Successful pregnancy in a hemodialysis patient with primary hyperoxaluria type 1.

Abstract

Dear Editor Better dialysis technique has contributed to improved outcomes of pregnancies in hemodialysis patients. However, conception rates are still limited and pregnancies are associated with a high risk of complications. Primary hyperoxalurias (PH) are a group of rare diseases caused by a genetic abnormality that results in excessive oxalate production. The most severe form, PH1, is caused by a mutation in alanine-glyoxylate aminotransferase gene which leads to progression to end-stage kidney disease by age of 60 years in 88% of patients [1, 2]. We present a case of a 25-year-old woman with chronic kidney disease secondary to PH1, diagnosed at the age of three when she presented with nephrolithiasis. The genetic analysis detected two mutations in the homozygous state in an AGTX gene: AGTX NM_000030.3:c.33dupC, p.(Lys12FInfs*156). Her parents were not blood relatives. She underwent multiple lithotripsies for the treatment of nephrolithiasis but was not in regular follow-ups due to noncompliance. In March 2020, she presented at the Emergency Department Unit in the terminal stage of kidney failure with the need for hemodialysis. The chronic hemodialysis protocol included four sessions weekly lasting for 4.5 h. Her menstrual cycles were irregular. On September 13, 2022, she reported amenorrhea. A gynecological workup revealed that she was approximately 24 weeks pregnant. She did not undergo genetic counseling before conception nor received any new medications. The hemodialysis program was intensified to five sessions per week, increasing dialysis time to 5 h. A Theranova 400 membrane (Baxter) was used and a dialysate bath was adjusted depending on laboratory results. Nadroparin was administered as an anticoagulant agent at a dose of 0.4 mL per session. She received paricalcitol, vitamin B6 3 50 mg, folic acid, pantoprazole 20 mg, and an oral nutritional supplement. Predialysis urea levels were maintained below 12.5 mmol/L. We also aimed to maintain normal calcium levels and hemoglobin concentration at approximately 110 g/L. Her dry weight was increased by 500 mg every 7 days corresponding to an increase in weight during normal pregnancies. The patient was hospitalized at 37 weeks of gestation and gave birth to a healthy 2450-g male baby 2 days later by Cesarean section. The postpartum course was uneventful. Her regular hemodialysis has been continued four times weekly. She is waiting for simultaneous liver–kidney transplantation and the approval of the use of lumasiran, with the skin ulcer on her leg indicating systemic oxalosis. Current treatment options for PH1 are limited. Simultaneous liver–kidney transplantation is used for patients with end-stage kidney failure [2]. Lumasiran is a novel liver-directed RNA interference therapeutic agent. It reduces hepatic oxalate production and increases concentrations of glycolate in patients with PH1, by degrading the messenger RNA that encodes glycolate oxidase, an enzyme upstream of alanineglyoxylate aminotransferase [3]. However, the treatment is extremely expensive and is not available in many countries. In the literature, pregnancies in PH patients are mostly presented in case reports. According to the largest series, 75% of pregnancies were carried to term with a live birth rate of 82.5% [4]. In conclusion, we report the first case of pregnancy in a hemodialysis patient with PH1. Intensive dialysis and meticulous follow-up enable a successful outcome of the pregnancy. It remains to wait for the results of lumasiran treatment which may further improve the outcomes of patients with PH1. However, the safety of lumasiran has not been tested in pregnant women. The patient has provided informed consent for the publication of the case.