Predictors of Pregnancy Outcome in Renal transplant Recipients

PREDICTORS OF PREGNANCY OUTCOME IN RENAL TRANSPLANT RECIPIENTS K. Mujaibel, MD, FRCSC,' D. Farquharson, MD, FRCSC,' R.D.Wilson, MD, FRCSC' I

Division of Maternal Fetal Medicine, British Columbia's Women's and Children's Hospital,Vancouver BC

Abstract Objective: To identify preconceptional risk predictors specific to renal transplant patients. Methods: Preconception selection criteria which influenced the perinatal outcome in 23 pregnancies in 20 renal transplant patients at British Columbia's Women's and Children's Hospital in the period I989 to 1999 were retrospectively analyzed. Successful pregnancy outcome in this series was defined as delivery after 34 weeks, birth weight appropriate for gestational age, stable renal graft function, and no evidence of rejection within at least two years after the pregnancy. Results: Seventy-five percent of patients with preconceptional serum creatinine of less than 125 jJmollL had successful pregnancy outcomes compared to 25 percent of those with serum creatinine greater than 125 jJmol/L (p = 0.1 I). Fifteen percent of patients with pre-existing proteinuria of one to three g per day had worsening proteinuria, renal graft function, and hypertension, and subsequently had graft rejection (p = 0.0006). Seventy-two percent of patients with poorly controlled hypertension delivered prior to 34 weeks (p = 0.008). Renal graft rejection was strongly associated with prepregnancy creatinine more than 125 jJmol/L (p = 0.004), preexisting proteinuria more than one g per day (p = 0.00 I), and poorly controlled chronic hypertension (p = 0.04). Prematurity due to obstetric intervention with worsening maternal or fetal condition (28%) was the major contributor to perinatal morbidity and mortality. Intrauterine growth restriction was observed in 23 percent of these pregnancies. Conclusion: Pregnancy does not have a detrimental effect on renal graft survival, provided that renal graft function is normal at the time of conception. Resume Objectif : Definir les predicteurs de risque preconceptionnels chez les patientes ayant subi une transplantation de rein. Methode: On a analyse, de maniere retrospective, des criteres de selection avant la conception ayant influence I'issue perina-

tale de 23 grossesses chez 20 patientes qui avaient subi une transplantation du rein au Women's and Children's Hospital de la Colombie-Britannique, de 1989 it 1999. Dans cette serie, Ie succes de I'issue de grossesse a ete defini comme un accouchement ayant lieu apres 34 semaines, un nouveau-ne ayant un poids de naissance adequat pour son age gestationnel, une fonction du rein transplante stable et aucun signe de rejet pendant au moins deux ans apres la grossesse. Resultats : Soixante-quinze pour cent des patientes dont la creatinine serique etait de moins de 125 mmol/l ont eu des issues de grossesse reussies, comparativement it 25 pour cent pour celles dont la creatine serique etait de plus de 125 jJmol/l (p = 0, I I). Quinze pour cent des patientes ayant une proteinurie pre-existante d'un a trois grammes par jour ont connu une aggravation de leur proteinurie, de la fonction du rein transplante et de I'hypertension et, plus tard, un rejet du rein transplante (p = 0,0006). Soixante-douze pour cent des patientes ayant une hypertension mal contr61ee ont accouche avant la 34e semaine (p = 0,008). Le rejet de la greffe renale eta it fortement lie it une concentration de creatinine, avant la grossesse, de plus de 125 jJmol/l (p = 0,004), une proteinurie pre-existante de plus d'un gramme par jour (p = 0,00 I) et une hypertension chronique mal contr61ee (p = 0,04). Le principal facteur contribuant it la morbidite et a la mortalite perinatales etait la prematurite due a une intervention obstetricale, en raison d'une situation maternelle ou fcetale qui s'aggravait (28 %). On a constate une restriction de croissance intra-uterine de 23 pour cent dans ces grossesses. Conclusion: La grossesse n'a pas un effet prejudiciable it la survie pour les patientes ayant eu une transplantation renale, pourvu que la fonction du rein transplante so it normale au moment de la conception.

J Obstet

Gynaecol Can 200 I;23( I0):939-44.

INTRODUCTION

After successful renal transplant, one in 50 women of childbearing age will become pregnant. 1 Davison 2 found 92 percent of pregnancies that persisted beyond the first trimester ended with delivery beyond 28 weeks while maintaining stable renal graft function, in a population of 2309 pregnancies in 1594 renal transplant patients. Acute allograft rejection occurred during nine percent of pregnancies, an incidence no different from

KeyWords Renal transplant, hypertension, immunosuppressive therapy, serum creatinine, proteinuria, intrauterine growth retardation Competing interests: none declared. Received on August 22, 2000. Revised and accepted on March 2, 200 I.

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that among nonpregnant renal transplant patients. 2 However, 30 percent of pregnancies were complicated by hypertension or preeclampsia. Preterm delivery was seen in 50 percent of cases, and 25 percent of newborn infants were small for gestational age. 2 Retrospective analyses of pregnancies in renal transplant recipients, including case reports, centre reports, and questionnaire surveys, have concluded that in the presence of stable renal function these high-risk pregnancies are generally well tolerated. 2-6 However, the majority of the liveborn outcomes are premature and many of the newborns are low birth weight. Potential maternal complications include an increased risk for the development of chronic hypertension,2 preeclampsia2 or permanent deterioration in renal graft function and allograft rejection. \-6 Continued efforts to identifY preconceptional risk factors specific to renal transplant patients as well as optimizing antenatal management strategies will help to improve pregnancy outcome in this population.

TABLE I ETIOLOGIES OF MATERNAL RENAL INSUFFICIENCY Etiology

n

Chronic pyelonephritis

4

Infantile polycystic kidney disease

4

Chronic glomerulonephritis

6

Chronic vasculitis

5

Hypoxic ischemic insult at birth

I

(due to vasa previa)

STATISTICS

METHODS

Analysis was performed using descriptive statistics in the SPSS 10.0 package. Statistical significance was evaluated using the chi-square test, with a p-value of < 0.05 considered statistically significant.

PROCEDURE

RESULTS

We conducted a retrospective chart review of women with a renal transplant referred for preconceptional counselling and pregnancy management to British Columbia's Women's and Children's Hospital from 1989 to 1999. All our subjects were maintained on a combination of prednisone, cyclosporine, and azathioprine. The following predictors of pregnancy outcome in renal transplant recipients were evaluated: • • • • • • • • •

underlying etiology of renal insufficiency transplant to pregnancy interval age at transplant type of graft age at first pregnancy after transplant number of pregnancies since transplant pre-existing hypertension/superimposed hypertension renal function prior to/during pregnancy the type of immunosuppressive treatment used.

Some of these preconceptual risk factors have been addressed previously. However, we intended to evaluate the effect of all the possible contributing £actors to provide sufficient information for proper counselling of this high-risk population. The pregnancy outcome was evaluated with reference to maternal and perinatal complications. Maternal outcome evaluation included worsening of existing hypertension, development of chronic hypertension, worsening renal function, and allograft rejection. Perinatal outcome evaluation included the risk of congenital malformation, prematurity, and growth restriction. Significant neonatal complications specific to the offipring of renal transplant patients, including respiratory distress syndrome, pancytopenia, and infections, were also evaluated. JOGC

Twenty-four patients with renal transplant were referred for preconceptional counselling and pregnancy management between 1989 and 1999. Twenty charts had sufficient information for inclusion. The etiologies of maternal renal insufficiency are shown in Table l. The mean age at transplant was 17 years (range 4-30). Seventy percent of subjects had cadaveric transplants, with the remainder being live related transplants. The average time from transplant to pregnancy was seven years (range 2-18). The average maternal age at conception was 28 ± 5.7 years (range 1939). There were a total of 25 pregnancies, with five women having two pregnancies after the transplant and one woman having twins. Eighty percent of pregnancies in this series occurred more than four years after renal transplant, with one subject having her first pregnancy 18 years after transplant. Twenty-five percent of subjects underwent renal transplant at less than 20 years of age. All subjects had maintained stable renal function during and after pregnancy. Maternal age was not associated with increased risk of deterioration in graft function or poor perinatal outcome. Subjects who had received cadaveric transplants and had stable renal function prior to pregnancy did not have significantly different pregnancy outcomes to those who had received live related transplants. Five subjects went on to have a second pregnancy. In three of these subjects renal function remained stable. Another subject had worsening proteinuria with elevation in serum creatinine that persisted after her second pregnancy. The fifth subject had deterioration in her graft function during the first pregnancy and subsequently underwent a second transplant. Her renal OCTOBER 200 I

function remained stable over the next two pregnancies. Her third pregnancy was a twin gestation and was well tolerated. In our series, two subjects had conditions causing renal compromise. One of these subjects had systemic lupus erythromatosus (SLE) with unstable graft function prior to conception, and subsequently developed worsening renal function and severe preeclampsia at 35 weeks. She delivered a growth-restricted baby, and underwent significant postpartum hemorrhage. Renal function continued to worsen postpartum, although it was unknown at the time of writing this paper whether this was due to reactivation of SLE, graft rejection, or hypoxic ischemic insult to the renal graft secondary to postpartum hemorrhage. The other subject had mixed connective tissue disease with stable renal function and well-controlled hypertension prior to pregnancy, and subsequently had two uneventful pregnancies. Pregnancy outcome was successful (as defined) in 11 of 16 subjects with preconceptional serum creatinine of less than 125 rmol/l, while only one of the four subjects with preconceptional serum creatinine higher than 125 rmolll had a successful outcome. A significant elevation in serum creatinine was observed in 15 (75%) of subjects, from a preconception baseline of 125 ± 58 rmolll to 147 ± 55 rmol/l (p = 0.04). However, this elevation persisted postpartum in only four of these subjects. Three of these subjects continued to have elevated levels six weeks postpartum; all three had superimposed severe gestational hypertension with a significant reduction in creatinine clearance during the pregnancy (p = 0.03). Four women had preconceptional proteinuria one to three giL per 24 hours, and all had demonstrated significant elevation of proteinuria during pregnancy (p = 0.001). The preconceptional proteinuria seen in three of these women worsened with advancing pregnancy together with diminishing renal graft function, increasing hypertension, and subsequent graft rejection. Four subjects developed proteinuria during their pregnancies, which persisted postpartum in three of them. Sixteen subjects had pre-existing hypertension, and in 12 of these it intensified during pregnancy. The remaining four women developed hypertension during pregnancy, which persisted postpartum. Five of seven subjects with poorly controlled hypertension prior to conception delivered before 34 weeks, and all of their babies were small for gestational age (IUGR). Three women had transient deterioration of renal graft function, defined as persistent elevation of serum creatinine, coupled with significant reduction of creatinine clearance or persistent proteinuria for six months postpartum. These patients also had uncontrolled hypertension of more than five years duration, which intensified during the pregnancy. However, none of these subjects had graft rejection in two years from the index pregnancy. Graft survival at two years postpregnancy was 85 percent, with graft rejection occurring in three subjects. These three subjects had a repeat transplant within two years of the pregnancy. JOGC

Graft rejection was strongly associated with a preconceptional creatinine of more than 125 rmol/l, pre-existing proteinuria of more than one g per 24 hours, and poorly controlled hypertension. The diagnosis of rejection was confirmed retrospectively by renal biopsy in one subject, and questioned in the other two. Factors associated with renal allograft rejection are shown in Table 2. NEONATAL OUTCOME

Eighteen subjects delivered at or beyond 34 weeks gestational age, six delivered between 28 and 33 weeks, and one delivered before 28 weeks. The most common indications for delivery were worsening hypertension and deterioration in renal function. There were 10 spontaneous vaginal deliveries and 15 Caesarean sections, most of which were done for obstetric reasons (fetal distress, failure to progress, repeat Caesarean section, antepartum hemorrhage). One Caesarean section was performed due to suspected obstructed labour by the renal graft. Nineteen infants were appropriate weight for gestational age (defined as the 10th to 90th percentile), and six were growrhrestricted (below the 10th percentile). Intrauterine growth restriction was associated with abnormal maternal renal function (p = 0.05) and poorly controlled hypertension prior to pregnancy (p = 0.03). The major predictors of neonatal morbidity were gestational age at delivery and birth weight. Respiratory distresses of varying severity and gestational age less than 34 weeks were the major predictors of neonatal intensive care unit admissions. There was no significant neonatal infection (either congenital or acquired) or myelosupression with in utero exposure to immunosuppressive therapy. Perinatal mortality was eight percent, which is higher than generally reported,7 but in neither case could the cause of death be directly attributed to maternal graft dysfunction. One fetus was stillborn at 24 weeks after idiopathic preterm rupture of membranes and chorioamnionitis. The other was diagnosed with congenital hydronephrosis and severe oligohydramnios at 20 weeks, was delivered by Caesarean section for fetal distress at 29 weeks, and subsequently died in the neonatal period due to severe respiratory distress TABLE 2

FACTORS ASSOCIATED WITH RENAL ALLOGRAFT REJECTION

·serum creatinine more than ISO ~mol/l prior to pregnancy ·prepregnancy proteinuria more than I giL per 24 hours ·significant decrease in creatinine clearance during pregnancy and postpartum ·chronic uncontrolled hypertension of more than five years duration ·cadaveric transplant ·transplant-pregnancy interval of more than five years ·evidence of rejection within at least one year prior to pregnancy OCTOBER 200 I

TABLE 3 MATERNAL FACTORS ASSOCIATED WITH POOR NEONATAL OUTCOMES·

• • • • • •

serum creatinine more than 125 ~molll preconception proteinuria greater than I gIL poorly controlled hypertension unstable renal function prior to or during pregnancy chronic hypertension of more than five years duration preeclampsia

* Poor neonatal outcome defined as delivery less than

32 weeks and/or intrauterine growth restriction and/or neonatal morbidity.

syndrome and pulmonary hypoplasia. Maternal risk factors associated with poor neonatal outcome are shown in Table 3. DISCUSSION

Childbearing in patients with renal transplant remains highrisk. Obstetric outcome in patients with renal graft is usually successful provided that renal function is stable and hypertension is controlled?-11 In general, pregnancy does not appear to adversely affect the natural history of renal disease. 10 In a casecontrolled study of 45 renal transplant SLE patients matched with a non-SLE transplant group, pregnancy rates and outcome were similar, with no deleterious effects on patients or the graft provided that disease remained quiescent during pregnancy and preconception renal function was stable. 12 In our series, the underlying etiology of renal insufficiency was not significantly associated with perinatal outcome. The National Transplantation Pregnancy Registry (NTPR) has found a significantly greater frequency of very low birth weight infants and neonatal death with shorter transplant-pregnancy intervals. 11 ,13 Extended intervals, however, were not associated with any deleterious effect on renal graft function or pregnancy outcome provided that renal function was well preserved and hypertension was controlled prior to conception. 13,14 Extended transplant-pregnancy interval in our series was not associated with poor perinatal outcome, deterioration in renal function, increased risk of rejection, or low birth weight. Cadaveric transplant may be a negative factor on graft survival due to pre-transplantation ischemic insults, which could be accentuated during pregnancy, IS but this was not found in other studies l6 or in our series. Repeated pregnancy does not adversely affect graft function. Enrich et at.17 reported successful subsequent pregnancies after renal transplant in 102 patients. Fourteen percent of these women who had a successful pregnancy after renal transplant subsequently had a second healthy baby. Ninetyfour percent of these women had the same renal graft in both pregnancies. 17 Four of our subjects maintained the original JOGC

renal graft throughout their second pregnancy. One of our subjects had unstable renal graft function and her graft was rejected after the second pregnancy. The overall outcome with multiple gestation is favourable in properly selected renal transplant recipients. 18 In our series, there was a successful rwin pregnancy after a second renal transplant. Renal function may deteriorate in 10 to 15 percent of renal transplant patients during the pregnancy, and this deterioration may be permanent. 19 Several case control studies, limited by small study populations, found no adverse effect of pregnancy on renal graft function as long as renal function was stable at the time of conception?,19 One case controlled study, also limited by the small sample, did suggest an adverse effect of pregnancy on renal function. 2o However, this decline in renal function cannot be attributed to pregnancy alone. 21,22 The sustained increase in glomerular filtration rate (CFR) characteristic of early pregnancy is evident in renal transplant recipients, even though the transplant is ectopic, denervated, potentially damaged by previous ischemia, and immunologically different from the recipient and her fetus. 22 -24 Therefore the more stable the renal function prior to pregnancy, the greater the increment in CFR during pregnancy and the greater the likelihood of successful pregnancy outcome. 22 .24 Worsening renal function during pregnancy could be attributed to preeclampsia, cyclosporine toxicity, rejection, pyelonephritis, volume contraction, recurrence of the underlying disease, or obstruction by the gravid uterus. It is vital to differentiate berween these factors. The specific cause must be quickly determined to prevent further renal damage. An appropriate workup for deteriorating renal graft function has been suggested by Hou.2l Preeclampsia developed in eight (40%) of our subjects, a slightly higher incidence than previously reported. Four of these women had unstable graft function and uncontrolled chronic hypertension prior to pregnancy. Hypertension, particularly before 28 weeks gestation, is associated with adverse perinatal outcome in renal graft recipients. 25 This could be due to covert microvascular changes that accompany or are aggravated by chronic hypertension. 25 Pregnancy is characterized by dilatation of the afferent arteriole of the glomerulus and greater transmission of systemic blood pressure into the glomeruli. Therefore, aggressive treatment of systemic hypertension prior to and during pregnancy may decrease the intraglomerular hydrostatic pressure and hence decrease the rate of deterioration in renal function. 23 ,25 In our series, successLtI pregnancy outcome was associated with the degree of control (p = 0.008) rather than the duration of hypertension (p = 0.3). Proteinuria prior to conception is a potent parameter to predict renal graft function deterioration following pregnancy.26 Proteinuria occurs near term in 40 percent of renal graft recipients but disappears within three months postpartum. 24 Our results, following Kozlowska et aL,27 showed that subjects suffering from graft deterioration following delivery demonstrated OCTOBER 200 I

a higher preconception proteinuria rate than subjects with stable graft function. Eventually these unstable patients developed typical features of chronic rejection. 27 Whether proteinuria developing for the first time during pregnancy, especially if associated with persistent elevation of serum creatinine, represents an acceleration of subclinical chronic rejection, remains unclear. 2o•27 It is essential to identifY the causes of elevation of serum creatinine or proteinuria in the postpartum period, as these may represent subclinical chronic renal graft rejection that may have become more pronounced during conception secondary to pregnancy-induced renal hyperfiltration. NTPR data supports maintaining immunosuppression at appropriate levels during pregnancy to avoid rejection. 28 At present, most immunosuppressive maintenance regimens include combination therapy, usually cyclosporine or tacrolimus (class C) based (Table 4). The incidence of congenital malformation is not increased above the background risk of three percent with the use of these regimens. There are inadequate long-term follow-up studies to address the possible risks of developmental abnormalities, childhood malignancy or infertility in the offspring of renal transplant recipients exposed to these drugs.28 Wong et al evaluated 10 children ages 15 months to 18 years who were born to women with renal grafts, and noted that TABLE 4

IMMUNOSUPPRESSIVE DRUGS USED IN RENAL TRANSPLANT2 I ,28 Drug (FDA classification) Prednisone (class B)

Comments - neonatal hypoglycemia - neonatal adrenal insufficiency - thymic hypolasia - maternal infection, glucose intolerance

Cyclosporine (class C)

- growth restriction - maternal hypertension

Azathioprine (class D)

- neonatal myelosuppression - growth restriction - reversible chromosomal damage

developmental milestones, school/work performance, and social behaviours were normal. 29 In our series, the incidence of maternal infection, liver or renal toxicity or myelosuppression did not increase. There was also no increased incidence of congenital anomalies, neonatal infections, adrenal suppression or thrombocytopenia with in utero exposure to maternal immunosuppressive treatment. Chronic rejection, which usually has a progressive subclinical course, remains the single most important cause of renal allograft loss after the first year post-transplant. 28 Whether pregnancy affects the course of chronic rejection remains unclear. The incidence of rejection in our subjects was 15 percent (3 women), similar to literature values (9_15%).8.19 These three subjects had unstable renal graft function and rejection episodes proven by biopsy within one year prior to pregnancy. As chronic rejection is the aggregate of irreversible immunological and non-immunological injuries to the renal graft over time,27 preconceptional renal evaluation is important to identifY the possible etiology of renal injury and establish a strategy that aims to minimize these insults during pregnancy. The incidence of neonatal morbidity, prematurity, and growth restriction is increased in pregnancies associated with renal graft. 30 The European Dialysis and Transplant Association Registry (EDTA)30,31 and NTPR8,32 have reported a two to 2.8 percent mortality rate for infants of mothers with a functioning renal graft. Within this group, the neonatal mortality rate was lower for those with maternal serum creatinine less than 160 )lmolll (1.2% compared to 5.5% if more than 160 )lffiolll)31 and in those pregnancies exposed to cyclosporine as compared to those not exposed (0.9% compared to 2.4%).8 Data from the NTPR8,32 and EDTA31 along with case series 21 ,29 reported a 50 percent incidence of preterm delivery « 37 weeks) in renal transplant recipients, with 30 percent of these deliveries occurring before 34 weeks, similar to our experience. In these reports, 14 to 45 percent of liveborn infants were growth restricted. 29 ,31 The relative risk for growth restriction in our series increased with maternal hypertension, prep regnancy serum creatinine of greater than 150 )lmolll, increasing serum creatinine during pregnancy, and graft dysfunction, similar to the data reported by NTPR.30

in peripheral blood lymphocyte Tacrolimus (class C)

- neonatal hyperkalemia and anuria - used only if cyclosporine is not effective in cases of repeated rejection

CONCLUSION

We have found, consistent with many international studies,8,9,17,19.31.32 that pregnancy has no detrimental effect on renal graft survival, provided that graft function was stable at the time of conception. Of the nine variables assessed in this first single tertiary centre experience in Canada, serum creatinine less than 125 )lmol/!, minimal proteinuria, no evidence of rejection, and a satisfactory degree of hypertension control were the major predictors of successful pregnancy outcome in renal graft recipients. Underlying etiology of renal insufficiency, duration of

Mycophenolate (class C) - no data in human pregnancy - embryo-toxic in animals

= no evidence of risk in humans = risk cannot be ruled out Class D = positive evidence of risk FDA = Food and Drug Administration Class B

Class C

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hypertension, maternal age at transplantation or first pregnancy, age of graft at conception, type of immunosuppressive drugs, and repeated pregnancies had no major impact on perinatal outcome, provided that renal function was well-preserved at the time of conception. Prematurity and birth weight are the major contributors to neonatal morbidity in renal graft recipients. Although there is no adverse effect of pregnancy on graft function or survival, women with a renal graft which has been functioning well prior to pregnancy should be counselled to expect an increased risk of pregnancy complications. REFERENCES I. 2. 3. 4. 5.

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19. Davison JM, Milne JEe. Pregnancy and renal transplantation. Br J Urol I997;80(suppl 1):29-32. 20. Salmela KT. Impaired renal function after pregnancy in renal transplant recipients. Transplantation 1993;56: 1372-5. 21. Hou S. Pregnancy in chronic renal insufficiency and end stage renal disease. Am J Kidney Dis 1999;33(2):235-52. 22. Davison JM. The effect of pregnancy on kidney function in renal allograft recipients. Kidney Int 1985;27:74-9. 23. Davison JM, Hytten FE. Glomerular filtration rate during and after pregnancy. J Obstet Gynaecol 1982;27:613-21. 24. Davison JM, Lindheimer MD. Pregnancy in renal transplant recipients. J Reprod Med 1982;27:613-21. 25. Sturgiss SN, Davison JM. Perinatal outcome in renal allograft recipients: prognostiC significance of hypertension and renal function before and during pregnancy. Obstet Gynecol 1991 ;78(4):573-7. 26. Kozlowska-Boszko B. Predictors of transplanted kidney deterioration following pregnancy: daily urine protein loss or serum creatinine concentration? Ann Transplant 1996; I (4):30-1. 27. Kozlowska-Boszko B, Lao Z, Gaciong J, et al. Chronic rejection as a risk factor for deterioration of renal allograft function following pregnancy. Transplant Proc 1997;29: 1522-3. 28. ArmentiVT, Moritz MJ, Davison JM. Drug safety issues in pregnancy following transplantation and immunosuppression: effect and outcome. Drug Saf 1998; 19(3):219-32. 29. Wong KM, Bailey RR, Lynn KL, Robson RA, Abbott GD. Pregnancy in renal transplant recipients: the Christchurch experience. NZ Med J 1995; I08: 190-2. 30. Blowey DL,Warady BA. Neonatal outcome in pregnancies associated with renal replacement therapy. Adv Ren Replace Ther I998;5( I): 1998. 31. Rizzoni G, Ehrich JH, Broyer M, Brunner FP. Brynger H, Fassbinder W, et al. Successful pregnancies in women on renal replacement therapy: report from the EDTA Registry. Nephrol Dial Transplant 1992;7:279-87. 32. ArmentiVT, McGrory CH, Cater JR, Radomski JS, Moritz MJ. Pregnancy outcomes in renal transplant recipients. Transplant Proc 1998;30: 1732-4.

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