In this retrospective single-center study, we included women with post-transplant pregnancies that started between 2003 and 2019 and who were regularly followed up in our transplant center at the Charité. Patients had received a kidney donation after brain death or a living donor kidney transplantation, except three of the women with a combined pancreas–kidney transplantation. Pregnancies were confirmed with a positive screening test and/or a positive serum ßHCG. All pregnancies resulting in birth, stillbirth, or miscarriages were included. From 63 identified pregnancies, 17 were excluded due to missing data or a lack of sufficient follow-up. Of note, data from 17 kidney transplant recipients (KTR) were published previously by Bachmann et al. [19 (link)]. However, detailed risk factors for adverse pregnancy and allograft outcomes and correlation to fetal sonographic findings were not analyzed previously, which is why we included data from these patients in the present study. Immunosuppression was modified in the case of a planned pregnancy: mycophenolic acid (MPA) was replaced with steroids or azathioprine, respectively. In the case of an unplanned pregnancy, the immunosuppressive regimen was modified immediately after confirmation of pregnancy.
We selected the following primary endpoints regarding maternal, fetal, and allograft outcome: first, the occurrence of an adverse pregnancy event (APE), defined as severe features of preeclampsia such as severe hypertension (>160/110 mmHg) and/or specific signs or symptoms of significant end-organ dysfunction, namely acute kidney injury (AKIN) level II or III, changes in laboratory parameters such as thrombocytopenia, hemolytic anemia, or organ dysfunction without alternative explainable reasons; and second, abortion ≥ 12 weeks, stillbirth, early preterm delivery ≤ 32 weeks of gestation, intrauterine growth restriction (IUGR), defined as early placental insufficiency with intrauterine growth retardation (growth <10th percentile and pathologic doppler-ultrasound of umbilical or uterine arteries). Second, we selected the allograft’s outcome as another primary endpoint, namely the occurrence of kidney failure defined as renal graft loss, or deterioration of estimated glomerular filtration rate (eGFR) ≥ 5 mL/min at 24 months follow-up after the end of pregnancy compared to the mean pre-pregnancy eGFR. If available, sFlt-1 and PlGF were assessed during the second and third trimesters of pregnancy and analyzed as the sFlt-1/PlGF-ratio. In the case of repeated measurements, the highest value of each trimester was taken into account.
The following factors were analyzed for risk associated with adverse maternal, fetal, or renal outcomes: time from transplantation, patient age, donor age, type of donation, systolic and diastolic blood pressure, pre-existing diabetes mellitus, immunosuppressive regimen, donor-specific antibody (DSA) positivity, amount of proteinuria, eGFR slope up to 24 months before, at the time of the start of and during pregnancy. Proteinuria was expressed as mg/g creatinine when available (otherwise set equal to mg per day for previous measurements). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was used to calculate the eGFR rates. The time interval from transplantation to pregnancy was set to the estimated date of conception, and in the case of several pregnancies, it was calculated separately for each pregnancy. Gestational age was calculated in weeks starting from the first day of the last menstrual period. In the presence of the first-trimester ultrasound, gestational age was calculated according to crown length. In the case of routine screening appointments at our center, fetal sonography was performed at least once every trimester of pregnancy. An experienced physician investigated patients with standardized ultrasound procedures. Mean pre-pregnancy eGFR was determined using the mean of at least two eGFR measures prior to conception (around −6, −12 months, and around the first day of the last menstrual period). The transplant outcome was followed until 31 December 2021. For data collection, our web-based electronic patient database “TBase” [20 (link)] and clinical charts yielding complete data sets were used. Neonatal outcome was assessed including birth weight, height, and gestational age.
We selected the following primary endpoints regarding maternal, fetal, and allograft outcome: first, the occurrence of an adverse pregnancy event (APE), defined as severe features of preeclampsia such as severe hypertension (>160/110 mmHg) and/or specific signs or symptoms of significant end-organ dysfunction, namely acute kidney injury (AKIN) level II or III, changes in laboratory parameters such as thrombocytopenia, hemolytic anemia, or organ dysfunction without alternative explainable reasons; and second, abortion ≥ 12 weeks, stillbirth, early preterm delivery ≤ 32 weeks of gestation, intrauterine growth restriction (IUGR), defined as early placental insufficiency with intrauterine growth retardation (growth <10th percentile and pathologic doppler-ultrasound of umbilical or uterine arteries). Second, we selected the allograft’s outcome as another primary endpoint, namely the occurrence of kidney failure defined as renal graft loss, or deterioration of estimated glomerular filtration rate (eGFR) ≥ 5 mL/min at 24 months follow-up after the end of pregnancy compared to the mean pre-pregnancy eGFR. If available, sFlt-1 and PlGF were assessed during the second and third trimesters of pregnancy and analyzed as the sFlt-1/PlGF-ratio. In the case of repeated measurements, the highest value of each trimester was taken into account.
The following factors were analyzed for risk associated with adverse maternal, fetal, or renal outcomes: time from transplantation, patient age, donor age, type of donation, systolic and diastolic blood pressure, pre-existing diabetes mellitus, immunosuppressive regimen, donor-specific antibody (DSA) positivity, amount of proteinuria, eGFR slope up to 24 months before, at the time of the start of and during pregnancy. Proteinuria was expressed as mg/g creatinine when available (otherwise set equal to mg per day for previous measurements). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was used to calculate the eGFR rates. The time interval from transplantation to pregnancy was set to the estimated date of conception, and in the case of several pregnancies, it was calculated separately for each pregnancy. Gestational age was calculated in weeks starting from the first day of the last menstrual period. In the presence of the first-trimester ultrasound, gestational age was calculated according to crown length. In the case of routine screening appointments at our center, fetal sonography was performed at least once every trimester of pregnancy. An experienced physician investigated patients with standardized ultrasound procedures. Mean pre-pregnancy eGFR was determined using the mean of at least two eGFR measures prior to conception (around −6, −12 months, and around the first day of the last menstrual period). The transplant outcome was followed until 31 December 2021. For data collection, our web-based electronic patient database “TBase” [20 (link)] and clinical charts yielding complete data sets were used. Neonatal outcome was assessed including birth weight, height, and gestational age.
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