Several factors contribute to the development of gestational hypertension and diabetes in KT recipients, including immunosuppressive medications (calcineurin phosphatase inhibitors and corticosteroids), allograft function, donor type, obesity, alcohol, smoking, and elevated renin levels [7]. In this study, the incidence of postoperative gestational hypertension, pre-eclampsia, and GDM in the KT group was significantly higher at 33.7%, 25%, and 21.2%, respectively, compared to 3.3%, 2.5%, and 17.5% in the non-KT group. These rates are also considerably higher than those in the general Chinese maternity population, where the incidence rates are 5%, 4.6%, and 8.8%, respectively [8, 9]. This highlights the increased risk of hypertension-related disorders in pregnancies of renal transplant recipients.
International comparisons reveal similar trends. A study in the United Kingdom [10] reported a 24% incidence of pre-eclampsia in KT recipients compared to 4% in controls, whereas a US meta-analysis showed pre-eclampsia in 27% and a GDM prevalence in 8% of KT pregnancies, compared to 4% for both conditions in the general population [11]. The higher prevalence of GDM in our study, compared to other countries, may be influenced by regional dietary habits in the Yangtze River Delta region of China, where sweet diets are common.
The study found no significant statistical difference in Scr and eGFR across the three time periods—pre-pregnancy, prenatal, and postpartum. Most patients’ renal function returned to normal within 6 months postpartum, though five patients experienced graft failure 2 years postpartum. These patients had significant pre-existing renal insufficiency before pregnancy, suggesting that although pregnancy generally does not significantly impact patients with good renal transplant function, it does adversely affect recipients with severe pre-existing renal insufficiency owing to the increased physiological demands during pregnancy.
A comparison with a similar study by Shah S et al. [3] showed that long-term renal function and graft survival in KT patients rates were similar between pregnant and non-pregnant groups, supporting the notion that pregnancy does not have long-term adverse effects on the transplanted kidney or patient survival. However, this study’s findings differ for recipients with significantly impaired renal function before pregnancy. Given the retrospective nature of this study, further research is needed to assess the long-term effects of pregnancy on the transplanted kidney.
Immunosuppressive drug regimens are usually tailored to individual needs and transplant center protocols, making it challenging to assess the drug variability. However, close monitoring of drug concentrations is essential. In this study, FK506 doses were increased during pregnancy and decreased after delivery to maintain therapeutic levels, reflecting the physiological changes in pregnant women. The unbound concentration of FK506 nearly doubled during pregnancy and postpartum period compared to the pre-pregnancy period [12]. Renal blood flow increases by approximately 35% and eGFR by 50% during late pregnancy, elevating drug clearance [13]. The mean oral apparent clearance (CL/F) of FK506 can reach (47.4 ± 12.6) L/h during the second and third trimesters, 39% higher than in the postpartum period [14]. Maintaining appropriate drug levels is crucial, emphasizing the need for dynamic dose adjustments based on perinatal monitoring. It has been suggested that the dose of FK506 should be increased to 25% of the pre-pregnancy dose to maintain effective therapeutic concentrations but it should be rapidly decreased after delivery to ensure patient blood levels [15]. Therefore, KT patients need to closely monitor perinatal blood concentration changes and dynamically adjust the dosage according to the monitoring results in order to maintain the blood concentration.
Although fertility is typically restored after KT, pregnancy and live birth rates remain significantly lower than in the general population [16, 17]. China’s 2020 Statistical Bulletin of Health Care Development [18] reports a national live birth rate of 99.46%, whereas a Canadian study [19] of 30,078 female KT recipients reported a live birth rate of 55%. In this study, the live birth rate was 85%, higher than in foreign studies but lower than in the general population. However, the preterm birth rate was 80%, markedly exceeding China’s overall preterm birth rate of 7.3% [20].
Compared with other studies in China, a 7-year single-center study [21] in Sichuan Province reported a neonatal preterm birth rate of 75% and a 4% induced abortion rate, similar to our findings of 80% and 3.8%, respectively. Internationally, a British study found a 52% preterm delivery rate in KT recipients compared to 8% in the general population [22]. In Poland, a 31-year study [2] reported a 10% spontaneous abortion rate and a 6.5% intrauterine death rate, compared to 4.8% and 1.9% in our study. The higher preterm delivery rate in this study may be owing to the common practice of cesarean sections in KT recipients to reduce risks to the transplanted kidney, although this approach often results in premature births and poor neonatal outcomes. Although the pelvic-transplanted kidneys of most patients do not obstruct the birth canal [23], medical staff often choose cesarean section over vaginal delivery to better control the risks to both mothers and infants. Additionally, the COVID-19 pandemic’s impact on healthcare access may have exacerbated these challenges [24].
The optimal time for conception after kidney transplantation remains debated. The American Society of Transplantation (AST) [25] recommends 1—2 years post-transplantation, whereas European guidelines suggest a delay of 2 years [23]. Early conception increases the risk of pre-eclampsia and preterm labor, whereas delaying conception leads to advanced maternal age, raising the risk of miscarriage and missed reproductive opportunities [2]. A study by Rose [26] that included 729 KT recipients indicated an increased risk of transplant failure within the first 3 years post-transplantation, suggesting that young recipients should delay conception. Similarly, Gonzalez et al. [27] found that the lowest live birth rate and the highest neonatal mortality rate occurred in pregnancies conceived within 2–3 years post-KT. In this study, the mean interval between renal transplantation and pregnancy was 4 years, with a mean maternal age of 31 years and a live birth rate of 85%. However, determining the optimal time for conception is challenging owing to the limitations of the study’s retrospective design, the small sample size, and the potential reporting bias from voluntary registry data. It is usually recommended that women wait at least 1 year after a living-related donor transplant and at least 2 years after a deceased donor transplant before attempting pregnancy. This waiting period helps reduce the risk of immunotherapy-induced complications and rejection. Additionally, the transplanted kidney should have a stable function with a blood creatinine level below 1.5 mg/dL and a urinary protein excretion rate under 500 mg/d [11].
This study has some limitations. First, the retrospective study only included renal transplant recipients from pregnancy to delivery without tracking neonatal growth and development. Second, the study’s small, regionally limited sample size may not be representative, necessitating larger, multicenter studies.
In conclusion, although pregnancy in renal transplant recipients is considered high-risk, the overall risk remains manageable. It is recommended to enhance the management of renal transplant patients with reproductive intent, monitor relevant indicators throughout the pregnancy in real-time, intervene early when necessary, and recommend appropriate intervals for post-transplantation pregnancy to improve maternal and infant outcomes. With the advancement of the “Internet + healthcare” model in China and the era of medical big data, future studies we plan to establish a real-time communication and intervention management platform for pregnant post-KT recipients, aiming to improve disease management and maternal and infant outcomes.