Pregnancy in women receiving renal dialysis or transplantation in Japan: a nationwide survey.

BACKGROUND: Since a report on the first successful pregnancy of a woman on long-term haemodialysis in Japan in 1977, there has been a growing number of case reports on successful pregnancy in patients on dialysis. We undertook a nationwide survey on pregnancy in women on renal replacement therapy in 1996. METHODS: A preliminary questionaire was sent to 2504 dialysis units and 143 renal transplant units in Japan. For each reported pregnancy, a more detailed questionaire was sent to collect nephrological, obstetric and neonatal information. RESULTS: There were 172 pregnancies (0.44%) reported in 38889 women on dialysis, with 90 successful pregnancies (0.23%), and 194 pregnancies reported in 852 female renal transplant recipients. Detailed pregnancy information was collected from 74 women on dialysis and 194 renal transplant recipients. Of the 74 pregnancies in the women on dialysis, 36 (48.6%) resulted in surviving infants, nine (12.2%) in neonatal death, nine (12.2%) spontaneous abortions and 14 (18.9% elective abortions were reported. The outcome of six pregnancies (8.1%) was unknown. Of 194 pregnancies in renal transplant recipients, 159 (82.0%) resulted in surviving infants, two (1.4%) in neonatal death and 28 (14.4%) in spontaneous or elective abortion. In five cases the pregnancy outcome was not reported. No congenital anomalies were reported, except two infants with mental retardation and one with epilepsy. CONCLUSION: The current survey revealed that the rate of successful pregnancy in women on dialysis has improved. More than half of the pregnancies resulted in infant survival. But, premature birth is a major problem for the children of women on dialysis and there is a higher rate of neonatal death. There are significant differences in gestational age, birth weight, frequency and severity of prematurity and rates of neonatal death between pregnancies of women undergoing dialysis and those who are renal transplant recipients.     

Pregnancy in systemic sclerosis

In the 1980's, pregnancies in systemic sclerosis (SSc) patients were considered to be at high risk for poor foetal and maternal outcome. Retrospective studies found an increased frequency of pre-term births and small full-term infants but the frequency of miscarriage and neonatal survival rate did not differ from healthy controls. The worst life-threatening complication of a pregnancy is scleroderma renal crisis. The use of ACE inhibitors is recommended in this case despite the risk of teratogenicity. In order to avoid complications, pregnancies in SSc should be planned when the disease is stable, and should be avoided in rapidly progressing diffuse SSc who are at a greater risk for developing serious cardiopulmonary and renal problems early in the disease. Hydroxychloroquine and low doses of steroids may be safely used. In order to minimize risks, a multidisciplinary approach is necessary to suggest the best timing for a pregnancy and provide adequate supportive treatment to SSc patients during the pregnancy.     

Pregnancy after organ transplantation: a report from the UK Transplant pregnancy registry

BACKGROUND: Maternal and fetal complications in pregnancies after renal transplantation have been highlighted in several reports, but information on their main predisposing factors is limited. The U.K. Transplant Pregnancy Registry was established in 1997 to obtain detailed information on pregnancies in female organ transplant recipients across the U.K. METHODS: For each female kidney, liver, or cardiothoracic organ transplant recipient who had had a recent pregnancy, data on maternal and fetal factors and pregnancy outcomes were collected using forms completed by their transplant follow-up and obstetric units. For kidney transplant recipients, the factors that influence pregnancy outcome were studied using logistic regression, and the effect of pregnancy on graft function was analyzed. RESULTS: There were live births in 83%, 69%, and 79% of pregnancies in cardiothoracic organ, liver, and kidney recipients, respectively. In 50% of live births from renal patients, delivery was preterm (<37 weeks), with 83% of the preterm infants delivered via caesarean. Preterm delivery was associated with maternal drug-treated hypertension and impaired renal function. A matched case-control study showed no evidence of increased renal allograft loss after pregnancy. A univariate survival analysis, however, suggested an association between drug-treated hypertension during pregnancy and poorer postpregnancy graft survival. In patients with prepregnancy serum creatinine (SCr) >150 micromol/L, a trend toward increased postpregnancy SCr was identified. CONCLUSIONS: Pregnancy is likely to end in a live birth in a majority of organ transplant recipients. In patients with greater prepregnancy SCr and/or drug-treated hypertension during pregnancy, however, subsequent renal function may be adversely affected.     

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.     

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 after renal transplantation: A single-center experience

Objectives:   To examine women with renal transplants who became pregnant, and delivered at our hospital.
Methods:   Twenty-six women who had undergone renal transplantation between 1977 and 2002 became pregnant, and delivered at Osaka University Hospital. Complete medical records of twenty of them were retrieved and retrospectively analyzed.
Results:   Overall, twenty-nine pregnancies occurred in these twenty women after renal transplantation. There were spontaneous abortions in three cases, whereas pregnancy was artificially terminated five times. Thus, neonates were delivered in 21 of 29 pregnancies. One woman delivered twice and two women delivered twins. As a result, a total of 23 neonates were delivered. Mean gestational period was 35.4 weeks (range, 27–41 weeks), and mean birth weight was 2229 g (range, 724–3544 g). Regarding fetal complications, intrauterine growth retardation was observed in three cases. One child with intrauterine growth retardation died at 3 months old due to respiratory distress syndrome. One child displayed double-outlet right ventricle and another child had congenital unilateral hydronephrosis. Regarding maternal complications, prevalence of toxemia of pregnancy was 38.1%. In four of the 21 deliveries (19.0%), renal function exacerbated after delivery. Rates of graft survival for the 20 women at 1, 5 and 10 years after delivery were 100%, 85.1% and 74.4%, respectively. Prognosis for renal transplant resulted to be significantly poorer for recipients with hypertension before pregnancy than for recipients without hypertension before pregnancy (log-rank test, P  = 0.043).
Conclusions:   Rates of graft survival after delivery were mostly favorable. However, prognosis for renal function was poorer for recipients who displayed hypertension prior to pregnancy.     

Obstetric and long‐term kidney outcomes in renal transplant recipients: a 40‐yr single‐center study

Female renal transplant recipients of childbearing age may ask what the outcomes are for pregnancy and whether pregnancy will affect graft function. We analyzed obstetric and transplant outcomes among renal transplant recipients in our center who have been pregnant between 1973 and 2013. A case?cohort study was performed identifying 83 pairs of pregnant and non‐pregnant controls matched for sex, age, transplant vintage, and creatinine. There were 138 pregnancies reported from 89 renal transplant recipients. There were live births in 74% of pregnancies with high prevalence of prematurity (61%), low birth weight (52%), and pre‐eclampsia (14%). Lower eGFR (OR 0.98; p = 0.05) and higher uPCR (OR 1.86; p = 0.02) at conception were independent predictors for poor composite obstetric outcome. Lower eGFR (OR 0.98; p = 0.04), higher uPCR (OR 1.50; p = 0.04), and live organ donation (OR 0.35; p = 0.02) were predictors of ≥20% loss of eGFR between immediately pre‐pregnancy and one yr after delivery. There was no difference in eGFR at one, five, and 10 yr in pregnant women compared with non‐pregnant controls and a pregnancy was not associated with poorer 10‐yr transplant or 20‐yr patient survival. Despite high rates of obstetric complications, most women had successful pregnancies with good long‐term transplant function.     

肾移植术后妊娠4例次报告并文献复习

目的 探讨肾移植术后妊娠对肾移植患者及胎儿的影响以及妊娠后免疫抑制药物的合理应用.方法 回顾分析4例次肾移植术后妊娠的临床资料并复习相关文献.结果 3例女性患者均接受同种异体肾移植术,术后妊娠4例次,1次因移植肾失功人工引产,二次肾移植后再次妊娠.移植术后至妊娠前2例患者应用环孢素(CsA)+麦考酚吗乙酯(MMF)+泼...     

The experience of pregnancy after renal transplantation: pregnancies even within postoperative 1 year may be tolerable

BACKGROUND: To identify factors related with successful pregnancy in renal transplant recipients and the effect of pregnancy on long-term graft outcome. METHODS: The study group consisted of 48 women who conceived after undergoing renal transplantation (total pregnancies 74). The control group consisted of 187 nonpregnant female renal transplant recipients. RESULTS: Mean ages at the time of transplantation and pregnancy were 28.0+/-4.0 years and 31.6+/-4.1 years, respectively. The mean interval from transplantation to pregnancy was 40.2+/-27.1 months. Outcomes included 49 live births, 12 terminations, 9 miscarriages, 3 stillbirths, and 1 ectopic pregnancy. Eleven of the 74 pregnancies (15%) were within 1 year of transplantation, resulting in seven live births, two miscarriages, and two terminations. Live births were associated with younger age at the time of transplantation (relative risk, 0.75; P=0.042) and younger age at the time of pregnancy (relative risk, 0.76; P=0.022). Graft failure rate from transplantation to end of follow-up did not differ between the pregnant and nonpregnant groups (19% vs. 21%, P=0.688). The 10-year graft survival rates were also similar in the 11 women who became pregnant less than or equal to 12 months after transplantation and the 37 who became pregnant more than 12 months after transplantation (78.8% vs. 78.6%, P=0.941). CONCLUSION: A younger age at transplantation and at pregnancy was associated with a greater likelihood of a live birth. Transplantation to conception interval of less than 1 year was not associated with a greater number of adverse pregnancy events when compared with the group with transplantation to conception interval greater than 1 year.     

Successful pregnancies in women on renal replacement therapy: report from the EDTA Registry.

This study reports the geographical incidence of successful pregnancies in women on renal replacement therapy (RRT) and related information on gestation and clinical status of newborns. The impact of successful pregnancy on graft function was assessed by means of a retrospective case-control study. Since 1977 special questionnaires have been sent to each dialysis and transplant centre which reported babies born to mothers on RRT on the yearly centre questionnaire. After 10 years of data collection, a total of 490 pregnancies and 500 babies were available for analysis. A percentage of 88.4 of the babies were born to mothers with a functioning graft, 11.2% to mothers on chronic haemodialysis, and the remaining 0.4% to mothers on CAPD. Almost 50% of all successful pregnancies were reported from the UK. The number of successful pregnancies increased steadily and in parallel with the increasing number of females of childbearing age with a functioning renal transplant. The majority of mothers delivered at age 24-32. For transplanted mothers delivery occurred most commonly during the 3rd and 4th year after successful transplantation. In approximately 85% of cases the duration of pregnancy was shorter than the lower 10th percentile of normal. Birthweight was reduced in accordance with gestational age. Newborn mortality was 1.8%. Fifty-three mothers with a successful pregnancy in 1984-1987 were computer matched with controls according to a number of criteria. The serum creatinine concentration recorded in coded form at the end of each year on the individual EDTA patient questionnaire was used to assess changes in graft function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Outcome of pregnancy after organ transplantation: a retrospective survey in Italy

Abstract The number of women who decide to have a child after organ transplantation has increased. We determined the outcomes of 67 pregnancies of women who had undergone kidney, liver or heart transplantation. All recipients had been maintained on immunosuppressive therapy before and during pregnancy. Pregnancy complications at term were observed in 17 out of 67 women (25%), hypertension being the most frequent complication (16.17%). Two transplant rejections were reported. Sixty-eight infants were delivered (including one pair of twins); five women had two pregnancies at term. Twenty-eight miscarriages (29.2%) were recorded. Of these 68 babies (including the pair of twins), 40 (58.8%) were born at term and 28 (41.2%) before term. The babies were followed-up for 2 months to 13 years. According to our previous experience, our study shows that patients who have undergone organ transplantation can give birth to healthy infants as long as they are monitored accurately during pregnancy.     

Prediction of pregnancy outcome in subgroups of women with renal disease

BACKGROUND: The preconception and intraconception parameters that are relevant to outcome in women with underlying renal disease remain controversial. SUBJECTS, MATERIALS AND METHODS: We analyzed the types and frequencies of short- and long-term (2 years after delivery) maternal and neonatal complications in 38 patients with primary renal disease (46 pregnancies), 24 IDDM patients with diabetic nephropathy (24 pregnancies), and 27 patients with a functioning renal allograft (42 pregnancies), most of them with mild renal insufficiency. Logistic regression models were formulated to predict successful outcome. RESULTS: Successful pregnancy outcome (live, healthy infant without severe handicap 2 years after delivery) was observed in 98% of the patients with primary renal disease, 96% of the IDDM patients with diabetic nephropathy, and 89% of the patients with a functioning renal allograft. Factors found to be significantly predictive of successful outcome were absence of preexisting hypertension in all groups, in addition to low preconception serum uric acid level in the primary renal disease patients, and long interval from transplantation to conception and use of a low dose ofprednisone in the renal transplant patients. CONCLUSION: Most women with different subtypes of renal disease have a successful pregnancy outcome with proper prenatal care. Worse pregnancy outcome was observed in women with moderate or severe renal failure. Fitted logistic models may provide useful guidelines for counseling women with preexisting renal disease about their prospects for a successful pregnancy in terms of immediate and long-term maternal and neonatal outcome.     

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.     

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.     

Pregnancy in heart transplant recipients.

The aim of this report is to present data from Italian cardiac transplant centers assessing pregnancy after cardiac transplantation. Our retrospective survey included 10 pregnancies occurring in 7 patients during January 1991 to February 2002. Eight pregnancies were completed successfully and 2 abortions were reported (frequency rate 20%). No complications were observed during pregnancy or after delivery. Of 8 infants studied, 6 (75%) were born at term and 2 (25%) pre-term. One baby presented congenital talipes valgus. Pediatric development was uneventful. The data from the literature and our series show that a multidisciplinary approach is mandatory. The course of pregnancy is usually normal and the maternal and fetal outcomes are usually favorable. Although no fetal malformations have been reported, prolonged follow-up of these infants is required.     

Pregnancy After Liver Transplantation: Risks and Outcomes

Objective

The aim of this study was to evaluate the outcomes of liver transplant recipients who became pregnant after transplantation.

Historical perspective of pregnancy in chronic kidney disease

Preeclampsia was first recognized as a cause of proteinuria unique to pregnancy in 1843 and the risk of pregnancy in women with preexisting renal disease was noted in the 1930s. Since then, we have recognized that the majority of women with kidney disease who become pregnant have surviving infants. The exception is women on dialysis whose pregnancies result in only 50% to 75% of infant survival. All women with renal disease are at increased risk for hypertension during pregnancy, but the risk of more rapid than expected progression of renal disease generally occurs in women with serum creatinines greater than 1.4 mg/dL, with an even higher risk in women with serum creatinines greater than 2 mg/dL. Dialysis patients conceive infrequently and have a high frequency of fetal loss and neonatal death. Fertility is restored by renal transplant and guidelines are being developed regarding the ideal timing of pregnancy, the kidney function required for a safe pregnancy, and the use of immunosuppressive drugs in pregnancy.     

PREGNANCY DURING CHRONIC HEMODIALYSIS: A SINGLE DIALYSIS-UNIT EXPERIENCE WITH FIVE CASES

Background: Pregnancy is uncommon in women with end-stage renal disease (ESRD) requiring chronic dialysis. An increasing number of successful pregnancies in women in hemodialytic treatment have been recently reported but few institutions experienced more than one or two cases of pregnancy. Methods: Between 1988–1998 five pregnancies in patients receiving hemodialysis were observed in our center. Medical records of these patients were reviewed. Results: At the conception the mean age was 27 years. One patient started dialysis after conception. All patients received bicarbonate dialysis. Three patients were dialyzed six times per week, the other two patients three-four times per week. The dry weight was increased progressively; on average of 1.2 ± 0.5 kg in the first trimester and of 0.5 kg per week since the second trimester. The predialysis BUN was maintained between 50–100 mg/dL (17.85–35,70 mmol/L) during the pregnancy. Four patients were treated with erythropoietin to maintain hematocrit between 30–35%. Erythropoietin related—complications were not observed. Polyhydramnios was observed in all cases. All deliveries occurred before term. The mean gestational age of infants was 28.6 ± 4 weeks. Four out of five pregnancies resulted in liveborn infants. Two infants had an Apgar score of zero. All neonates were of low birth weight (1431 ± 738 g) with percentile of birth weight in the normal range. No one was small for date. Conclusion: A successful pregnancy is possible in women on chronic dialysis. Prematurity occurs frequently as well as low weight birth leading to increased perinatal morbidity and mortality.     

Pregnancy after renal transplantation: ten-year single-center experience

There has been an increase in the number of pregnancies among renal transplant recipients. Our experience included 61 pregnancies in 53 patients from January 1997 to April 2007, with 6 patients having multiple pregnancies. Patients were studied for clinical, obstetrical, and perinatal outcomes. The mean patient age was 24.5 years (range, 19-38). They all received living donor kidneys. The mean transplantation-pregnancy interval was 2.7 years (range, 1.7-5.3 years). Immunosuppressive drugs consisted of cyclosporine (CsA), mycophenolate mofetil (MMF), and prednisolone (pred) in 38 patients (72%); CsA, azathioprine (AZA), plus pred were used in 15 patients (28%). Pregnancy complications were chronic hypertension in 21 patients (40%), anemia in 28 (52.6%), and urinary tract infection in 18 (34%). Twelve patients (22.6%) received blood transfusions. Pre-eclampsia was diagnosed in 14 cases (26.4%) and renal dysfunction in 11 (20.7%) with pre-eclampsia assumed to be the main cause. Three patients (5.6%) had graft losses as a result of hemorrhagic shock, sepsis, and eclampsia. Premature rupture of membranes occurred in 6 cases (11.3%), and preterm delivery occurred in 14 cases (26.4%). Eleven (20.7%) newborns were small for gestational age. One club foot and one large facial hemangioma occurred in 2 infants, respectively. One case of neonatal death was registered as a result of excessive prematurity. One mother died due to sepsis. Cesarean section was performed in 24 patients (45.2%), the main indications being related to hypertension and fetal distress. There were no significant differences between MMF-treated and AZA-treated patients with respect to clinical, obstetrical, and perinatal outcomes. This group of patients was characterized by a wide range of antenatal and perinatal problems that must be managed in specialized tertiary units to achieve the best results. MMF may be as safe as AZA in pregnancy.     

Prednisone dosage and pregnancy outcome in renal allograft recipients

BACKGROUND: The literature contains reports of 2309 pregnancies in some 1600 women who have undergone renal transplantation. Certain pre- pregnancy factors, especially hypertension, renal graft dysfunction, short interval between transplant and pregnancy, and high immunosuppressive drug dosage, appear to increase the neonatal risks. METHOD: We describe the outcome of 42 pregnancies in 27 allograft recipients at Rabin Medical Center (Beilinson Campus) in Israel during the last 8 years. All were treated with combination immunosuppression regimens. RESULTS: The average interval from transplantation to conception was 3.7 +/- 0.4 years (2 months to 9 years). Rejection episodes occurred in 37% prior to pregnancy but in none during or immediately after pregnancy. Twenty-eight percent of the pregnancies ended in therapeutic or spontaneous abortions, and 29 of the 30 deliveries ended in a live birth. The prematurity rate (63%) was similar to that described in the literature for this patient group. Renal deterioration was evident in seven women (26%) within 2 years after delivery. Use of 7.5 mg/d prednisone (vs. 10 mg/d) before pregnancy was observed as the most significant preconception parameter related to better pregnancy outcome. A long interval from transplantation to conception and lack of pre-existing hypertension were also significant. CONCLUSION: The better pregnancy outcome associated with lower prednisone dosage is probably related to the fact that the patients selected to receive the low-dose regimen have had a longer and less complicated post-transplantation course.