improved results. Four case reports have described favorable outcomes in pregnant patients on hemodiafiltration (HDF) [69]. In all but 1 patient, who presented with metrorrhagia and a small placental hematoma, there were no complications from the use of bicarbonate dialysate acidified with citrate in pre-dilutional HDF [8]. We report the first case of a pregnant hemodialysis-dependent patient on daily high-volume online post-dilution HDF with citrate-acidified dialysate. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see www.karger.com/doi/10.1159/000528725).

Case Report

A 28-year-old woman with chronic kidney disease secondary to IgA nephropathy was started on hemodialysis in November 2015. Her medical history included a sleeve gastrectomy in 2017, 2 voluntary terminations of pregnancy, and a miscarriage at 8 weeks of pregnancy in January 2020.

She received a deceased donor renal transplant in March 2017. Two years later, she presented with acute antibody-mediated rejection treated with 4 plasma exchanges, corticoids, and monthly immunoglobulins for 6 months. The evolution was unfavorable with a return to dialysis in March 2020. She was dialyzed on a proximal radio-radial arteriovenous fistula on the left side. She was detransplanted 24 April 2020.

Start of pregnancy was July 2020. She received daily hemodialysis sessions in another center. In September 2020, the patient was hospitalized for a Covid infection with dyspnea and fever of 39°C. Her infection resolved and she was discharged.

The subject subsequently continued daily HDF sessions in our center (it was the first time she received HDF), with 4.5 h post-dilution high-volume online HDF sessions 6 days a week using bicarbonate dialysate acidified with citrate. Sodium, chloride, and glucose dialysate concentration were 137 mmol/L, 107 mmol/L, and 1 g/L, respectively. The dialysate temperature was 37°C. We did not initiate heparin treatment. Blood flow was maintained at 350 mL/min and dialysate flow adapted to the blood flow according to the AutoFlow mode of the 5008 Cordiax machine (Fresenius Medical Care). NS 1.8 filters (Meditor) were used. The patient received darbepoetin alfa 100 µg per week and iron 100 mg weekly with stable hemoglobin of 12 g/dL. She received no treatment for hypertension but was given supplementary folate and vitamin B. Mean blood pressure was 125/80, without intradialytic hypotension. There was a threat of preterm birth at about 28 weeks, but evolution was favorable.

The diffusive dialysis dose was determined in each session using ionic dialysance Kt/V by online clearance monitoring. Weekly kt/v was at 12. Table 1 shows the results for the ratio of soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PIGF).

Table 1.

Soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PIGF) ratio

Weeks of gestationsFlt-1/PIGF ratio19 weeks + 4 days13.528 weeks + 2 days3.99431 weeks + 6 days9.233 weeks + 3 days2435 weeks + 4 days23

The patient was closely monitored by an obstetrician with regular ultrasounds in which normal Doppler waveforms in both maternal and fetal vessels showed that there was successful intrauterine fetus growth. She gave birth vaginally at 37 weeks + 1 day after induction of labor. Her new-born baby girl weighed 2.3 kg and was in good health. There was no need of transfer to the intensive care unit (ICU).

Discussion

Providing more frequent and longer dialysis decreases the risk of polyhydramnios, helps control hypertension, increases birth weight and gestational age, improves maternal nutrition, and increases the chances of a live birth. HDF combines convective with diffusive clearance. Therefore, HDF removes more middle-molecular-weight solutes and increases dialysis dose when compared with standard hemodialysis. HDF has been associated with better intradialytic hemodynamic stability. This technique could avoid intradialytic hypotension in pregnant women, preventing hemodynamic placenta stress in particular. For these reasons, we proposed online post-dilution HDF for 36 h a week to our patient.

There is scarce data on HDF in the literature. In 2005, Haase et al. [6] reported low convective dose HDF 6 times per week in 5 pregnant women in the ICU. Althaf et al. [7] in 2014, reported low convective volume post-dilution HDF in 2 patients with lupus nephritis, also treated in the ICU.

In 2020, Puddu and colleagues described 2 pregnant women on high-volume HDF whose pregnancies went to term and who gave birth to healthy infants [8]. In the same year, Crucelegui et al. [9] described a 32-year-old hemodialysis-dependent woman on pre-dilutional HDF who had a successful pregnancy and delivered a healthy new-born baby.

In a citrate-containing dialysis fluid, the free calcium ions form a calcium-citrate complex, which is responsible for an anticoagulant effect. In the literature, this dialysate has been used to avoid an anticoagulant dose in only one case (a pregnant patient who presented with metrorrhagia and a small placental hematoma). Reducing coagulation during dialysis is important to improve dialysis efficiency. Thus, citrate dialysate is associated with increased solute removal [10] and this is of particular interest in pregnant women. The reduction of the clotting cascade also decreases the inflammatory proteins which may be partly responsible for a dialysis-induced inflammatory response. The reduction of inflammation and oxidative stress could be beneficial for pregnant patients. In our case, we used dialysate acidified with citrate to increase dialysis dose. We used a dialysate potassium of 3 mEq/L to avoid hypokalemia. Tolerance was excellent.

It is also known that citric acid leads to changes in ionized calcium level during the hemodialysis session, with an increased risk of hypocalcemia. The calcium concentration in the dialysis fluid in our patient was increased by 1.5 mmol/L to achieve normal calcium homeostasis between mother and fetus. We closely monitored the calcium level, and no hypocalcemia was observed. Thomas and team found that normal fetal and neonatal calcium homeostasis is dependent upon an adequate supply of calcium from maternal sources. Both maternal hypercalcemia and hypocalcemia can cause metabolic bone disorders of calcium homeostasis in neonates.

The magnesium concentration in the dialysis fluid was 0.5 mmol/L. We carefully monitored magnesium levels, which remained stable.

Citrate is an indirect buffer base that must be converted to bicarbonate in the liver and muscle cells. By means of the so-called citric acid cycle, 3 bicarbonate ions are formed from 1 citrate ion. Citrate appears to prevent post-dialytic overcorrection of bicarbonate, without disturbing the status of the pre-dialysis acid base, which was the case in our patient.

Increased levels of sFlt-1 and reduced levels of PIGF predict the subsequent development of preeclampsia [11]. In our patient, the ratio sFlt-1/PIGF remained normal and encouraged us to continue the pregnancy. Four case reports have studied the sFlt-1/PIGF ratio in pregnant woman on dialysis who developed severe hypertension [1215]. Further evaluation is needed to identify the role of antiangiogenic factors in hemodialysis-dependent pregnant patients.

Conclusion

This case confirms the safety and efficacy of high-volume online post-dilution HDF with a dialysate acidified with citrate in pregnancy. To ensure that overall fetal survival in hemodialysis patients becomes comparable to fetal prognosis in the transplanted population, more case reports and a registry are required to confirm that high-volume post-dilution HDF with a citrate dialysate acidification should become the preferred hemodialysis method in pregnancy. It is now time to have clear and specific recommendations for pregnant patients on dialysis.

Statement of Ethics

Ethical approval is not required for this case report in accordance with our national guidelines. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

The authors received no financial support for the research, authorship, and/or publication of this article.

Author Contributions

G. Pelle, P. Rieu, J. Attias, and S. Fay participated in the clinical care of the patient. G. Pelle, A. Jalal Eddine, and A. Hertig analyzed the patient data and wrote the manuscript. G. Pelle, A. Jalal Eddine, P. Rieu, J. Attias, S. Fay, and A. Hertig read and approved the final manuscript.

Data Availability Statement

The data that support the findings of this case report are included in this article. Further inquiries can be directed to the corresponding author.

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