Minor negative effects of calcineurin inhibitor based immunosuppression on pregnancy outcomes after renal transplantation in the Netherlands

L.M. Koenjer, J.R. Meinderts, A.T. Lely, M.F.C. de Jong, O.W.H. van der Heijden, R.G. van der Molen, H.W. van Hamersvelt

Thursday 5 march 2020

14:20 - 14:30h at Leo Franssen zaal

Parallel session: Parallel sessie XIV– Klinische abstracts

Background: Pregnancies after renal transplantation have been more frequent over the past years, also in patients with a compromised renal function. Immunosuppression may influence pregnancy outcome. It is not yet clear whether replacing a calcineurin inhibitor (CNI) by azathioprine favourably influences pregnancy outcomes of mother or child. We therefore compared maternal and fetal outcomes of pregnancies after renal trans­plant using CNI-based or CNI-free immunosuppression.

Methods: We retrospectively analyzed pregnancy outcomes in women with a renal transplant in the Netherlands between 1986 and 2017 by checking their medical records. Patients were divided in two groups based on the use of a CNI during the first trimester of pregnancy. For statistical analyses we used one-sample T, Mann-Whitney-U and Chi-square tests.

Results: We identified 254 pregnancies in 177 renal transplant recipients: 129 with CNI during pregnancy (CNI+) and 125 without CNI (CNI-). Demographic statistics did not differ between the two groups except for higher BMI in CNI+ (25.3 vs 23.7, P=0.01) and year of renal transplant (median 2000 for CNI+ vs 1989 for CNI-, P<0.01). Preconceptionally, in the 1^st and 2^nd trimester of pregnancy creatinin levels were slightly, but not significantly higher in CNI+. In the 3^rd trimester creatinin levels were significantly higher in CNI+ (127 vs 105, P<0.01). The percentual increase in creatinin from preconceptional to the 3^rd trimester level was also higher in CNI+ (+3.1% vs -2.2%, P=0,05). In both CNI+ and CNI- groups, a postpartum 11-12% increase of creatinin from preconceptional level was observed, which was comparable in CNI+ and CNI- groups (p=0,92). Regarding fetal outcomes, in CNI+ more children were born with birth weight less then 2500 gr (27% vs 19%, p=0,07). Other obstetric and fetal outcomes were comparable in both groups.

Conclusions: Our data indicate that CNI do not negatively influence the course of renal function on the long term after pregnancy in renal transplant patients, but only temporarely cause a higher increase in serum creatinin levels towards the end of pregnancy. These results suggest that it is not necessary to replace CNI by azathioprine in renal transplant recipients to preserve renal function. However, the multidisciplinary team taking care of these high risk pregnancies needs to be aware of the lower birth weights observed in neonates born to women using a CNI. Our data do not allow to draw conclusions on possible long term effects of CNI on overall health outcome, renal function or hypertension in the children. This will be subject of future studies.