Renal Allograft Function and Cardiovascular Risk in Recipients of Kidney Transplantation After Successful Pregnancy

doi:10.1016/j.transproceed.2009.06.042

Transplantation Proceedings

Volume 41, Issue 6, July–August 2009, Pages 2399-2402

https://doi.org/10.1016/j.transproceed.2009.06.042 Get rights and content

Abstract

Successful pregnancy is one of the better indicators of quality of life for women who are of child-bearing age with restored fertility after kidney transplantation. Our objective was to evaluate whether pregnancy represented a risk factor for worsening of renal function or for cardiovascular disease among renal transplant recipients. From 1976 to 2007, we followed 30 successful pregnancies in 27 renal recipients in our hospital; three women had two twin gestations. We compared this population with 27 women with renal transplants who were not pregnant. They were of similar ages at transplantation (pregnant 31.1 ± 5.4 years vs not pregnant 31.3 ± 5.4 years, P = NS) and similar evolution time between kidney transplantation and pregnancy (51.5 ± 36 months vs 47.2 ± 41 months respective; P = NS). There were no acute rejection episodes or graft losses. Renal function measured by serum creatinine and MDRD4 at the end of pregnancy was lower among the pregnant compared with the control group: mainly, 1.1 ± 0.2 mg/dL versus 0.9 ± 0.2 mg/dL (P = .05), and 66 ± 20 mL/min/1.73 m² versus 80 ± 26 mL/min/1.73 m² (P = .03). At 1 and 10 years, renal function was similar among the groups. Ten pregnant women developed preeclampsia (37%) and three, gestational diabetes mellitus (11%). There was one major cardiovascular event (4%; acute myocardial infarction) among the pregnant group, whereas there were two in the control group (7.4%; stroke and severe hypertensive retinopathy). One death occurred in each group secondary to cardiovascular complications. Our results showed that successful pregnancy after renal transplantation did not represent a long-term risk factor to worsen renal function and or produce severe cardiovascular complications. Therefore, pregnancy should be promoted. for young women with renal transplants that show excellent function.

Section snippets

Patients and Methods

From 1976 to 2007, 30 successful pregnancies were achieved in 27 renal recipients followed in our hospital; three women had two sets of twin gestations. We compared this population with a similar-aged group of 27 nonpregnant renal transplant recipients of similar age and similar follow-up time after transplantation: pregnant = 31.1 ± 5.4 years versus not pregnant = 31.3 ± 5.4 years (P = ns) and 51.5 ± 36 months versus 47.2 ± 41 months respectively (P = NS). This retrospective observational

Kidney Allograft Function

As expected, before pregnancy, both groups displayed good renal function (MDRD4 = 70.7 ± 21 mL/min/m² vs 79 ± 21 mL/min/m², P = NS), without proteinuria (0.13 ± 0.1 g/d vs 0.14 ± 0.1 g/d, P = NS). There were no acute rejection episodes or graft losses during pregnancy and puerperium. Renal function as measured by serum creatinine and MDRD4 glomerulas filtration at the end of pregnancy was lower among the pregnant group: 1.1 ± 0.2 mg/dL versus 0.9 ± 0.2 mg/dL (P = .05), and 66 ± 20 mL/min/1.73 m²

Discussion

These results emphasized that, in selected renal transplant recipients, pregnancy is good option with excellent results. Therefore, we should encourage young women with excellent renal function to get pregnant. Our experience is similar to data from single centers or registries but until now there has been little information concerning the long-term cardiovascular risks in women with successful pregnancies.

Before pregnancy, both populations were similar. After a successful pregnancy, despite an

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Cited by (20)

Pregnancy in Renal Transplant Recipients and Donors
2017, Seminars in Nephrology
Citation Excerpt :
Researchers using data from the Australian and New Zealand Dialysis and Transplant Registry did not detect a difference in rates of graft loss at 20 years between 120 women with renal transplants with pregnancies and nulliparous controls matched for graft vintage, age, and graft function.2 Numerous single center studies also support that gestation does not have a detrimental effect on renal function.43,44 Data from the US National Transplant Pregnancy Registry (NTPR) indicated that women with graft loss during or after pregnancy were more likely to have higher prepregnancy creatinine than those with stable graft function (1.5 ± -0.6 mg/dL versus 1.3 ± 0.4 mg/dL),29 and African-American women have an increased risk for graft loss within 2 years of delivery (13%) in comparison with whites (5%).14
Women with renal transplants have restoration of fertility with improved kidney function; however, pregnancy rates in renal transplant recipients appear to be lower than the general population, which might be influenced by patient choice. Women with renal transplants need to evaluate potential neonatal outcomes, graft outcomes, and risks to their own health to make informed decisions about conception. Pregnancy should be carefully planned in renal transplant recipients to reduce risk for graft loss, optimize pregnancy outcomes, and ensure immunosuppression regimes are nonteratogenic. Neonatal outcomes remain significantly worse for women with renal transplants than healthy controls, particularly for those with reduced graft function, hence prepregnancy, antenatal, and postpartum care of women with renal transplants should be guided by a multidisciplinary team of nephrologists and specialist obstetricians.
Association Between the Fertile Period and Live Birth Post–Kidney Transplantation: A Retrospective Single-Center Cohort Study
2017, Transplantation Proceedings
Despite restoration of fertility after kidney transplantation, the benefit is limited in female kidney recipients. Our objective is to determine the reasons for this discrepancy.
We evaluated 315 women who underwent kidney transplantation from 1983 to 2015 (a median of age at transplantation [10th–90th percentile] of 32 years [7–55 years]); 230 recipients between the ages of 15 to 49 years old as of March 2016 were observed.
We experienced 10 abortions and 21 live births from our 23 recipients and 2 abortions and 7 live births in 7 recipients from other transplant center. The live birth rate was 8.9 per 1000 female transplant recipients of childbearing age. Seven recipients received either treatments of artificial insemination or in vitro fertilization. Average age at pregnancy was 33.2 ± 3.2 years old, and the fertile period post-transplantation was longer in recipients with live births than those without live births (14.1 ± 7.1 vs 9.9 ± 7.3 years, P < .05). In 42.9% of recipients with live birth, pregnancy-induced hypertension was observed in the last trimester. The gestational age and the average birth weight were 32.8 ± 5.0 months and 2184 ± 632 g, respectively. During follow-up of 14.5 years, there was one case of graft loss, which is a rate of 2.5 per 1000 female recipients.
Although pregnancy complications are often observed in kidney recipients, graft survival is less influenced by pregnancy. Importantly, kidney disease at childbearing age disrupts pregnancy even after kidney transplantation.
Arterial stiffness and pulse pressure in CKD and ESRD
2012, Kidney International
Citation Excerpt :
Patients with CKD stage 4 are more likely to die than to progress to ESRD, and most of their deaths are due to cardiovascular diseases.112,113 CKD is characterized by a high prevalence of conventional (hypertension, diabetes, dyslipidemia) and nonconventional (oxidative stress, inflammation, anemia, mineral-metabolism disturbance(s)) cardiovascular risk factors.114–116 Exposing the arteries to this environment might influence arterial structure and induce arterial remodeling and stiffening (Figure 4a and b).
We recognize that increased systolic pressure is the most challenging form of hypertension today and that pulse pressure as an independent cardiovascular risk factor has focused attention on arterial stiffness and wave reflections as the most important factors determining these pressures. In recent years, many studies emphasized the role of arterial rigidity in the development of cardiovascular diseases, and it was shown that stiffening of arteries is associated with increased cardiovascular mortality and morbidity. Moreover, arterial stiffening is linked to decreased glomerular filtration rate, and is predictive of kidney disease progression and the patient's cardiovascular outcome. Premature vascular aging and arterial stiffening are observed with progression of chronic kidney disease (CKD) and in end-stage renal disease (ESRD). This accelerated aging is associated with outward remodeling of large vessels, characterized by increased arterial radius not totally compensated for by artery wall hypertrophy. Arterial stiffening in CKD and ESRD patients is of multifactorial origin with extensive arterial calcifications representing a major covariate. With aging, the rigidity is more pronounced in the aorta than in peripheral conduit arteries, leading to the disappearance or inversion of the arterial stiffness gradient and less protection of the microcirculation from high-pressure transmission. Various non-pharmacological or pharmacological interventions can modestly slow the progression of arterial stiffness, but arterial stiffness is, in part, pressure dependent and treatments able to stop the process mainly include antihypertensive drugs.
Pregnancy in renal transplantation: Recipient and donor aspects in the Arab world
2012, Arab Journal of Urology
Citation Excerpt :
Whether or not the treatment with erythropoietin is beneficial needs further investigation. Kidney allograft survival does not seem to be affected by pregnancy in recipients with a good graft function [35]. However, those with elevated creatinine levels might have accelerated graft loss.
There are many kidney transplant recipients and living donors of reproductive age, and the prevalence of pregnancies in kidney transplant recipients can reach 55% in the Middle Eastern countries. Living kidney donation is predominant in this region. As the risks and outcomes of pregnancy should be a part of counselling for both recipients and donors, we reviewed available reports on maternal and foetal outcomes in these particular populations.
Information was obtained from retrospective analyses of a large database, and from single-centre reports indexed in PubMed on pregnancy in donors and kidney transplant recipients. The keywords used for the search included ‘fertility’, ‘kidney disease’, ‘pregnancy’, ‘maternal/foetal outcomes’, ‘kidney transplant recipient’, ‘immunosuppression side-effects’, ‘living donor’ and ‘Arab countries’.
Pregnancies in kidney transplant recipients are most successful in those with adequate kidney function and controlled comorbidities. Similarly to other regions, pregnant recipients in the Middle East had a higher risk of pre-eclampsia (26%) and gestational diabetes (7%) than in the general population. Caesarean section was quite common, with an incidence rate of 61%, and the incidence of pre-term birth reached 46%.
Most living donors can have successful pregnancies and should not be routinely discouraged. Women who had pregnancies before and after donation were more likely to have adverse maternal outcomes (gestational diabetes, hypertension, proteinuria, and pre-eclampsia) in the latter, but no adverse foetal outcomes were found after donation. The evaluation before donation should include a gestational history and counselling about the potential risks.
Pregnancy outcomes in kidney transplant recipients: A systematic review and meta-analysis
2011, American Journal of Transplantation
Approximately 50 000 women of reproductive age in the United States are currently living after kidney transplantation (KT), and another 2800 undergo KT each year. Although KT improves reproductive function in women with ESRD, studies of post-KT pregnancies are limited to a few voluntary registry analyses and numerous single-center reports. To obtain more generalizable inferences, we performed a systematic review and meta-analysis of articles published between 2000 and 2010 that reported pregnancy-related outcomes among KT recipients. Of 1343 unique studies, 50 met inclusion criteria, representing 4706 pregnancies in 3570 KT recipients. The overall post-KT live birth rate of 73.5% (95%CI 72.1–74.9) was higher than the general US population (66.7%); similarly, the overall post-KT miscarriage rate of 14.0% (95%CI 12.9–15.1) was lower (17.1%). However, complications of preeclampsia (27.0%, 95%CI 25.2–28.9), gestational diabetes (8.0%, 95%CI 6.7–9.4), Cesarean section (56.9%, 95%CI 54.9–58.9) and preterm delivery (45.6%, 95%CI 43.7–47.5) were higher than the general US population (3.8%, 3.9%, 31.9% and 12.5%, respectively). Pregnancy outcomes were more favorable in studies with lower mean maternal ages; obstetrical complications were higher in studies with shorter mean interval between KT and pregnancy. Although post-KT pregnancy is feasible, complications are relatively high and should be considered in patient counseling and clinical decision making.
Pregnancy after renal transplantation: An evaluation of the graft function
2011, European Journal of Obstetrics and Gynecology and Reproductive Biology
Citation Excerpt :
Pregnant renal transplant recipients have pre-eclampsia rates well above the normal population [11]. Recently, Gutierrez et al. reported pre-eclampsia in 37% of patients in their series [12]. We emphasize that sometimes the diagnosis of pre-eclampsia can be very difficult in these patients as most of them have hypertension and significant proteinuria diagnosed before pregnancy.
To evaluate pregnancy outcomes and graft function in renal transplant recipients.
Thirty-four pregnancies in 31 patients were evaluated. Graft dysfunction was defined as an increase of 0.3 mg/dL (215 μmol/L) or more in serum creatinine (SCr) during pregnancy. Twenty-eight patients were also evaluated at one, six and twelve months after delivery to analyze the evolution of the graft function.
Fifteen patients experienced graft dysfunction during pregnancy, 10 related to preeclampsia, two related to rejection, one related to allograft obstruction and one related to urinary tract infection. One patient did not have an identified cause. In one patient, graft rejection ended in graft loss. The mean SCr level in the first trimester was 0.9 mg/dL (range: 0.5–2.1) among women who did not have graft dysfunction and 1.1 mg/dL (range: 0.5–1.9) among patients who had graft dysfunction (P = 0.66). The mean SCr level one year after delivery was 1.18 mg/dL in the first group and 1.21 mg/dL in the second group (P = 0.74). There was no difference in SCr level from the first trimester of pregnancy to one year after delivery in both groups evaluated (P = 0.35 and P = 0.13).
Although graft dysfunction may occur during pregnancy, it seems to be temporary in the majority of the cases. It is important to emphasize that rejection is still a cause of graft loss during pregnancy.

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Kidney transplantationComplication: MetabolicRenal Allograft Function and Cardiovascular Risk in Recipients of Kidney Transplantation After Successful Pregnancy

Abstract

Section snippets

Patients and Methods

Kidney Allograft Function

Discussion

Am J Kidney Dis

Transplant Proc

Am J transp

Kidney transplantation
Complication: Metabolic
Renal Allograft Function and Cardiovascular Risk in Recipients of Kidney Transplantation After Successful Pregnancy