Comparison of pregnancy outcomes in Dutch kidney recipients with and without calcineurin inhibitor exposure: a retrospective study

Abstract

Within pregnancies occurring between 1986 and 2017 in Dutch kidney transplant recipients (KTR), we retrospectively compared short-term maternal and foetal outcomes between patients on calcineurin inhibitor (CNI) based (CNI+) and CNI-free immunosuppression (CNIÀ). We identified 129 CNI+ and 125 CNIÀ pregnancies in 177 KTR. Demographics differed with CNI+ having higher body mass index (P = 0.045), shorter transplant-pregnancy interval (P < 0.01), later year of transplantation and -pregnancy (P < 0.01). Serum creatinine levels were numerically higher in CNI+ in all study phases, but only reached statistical significance in third trimester (127 vs. 105 µM; P < 0.01), where the percentual changes from preconceptional level also differed (+3.1% vs. À2.2% in CNIÀ; P = 0.05). Postpartum both groups showed 11-12% serum creatinine rise from preconceptional level. Incidence of low birth weight (LBW) tended to be higher in CNI+ (52% vs. 46%; P = 0.07). Both groups showed equal high rates of preterm delivery. Using CNIs during pregnancy lead to a rise in creatinine in the third trimester but does not negatively influence the course of graft function in the first year postpartum or direct foetal outcomes. High rates of preterm delivery and LBW in KTR, irrespective of CNI use, classify all pregnancies as high risk.

A nationwide Dutch cohort study shows relatively good pregnancy outcomes after kidney transplantation and finds risk factors for adverse outcomes

“…The PARTOUT network investigated pregnancy outcomes stratified per use of CNIs earlier. 37 Therefore, we provide only an overview of baseline characteristics and outcomes of CNI use and a compact prediction analysis. Likewise, the influence of pregnancy on graft loss was earlier investigated and therefore only concisely investigated in this study.…”

“…Although the intuitive relationship between adverse pregnancy outcomes and graft loss can be seen, it does not prove to be a predictor for graft loss on its own. Koenjer et al 37 investigated the influence of CNIs on pregnancy outcomes and found no significant adverse outcomes. However, there is a time effect leading to bias because of the introduction of CNIs only in the 1990s and mostly women with good kidney function getting pregnant at that time.…”

Parenthood With Kidney Failure: Answering Questions Patients Ask About Pregnancy

“…97 Calcineurin inhibitor toxicity maybe confused with pre-eclampsia as both cause graft dysfunction, thrombotic microangiopathy, and hypertension. 79,98 Tacrolimus levels are difficult to interpret in pregnancy because of the change in the free versus bound tacrolimus ratio. 99 Whole blood tacrolimus levels fall in the second trimester.…”

“…79 Clinicians may escalate dosing in response, leading to third trimester blood pressure and creatinine creep which may be diagnosed as preeclampsia and precipitate early delivery, although high preterm delivery rates have been observed irrespective of calcineurin inhibitor use. 98 Finally, clinician reluctance to progress with pregnancy in later gestation (where risks of continuing pregnancy outweigh risks of early delivery) may drive preterm birth. Regardless, women and clinicians should anticipate possible preterm delivery and undertake shared decision-making about timing of delivery.…”

“…Temporary or permanent graft dysfunction is dependent on preconception graft function. 69,78,79,98,115 Even in women with "good" graft function (serum creatinine <110 mmol/l), a proportion of women have decline in function antenatally and postpartum "stageshift," 69,79 ; however, further studies have not linked this GFR drop to excessive graft failure. 116 Late cessation of mycophenolic acid derivatives (<6 weeks prepregnancy) has been associated with increased risk of graft loss at 5 years, 117 possibly reflecting unplanned pregnancy.…”