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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">In the first ages of renal transplantation pregnancy was contraindicated&#44; however the first offspring of a renal transplanted woman was born 48 years ago<span class="elsevierStyleSup">1</span> and since then the concepts have progressively changed&#44; so that nowadays it is considered that pregnancy is just another positive aspect of kidney transplant&#59; there are still several concerns about its effects on the mother and the fetus&#46;<span class="elsevierStyleSup">2</span> The patients with advanced chronic renal disease present hypothalamic-gonadal dysfunction leading to infertility in virtually all cases&#59; however&#44; 6 months after the transplant this gonadal dysfunction disappears giving rise to the possibility of conception&#46;</p><p class="elsevierStylePara">The most accurate data have been obtained from three specific registers on pregnancy and transplantation &#40;the European&#44; the American&#44; and the British&#41;<span class="elsevierStyleSup">3-5</span> reporting on the peculiarities that pregnancy entails for kidney-transplanted patients&#46; The most relevant data show that 24&#37;-34&#37; of them present a therapeutic or spontaneous miscarriage&#44; the prevalence of AHT is high&#44; preeclampsia is increased&#44; and in more than 50&#37; of the cases prematurity and low birth weight will occur&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHODS</span></p><p class="elsevierStylePara">An observational prospective study was carried out analyzing 10 kidney-transplanted patients that got pregnant&#44; with a mean age of 28&#46;9 years &#40;18-36&#41;&#46; The average post-transplantation time was 44 months &#40;12-113&#41;&#46; The mean glomerular filtration rate estimated by the MDRD equation was 64 mL&#47;min &#40;49-82&#41;&#44; and the immunosuppressive therapy that was given to all patients was prednisone 5 mg&#47;day and tacrolimus &#40;variable dosing to achieve plasma levels of 6-8 ng&#47;mL&#41;&#46;</p><p class="elsevierStylePara">We assessed different variables related with the renal graft&#44; during both the pregnancy months and after the delivery &#40;renal function&#44; proteinuria&#44; blood pressure&#44; tacrolimus doses and levels&#41;&#44; as well as other variables related with the delivery and the neonate&#46;</p><p class="elsevierStylePara">The results are expressed as means&#44; with the minimal and maximal values between brackets&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">After revising the course during gestation and the months after&#44; we observed that pregnancy was completed in nine patients and there was one spontaneous miscarriage during the first trimester&#46; The delivery was through natural way in 6 cases and a cesarean section was needed in 3 patients&#46;</p><p class="elsevierStylePara">The analysis of the blood pressure revealed an increase towards the end of the pregnancy&#44; of both the systolic BP and diastolic BP &#40;table I&#41;&#46; Only one patient was on hypotensive therapy before the pregnancy &#40;amlodipine&#41;&#44; which was maintained through it&#44; adding alpha-metildopa during the third trimester&#46; The remaining patients were not on anti-hypertensive therapy before the pregnancy and it was necessary to prescribe alpha-metildopa in one patient during the third trimester&#44; requiring an emergency cesarean section due to preeclampsia&#46;</p><p class="elsevierStylePara">Table I shows the renal function monitoring&#44; which remained stable during the pregnancy&#44; and proteinuria&#44; which slightly increased during the third trimester&#46; This table also shows that the dose of tacrolimus had to be increased to achieve the target plasma levels&#46; There was no case of acute rejection and there was only one case of preeclampsia that was resolved with the cesarean section&#46;</p><p class="elsevierStylePara">The delivery occurred at 37&#46;2 &#40;34-40&#41; weeks&#44; and the newborns weighed 2&#44;809 &#40;2&#44;040-3&#44;760&#41; grams&#44; with two newborns affected of prematurity-low birth weight&#46; However&#44; none of these neonates had remarkable complications&#46; </p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">Our experience on the follow-up of post-transplantation pregnancy using prednisone and tacrolimus is satisfactory since there have not been any complications&#44; either in the mother or the fetus&#46; This is likely due to the fact that the patients met the recommendations set forth by both the &#171;Report on the AST Consensus Conference on Reproductive Issues and Transplantation&#187;<span class="elsevierStyleSup">6</span> and the European Guidelines<span class="elsevierStyleSup">7</span> for considering a pregnancy after renal transplantation &#40;table II&#41;&#46;</p><p class="elsevierStylePara">When analyzing the different published reviews of kidneytransplanted patients&#44; we observed that high blood pressure is prevalent among patients on calcineurin antagonists&#44; varying 47&#37;-73&#37; according to the different registers&#46;<span class="elsevierStyleSup">8-11</span> In our study&#44; we observed an increase in both systolic and diastolic blood pressure&#46; Preeclampsia occurs in 30&#37; of pregnant transplanted patients&#44;<span class="elsevierStyleSup">11&#44; 12</span> being a difficult diagnosis since blood pressure tends to increase after week 20&#44; and many patients already have mild proteinuria before the pregnancy&#44; in addition to increased uric acid levels&#46; Arterial hypertension may explain&#44; at least in part&#44; the fact that more than half of the pregnancies end up before the due date&#46; The management of AHT has to be aggressive<span class="elsevierStyleSup">13</span> and metildopa&#44; labetalol&#44; and calcium-hannel blockers may be safely used&#46;<span class="elsevierStyleSup">14 </span>Angiotensin-renin system inhibitors are formally contraindicated after the first trimester of pregnancy and&#44; id possible&#44; they should be discontinued before conception&#46; Since the effective plasma volume is decreased during the pregnancy&#44; diuretics are not recommended either&#44; with the exception of thiazides if the patient was taking them before&#46;</p><p class="elsevierStylePara">When analyzing the renal function&#44; we may highlight that in those patients with pre-existent renal dysfunction &#40;creatinine &#62; 1&#46;5 mg&#37; - &#62; 133 &#956;mol&#47;L&#41; the risk for graft loss is increased&#44; during both the pregnancy and after it&#44; so that pregnancy is not recommended in patients with values higher than these&#46; Although a study<span class="elsevierStyleSup">15</span> published in 1993 reported that the graft survival at 10 years was lower in patients that had got pregnant&#44; as compared with those that had not&#44; recent publications<span class="elsevierStyleSup">16</span>&#44;<span class="elsevierStyleSup">17</span> show that the survival rates for the graft and the patient after 15 years of follow-up are the same in transplanted patients that got pregnant after the transplant and in those that did not&#46; Graft dysfunction may be difficult to detect during the pregnancy given that usually creatinine levels go down during gestation&#44; particularly during the first and second trimesters&#44; as is observed in our sample&#59; sometimes rejection only manifests as mild increases of plasma creatinine levels&#46; If rejection presents&#44; it usually responds to methylprednisolone&#46; The safety of anti-lymphocytic globulins and rituximab is unknown&#46;</p><p class="elsevierStylePara">Adequate immunosuppression levels are necessary during the pregnancy&#46; As observed in our analysis&#44; the plasma levels of calcineurin antagonists may vary since during gestation there are changes in the distribution volume and the extracellular volume&#46;<span class="elsevierStyleSup">7&#44; 18</span> However&#44; most of the studies published have not recorded these levels&#46; In our study&#44; after analyzing the levels of tacrolimus&#44; we observed that the doses must be increased in order to reach the target range&#44; which is in agreement with those works monitoring this treatment&#46;<span class="elsevierStyleSup">19</span> On the other hand&#44; in a study carried out in 21 patients without modifying the dose of tacrolimus&#44; no episodes of acute rejection were observed&#46;<span class="elsevierStyleSup">20</span></p><p class="elsevierStylePara">According to the published guidelines&#44; although gestation in a kidney-transplanted patient should be considered a highrisk pregnancy&#44; the cesarean section would only be indicated for obstetric reasons&#59; however&#44; although in our series this occurred in 33&#37; of the patients&#44; other series have reported to occur in 50&#37; of the deliveries&#46;</p><p class="elsevierStylePara">The final outcome of only 10&#37; of miscarriages in our series differs from the data obtained when reviewing the European&#44; American&#44; and British registers&#44;<span class="elsevierStyleSup">3-5</span> in which spontaneous or therapeutic abortion occurs in 24-34&#37; of pregnant women&#46;</p><p class="elsevierStylePara">In our experience&#44; only two patients had non-complicated urinary tract infection&#46; The pregnancy in the kidney-transplanted patient increases the risk for infection&#44; especially bacterial infections&#46; About 40&#37; of pregnant women have urinary infection&#44; particularly in patients with chronic pyelonephritis or vesicouretheral reflux as the primary cause of renal disease &#40;a criterion that was met by our two patients&#41;&#46; For this reason&#44; it is recommended to perform a sediment analysis and urine culture monthly&#44; and if asymptomatic bacteriuria is present to treat with antibiotics for two weeks and then administering them prophylactically until delivery&#46;<span class="elsevierStyleSup">7</span></p><p class="elsevierStylePara">When analyzing the fetal complications&#44; we may highlight that the risk for prematurity and low birth weight is higher than 50&#37;&#44; and that for delayed intrauterine growth higher than 20&#37; according to the different series&#44;<span class="elsevierStyleSup">4&#44; 21</span> the percentage in our modest sample being of 22&#37;&#46;</p><p class="elsevierStylePara">All immunosuppressants go through the placental barrier&#44; so that the fetus is exposed to the toxicity of the different drugs&#46; With prednisone&#44; 90&#37; of the dose administered is metabolized at the placenta before reaching the fetus&#59; however&#44; there have been cases reported of adrenal suppression in the fetus&#46; With calcineurin-antagonists&#44; plasma levels have been detected in the fetus&#44; although at a concentration lower than in the mother&#46;<span class="elsevierStyleSup">22</span> The potential adverse effects may vary from major malformations to neurocognitive defects that may be only detected after birth&#46; According to the European Guidelines&#44; if the immunosuppressive therapy is based on calcineurin antagonists&#44; with or without steroids or azathioprine&#44; the patient may continue with the same treatment throughout the pregnancy&#46; Other drugs&#44; such as mycofenolate mofetil or mTOR inhibitors are not recommended&#46;<span class="elsevierStyleSup">7</span></p><p class="elsevierStylePara">We did not observe any malformation in the newborns&#46; According to the American Register&#44; the prevalence of structural malformations is 4-5&#37;&#44; very similar to the figure of 3&#37; in the series of pregnancies in the general population&#46;<span class="elsevierStyleSup">4&#44; 23</span> However&#44; although a particular pattern of malformation has not been shown to be associated with prednisone&#44; azathioprine or calcineurin antagonists&#44; some malformations have been related with the administration of mycofenolate mofetil&#44; so that it is recommended to discontinue this drug before conception&#46; <span class="elsevierStyleSup">24</span> The long-term effects from the exposure to immunosuppressants during the pregnancy are unknown&#46; In a study carried out on 48 children followed for an average time of 5&#46;2 years&#44;<span class="elsevierStyleSup">25</span> no structural or developmental abnormalities were observed&#44; although in this series the prematurity rate was 56&#37;&#46; In the American Register&#44;4 four percent of the newborns from a cohort of 164 patients transplanted with different solid organs had some structural abnormality&#44; although long-term followup of these children is not available&#46; In another study on 175 children exposed to cyclosporin during gestation&#44;<span class="elsevierStyleSup">26</span> 71 attended the primary school &#40;5-12 years&#41; and 24&#37; of them had delayed mental development&#46; Although not conclusive&#44; these data do indicate that it seems necessary that these children have a long-term neurocognitive follow-up&#46; It is likely that the data from the registers underestimate complications such as delayed fetal development&#44; preeclampsia&#44; and premature births&#44; all of them risk factors for neurocognitive impairment&#46;</p><p class="elsevierStylePara">Although our experience with only 10 cases has been satisfactory&#44; we may comment on two final issues&#46; In the first place&#44; many kidney-transplanted patients are not receiving the same immunosuppressive regimen as ours&#44; either because of early withdrawal of steroids&#44; or because of the combination with mycofenolate mofetil or switch from calcineurin antagonists to an mTOR inhibitor&#46; Since there are no safety data with these regimens&#44; they should be modified before the pregnancy&#44; taking into account the risks that this modification may represent&#46; On the other hand&#44; the information should be exact and individualized to each patient&#44; explaining in detail the potential risks&#44; although preserving the mother&#191;s right to choose&#46;</p><p class="elsevierStylePara">Although there are not definitive data in the literature&#44; and given that immunosuppressants have been detected in the breast milk at variable concentrations&#44; it seems wise to advise against breastfeeding&#44; which was done in our patients&#46;</p><p class="elsevierStylePara">To conclude&#44; post-renal transplantation pregnancy is quite safe with an immunosuppressive regimen based on steroids and tacrolimus&#44; with good outcomes when renal function is adequate before the pregnancy&#44; there is no proteinuria&#44; and the blood pressure is under control&#46; However&#44; post-renal transplantation pregnancy should still be considered as a high-risk gestation due to the complications that may occur in both the mother &#40;infection&#44; proteinuria&#44; anemia&#44; AHT&#44; and acute rejection&#41; and the fetus &#40;prematurity and low birth weight&#41;&#44;<span class="elsevierStyleSup">7</span> so that it should be approached in a multidisciplinary way&#44; and both the follow-up visits and immunosuppressants monitoring should be carried out more often&#46; </p>"
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        "resumen" => "El embarazo se contraindicaba en los inicios del trasplante renal&#44; pero actualmente la gestaci&#243;n es una parte m&#225;s de los beneficios que aporta el mismo&#46; El objetivo del estudio es analizar la viabilidad del embarazo post-trasplante renal y sus consecuencias a nivel de la paciente&#44; el injerto renal y el neonato&#46; Se revisaron diez pacientes trasplantadas renales embarazadas con una edad media de 29 a&#241;os y un tiempo medio post-trasplante de 44 meses&#46; El filtrado glomerular estimado medio fue de 64 ml&#47;min y la inmunosupresi&#243;n fue con corticoides y tacrolimus&#46; Se analiz&#243; la evoluci&#243;n de diferentes variables durante los meses de gestaci&#243;n y despu&#233;s del parto&#44; inherentes a la madre&#44; al injerto renal y al reci&#233;n nacido&#46; El embarazo lleg&#243; a t&#233;rmino en nueve de las diez pacientes&#44; seis por v&#237;a vaginal y tres con ces&#225;rea&#44; con solo un aborto espont&#225;neo en el primer trimestre&#46; La presi&#243;n arterial aument&#243; al final del embarazo y la creatinina se mantuvo estable durante los nueve meses con un incremento de la proteinuria a partir del tercer trimestre del embarazo&#46; La dosis de tacrolimus se tuvo que aumentar en el tercer trimestre del embarazo para conseguir los niveles deseados y no se detect&#243; ning&#250;n rechazo agudo durante el seguimiento&#44; apareciendo como &#250;nica complicaci&#243;n una pre-eclampsia que se resolvi&#243; con una ces&#225;rea&#46; El parto tuvo lugar a las 37&#44;2 semanas de media y los reci&#233;n nacidos presentaron un peso medio de 2&#46;809 g&#44; destacando dos reci&#233;n nacidos afectos de prematuridad&#47; bajo peso al nacer sin surgir ninguna complicaci&#243;n de inter&#233;s en los neonatos&#46; El embarazo post- trasplante renal es seguro con una pauta inmunosupresora basada en esteroides y tacrolimus&#44; con buenos resultados cuando antes del embarazo la funci&#243;n renal es correcta&#44; no hay proteinuria y la presi&#243;n arterial est&#225; controlada&#46;"
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        "resumen" => "When the field of transplantation was first developing&#44; physicians worried about the teratogenicity of immunosuppressive medications and considered pregnancy ill-advised&#46; The purpose of this study is to analyze pregnancy after kidney transplantation and their consequences on mother&#44; graft and child&#46; We rewiew ten pregnant women with kidney transplantation&#44; average of 29 years old and 44 months post-kidney transplantation&#46; The mean glomerular filtration rate was 64 ml&#47;min and the immunosuppression was with prednisone and tacrolimus&#46; We analyze outcomes of differents variables before and during pregnancy&#44; and after labour&#46; Pregnancy finished in nine of ten patients&#46; Three patients needed cesarean section and only one patient had a miscarriage on the first term&#46; Blood arterial pressure increased at the end of pregnancy and the creatinine level was stable with a few increase of proteinuria at the third term&#46; We increased the tacrolimus dose to obtain the correct blood levels and any rejection was detected&#46; We had only one patient with preeclampsia that we solved with a cesarean section&#46; Labours were a mean of 37&#46;2 weeks and the mean birth weight of infant was 2&#44;809 g&#46; Two newborns had prematurity without structural malformations&#46; Pregnancy after kidney transplantation is safe with prednisone and tacrolimus when the renal function is good&#44; proteinuria doesn&#191;t exist and blood pressure is controlled&#46;"
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                  "referenciaCompleta" => "Sgro MD, Barozzino T, Mirghani HM y cols. Pregnancy outcome post renal transplantation. Teratology 2002; 65: 5-9.  <a href="http://www.ncbi.nlm.nih.gov/pubmed/11835226" target="_blank">[Pubmed]</a>"
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Pregnancy in recipients of kidney transplantation: effects on the mother and the child
Embarazo en receptoras de trasplante renal: efectos en la madre y en el niño
Joan Manuel Díaz Gómeza, C.. Canala, I.. Giméneza, L.. Guiradoa, C.. Facundoa, R.. Solàa, J.. Ballarína
a Servicio de Nefrología, Fundació Puigvert, Barcelona, Barcelona, España,
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    "textoCompleto" => "<p class="elsevierStylePara"><span class="elsevierStyleBold">INTRODUCTION</span></p><p class="elsevierStylePara">In the first ages of renal transplantation pregnancy was contraindicated&#44; however the first offspring of a renal transplanted woman was born 48 years ago<span class="elsevierStyleSup">1</span> and since then the concepts have progressively changed&#44; so that nowadays it is considered that pregnancy is just another positive aspect of kidney transplant&#59; there are still several concerns about its effects on the mother and the fetus&#46;<span class="elsevierStyleSup">2</span> The patients with advanced chronic renal disease present hypothalamic-gonadal dysfunction leading to infertility in virtually all cases&#59; however&#44; 6 months after the transplant this gonadal dysfunction disappears giving rise to the possibility of conception&#46;</p><p class="elsevierStylePara">The most accurate data have been obtained from three specific registers on pregnancy and transplantation &#40;the European&#44; the American&#44; and the British&#41;<span class="elsevierStyleSup">3-5</span> reporting on the peculiarities that pregnancy entails for kidney-transplanted patients&#46; The most relevant data show that 24&#37;-34&#37; of them present a therapeutic or spontaneous miscarriage&#44; the prevalence of AHT is high&#44; preeclampsia is increased&#44; and in more than 50&#37; of the cases prematurity and low birth weight will occur&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">MATERIAL AND METHODS</span></p><p class="elsevierStylePara">An observational prospective study was carried out analyzing 10 kidney-transplanted patients that got pregnant&#44; with a mean age of 28&#46;9 years &#40;18-36&#41;&#46; The average post-transplantation time was 44 months &#40;12-113&#41;&#46; The mean glomerular filtration rate estimated by the MDRD equation was 64 mL&#47;min &#40;49-82&#41;&#44; and the immunosuppressive therapy that was given to all patients was prednisone 5 mg&#47;day and tacrolimus &#40;variable dosing to achieve plasma levels of 6-8 ng&#47;mL&#41;&#46;</p><p class="elsevierStylePara">We assessed different variables related with the renal graft&#44; during both the pregnancy months and after the delivery &#40;renal function&#44; proteinuria&#44; blood pressure&#44; tacrolimus doses and levels&#41;&#44; as well as other variables related with the delivery and the neonate&#46;</p><p class="elsevierStylePara">The results are expressed as means&#44; with the minimal and maximal values between brackets&#46;</p><p class="elsevierStylePara"><span class="elsevierStyleBold">RESULTS</span></p><p class="elsevierStylePara">After revising the course during gestation and the months after&#44; we observed that pregnancy was completed in nine patients and there was one spontaneous miscarriage during the first trimester&#46; The delivery was through natural way in 6 cases and a cesarean section was needed in 3 patients&#46;</p><p class="elsevierStylePara">The analysis of the blood pressure revealed an increase towards the end of the pregnancy&#44; of both the systolic BP and diastolic BP &#40;table I&#41;&#46; Only one patient was on hypotensive therapy before the pregnancy &#40;amlodipine&#41;&#44; which was maintained through it&#44; adding alpha-metildopa during the third trimester&#46; The remaining patients were not on anti-hypertensive therapy before the pregnancy and it was necessary to prescribe alpha-metildopa in one patient during the third trimester&#44; requiring an emergency cesarean section due to preeclampsia&#46;</p><p class="elsevierStylePara">Table I shows the renal function monitoring&#44; which remained stable during the pregnancy&#44; and proteinuria&#44; which slightly increased during the third trimester&#46; This table also shows that the dose of tacrolimus had to be increased to achieve the target plasma levels&#46; There was no case of acute rejection and there was only one case of preeclampsia that was resolved with the cesarean section&#46;</p><p class="elsevierStylePara">The delivery occurred at 37&#46;2 &#40;34-40&#41; weeks&#44; and the newborns weighed 2&#44;809 &#40;2&#44;040-3&#44;760&#41; grams&#44; with two newborns affected of prematurity-low birth weight&#46; However&#44; none of these neonates had remarkable complications&#46; </p><p class="elsevierStylePara"><span class="elsevierStyleBold">DISCUSSION</span></p><p class="elsevierStylePara">Our experience on the follow-up of post-transplantation pregnancy using prednisone and tacrolimus is satisfactory since there have not been any complications&#44; either in the mother or the fetus&#46; This is likely due to the fact that the patients met the recommendations set forth by both the &#171;Report on the AST Consensus Conference on Reproductive Issues and Transplantation&#187;<span class="elsevierStyleSup">6</span> and the European Guidelines<span class="elsevierStyleSup">7</span> for considering a pregnancy after renal transplantation &#40;table II&#41;&#46;</p><p class="elsevierStylePara">When analyzing the different published reviews of kidneytransplanted patients&#44; we observed that high blood pressure is prevalent among patients on calcineurin antagonists&#44; varying 47&#37;-73&#37; according to the different registers&#46;<span class="elsevierStyleSup">8-11</span> In our study&#44; we observed an increase in both systolic and diastolic blood pressure&#46; Preeclampsia occurs in 30&#37; of pregnant transplanted patients&#44;<span class="elsevierStyleSup">11&#44; 12</span> being a difficult diagnosis since blood pressure tends to increase after week 20&#44; and many patients already have mild proteinuria before the pregnancy&#44; in addition to increased uric acid levels&#46; Arterial hypertension may explain&#44; at least in part&#44; the fact that more than half of the pregnancies end up before the due date&#46; The management of AHT has to be aggressive<span class="elsevierStyleSup">13</span> and metildopa&#44; labetalol&#44; and calcium-hannel blockers may be safely used&#46;<span class="elsevierStyleSup">14 </span>Angiotensin-renin system inhibitors are formally contraindicated after the first trimester of pregnancy and&#44; id possible&#44; they should be discontinued before conception&#46; Since the effective plasma volume is decreased during the pregnancy&#44; diuretics are not recommended either&#44; with the exception of thiazides if the patient was taking them before&#46;</p><p class="elsevierStylePara">When analyzing the renal function&#44; we may highlight that in those patients with pre-existent renal dysfunction &#40;creatinine &#62; 1&#46;5 mg&#37; - &#62; 133 &#956;mol&#47;L&#41; the risk for graft loss is increased&#44; during both the pregnancy and after it&#44; so that pregnancy is not recommended in patients with values higher than these&#46; Although a study<span class="elsevierStyleSup">15</span> published in 1993 reported that the graft survival at 10 years was lower in patients that had got pregnant&#44; as compared with those that had not&#44; recent publications<span class="elsevierStyleSup">16</span>&#44;<span class="elsevierStyleSup">17</span> show that the survival rates for the graft and the patient after 15 years of follow-up are the same in transplanted patients that got pregnant after the transplant and in those that did not&#46; Graft dysfunction may be difficult to detect during the pregnancy given that usually creatinine levels go down during gestation&#44; particularly during the first and second trimesters&#44; as is observed in our sample&#59; sometimes rejection only manifests as mild increases of plasma creatinine levels&#46; If rejection presents&#44; it usually responds to methylprednisolone&#46; The safety of anti-lymphocytic globulins and rituximab is unknown&#46;</p><p class="elsevierStylePara">Adequate immunosuppression levels are necessary during the pregnancy&#46; As observed in our analysis&#44; the plasma levels of calcineurin antagonists may vary since during gestation there are changes in the distribution volume and the extracellular volume&#46;<span class="elsevierStyleSup">7&#44; 18</span> However&#44; most of the studies published have not recorded these levels&#46; In our study&#44; after analyzing the levels of tacrolimus&#44; we observed that the doses must be increased in order to reach the target range&#44; which is in agreement with those works monitoring this treatment&#46;<span class="elsevierStyleSup">19</span> On the other hand&#44; in a study carried out in 21 patients without modifying the dose of tacrolimus&#44; no episodes of acute rejection were observed&#46;<span class="elsevierStyleSup">20</span></p><p class="elsevierStylePara">According to the published guidelines&#44; although gestation in a kidney-transplanted patient should be considered a highrisk pregnancy&#44; the cesarean section would only be indicated for obstetric reasons&#59; however&#44; although in our series this occurred in 33&#37; of the patients&#44; other series have reported to occur in 50&#37; of the deliveries&#46;</p><p class="elsevierStylePara">The final outcome of only 10&#37; of miscarriages in our series differs from the data obtained when reviewing the European&#44; American&#44; and British registers&#44;<span class="elsevierStyleSup">3-5</span> in which spontaneous or therapeutic abortion occurs in 24-34&#37; of pregnant women&#46;</p><p class="elsevierStylePara">In our experience&#44; only two patients had non-complicated urinary tract infection&#46; The pregnancy in the kidney-transplanted patient increases the risk for infection&#44; especially bacterial infections&#46; About 40&#37; of pregnant women have urinary infection&#44; particularly in patients with chronic pyelonephritis or vesicouretheral reflux as the primary cause of renal disease &#40;a criterion that was met by our two patients&#41;&#46; For this reason&#44; it is recommended to perform a sediment analysis and urine culture monthly&#44; and if asymptomatic bacteriuria is present to treat with antibiotics for two weeks and then administering them prophylactically until delivery&#46;<span class="elsevierStyleSup">7</span></p><p class="elsevierStylePara">When analyzing the fetal complications&#44; we may highlight that the risk for prematurity and low birth weight is higher than 50&#37;&#44; and that for delayed intrauterine growth higher than 20&#37; according to the different series&#44;<span class="elsevierStyleSup">4&#44; 21</span> the percentage in our modest sample being of 22&#37;&#46;</p><p class="elsevierStylePara">All immunosuppressants go through the placental barrier&#44; so that the fetus is exposed to the toxicity of the different drugs&#46; With prednisone&#44; 90&#37; of the dose administered is metabolized at the placenta before reaching the fetus&#59; however&#44; there have been cases reported of adrenal suppression in the fetus&#46; With calcineurin-antagonists&#44; plasma levels have been detected in the fetus&#44; although at a concentration lower than in the mother&#46;<span class="elsevierStyleSup">22</span> The potential adverse effects may vary from major malformations to neurocognitive defects that may be only detected after birth&#46; According to the European Guidelines&#44; if the immunosuppressive therapy is based on calcineurin antagonists&#44; with or without steroids or azathioprine&#44; the patient may continue with the same treatment throughout the pregnancy&#46; Other drugs&#44; such as mycofenolate mofetil or mTOR inhibitors are not recommended&#46;<span class="elsevierStyleSup">7</span></p><p class="elsevierStylePara">We did not observe any malformation in the newborns&#46; According to the American Register&#44; the prevalence of structural malformations is 4-5&#37;&#44; very similar to the figure of 3&#37; in the series of pregnancies in the general population&#46;<span class="elsevierStyleSup">4&#44; 23</span> However&#44; although a particular pattern of malformation has not been shown to be associated with prednisone&#44; azathioprine or calcineurin antagonists&#44; some malformations have been related with the administration of mycofenolate mofetil&#44; so that it is recommended to discontinue this drug before conception&#46; <span class="elsevierStyleSup">24</span> The long-term effects from the exposure to immunosuppressants during the pregnancy are unknown&#46; In a study carried out on 48 children followed for an average time of 5&#46;2 years&#44;<span class="elsevierStyleSup">25</span> no structural or developmental abnormalities were observed&#44; although in this series the prematurity rate was 56&#37;&#46; In the American Register&#44;4 four percent of the newborns from a cohort of 164 patients transplanted with different solid organs had some structural abnormality&#44; although long-term followup of these children is not available&#46; In another study on 175 children exposed to cyclosporin during gestation&#44;<span class="elsevierStyleSup">26</span> 71 attended the primary school &#40;5-12 years&#41; and 24&#37; of them had delayed mental development&#46; Although not conclusive&#44; these data do indicate that it seems necessary that these children have a long-term neurocognitive follow-up&#46; It is likely that the data from the registers underestimate complications such as delayed fetal development&#44; preeclampsia&#44; and premature births&#44; all of them risk factors for neurocognitive impairment&#46;</p><p class="elsevierStylePara">Although our experience with only 10 cases has been satisfactory&#44; we may comment on two final issues&#46; In the first place&#44; many kidney-transplanted patients are not receiving the same immunosuppressive regimen as ours&#44; either because of early withdrawal of steroids&#44; or because of the combination with mycofenolate mofetil or switch from calcineurin antagonists to an mTOR inhibitor&#46; Since there are no safety data with these regimens&#44; they should be modified before the pregnancy&#44; taking into account the risks that this modification may represent&#46; On the other hand&#44; the information should be exact and individualized to each patient&#44; explaining in detail the potential risks&#44; although preserving the mother&#191;s right to choose&#46;</p><p class="elsevierStylePara">Although there are not definitive data in the literature&#44; and given that immunosuppressants have been detected in the breast milk at variable concentrations&#44; it seems wise to advise against breastfeeding&#44; which was done in our patients&#46;</p><p class="elsevierStylePara">To conclude&#44; post-renal transplantation pregnancy is quite safe with an immunosuppressive regimen based on steroids and tacrolimus&#44; with good outcomes when renal function is adequate before the pregnancy&#44; there is no proteinuria&#44; and the blood pressure is under control&#46; However&#44; post-renal transplantation pregnancy should still be considered as a high-risk gestation due to the complications that may occur in both the mother &#40;infection&#44; proteinuria&#44; anemia&#44; AHT&#44; and acute rejection&#41; and the fetus &#40;prematurity and low birth weight&#41;&#44;<span class="elsevierStyleSup">7</span> so that it should be approached in a multidisciplinary way&#44; and both the follow-up visits and immunosuppressants monitoring should be carried out more often&#46; </p>"
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        "resumen" => "El embarazo se contraindicaba en los inicios del trasplante renal&#44; pero actualmente la gestaci&#243;n es una parte m&#225;s de los beneficios que aporta el mismo&#46; El objetivo del estudio es analizar la viabilidad del embarazo post-trasplante renal y sus consecuencias a nivel de la paciente&#44; el injerto renal y el neonato&#46; Se revisaron diez pacientes trasplantadas renales embarazadas con una edad media de 29 a&#241;os y un tiempo medio post-trasplante de 44 meses&#46; El filtrado glomerular estimado medio fue de 64 ml&#47;min y la inmunosupresi&#243;n fue con corticoides y tacrolimus&#46; Se analiz&#243; la evoluci&#243;n de diferentes variables durante los meses de gestaci&#243;n y despu&#233;s del parto&#44; inherentes a la madre&#44; al injerto renal y al reci&#233;n nacido&#46; El embarazo lleg&#243; a t&#233;rmino en nueve de las diez pacientes&#44; seis por v&#237;a vaginal y tres con ces&#225;rea&#44; con solo un aborto espont&#225;neo en el primer trimestre&#46; La presi&#243;n arterial aument&#243; al final del embarazo y la creatinina se mantuvo estable durante los nueve meses con un incremento de la proteinuria a partir del tercer trimestre del embarazo&#46; La dosis de tacrolimus se tuvo que aumentar en el tercer trimestre del embarazo para conseguir los niveles deseados y no se detect&#243; ning&#250;n rechazo agudo durante el seguimiento&#44; apareciendo como &#250;nica complicaci&#243;n una pre-eclampsia que se resolvi&#243; con una ces&#225;rea&#46; El parto tuvo lugar a las 37&#44;2 semanas de media y los reci&#233;n nacidos presentaron un peso medio de 2&#46;809 g&#44; destacando dos reci&#233;n nacidos afectos de prematuridad&#47; bajo peso al nacer sin surgir ninguna complicaci&#243;n de inter&#233;s en los neonatos&#46; El embarazo post- trasplante renal es seguro con una pauta inmunosupresora basada en esteroides y tacrolimus&#44; con buenos resultados cuando antes del embarazo la funci&#243;n renal es correcta&#44; no hay proteinuria y la presi&#243;n arterial est&#225; controlada&#46;"
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        "resumen" => "When the field of transplantation was first developing&#44; physicians worried about the teratogenicity of immunosuppressive medications and considered pregnancy ill-advised&#46; The purpose of this study is to analyze pregnancy after kidney transplantation and their consequences on mother&#44; graft and child&#46; We rewiew ten pregnant women with kidney transplantation&#44; average of 29 years old and 44 months post-kidney transplantation&#46; The mean glomerular filtration rate was 64 ml&#47;min and the immunosuppression was with prednisone and tacrolimus&#46; We analyze outcomes of differents variables before and during pregnancy&#44; and after labour&#46; Pregnancy finished in nine of ten patients&#46; Three patients needed cesarean section and only one patient had a miscarriage on the first term&#46; Blood arterial pressure increased at the end of pregnancy and the creatinine level was stable with a few increase of proteinuria at the third term&#46; We increased the tacrolimus dose to obtain the correct blood levels and any rejection was detected&#46; We had only one patient with preeclampsia that we solved with a cesarean section&#46; Labours were a mean of 37&#46;2 weeks and the mean birth weight of infant was 2&#44;809 g&#46; Two newborns had prematurity without structural malformations&#46; Pregnancy after kidney transplantation is safe with prednisone and tacrolimus when the renal function is good&#44; proteinuria doesn&#191;t exist and blood pressure is controlled&#46;"
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Article information
ISSN: 20132514
Original language: English
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