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

Although numbers of pregnancy after kidney transplantation (KT) are rising, high risks of adverse pregnancy outcomes (APO) remain. Though important for pre-conception counselling and pregnancy monitoring, analyses of pregnancy outcomes after KT per pre-pregnancy estimated glomerular filtration rate-chronic kidney disease (eGFR-CKD)-categories have not been performed on a large scale before. To do this, we conducted a Dutch nationwide cohort study of consecutive singleton pregnancies over 20 weeks of gestation after KT. Outcomes were analyzed per pre-pregnancy eGFR-CKD category and a composite APO (cAPO) was established including birth weight under 2500 gram, preterm birth under 37 weeks, third trimester severe hypertension (systolic blood pressure over 160 and/or diastolic blood pressure over 110 mm Hg) and/or over 15% increase in serum creatinine during pregnancy. Risk factors for cAPO were analyzed in a multilevel model after multiple imputation of missing predictor values. In total, 288 pregnancies in 192 women were included. Total live birth was 93%, mean gestational age 35.6 weeks and mean birth weight 2383 gram. Independent risk factors for cAPO were pre-pregnancy eGFR, midterm percentage serum creatinine dip and midterm mean arterial pressure dip; odds ratio 0.98 (95% confidence interval 0.96–0.99), 0.95 (0.93-0.98) and 0.94 (0.90-0.98), respectively. The cAPO was a risk indicator for graft loss (hazard ratio 2.55, 1.09-5.96) but no significant risk factor on its own when considering pre-pregnancy eGFR (2.18, 0.92-5.13). This was the largest and most comprehensive study of pregnancy outcomes after KT, including pregnancies in women with poor kidney function, to facilitate individualized pre-pregnancy counselling based on pre-pregnancy graft function. Overall obstetric outcomes are good. The risk of adverse outcomes is mainly dependent on pre-pregnancy graft function and hemodynamic adaptation to pregnancy

Effect of Pregnancy on eGFR after Kidney Transplantation:A National Cohort Study

BACKGROUND: The effect of pregnancy on the course of estimated glomerular filtration rate (eGFR) is unknown in kidney transplant recipients (KTRs). METHODS: We conducted a nationwide multicenter cohort study in KTRs with pregnancy (>20 weeks) after kidney transplantation (KT). Annual eGFR's after KT until death or graft loss and additional eGFR's before each pregnancy were collected according to protocol. Changes in eGFR slope before and after each pregnancy were analyzed by generalized estimating equations (GEE) multilevel analysis adjusted for transplant vintage. RESULTS: We included 3194 eGFR measurements before and after pregnancy in 109 (55%) KTRs with 1, 78 (40%) with 2 and 10 (5%) with 3 pregnancies after KT. Median follow-up after first delivery post-KT was 14 years (IQR 18 years). Adjusted mean eGFR pre-pregnancy was 59 ml/min/1.73m2 (SEM 1.72; 95% CI 56-63), after first pregnancy 56 ml/min/1.73m2 (SEM 1.70; 95% CI 53-60), after second pregnancy 56 ml/min/1.73m2 (SEM 2.19; 95% CI 51-60) and after third pregnancy 55 ml/min/1.73m2 (SEM 8.63; 95% CI 38-72). Overall eGFR slope after first, second and third pregnancy was not significantly worse than pre-pregnancy (p = 0.28). However, adjusted mean eGFR after first pregnancy was 2.8 ml/min/1.73m (p = 0.08) lower than pre-pregnancy. CONCLUSIONS: First pregnancy has a small, but no significant, effect on eGFR slope in KTR. Midterm hyperfiltration, a marker for renal reserve capacity, was associated with better eGFR and death-censored graft survival. In this KTR cohort with long-term follow-up, no significant effect of pregnancy on kidney function was detected

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

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 (CNI-). We identified 129 CNI+ and 125 CNI- 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 mu m; P < 0.01), where the percentual changes from preconceptional level also differed (+3.1% vs. -2.2% in CNI-; 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