- Email: [email protected]
Pregnancy in Renal Transplant Recipients
Pregnancy in Renal Transplant Recipients M.J. Gutiérrez, M. Acebedo-Ribó, J.A. Garcı´a-Donaire, M.J. Manzanera, A. Molina, E. González, N. Nungaray, A. Andrés, and J.M. Morales ABSTRACT Fertility is restored after renal transplantation when good function is achieved. Our aim was to describe the gestations of our transplanted patients, analyzing outcomes and complications as well as long-term evolution of renal function. From 1976 to 2004, 43 gestations occurred in 35 renal transplanted women: their mean age was 31.7 ⫾ 4.06 years, with a mean time from the transplant to pregnancy of 4.32 years (0.4 –13). At conception, all showed normal renal function (SCr 1.05 ⫾ 0.2 mg/dL). There were 19 abortions (43.8%), 9 of them spontaneous (21%) and 10 therapeutic (six cases for noncompliance with described criteria of European Best Practice Guidelines for Renal Transplantation, especially pregnancy less than 6 months after transplantation). Excluding these six cases of therapeutic abortions, 24 successful pregnancies occurred in 37 women (65.7%), although eight (29.1%) had premature delivery with live fetuses. Arterial hypertension was the most frequently complication (64%). Preeclampsia occurred in nine (37.5%) pregnancies, with proteinuria in five and only two with mild renal function deterioration. The majority of patients received cyclosporine (n ⫽ 20) or tacrolimus (n ⫽ 19). Since 1996, mycophenolate mofetil and sirolimus were stopped before conception. Birth weight was lower than 2500 g in 33.3% of pregnancies. Every newborn baby was healthy. Afterward, of the 24 patients with successfully pregnancy, 21 (87.5%) have functioning renal transplants at 53.2 months. After delivery, all currently show good renal function (SCr 1.16 ⫾ 0.35 mg/dL, CrCl 91 ⫾ 28.45 mL/m). In conclusion, pregnancy in our renal transplant women shows a success rate of 65.6%. However, complications related to arterial hypertension such as preeclampsia are frequent. The incidence of spontaneous abortions was similar to other series (21%). Long-term graft survival does not seem to be negatively affected by pregnancy.
F
ERTILITY IS RESTORED after renal transplantation when good function is achieved. In fact, pregnancy is one of the best rehabilitation events after transplantation in women of fertile age.1 The aim of this work was to describe the gestations of our transplant patients, analyzing outcomes and complications as well as long-term evolution of renal function.2
evidence of ongoing rejection; and with a normal allograft ultrasound.3 During the pregnancy, the patients were seen monthly in the obstetrical department (monitoring fetal status and development) and renal transplant outpatient office to monitor renal function (complete blood count, chemistry panel, electrolytes, serum creatinine, and creatinine clearance), proteinuria, blood levels immunosuppressive drugs, arterial hypertension, and treatment.
RESULTS PATIENTS AND METHODS From 1976 to 2004, 43 gestations occurred in 35 patients with normal functioning renal transplants among 2080 transplant. According to European Best Practice Guidelines for Renal Transplantation (EBPG), we considered a pregnancy safe about 2 years after transplantation in women with good and stable renal function: creatinine levels below 2 mg/dL, below 1.5 mg/dL preferable; without proteinuria; without arterial hypertension or mild arterial hypertension (under only one antihypertensive drug); with no
At pregnancy, the mean age of women was 31.7 ⫾ 4.06 years, with a mean time from the transplant to pregnancy of From the Renal Transplant Unit, Nephrology Department, Hospital 12 Octubre, Madrid, Spain. Address reprint requests to Ma José Gutiérrez, Servicio de Nefrologı´a, Hospital Universitario 12 Octubre, Avd. Córdoba s/n, 28041 Madrid, España. E-mail: [email protected]
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.09.175
Transplantation Proceedings, 37, 3721–3722 (2005)
3721
3722
4.32 years (0.4 –13). All showed normal renal function (SCr 1.05 ⫾ 0.2 mg/dL), with negative or minimal proteinuria (0.2 ⫾ 0.15 g/d) but 11 (25.6%) suffered from mild arterial hypertension (controlled with just one antihypertensive drug). Five patients had anti-VHC positive antibodies. There were 19 abortions (43.8%), nine (21%) of which were spontaneous eight of them inside the first trimester and one of them in the fifth month due to severe arterial hypertension) and 10 were therapeutic (six cases for not complying with previously described criterions of EBPG, especially pregnancy less than 6 months after transplantation; two cases for uncontrolled preeclampsia, one case from cardiac malformations and one case from hemolytic-uremic syndrome). Excluding these six cases of therapeutic abortions, 24 successful gestations occurred in 37 women (65.7%), although in eight (29.1%) premature delivery was evident, with a live fetus in every case (one pregnancy was twins). Arterial hypertension was the most frequent complication (64%). The antihypertensive drug of choice was ␣-methyldopa. Preeclampsia occurred in nine (35%) pregnancies, with proteinuria in five, in general moderate (1.48 ⫾ 0.4 g/d), accompanied by a mild increase in serum creatinine in only two cases (mean SCr 1.4 ⫾ 1 mg/dL), needing the induction of delivery in five patients. No acute rejection was observed during pregnancy or after delivery. Three patients (12.5%) developed gestational diabetes, which resolved 3 months after delivery. Regarding immunosuppressive therapy, since 1996 mycophenolate mofetil and sirolimus were stopped before conception. The majority of patients received cyclosporine (n ⫽ 20) with or without azathioprine versus tacrolimus (n ⫽ 19); monotherapy in one case; two patients, steroids and azathioprine; and one corticosteroid monotherapy. During pregnancy, cyclosporine/tacrolimus doses needed to be increased to achieve therapeutic blood levels. During the postnatal period, steroid dose was preventively increased. There was no important side effect due to immunosuppressive drugs. Premature delivery was observed in 29.1% of live births. Forty-six percent of pregnancies were successfully delivered by Caesarean section and 54% through spontaneous vaginal delivery. Birth weight was lower than 2500 g in 33.3% of pregnancies. Every newborn baby was healthy, requiring initial respiratory support only in one case. No congenital anomalies were documented. Afterward, from the 24 patients with successfully pregnancy, 21 (87.5%) have functioning grafts at 53.2 months after delivery. Currently, all show good renal function (SCr 1.16 ⫾ 0.35 mg/dL, CrCl 91 ⫾ 28.45 mL/m), negative proteinuria in 85.7% and in three cases mild or moderate proteinuria (mean 0.6 ⫾ 0.9 g/d). Ten cases (47.6%)
GUTIÉRREZ, ACEBEDO-RIBÓ, GARCÍA-DONAIRE ET AL
showed normal blood pressure. Two patients lost renal grafts because of chronic nephropathy (more than 5 years after gestation). There was one death due to cardiovascular disease at 7 years after delivery. DISCUSSION
Our study shows that pregnancy in renal transplant women have a success rate of 61.5%, which is similar to other series.4 However, complications related to arterial hypertension such as preeclampsia were frequent, namely two to three times greater than the general population. The preeclampsia was mild in most cases. In our series, arterial hypertension was the most important problem during pregnancy (64%), although 25.6% of them already suffered mild arterial hypertension at the preconception stage, which would explain the higher rate of preeclampsia. Therefore, in these transplanted women, strict control and monitoring of arterial hypertension is mandatory. Therapy with ␣-methyldopa should be started early. Also, renal function and proteinuria should be closely monitored in these patients with arterial hypertension. In some pregnant women, abortion was induced because of early pregnancy (less than 6 months), hereditary disease, or X-ray exposure. If we consider only pregnant women who meet EBPG criteria, the rate of abortion seems to be similar to the general population, although there is a higher incidence of preterminal births of underweight newborn children. Nevertheless, this did not seem to have repercussions on morbidity and mortality. Finally, although others studies observed a negative impact of pregnancy on renal function,5 our results show that the survival of the long-term renal graft does not seem to be negatively affected by the pregnancy. However, larger studies are needed to know the real impact pregnancy in renal transplant women. REFERENCES 1. Davison JM: Dialysis, Transplantation and Pregnancy. Am J Kidney Dis 18:621, 1991 2. Armenti VT, Radomski JS, Moritz MJ, et al: Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation. Clin Transpl 131, 2003 3. EBPG Expert Group on Renal Transplantation: European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.10. Pregnancy in renal transplant recipients. Nephrol Dial Transplant 17:50, 2002 4. Stratta P, Canavese C, Giacchino F, et al: Pregnancy in kidney transplantation: satisfactory outcomes and harsh realities. J Nephrol 16:792, 2003 5. Sturgiss SN, Davison JM: Effect of pregnancy on the longterm function of renal allografts: an update. Am J Kidney Dis 26:54, 1995
F
ERTILITY IS RESTORED after renal transplantation when good function is achieved. In fact, pregnancy is one of the best rehabilitation events after transplantation in women of fertile age.1 The aim of this work was to describe the gestations of our transplant patients, analyzing outcomes and complications as well as long-term evolution of renal function.2
evidence of ongoing rejection; and with a normal allograft ultrasound.3 During the pregnancy, the patients were seen monthly in the obstetrical department (monitoring fetal status and development) and renal transplant outpatient office to monitor renal function (complete blood count, chemistry panel, electrolytes, serum creatinine, and creatinine clearance), proteinuria, blood levels immunosuppressive drugs, arterial hypertension, and treatment.
RESULTS PATIENTS AND METHODS From 1976 to 2004, 43 gestations occurred in 35 patients with normal functioning renal transplants among 2080 transplant. According to European Best Practice Guidelines for Renal Transplantation (EBPG), we considered a pregnancy safe about 2 years after transplantation in women with good and stable renal function: creatinine levels below 2 mg/dL, below 1.5 mg/dL preferable; without proteinuria; without arterial hypertension or mild arterial hypertension (under only one antihypertensive drug); with no
At pregnancy, the mean age of women was 31.7 ⫾ 4.06 years, with a mean time from the transplant to pregnancy of From the Renal Transplant Unit, Nephrology Department, Hospital 12 Octubre, Madrid, Spain. Address reprint requests to Ma José Gutiérrez, Servicio de Nefrologı´a, Hospital Universitario 12 Octubre, Avd. Córdoba s/n, 28041 Madrid, España. E-mail: [email protected]
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.09.175
Transplantation Proceedings, 37, 3721–3722 (2005)
3721
3722
4.32 years (0.4 –13). All showed normal renal function (SCr 1.05 ⫾ 0.2 mg/dL), with negative or minimal proteinuria (0.2 ⫾ 0.15 g/d) but 11 (25.6%) suffered from mild arterial hypertension (controlled with just one antihypertensive drug). Five patients had anti-VHC positive antibodies. There were 19 abortions (43.8%), nine (21%) of which were spontaneous eight of them inside the first trimester and one of them in the fifth month due to severe arterial hypertension) and 10 were therapeutic (six cases for not complying with previously described criterions of EBPG, especially pregnancy less than 6 months after transplantation; two cases for uncontrolled preeclampsia, one case from cardiac malformations and one case from hemolytic-uremic syndrome). Excluding these six cases of therapeutic abortions, 24 successful gestations occurred in 37 women (65.7%), although in eight (29.1%) premature delivery was evident, with a live fetus in every case (one pregnancy was twins). Arterial hypertension was the most frequent complication (64%). The antihypertensive drug of choice was ␣-methyldopa. Preeclampsia occurred in nine (35%) pregnancies, with proteinuria in five, in general moderate (1.48 ⫾ 0.4 g/d), accompanied by a mild increase in serum creatinine in only two cases (mean SCr 1.4 ⫾ 1 mg/dL), needing the induction of delivery in five patients. No acute rejection was observed during pregnancy or after delivery. Three patients (12.5%) developed gestational diabetes, which resolved 3 months after delivery. Regarding immunosuppressive therapy, since 1996 mycophenolate mofetil and sirolimus were stopped before conception. The majority of patients received cyclosporine (n ⫽ 20) with or without azathioprine versus tacrolimus (n ⫽ 19); monotherapy in one case; two patients, steroids and azathioprine; and one corticosteroid monotherapy. During pregnancy, cyclosporine/tacrolimus doses needed to be increased to achieve therapeutic blood levels. During the postnatal period, steroid dose was preventively increased. There was no important side effect due to immunosuppressive drugs. Premature delivery was observed in 29.1% of live births. Forty-six percent of pregnancies were successfully delivered by Caesarean section and 54% through spontaneous vaginal delivery. Birth weight was lower than 2500 g in 33.3% of pregnancies. Every newborn baby was healthy, requiring initial respiratory support only in one case. No congenital anomalies were documented. Afterward, from the 24 patients with successfully pregnancy, 21 (87.5%) have functioning grafts at 53.2 months after delivery. Currently, all show good renal function (SCr 1.16 ⫾ 0.35 mg/dL, CrCl 91 ⫾ 28.45 mL/m), negative proteinuria in 85.7% and in three cases mild or moderate proteinuria (mean 0.6 ⫾ 0.9 g/d). Ten cases (47.6%)
GUTIÉRREZ, ACEBEDO-RIBÓ, GARCÍA-DONAIRE ET AL
showed normal blood pressure. Two patients lost renal grafts because of chronic nephropathy (more than 5 years after gestation). There was one death due to cardiovascular disease at 7 years after delivery. DISCUSSION
Our study shows that pregnancy in renal transplant women have a success rate of 61.5%, which is similar to other series.4 However, complications related to arterial hypertension such as preeclampsia were frequent, namely two to three times greater than the general population. The preeclampsia was mild in most cases. In our series, arterial hypertension was the most important problem during pregnancy (64%), although 25.6% of them already suffered mild arterial hypertension at the preconception stage, which would explain the higher rate of preeclampsia. Therefore, in these transplanted women, strict control and monitoring of arterial hypertension is mandatory. Therapy with ␣-methyldopa should be started early. Also, renal function and proteinuria should be closely monitored in these patients with arterial hypertension. In some pregnant women, abortion was induced because of early pregnancy (less than 6 months), hereditary disease, or X-ray exposure. If we consider only pregnant women who meet EBPG criteria, the rate of abortion seems to be similar to the general population, although there is a higher incidence of preterminal births of underweight newborn children. Nevertheless, this did not seem to have repercussions on morbidity and mortality. Finally, although others studies observed a negative impact of pregnancy on renal function,5 our results show that the survival of the long-term renal graft does not seem to be negatively affected by the pregnancy. However, larger studies are needed to know the real impact pregnancy in renal transplant women. REFERENCES 1. Davison JM: Dialysis, Transplantation and Pregnancy. Am J Kidney Dis 18:621, 1991 2. Armenti VT, Radomski JS, Moritz MJ, et al: Report from the National Transplantation Pregnancy Registry (NTPR): outcomes of pregnancy after transplantation. Clin Transpl 131, 2003 3. EBPG Expert Group on Renal Transplantation: European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.10. Pregnancy in renal transplant recipients. Nephrol Dial Transplant 17:50, 2002 4. Stratta P, Canavese C, Giacchino F, et al: Pregnancy in kidney transplantation: satisfactory outcomes and harsh realities. J Nephrol 16:792, 2003 5. Sturgiss SN, Davison JM: Effect of pregnancy on the longterm function of renal allografts: an update. Am J Kidney Dis 26:54, 1995