Renal transplantation and pregnancy

Renal transplantation is usually accompanied by an improvement in reproductive function. The possibility of conception in women of childbearing age emphasizes the need for counseling, and couples who want a child should be encouraged to discuss all implications, with the advice based on strict guidelines. If a recipient becomes pregnant, she must be monitored as a high-risk patient. Management requires particular attention to BP control, renal function, and all infection, as well as fetal surveillance. Just under 40% of conceptions do not go beyond the first trimester, but of those that do, greater than 90% end successfully. In most patients, renal hemodynamics improve during gestation, but permanent impairment occurs in 15% of pregnancies. Other patients may experience transient deterioration in late pregnancy (with or without proteinuria). Patients have a 30% chance of developing hypertension, preeclampsia, or both. Despite its pelvic location, the transplanted kidney rarely produces dystocia and experiences no apparent mechanical injury during vaginal delivery. Thus, cesarean section should be reserved for obstetric reasons only. Aseptic technique, bacterial prophylaxis even for trivial surgery, and steroid augmentation are necessary. Preterm deliveries occur in 45% to 60%, and intrauterine growth retardation in at least 20%, of gestations. Neonatal complications include respiratory distress syndrome, leukopenia, thrombocytopenia, adrenocortical insufficiency, and infection. No predominant or frequent developmental abnormalities have been described, and data on infancy and childhood are encouraging. Future goals should be to improve prepregnancy assessment criteria, to reassess the rationale and implications of immunosuppression during pregnancy, and to monitor the remote effects of pregnancy on both renal prognosis and the offspring.     

Pregnancy and renal transplantation

Ovarian dysfunction, anovulatory vaginal bleeding, amenorrhea, high prolactin levels, and loss of libido are the causes of infertility in women with chronic renal failure. After renal transplantation, endocrine function generally improves after recovery of renal function. In this study we retrospectively evaluated the prepregnancy and postdelivery renal function, outcome of gestation, as well as maternal and fetal complications for eight pregnancies in eight renal transplant recipients between November 1975 and March 2003 of 1095 among 1425. Eight planned pregnancies occurred at a mean of 3.6 years posttransplant. Spontaneous abortion occured in the first trimester in one case. One intrauterine growth retardation was observed with a full-term pregnancy; one intrauterine growth retardation and preterm delivery; one preeclampsia with preterm delivery and urinary tract infection; and one preeclampsia with preterm delivery and oligohydramnios. The mean gestation period was 35.5 +/- 3.0 weeks (31.2 to 38.0). Pregnancy had no negative impact on renal function during a 2-year follow-up. No significant proteinuria or acute rejection episodes were observed. Among the seven deliveries, no congenital anomaly was documented and no postpartum problems for the child and the mother were observed. Our study suggests that successful pregnancy is possible in renal transplant recipients. In cases with good graft function and absence of severe proteinuria or hypertension, pregnancy does not affect graft function or patient survival; however, fetal problems are encountered such as intrauterine growth retardation, low birth weight, and preeclampsia.     

Pregnancy in renal transplant recipients

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.     

Outcome of Pregnancy in Women with Glomerular Diseases

Over the last 16 years the evolution of 24 pregnancies in 17 women with biopsy-proven glomerular disease was analyzed. The underlying renal histology was IgA nephropathy in 8 cases, lupus nephritis in 7, mesangiocapillary glomerulonephritis type I in 1, and focal segmental glomerulosclerosis in 1. All but 2 had normal renal function before conception and 3 were hypertensive. Fetal survival rate was 75%. There were 6 preterm deliveries (33.3%), 3 newborns small for gestational age (17%), 1 stillbirth, and 5 therapeutic abortions. The perinatal mortality was 5.5%. De novo hypertension occurred in 8 pregnancies (33.3%). In 11 pregnancies (46%) increased proteinuria was diagnosed and in 6 (25%) a decline in maternal renal function was recorded. Permanent impairment of renal function was seen in 2 women with renal insufficiency before conception. Maternal hypertension and renal function impairment were associated more frequently with obstetric complications. In conclusion, pregnancy is safe for normotensive mothers with glomerular diseases and normal renal function. Hypertension and impaired renal function at conception seem to carry increased risk for mothers and fetuses. Low-dose immunosuppressive treatment during pregnancy is not harmful for the fetus.     

Pregnancy in renal transplant patients: a review.

A questionnaire survey and review of the literature show that pregnancy can be well tolerated in most women with renal transplants. Fifty-two per cent of the renal transplant recipients who became pregnant had full-term infants with no serious complications. With therapeutic abortions, excluded, 71% of the 308 pregnancies permitted to continue resulted in full-term infants. Rejection episodes were occasionally a serious problem, occurring in 9% of the pregnancies. Mechanical interference with renal excretion or preventing vaginal delivery occurred in 5.6% of the cases. Hypertension and proteinuria, often existing prior to pregnancy, became frequently increased during pregnancy. Infections not associated with rejection were common but easily controlled in most cases. Prematurity was frequent but related to renal function and the time interval from transplant to conception. The most serious infant complications were related to prematurity. Unknown is the future of these infants and their progeny because of their intrauterine exposure to immunosuppressive drugs.     

Pregnancy in women with chronic renal disease: a 14-year study.

Between 1975 and 1988 authors encountered 44 pregnancies in 26 women who had had chronic renal disease and unimpaired renal function before the conception. Complications during pregnancy and the outcome of pregnancy were studied. There were 5 spontaneous abortions between the 11th and 20th weeks of gestation, 1 therapeutic abortion, 3 still births at weeks 28, 32 and 33, 6 neonatal deaths at age of 26 to 35 weeks, 11 preterm newborns, 35 live births, 9 infants with intrauterine growth retardation including 4 preterm newborns and 1 fetal malformation and 2 cases with premature rupture of the fetal membranes. The pregnancies were complicated with anaemia in 23 cases, with urinary tract infection in 19, with hypertension in 16, with proteinuria in 12 and with edema in 11 cases. Increase in the serum creatinine value during pregnancy was found in 6 cases. These data indicate that the pregnancy in patients with chronic renal disease who had normal renal function before the planned conception, is accompanied with increased risk for both the mother and child.     

Pregnancy outcome after renal transplantation

AIMS: The aim of our study was to evaluate the frequency and the outcome of pregnancies in renal transplant recipients at our center. METHODS: This study involved the retrospective analysis of 405 childbearing female renal recipients for presence of risk factors, the outcome of pregnancy, and maternal and fetal complications. RESULTS: Fourty-four pregnancies occurred in 41 patients (10.8%). Mean age at transplantation was 23.6 +/- 6.3 years (range, 12-38 years). Only in 5 pregnancies were there no risk factors. In 13 (29.5%) pregnancies, the previous creatinine level was >1.5 mg/dL, in 16 (36.45%), proteinuria was >500 mg/24 hours; 29 (65.9%) were hypertensive; 14 (31.8%) had a time between transplantation and pregnancy less than 2 years (mean time, 35.5 +/- 30.9 months; range, 3-120 months). The outcomes were 27 (61.4%; 11 term and 16 premature delivery) successful pregnancies, 6 (13.6%) spontaneous abortions, 10 (22.7%) therapeutic abortions, and 1 (3.2%) fetal death. Pre-eclampsia occurred in 9 (20.4%) pregnancies and eclampsia in 1 (2.2%). The mean weight of the offspring was 2195 +/- 490 g (range, 1300- 2980 g). There were 2 cases of acute fetal distress and 1 oligodramnios. Median creatinine level was 1.0 (range, 0.4-3.0) mg/dL before conception and 1.2 (range, 0.7-9.0) mg/dL 6 month after pregnancy (P <.001). The long-term patient and graft survival rates were similar for pregnant versus nonpregnant recipients in the childbearing age. CONCLUSION: Most pregnancies were successful, although the premature delivery rate was high (36.4%). Only 5 conceptions occurred in the absence of risk factors. Pregnancy did not impair the patient and graft survival during long-term follow-up.     

Membranous glomerulonephritis and pregnancy

The clinical courses of 33 pregnancies in 24 patients with biopsy proven membranous glomerulonephritis have been analyzed. Twenty-four percent (8) of pregnancies resulted in fetal loss, 43% (14) in premature delivery and 33% (11) in a live birth after 36 weeks gestation. Maternal renal function declined during pregnancy in 9% (3) of the pregnancies and in 46% (15) hypertension developed. In 55% (18) proteinuria increased significantly during pregnancy. In 30% (10) nephrotic range proteinuria was recorded in the first trimester. Presence of nephrotic range proteinuria during the first trimester correlated with both poor fetal and poor maternal outcome (p less than 0.0004 and p less than 0.0002, respectively). It is concluded that pregnancy in patients with membranous glomerulonephritis is associated with increased fetal loss and, in some instances, a worsening in maternal renal function. The literature on this topic is reviewed in relation to these findings.     

Pregnancy in women with diffuse mesangial proliferative glomerulonephritis

The clinical course of 168 pregnancies in 91 women with non-IgA diffuse mesangial proliferative glomerulonephritis has been analyzed. Twenty percent (33) of pregnancies resulted in fetal loss, 18% (31) in premature delivery and 62% (105) in a term infant. Maternal renal function declined, reversibly, in 3% (5) of pregnancies and in 48% (80) hypertension developed. In 53% (89) a significant increase in proteinuria occurred in pregnancy. Fetal and maternal complications of pregnancy occurred more frequently in patients with pre-existing hypertension although differences failed to reach statistical significance (p greater than 0.01). The presence of severe vessel lesions on the diagnostic renal biopsy was associated with a significantly higher fetal loss and prematurity rate (p less than 0.0005 and p less than 0.005, respectively).     

Influences of pregnancy on the natural course of chronic glomerulonephritis with impaired renal function]

In an attempt to clarify the influence of pregnancy on the natural course of the chronic glomerulonephritis with impaired renal function (glomerular filtration rate: GFR less than or equal to 70 ml/min), the courses of 14 pregnancies occurring in 10 patients (seven with IgA nephropathy, one with membranoproliferative glomerulonephritis, one with membranous nephropathy and one with hereditary nephropathy) were studied. In 8 patients GFR measured before pregnancies ranged from 46 to 70 ml/min and in the other two creatinine clearance estimated in the first trimester of pregnancies was 62 and 49 ml/min, respectively. The pregnancies resulted in 10 live births, one spontaneous abortion, one artificial abortion and 2 neonatal deaths. In 2 out of 10 live births fetal weight was less than 2500 g. In 3 of 11 pregnancies there was neither increase in urinary protein nor elevation of blood pressure during pregnancies, while seven (64%) had increased proteinuria during the third trimester, and 4 of them were also complicated with hypertension. In 6 of 10 patients, there was no decrease in GFR during pregnancies. In three patients GFR was decreased from 70 to 36 ml/min, 70 to 58 ml/min and 62 to 48 ml/min, respectively. However, these reductions were considered to go with the natural course of respective patients because the reduction slopes were almost the same or rather mild in comparison with those estimated before or after pregnancies. The other patient also had a transient increase in serum creatinine level during two pregnancies, but the reciprocals of serum creatinine concentration before and after the pregnanciesdeclined linearly with time. These data suggest that pregnancy might have little influence on the natural course of the chronic glomerulonephritis even if complicated with renal functional impairment defined as GFR of 70 ml/min or less.     

Pregnancy in IgA nephropathy.

The impacts of IgA nephropathy and pregnancy on each other were evaluated in 118 women who conceived 168 times between 1970 and 1988. Rates of spontaneous abortion, normal delivery, live birth and perinatal death were 9, 66, 87 and 4%, respectively. Infants born to women with glomerular filtration rates (GFR) lower than 70 ml/min prior to conception had a higher perinatal mortality rate (14% vs. 3%, P less than 0.001). This was also true if pre-pregnancy blood pressures were consistently higher than 140/90 mm Hg (33% vs. 1%, P less than 0.001). These were the figures for the whole 18 year period, but stratification of the data revealed that most adverse results occurred in the 1970's, during which the perinatal death rate was 9%, while it was 0% in the 1980's. Eighty-five women were followed for three years or more. At final follow-up, the rates of decrease in GFR, and increases in blood pressure and proteinuria were 19, 11 and 7%, respectively. In most patients the natural history of IgA nephropathy was similar to that of women who had not experienced pregnancy, but there were five instances where gestation seemed to accelerate functional loss, with rapid development of end-stage or near end-stage renal failure. Most women with IgA nephropathy should anticipate few problems with pregnancy, if they are normotensive and their preconception GFR exceeds 70 ml/min. The gestation in such instances should have little influence on the natural history of their nephropathy.     

Glomerular disease and pregnancy. A study of 123 pregnancies in patients with primary and secondary glomerular diseases

The clinical course of 123 pregnancies in 86 patients with biopsy-proven glomerular diseases have been studied. In 35 women the onset of nephropathy occurred during pregnancy. No complications were observed in more than half of the pregnancies. In the others, one third of the complications were obstetrical or fetal accidents, one third were renal manifestations (hypertension or deterioration of renal function) and one third were both causes. The lowest incidence of complications was observed in patients with membranous nephropathy and the highest in membranoproliferative glomerulonephritis patients. There were 6 spontaneous late abortion, 6 stillbirths and 5 neonatal deaths. 17 deliveries were preterm and 7 fetuses were small for gestational age. Hypertension appeared in 24 pregnancies, in 13 of which it was reversible and related to superimposed preeclampsia and in 11 it persisted after delivery (5 of these 11 pregnancies were in patients with IgA nephropathy). Renal function deteriorated in 10 cases during pregnancy. The deterioration was reversible in 6 and progressive in 4 (2 of whom had membranoproliferative glomerulonephritis). It is suggested that in most patients pregnancy does not change the natural history of glomerular disease.     

Pregnancy in IgA nephropathy, reflux nephropathy, and focal glomerular sclerosis

Fetal outcome was retrospectively studied in 217 pregnancies observed during the past two decades in 93 patients, 34 suffering from IgA nephropathy (IgAGN, 69 pregnancies), 53 from reflux nephropathy (RN, 137 pregnancies), and six from focal glomerular sclerosis (FGS, 10 pregnancies). Overall incidence of live births was 175 in 217 (81%). Fetal loss, corrected for induced abortions, was 10 in 66 (15%) in IgAGN, 18 in 129 (14%) in RN, and 2 in 10 in FGS. Renal failure and hypertension preexisting prior to conception or developing early in pregnancy were the most important factors associated with unsuccessful fetal outcome whereas urinary tract infection had limited effects in RN patients. Influence of pregnancy on the course of maternal renal disease was evaluated in the same groups of patients. An abnormally rapid deterioration of renal function was observed in three of the women with IgAGN and in one of the RN patients (with an additional case among 46 further female RN patients) but in none in the FGS group. All five women experiencing functional deterioration had a serum creatinine (SCr) level of greater than or equal to 200 mumol/L (2.3 mg/dL) and hypertension at conception. Hypertension in pregnancy was highly predictive of recurrence of hypertension in subsequent pregnancy and of the remote development of permanent hypertension in IgAGN patients. We conclude that when renal function is preserved, pregnancy is usually successful and no deleterious effects on maternal renal disease are to be expected in patients with IgAN, RN, and probably FGS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of gestation on renal function in gravida with IgA nephropathy

Nineteen pregnancies in 17 women with IgA nephropathy (IgAGN) were studied in terms of the influence of gestation on the natural course of renal function in IgAGN. We performed serial examinations of the serum creatinine (S-Cr) levels before and during pregnancy and after delivery. Group I comprised 11 pregnancies in 10 gravida who revealed proteinuria (1.1 +/- 0.7 g/day; mean +/- SD) and microhematuria before pregnancy. The S-Cr before pregnancy averaged 0.86 +/- 0.13 mg/dl. Group II comprised 8 pregnancies in 7 gravida who showed isolated microhematuria. The S-Cr before pregnancy averaged 0.81 +/- 0.06 mg/dl. In group I, S-Cr did not decrease during pregnancy and was elevated at delivery and at 1-4 weeks after delivery (1.03 +/- 0.29 mg/dl, p less than 0.05) in comparison with the level before pregnancy. In group II, S-Cr decreased significantly during pregnancy and was not elevated at delivery or after delivery. The above results suggest that gestation had a slight and transient adverse effect on renal function in IgAGN with proteinuria.     

Repeated pregnancies in patients with primary membranous glomerulonephritis

This retrospective study was carried out in patients with membranous glomerulonephritis (MGN) and repeated pregnancies, the aim being to see how one influences the other. Patients with two or more pregnancies after MGN were included in the study. Nine patients underwent 51 pregnancies (range 2-12, mean 5.6) and 30 were post-MGN (range 2-5, mean 3.2). Their ages were 27-44 (32 +/- 5.7) years. The duration of follow-up was 2-10 (5.6 +/- 2.5) years. The pregnancy outcome, i.e., number of full-term deliveries (FT), spontaneous abortion, preterm deliveries (PT), perinatal mortality (PM), low-birth-weight babies (LBW) and cesarean section (CS), was noted. In the pre-MGN group (n = 21), there were 20 (95.2%) live births and 1 (4.7%) abortion; none had PT, PM, LBW or CS. In the post-MGN group (n = 30), there were 27 (90%) live births, 2 (6.6%) PT, 1 (3.3%) abortion, 1 (3.3%) PM, 3 (10.0%) LBW babies and 3 (10.3%) CS. However, in comparison, there was no statistically significant difference in the pregnancy outcome between the two groups (p > 0.05 in all). Comparing the incidence of hypertension, proteinuria and serum creatinine levels between the first and the last post-MGN pregnancies, there was no statistically significant difference between the two groups. Only 1 patient developed renal insufficiency (serum creatinine 220 micromol/l) after undergoing 5 pregnancies and follow-up of 6 years. In conclusion, the outcome of repeated pregnancies in patients with MGN is good with 90% live births. Repeated pregnancies do not influence the course of MGN.     

IgA glomerulonephritis and pregnancy

One hundred and sixteen pregnancies in 70 women with a biopsy-proven diagnosis of IgA glomerulonephritis have been analysed. Thirty percent (35) of the fetuses died, 22% (26) were premature and 44% (52) were full term. Maternal renal function declined during pregnancy in 26% (30) and in 2% (2) this was irreversible post-partum. Hypertension developed in 52% (61) of the pregnancies and in 13% (15) this was irreversible. Increased proteinuria was recorded in 62% (74) of the pregnancies. Fetal loss in pregnancies taking place after biopsy diagnosis was lower (16%) than those in which biopsy was performed either during or following the pregnancy (36%).     

Unwanted pregnancy among kidney transplant recipients in Iran

To investigate the incidence of unwanted pregnancy among kidney transplant recipients, we studied 86 pregnancies in 64 women with a transplanted kidney. Twenty-five pregnancies were unwanted (29.1%). Pregnancy was terminated by induced abortion in seven patients, and four pregnancies were lost due to spontaneous abortion with one intrauterine fetal death. Only 13 (52%) pregnancies resulted in a live birth. Most of the unwanted pregnancies occurred in women using coitus interruptus (92%) as the only method of contraception. It is concluded that because fertility greatly improves after kidney transplantation, it is necessary to have a family planning counseling session before surgery. If a patient is not interested in future pregnancy, an effective method of contraception should be offered. A woman who has decided against childbearing in the future may decide to have a tubal ligation at the time of transplantation surgery.     

Consecutive Spontaneous Triplet and Twin Pregnancies in a Woman After Renal Transplantation

BackgroundThere are numerous reports of successful pregnancies following kidney transplantation. However, little information is available regarding the management and evolution of multiple pregnancies in a kidney-transplanted woman.Case reportWe report the case of successful consecutive spontaneous triplet and twin pregnancies in a woman who had undergone kidney transplantation at 30 years of age, 12 years before the first pregnancy, as a result of end-stage renal disease secondary to chronic glomerulonephritis due to diffuse proliferative lupus nephritis. An integrated multidisciplinary team closely followed progress during the pregnancies. Maternal complications during the pregnancies included light proteinuria, controlled hypertension, and anemia. No graft rejection episodes or deterioration of renal function was noted during the pregnancies or after the deliveries.ConclusionCurrently, more than 2 years after her last pregnancy, the mother and all 5 babies are healthy and the mother’s renal transplant function is normal.     

Pregnancy and lupus nephritis.

Family planning and pregnancy are important and usually problematic issues for a young woman with lupus nephritis. Moderate renal insufficiency and previous use of alkylating cytotoxic drugs are associated with decreased fertility. Oral contraceptives containing synthetic estrogens are contraindicated in women with active lupus nephritis, uncontrolled hypertension, history of thromboembolic diseases or high levels of antiphospholipid antibodies. Mild flares of systemic lupus erythematosus (SLE) are common during pregnancy, severe renal flares and permanent impairment of renal function are uncommon. The outlook of pregnancy for women with lupus nephritis is usually favourable if the disease (both renal and nonrenal) has been quiescent for at least 6 months before pregnancy, and if, at conception, serum creatinine is less than 140 micromol/l, proteinuria less than 3 g/24 h and blood pressure controlled. The risk of fetal loss is, however, at least 2-3 times higher than in the normal population and pre-eclampsia, prematurity and fetal growth retardation frequently complicate these pregnancies. Especially poor fetal outcome is associated with antiphospholipid antibodies. Pregnancies in women with lupus nephritis require intense fetal and maternal surveillance.     

Outcome of 234 pregnancies in 140 renal transplant recipients from five middle eastern countries

OBJECTIVE: To study the pregnancy and offspring outcomes in postrenal transplant recipients. METHODS: This is a retrospective case-note review study investigating the outcome of 234 pregnancies in 140 renal transplant recipients from five different Middle Eastern countries. RESULTS: Of the overall pregnancies 74.4% were successful albeit with high prevalences of preterm and Caesarean deliveries (40.8% and 53%, respectively). The mean serum creatinine did not rise significantly during pregnancy in the group as a whole but did so in patients who had serum creatinine of or above 150 micromol/L at the beginning of their pregnancies. The mean birth weight was (2,458 g) with 41.3% of the newborns being of low birth weight (<2,500 g). The prevalences of stillbirths were 7.3% and of spontaneous abortion was 19.3%. Preeclampsia and gestational diabetes were observed in 26.1% and 2% of pregnancies, respectively. CONCLUSIONS: In the presence of good allograft function, the majority of pregnancies in renal transplant recipients have a good outcome but with increased incidence of preeclampsia, reduced gestational age, and low birth weights. Patients with baseline serum creatinine of above 150 micromol/L have an increased risk of allograft dysfunction resulting from the pregnancy.