Pancreas Transplantation

The core data structure of the STCS is the patient-case system, a framework that reflects the post-transplant patient process involving a multitude of information on patients and allografts, including function and interventions from transplantation until end of follow-up (Fig. 1).Fig. 1

Organization of the Swiss Transplant Cohort Study patient-case system based on a hypothetical complex transplantation scenario

The STCS patient-case system allows distinguishing data that accrue in relation to the patient from data related to the transplanted organ(s). We therefore define a “case” as any SOT of a given patient. A patient may have one or several cases, and one case can involve one, or more than one allograft. Each case nested within a patient has its own time axis and follow-up (“case clock”, Fig. 1).
Patient-data captures information which is of systemic nature and that relates to the patient, but not to the transplant itself. In contrast case-data captures information restricted to the allograft(s). The first case is the transplant event that leads to enrolment in our study. Later cases are termed re-transplants or second transplants. A re-transplant is a repetition of the same SOT after failure of the previous transplant; e.g. a kidney re-transplanted after loss of function of the previous kidney allograft. A second transplant refers to a subsequent transplantation of a different type of allograft; e.g. a pancreas transplantation following a successfully implanted kidney allograft. Each instance can either be a single or a double transplantation. Double transplantation refers to concomitant transplantation of two organs originating from the same donor.
Thus three classification layers can be distinguished: (1) the patient; (2) the SOT (classified into single or double/complex SOT and into first, second- or re-transplantation); (3) the implanted organ. E.g. both allografts of a kidney-pancreas double transplantation are treated as separate instances. Patients are usually classified by their first STCS (enrolment) transplantation.
Our patient-case system assigns unique patient and case identification numbers. Linkage of patient and case data allows reconstructing the transplantation process (Figs. 1 and 2) with longitudinal updating of both patient and case information, as well as capture of intermediate events. Donor-recipient linkage is ensured via the unique Swiss organ allocation number (SOAS-ID), which is generated within the national Swiss Organ Allocation System (SOAS) and is transferred to the STCS. Donor data specification is detailed in the Appendix (in ESM).Fig. 2

Overall patient survival by first transplantation in the Swiss Transplant Cohort Study (1.5.2008 until 30.09.2011)

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.

Forty transplant recipients who received a single, double or combined kidney–pancreas or kidney–liver transplants between 2019 and 2021 at the Kidney–Pancreas Transplant Unit of Padova University Hospital were enrolled. The patients were randomized to receive either Ultramag^® or Mag2^®.
All the study participants were followed at the Kidney–Pancreas Transplant Ambulatory Unit of Padova University Hospital. Treatment was started with very low levels of serum Mg (HypoMg is defined below 0.7 mmol/L or 1.7 mg/dL), developed within 6 months/1 year from transplantation. Patients’ tacrolimus trough levels were the same for both groups (between 6.5 and 8 μg/L). In total, 27 out of 40 patients were supplemented with 1 sachet of Ultramag^® (375 mg of Mg element)/day, while 16 were treated with 3 vials of Mag2^® (370 mg of Mg element/day) (Table 1). Three patients of the Mag2^® arm dropped out due to side effects after 1 month (diarrhea). Adult subjects (>18 years) of either gender were eligible. Other inclusion criteria were that patients must have undergone a single, double or combined kidney–pancreas or kidney–liver transplant between 2019 and 2021, and maintenance immunosuppressive therapy that consisted of CNI, mycophenolate/mTOR inhibitor and steroid, or CNI plus steroid-only treatment.
Patients were excluded if they had a history of intestinal resection, inflammatory disease of the gastrointestinal tract, malabsorption, presence of other drugs potentially affecting Mg reabsorption, such as diuretics, or genetic and familiar HypoMg.

This retrospective study included 2,330 patients who received kidney transplantation at Asan Medical Center between March 2009 and February 2017. Of these, 59 patients were diagnosed with PCP. Nine patients were excluded; eight underwent simultaneous pancreas-kidney transplantation, and one was under the age of 16. As a result, 50 patients were included for analysis (Fig. 1). Later, we retrospectively reviewed medical records and radiographs of the patients. Collected patient information included demographics, PCP prophylaxis, kidney donation type, operation type (living vs. deceased), acute rejection, and time from symptom onset to hospital admission. Clinical data such as laboratory results were also collected, including white blood cell count and total lymphocyte count (TLC), and the presence of combined infection, such as BK virus and CMV. The institutional review board of Asan Medical Center approved the conduction of this study (no.2020 − 0737).
Fig. 1

Patients enrolled in this study