LAUSR

A 33-year-old female received a living-related kidney transplant from her mother following haemodialysis for one year due to chronic renal failure owing to a congenital dysplastic kidney disease at the age of 13 years. The maintenance immunosuppressive therapy included cyclosporine (target trough level: 30–50 ng/ml), mycophenolate mofetil (1000mg daily), and prednisone (2mg daily). Her postoperative course was good, with no evidence of acute rejection. Her serum creatinine level and estimated glomerular filtration rate (eGFR) level was 2.1 ±0.3mg/dl and 25 ±4mL/min/1.73 m, respectively, 20 years after the transplantation. Her blood pressure was 112 ±11/64 ±8mm Hg and proteinuria was not detected. Although the pregnancy for this patient was challenging according to the literature (Hou 2013), she wished to bear children when she was 33 years old. Mycophenolate mofetil was replaced with azathioprine (50mg daily); her renal function was stable after this adjustment. The haemoglobin level at 20 years after transplantation was 8.8 ±0.6 g/ dl. Darbepoetin alfa was administered subcutaneously every four weeks for two years. Then, the patient conceived naturally and darbepoetin alfa was temporarily discontinued, because of the lacking evidence on its safety during the period of organogenesis. Ultrasound examination showed the presence of a dichorionic diamniotic twin pregnancy. The patient’s haemoglobin level dropped to 6.4 g/dl in the 14th week of gestation, and she received a transfusion (Figure 1(A)). In the 18th week of gestation, albeit a gradual decrease in haemoglobin level the patient refused to receive transfusion to avoid the risk of transmitted viral infections. Thus, biweekly darbepoetin alfa treatment at 30lg was resumed. Her blood pressure was within normal limits (122 ±10/72 ±7mm Hg) during this time (Figure 1(B)). In the 25th week of gestation, emergency hospitalisation was required with a diagnosis of threatened premature delivery. Ritodrine hydrochloride treatment was introduced immediately at admission. Because her haemoglobin level dropped to less than 8 g/dl, the dose of darbepoetin alfa was increased to 60 lg (Figure 1(C)); no hypertensive effects were observed after dose escalation (Figure 1(D)). However, anaemia developed in the 30th week of gestation despite the increased dose of darbepoetin alfa, and she received two units of transfusion. Following transfusion, her haemoglobin level was stable at 8 ±0.9 g/dl with darbepoetin alfa. On day 5 of the 33rd week of gestation, her serum creatinine level increased to 3.45mg/dl. We assumed that the acute impairment of the kidney function was due to the compression by the uterus. The patient underwent a caesarean section to deliver twins who weighed 1095 and 1859 g. The ultrasound examinations in the prenatal period revealed that one of the twins had a unilateral multicystic dysplasia of the kidney and the other had no obvious anomalies. However, both newborns had a mutation in HNF1B gene, one of the major causes of congenital anomalies of the kidney and urinary tract (CAKUT). Therefore, the cause of unilateral multicystic dysplasia of the kidney in one twin was probably related, not to a darbepoetin-induced side effect but to a gene mutation for CAKUT. The haemoglobin level of the patient on the day of the delivery was 8.1 g/dl. The haemoglobin levels of the twins were 12.6 and 13.4 g/dl, without the evidence of polycythaemia. After delivery, the mother’s serum creatinine level immediately decreased to below 2.5mg/dl, and her haemoglobin level increased to 10 ±0.4 g/dl without the use of darbepoetin alfa (Figure 1(C)). The twins have grown up to four years old with the height and weight within -1 SD according to the growth chart for Japanese children. The creatinine-eGFR and cystatineGFR levels in the one with unilateral multicystic dysplasia of the kidney were 43.13mL/min/1.73 m and 46.99mL/min/ 1.73 m, and those in the other were 70.16mL/min/1.73 m and 68.19mL/min/1.73 m, respectively.