| Abstract|| |
To evaluate the maternal and fetal outcomes in renal transplant female recipients who became pregnant from 1989 to 2005 in our center, we retrospectively studied 20 incident pregnancies in 12 renal transplant recipients; 5 (41.7 %) of them from living related, 4 (33.3%) from deceased, and 3 (25%) from living unrelated donors. The mean age at pregnancy was 30.5 ± 4.5 years and mean interval from transplantation to pregnancy was 21 ± 5.7 months with the interval was < 1 year in one patient. The mean serum creatinine (SCr) before pregnancy vs 6 months post delivery was 110 ± 24.3, and 156 ± 190 µmol/ L, respectively, (p = 0.2). All patients were normotensive during the prenatal period except two who were hypertensive, none was markedly proteinuric, and only one acute rejection episode occurred during one pregnancy. Graft loss one year post delivery occurred in 2 patients; one with elevated prenatal SCr > 132 µmol/L, and another with short interval from transplantation to pregnancy < 1 year, while the remaining 10 patients revealed current mean SCr of 105 ± 18.2 µmol/L. Complications during pregnancy included pre-eclampsia in (25%), UTI (25%), preterm delivery < 37 weeks (30%), however, none of the pregnancies ended by abortion. Normal vaginal delivery vs cesarean section was 70% vs 30%, respectively. Gestational age at delivery was 36.3 ± 3.9 weeks, and mean fetal birth weight was 2349 ± 574 gm. Apgar score was 9-10 in all of the 20 babies, and none revealed intrauterine growth retardation or congenital anomalies. We conclude that consecutive pregnancies demonstrate long-term maternal and fetal survival and function. The major risk factors are elevated starting serum creatinine, hypertension, and short time interval from transplantation to pregnancy.
Keywords: Pregnancy, Transplantation, Renal, Kidney, Pre-eclampsia, Proteinuria, Graft
|How to cite this article:|
Alfi AY, Al-essawy MA, Al-lakany M, Somro A, Khan F, Ahmed S. Successful Pregnancies Post Renal Transplantation. Saudi J Kidney Dis Transpl 2008;19:746-50
|How to cite this URL:|
Alfi AY, Al-essawy MA, Al-lakany M, Somro A, Khan F, Ahmed S. Successful Pregnancies Post Renal Transplantation. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2019 May 22];19:746-50. Available from: http://www.sjkdt.org/text.asp?2008/19/5/746/42446
| Introduction|| |
The dream to be pregnant in chronic renal failure women of child bearing age after renal transplantation has become reality. This dream to come true is the result of advances in transplantation science and the increasing reports of successful pregnancies after renal transplantion. Today, there are more than 15000 pregnancies recorded in > 12000 renal transplant recipient women worldwide with a favorable outcome in 65–92% of cases.  However, important changes in glomerular haemodynamics are known to occur in pregnancy (hyperfiltration) which may adversely affect longterm graft prognosis.  Indeed, approximately 35% of pregnancies do not progress beyond the 1st trimester due to spontaneous or therapeutic abortion, but the overall success rate is > 90% after the 1st trimester. ,
We performed a retrospective study to analyze fetal, maternal and graft outcomes in our renal transplant women who became pregnant from 1989 to 2005 in our center.
| Methods|| |
We retrospectively reviewed all our female renal transplant recipients from 1989 to 2005. We included those who aged 16–45 years and of them we identified those who became pregnant. Inpatient and outpatient medical record files were reviewed. Missing and additional data were collected through outpatient questionnaire during regular visits of the patients. We found 20 pregnancies in 12 patients.
Data collection included information in respect to age at pregnancy, interval between transplantation and pregnancy, immunosuppressive drugs, known hypertensive, known diabetic, pregnancy outcome, complications during pregnancy, delivery mode, and graft function. We compared the graft function exemplified by serum creatinine (SCr) levels before conception with those at each trimester, 6 months post partum, and at the current clinic visit. Increase in SCr 25% more than the baseline was considered significant change. We also compared the incidence of proteinuria during the pre-pregnancy period with that during each trimester and 6 months post partum.
Fetal information included pre-term delivery (< 37 weeks), gestational age, low birth weight (< 2500 g), very low birth weight (< 1500 g), Apgar score, fetal growth restriction, and small for gestational age.
| Statistical analysis|| |
Statistical analysis was performed using the Microsoft Analysis Tool Pack. Data was expressed as mean ± SD. Statistical significance was evaluated by the Student's t test, and the significance level was considered as p < 0.05.
| Results|| |
Five (41.7%) of the study pregnant patients received renal transplants from living related, 4 (33.3%) from deceased, and 3 (25%) from living unrelated donors. The mean age at pregnancy was 30.5 ± 4.5 years and mean interval from transplantation to pregnancy was 21 ± 5.7 months with the interval was < 1 year in one patient. All patients were normotensive during the prenatal period except two who were hypertensive, none was markedly proteinuric, and only one acute rejection episode occurred during one pregnancy,[Table 1].
The mean serum creatinine (SCr) before pregnancy vs 6 months post delivery was 110 ± 24, and 156 ± 190 µmol/L, respectively, (p = 0.2). Graft loss one year post delivery occurred in 2 patients; one with elevated prenatal SCr > 132 µmol/L, and another with short interval from transplantation to pregnancy < 1 year, while the remaining 10 patients revealed current mean SCr of 105 ± 18.2 µmol/L, [Table 2]. Proteinuria was not significantly different before, during, and after conception, [Table 3].
Complications during pregnancy included preeclampsia in (25%), UTI (25%), preterm delivery < 37 weeks (30%), however, none of the pregnancies ended by abortion. Normal vaginal delivery vs cesarean section was 70% vs 30%, respectively, [Table 4]. Gestational age at delivery was 36.3 ± 3.9 weeks, and mean fetal birth weight was 2349 ± 574 gm. Apgar score was 9–10 in all of the 20 babies, and none revealed intrauterine growth retardation or congenital anomalies, [Table 5].
| Discussion|| |
Women during childbearing age should seek advice about the possibility and risks of pregnancy after kidney transplantation. For example, women who are not rubella immune should receive the vaccine before transplantation, because live virus vaccines are contraindicated after a transplant.  Criteria for considering pregnancy in renal transplant women was set out in the European Best Practice Guidelines (EBPG).  They concluded that pregnancy could be safe after 2 years of renal transplantation in women with good renal function (SCr < 1.33 µmol/L) without that includes absence of proteinuria, controlled blood pressure, absence of allograft rejection, and within normal limits allograft ultrasound.  Almost all of our patients satisfied the criteria of the EBPG. The only patient, who refused the advice and became pregnant 6 months after receiving her deceased graft, lost it one year after delivery, although her SCr was 117 µmol/L at time of pregnancy. The other patient, who lost her graft one year post partum, insisted on pregnancy, although her SCr was 189 µmol/L after 17 months of transplantation.
A physiological increase in the glomerular filtration rate (GFR) during pregnancy and transient decrease in renal function in the final 12 weeks were demonstrated by other authors. , In our results there was a transient decrease in GFR in the third trimester, but this decrease was insignificant. However, after exclusion of the two patients who lost their graft, there was a significant difference between SCr in the pre-pregnancy period and that during the third trimester (p = 0.002).
The incidence of graft rejection during pregnancy was very low in our patients (5%), in contrast to 14.5% in other reports. ,
Davison et al reported the most important series of pregnancies after renal transplantation: 3382 in 2409 women, showing that 34% finished in therapeutic (20%) or spontaneous abortion (14%), comparable with that of the general population. Notably, of the gestations that continued beyond the first trimester, 94% ended successfully. However, the incidence of pre-term delivery was 50%, and intrauterine growth retardation was seen in at least 20% of pregnancies with neonates of very low birth weight.  In our study the pregnancy success was 100% with no abortions. In addition, the incidence of preterm delivery was 30%, and there was no intrauterine growth retardation, except a 10% incidence of very low birth weights. These results may be subsequent to the education we routinely conveyed to our patients about pregnancy and the high frequency of outpatient visits, which recorded as 3.6 ± 1 visit per month, during the period of pregnancy.
There is a 30% chance of developing hypertension, pre-eclampsia or both.  Cyclosporine may be involved in the pathogenesis of preeclampsia because it increases the production of thromboxane and endothelin, which are implicated in the pathogenesis of pre-eclampsia.  Moreover, cyclosporine can exacerbate hypertension in renal transplant recipients.  We did not encounter in our study incidence of new onset hypertension or gestational diabetes, however, pre-eclampsia occurred in 5 pregnancies (25%).
Close monitoring of cyclosporine blood levels is a very important issue. Armenti et al, suggested that the increased distribution volume usually produces low maternal cyclosporine levels.  Requirements of our patients to CsA were increased by 25% as appeared by low blood level particularly during the 2 nd and 3 rd trimesters.
Finally, in our study, there were 3 patients with 3 pregnancies and 2 patients with two, which are compatible with the conclusions of Owda et al who found that in patients with well-functioning grafts, repeated pregnancies resulted in no adverse effects on renal graft function, maternal or fetus morbidity and mortality in the absence of other complicating factors, especially hypertension. 
We conclude that not only single but also consecutive pregnancies are quite possible after kidney transplantation and long-term development of children occurs appropriately. Graft, maternal and fetal risks should be explained to patients. The major risk factors are high initial serum creatinine and short time interval from transplantation to pregnancy.
| References|| |
|1.||Stratta P, Canavese C, Giacchino F, Mesiano P, Quaglia M, Rossetti M. Pregnancy in kidney transplantation: satisfactory outcomes and harsh realities. J Nephrol 2003;16 (6):792-806. |
|2.||First MR, Pollak VE. Pregnancy and renal disease. In: Schrier RW, Gottschalk, (eds). Diseases of the kidney. Boston, Little Brown, 1993,2287. |
|3.||Lindheimer MD, Davison JM, Katz AI. The kidney and hypertension in pregnancy: Twenty exciting years. Semin Nephrol 2001;21(2):173-89. |
|4.||Miranda CT, Melaragno C, Camara NO, Pacheco-Silva A, Medina-Pestana PJ. Adverse effects of pregnancy on renal allograft function. Transplant Proc 2002;34(2):506-7. |
|5.||Miniero R, Tardivo I, Curtoni ES, et al. Pregnancy after renal transplantation in Italian patients: focus on fetal outcome. J Nephrol 2002;15(6):626-32. |
|6.||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 2002;17(Suppl 4):50-5. |
|7.||Davison JM. The effect of pregnancy on kidney function in renal allograft recipients. Kidney Int 1985;27(1):74-9. |
|8.||First RM, Combs CA, Weiskittel P, Miodovnik M. Lack of effect of pregnancy on renal allograft survival or function. Transplantation 1995;59(4):472-6. |
|9.||Davison JM. Dialysis, transplantation and pregnancy. Am J Kidney Dis 1991;17(2):127-32. |
|10.||Armenti VT, Ahlswede MJ, Moritz MJ, Jarrell BE. National transplantation pregnancy Registry: Analysis of pregnancy outcomes of female kidney recipients with relation to time interval from transplant to conception. Transplant Proc 1993;25(1.2):1036-7. |
|11.||Davison JM, Milne JEC. Pregnancy and renal transplantation. Br J Urol 1997;80[Suppl 1]:29-32. |
|12.||Davison JM. Pregnancy in renal allograft recipients: Problems, prognosis and practicalities. Baillieres Clin Obstet Gynaecol 1994;8(2): 501-25. |
|13.||Hou S. Pregnancy in chronic renal insufficiency and end-stage renal disease. Am J Kidney Dis 1999;33(2):235-52. |
|14.||Rieu P, Neyrat N, Hiesse C, Charpentier B. Thirty-three pregnancies in population of 1725 renal transplant patients. Transplant Proc 1997; 29(5):2459-60. |
|15.||Armenti VT, Wilson GA, Radomski JS, Moritz MJ, McGrory Ch, Coscia LA. Report from the National Transplantation Pregnancy Registry (NTPR): Outcomes of pregnancy after transplantation. Clin Transplant 1999;:111-9. |
|16.||Owda AK, Abdalla AH, Al-Sulaiman MH, et al. No evidence of functional deterioration of renal graft after repeated pregnancies: a report on three women with 17 pregnancies. Nephrol Dial Transplant 1998;13(5):1281-4. |
Adnan Yaseen Alfi
Nephrology Department, King Abdul-Aziz Hospital and Oncology Center, Jeddah
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]