Female Kidney Transplant Recipients Research Articles

Pregnancy after liver transplantation

The first known posttransplantation pregnancy was in 1958 in a renal transplant recipient who had received a kidney from her identical twin sister. The first known posttransplantation pregnancy in a liver transplant recipient was in 1978. Information available from female kidney transplant recipients helped in the decision making involved in the management of this case, as well as those that followed. Over the last 20 years, issues specific to liver transplantation and pregnancy have been identified. Similar to the kidney transplant recipient population, when prepregnancy recipient graft function is stable and adequate, pregnancy appears to be well tolerated. Also similar to kidney transplant recipients, there has been no evidence of a specific malformation pattern among the children, and although prematurity and low birth weight occur, overall newborn outcomes have been favorable. Pregnancy in the setting of recurrent liver disease, such as recurrent hepatitis C, poses a potential problem among liver transplant recipients, as well as the possible adverse effects of immunosuppression on maternal kidney function. Also of significance, peripartum graft deterioration has more severe consequences in this transplant recipient population. Therefore, pregnancy must be considered carefully in this transplant recipient group. Since 1991, the National Transplantation Pregnancy Registry (NTPR) has studied the safety of pregnancy outcomes in solid-organ transplant recipients. The purpose of this review is to catalog studies in the literature, as well as to present current data from the registry with management guidelines.

Strong inflammatory cytokine response in male and strong anti-inflammatory response in female kidney transplant recipients with urinary tract infection

Urinary tract infection (UTI) is the most common post-transplant infection in renal transplant recipients. The relationship of plasma and urine cytokines with UTI after kidney transplantation has not yet been delineated and literature reports on cytokine and UTI are rare. In a retrospective study, we compared post-transplant plasma and urine cytokine levels of 132 outpatient renal transplant recipients with or without UTI. Soluble interleukin-1 receptor antagonist (sIL-1RA), IL-2, sIL-2R, IL-3, IL-4, IL-6, sIL-6R, IL-8, IL-10, transforming growth factor-beta2 (TGF-beta2), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) levels were determined using commercially available enzyme-linked immunosorbent assay (ELISA) kits. We found gender-related urine cytokine patterns. Anti-inflammatory sIL-1RA was significantly higher in females than in males and this gender-related difference was more pronounced in bacteriuric (P < 0.0001) than in nonbacteriuric (P = 0.001) patients. Urine proinflammatory cytokines IL-6 (P = 0.001) and IL-8 (P = 0.007) were significantly higher in male patients with bacteriuria than in males without bacteriuria and sIL-2R (P = 0.001) and sIL-6R (P = 0.03) were significantly higher in males with leukocyturia than in males without leukocyturia. Bacteriuria in males was associated with higher doses of immunosuppressive drugs (P = 0.02). Male renal transplant recipients with UTI have a strong inflammatory cytokine response with activation of IL-6, IL-8, sIL-2R and sIL-6R producing cells, whereas female patients with UTI block the inflammatory response to UTI by production of sIL-1RA.

Menstrual characteristics and pregnancy in women after renal transplantation

Objectives: To evaluate menstrual characteristics and pregnancy complications after renal transplantation in women of childbearing age. Methods: A 10-year retrospective case-control study was carried out in Esfahan Teaching Hospitals, Esfahan, Iran. The case group consisted of 50 female kidney transplant recipients of childbearing age and the control group of 100 women who were matched for age (±2 years) and parity with the study group. Menstrual characteristics and pregnancy data were collected by questionnaire and analyzed by χ 2 and t-tests. Results: Menstrual characteristics were improved in the 50 women who had renal transplantation, 18 of them conceived, and 20 pregnancies were evaluated. The mean interval between transplantation and pregnancy was 35.5 months and the birth weight of 44% of the newborns was less than 2500 g. Pregnancy complications included hypertension (65%), premature labor (35%) and decreased GFR (15%) during pregnancy, with a mean gestational age at delivery of 34.8 weeks. The women who conceived during the first 2 years after renal transplantation had more maternal and neonatal complications. Conclusions: Pregnancy is possible and can be successful and safe after renal transplantation in recipients with normal kidney function. However, maternal and neonatal complications are common and occur more often in patients who conceive within 2 years of transplantation. Post-transplantation pregnancies are high risk and they should be managed in a tertiary center.

Successful pregnancies in female kidney-transplant recipients with hepatitis C virus infection

Successful pregnancies in female kidney-transplant recipients with hepatitis C virus infection

Fungal Arthritis of the Knee Caused by Candida parapsilosis in a Kidney Transplant Recipient

Fungal arthritis is a rare infection usually caused by Candida species. Candida parapsilosis has emerged as a new pathogen and has been implicated in several cases of fungal arthritis, mostly associated with a joint prosthesis or after arthrocentesis. We report an unusual case of fungal arthritis of the knee caused by this organism in a 38-year-old female kidney transplant recipient, who had no previous invasive procedures on her knee. Systemic and intraarticular antifungal therapy combined with surgical debridement proved to be an effective treatment of this clinically difficult condition. To our knowledge, this case is the first report of fungal arthritis caused by C. parapsilosis in a transplant recipient. The multimodality approach used in the treatment of this patient should be considered in similar forms of fungal arthritis in immunocompromised patients.

Placental imbalance of vasoactive factors does not affect pregnancy outcome in patients treated with Cyclosporine A after transplantation

Endothelin-1 (ET-1) and nitric oxide (NO) have been suggested to have a focal role in the regulation of placental and fetal growth. Cyclosporine A (CsA) has been shown to strongly modulate ET-1 and NO synthesis and thus has the potential to affect fetal growth and maternal state. Eleven CsA-treated female kidney transplant recipients were recruited. Fourteen healthy pregnant women served as controls. Placental expression of ET-1 and tissue factor (TF) was evaluated by in situ hybridization, and NO synthase (NOS) was evaluated by staining with the reduced form of nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase and in situ hybridization. Kidney transplant recipients showed a marked reduction in NADPH-diaphorase staining, as well as endothelial constitutive NOS (ecNOS) messenger RNA, whereas inducible NOS expression was unchanged. Normal placenta showed a strong positive ET-1 signal along the endothelium of uteroplacental arteries within the basal plate, which increased markedly in decidua of transplant recipients. Thus, transplant recipients showed a remarkable alteration in ET-1/ecNOS balance without alteration in fetal growth or maternal renal function. Next, we explored the state of placental endothelial cell activation downstream from vasoactive factors by evaluating TF gene expression. Transplant recipients did not show modification of TF transcript compared with healthy pregnant women. CsA potently affected the placental ET-1/ecNOS vasoactive balance. Nevertheless, newborns from transplant recipient mothers were appropriate for gestational age, and transplant recipients did not show systemic hypertension or impending renal damage. It is suggested that CsA may blunt the activation of endothelial cells and priming of endothelial-derived substances, which possibly lie downstream from the cited vasoactive agents. © 2002 by the National Kidney Foundation, Inc.

Immunologic evaluation during the first year of life of infants born to cyclosporine-treated female kidney transplant recipients: analysis of lymphocyte subpopulations and immunoglobulin serum levels.

In rodents, CsA has been shown to affect T-cell development, giving rise to an abnormal production of mature T cells and the absence of many T-cell subsets as well as to autoimmunity. Surprisingly, only a few studies investigated the effect of the immunosuppressive drug on the immune system of the human fetus. We examined six infants born to female kidney transplant recipients who had received cyclosporine and methylprednisolone throughout their pregnancies. Peripheral blood was obtained 1 day and 2, 4, 6, and 12 months after birth, and two-color flow cytometric immunophenotyping of lymphocytes was performed. Total T cells, as well as CD4+ and CD8+ T cells, were low at birth, but normalized thereafter. Among T-cell activation markers, the expression of CD25, the alpha chain of the interleukin-2 receptor, was below the normal range or low range throughout the study period, and HLA-DR expression was extremely low at birth and failed to increase up to 12 months. The number of total B cells was lower than normal at birth, but steeply increased over time. In contrast, B-cell subset bearing CD5 antigen was severely depleted throughout the first year of life. Total IgG concentration was significantly lower than in controls at 2 months, mainly because of subnormal levels of IgG1 and IgG3 subclasses, which remained in the low range up to 6 months. Finally, infants showed normal numbers of true natural killer (NK) cells (CD3-CD16+CD56+), whereas the expression of CD57 antigen, defining non-MHC-restricted cytotoxic lymphocytes, was barely detectable at birth and failed to increase over time, in both CD8+ and CD8- subsets. Of note, none of the infants had clinical evidence of an immunodeficient state. continuous exposure to CsA in utero seemingly impairs T-, B-, and NK-cell development and/or maturation, and most of its effects are still apparent at 1 year, which might suggest that conventional vaccinations should be delayed in these infants.

NATIONAL TRANSPLANTATION PREGNANCY REGISTRY: PREGNANCY OUTCOMES IN FEMALE KIDNEY RECIPIENTS TREATED WITH CYCLOSPORINE MICROEMULSION (NEORAL) OR TACROLIMUS VS. CYCLOSPORINE

299 This study analyzes pregnancy outcomes in female kidney recipients treated with newer immunosuppressives, [cyclosporine microemulsion (Neoral) and tacrolimus (Prograf)], compared to cyclosporine (CsA). Data were obtained from questionnaires, interviews and hospital records. Outcomes analyzed included: treated hypertension during pregnancy (HTN), pre-eclampsia, livebirths, mean gestational age (GA), prematurity, mean birthweight (BW), mean serum creatinine (mg/dL) before (CrB), during (CrD), and after (CrA) pregnancy, and rejection during pregnancy. Data were analyzed by analysis of variance or Fisher's exact test. TableSignificant differences were noted in HTN (comparing Prograf to CsA, p=.03), and GA (Prograf to CsA, p=.006; Prograf to Neoral p=.02). In the recipients on newer regimens, no structural malformations were noted in any of the newborns. In the Prograf group, one recipient also received mycophenolate mofetil during pregnancy and delivered a liveborn (32 wks, 2240 gms); another had a biopsy proven rejection early in pregnancy. Conclusions: Despite differences in maternal conditions, newborn and recipient outcomes were not markedly different among the groups analyzed. Although most of these women were on additional immunosuppressives, these 3 drugs with similar mechanisms of action appear to have similar effects on pregnancy when taken by female kidney transplant recipients.

Gender differences in a kidney transplant population.

The purpose of this study was to compare female and male kidney transplant recipients. Of 1095 consecutive kidney transplants, 63.7% were to male recipients. Detailed demographic background data and follow-up data were used in the analysis. Female and male recipients were the same age, median 44, range 1-71 years. The male/female ratio was increased in all adult age groups, and most pronounced in the middle-aged. The proportions of first transplants and of preemptive transplants were not different, and 22.0% of men compared with 24.4% of women had living donors. Biopsy-verified chronic glomerulonephritis was found 2.4 times more often in men than in women, unknown diagnosis including non-biopsy-verified chronic glomerulonephritis 2.3 times, and adult dominant polycystic kidney disease 1.8 times. A larger proportion of men than women received antirejection treatment, 59.5% vs 49.5% (P = 0.002). Cumulative survival of patients or grafts was not different, but women > or = 50 years of age tended to have poorer 1-year graft survival than men, 69% vs 78% (P = 0.06). It is concluded that the increased proportion of men in our transplant programme is mainly due to their higher requirement of renal replacement therapy.

National transplantation pregnancy registry: Report on outcomes in cyclosporine-treated female kidney transplant recipients with an interval from transplant to pregnancy of greater than five years

Successful renal transplantation enables previously infertile females to conceive and carry a pregnancy. Much of the reported data on posttransplantation pregnancy accrued before the advent of cyclosporine, when steroids and azathioprine were the mainstays of maintenance immunosuppression. One factor affecting pregnancy outcome in kidney recipients is the length of time from transplantation to conception or transplant interval. It has been recommended that patients wait at least 2 years posttransplantation to conceive, as transplant intervals of shorter duration have had less favorable outcomes. Some have suggested that extended transplant intervals (>5 years) paradoxically result in adverse outcomes. We have extracted data on cyclosporine-treated recipients with transplant intervals longer than 5 years from the National Transplantation Pregnancy Registry, and report 17 pregnancies from 15 recipients (transplant interval, 5.9 ± 0.9 years). There were 13 live births (76.5%) and four spontaneous abortions (23.5%). The mean gestational age was 37.7 ± 2.04 weeks and mean birth weight was 2,753 ± 679 g. Prematurity occurred in 30.8%, low birth weight in 15.4%, very low birth weight in 7.7%, and neonatal complications in 15.4%. There were no maternal or neonatal deaths. The mean serum creatinine before pregnancy was 1.31 mg/dL, and there was no significant change during or after pregnancy. There were no rejections during or up to 3 months postpartum. Graft survival at 2 years was 100%. We conclude that most pregnancy outcomes in cyclosporine-treated recipients with transplant intervals greater than 5 years are favorable for the newborn, recipient, and graft.

Experience of 28 deliveries in 21 kidney transplant recipients

Risk factors to induce graft dysfunction during pregnancy in kidney transplant recipients were studied. A total of 28 deliveries from 21 female kidney transplant recipients were analyzed. All recipients were maintained on either azathioprine-based (n = 17) or cyclosporine-based (n = 11) immunosuppressive regimens. Graft dysfunction (creatinine clearance < 40 ml/min) occurred in 8 cases (8 patients) during pregnancy. No acute rejection, however, could be observed. In a case-controlled study comparing a group with graft dysfunction vs. a group with good graft function, there were significantly differences in the incidence of the cases with pre-existing hypertension (62.5% vs. 10.0%), the age of the grafted kidney (58.1 vs 47.6 year), the maternal anemia (Hb: 10.3 vs. 11.8 g/dl) and the creatinine level (1.4 vs. 1.0 mg/dl) at the first trimester. These findings suggested that poorer graft function had been underlying before pregnancy and that additional loading of the pregnancy reduced further graft function, while the deterioration would be recovered after delivery in all cases except one case. Risk factors to induce graft dysfunction during pregnancy are as follows. 1) high age of the grafted kidney (> 50 year), 2) pre-existing hypertension, 3) maternal anemia (Hb: < 11 g/dl) and 4) high creatinine level (> 1.3 mg/dl) at the first trimester.

VARIABLES AFFECTING BIRTHWEIGHT AND GRAFT SURVIVAL IN 197 PREGNANCIES IN CYCLOSPORINE-TREATED FEMALE KIDNEY TRANSPLANT RECIPIENTS1,2

Outcomes from 197 pregnancies in 141 female kidney transplant recipients were analyzed from data collected via questionnaires, hospital records, and phone interviews. All recipients were maintained on cyclosporine (CsA) before and during pregnancy. Of the livebirths, 54% were premature (< 37 wk) and 50% were low-birthweight (LBW) (< 2500 g). The incidence of recipient drug-treated hypertension (HTN) was 56%; preeclampsia, 29%; infections and complications 22%; and rejection during pregnancy and up to 3 mo. post delivery (rej.), 11%. Graft loss within 2 years of delivery occurred in 9% of recipients (GrL < 2). No recipients reported a pregnancy after a postpregnancy graft loss. Mean serum creatinine was reported before, during, and after pregnancy. Mean cyclosporine doses were similar in recipients during and after pregnancy. Data were analyzed by logistic regression using SAS. Outcomes included prematurity, LBW, rej., and GrL < 2. In a case-controlled study comparing a recipient group with graft dysfunction during pregnancy vs. a group with good graft function, there was a trend toward lower mean prepregnancy CsA doses (in mg/kg) in the graft dysfunction group. A decline in recipient graft function during pregnancy is associated with lower newborn birthweights and lower maternal graft survival in cyclosporine treated female kidney recipients. Pregnancy-related infections and complications are associated with rejection and graft loss in this population. Close monitoring of CsA dosing and serum creatinine levels during pregnancy and immediately postpartum is recommended as CsA dosage adjustment may be required.

VARIABLES AFFECTING BIRTHWEIGHT AND GRAFT SURVIVAL IN 197 PREGNANCIES IN CYCLOSPORINE-TREATED FEMALE KIDNEY TRANSPLANT RECIPIENTS1,2

Outcomes fr3om 197 pregnancies in 141 female kidney transplant recipients were analyzed from data collected via questionnaires, hospital records, and phone interviews. All recipients were maintained on cyclosporine (CsA) before and during pregnancy. Of the livebirths, 54% were premature (<37 wk) and 50% were low-birthweight (LBW) (<2500 g). The incidence of recipient drug-treated hypertension (HTN) was 56%; preeclampsia, 29%; infections and complications 22%; and rejection during pregnancy and up to 3 mo. post delivery (rej.), 11%. Graft loss within 2 years of delivery occurred in 9% of recipients (GrL <2). No recipients reported a pregnancy after a postpregnancy graft loss. Mean serum creatinine was reported before, during, and after pregnancy. Mean cyclosporine doses were similar in recipients during and after pregnancy. Data were analyzed by logistic regression using SAS. Outcomes included prematurity, LBW, rej., and GrL <2. In a case-controlled study comparing a recipient group with graft dysfunction during pregnancy vs. a group with good graft function, there was a trend toward lower mean prepregnancy CsA doses (in mg/kg) in the graft dysfunction group. A decline in recipient graft function during pregnancy is associated with lower newborn birthweights and lower maternal graft survival in cyclosporine treated female kidney recipients. Pregnancy-related infections and complications are associated with rejection and graft loss in this population. Close monitoring of CsA dosing and serum creatinine levels during pregnancy and immediately postpartum is recommended as CsA dosage adjustment may be required.

Transurethral Clot Evacuation from a Bladder with a Catheter Irrigating Syringe

After other methods of clot evacuation failed, transurethral insertion of the tip of a catheter irrigating syringe directly into the bladder of a female kidney transplant recipient resulted in the successful evacuation of an adherent hematoma.

NATIONAL TRANSPLANTATION PREGNANCY REGISTRY—OUTCOMES OF 154 PREGNANCIES IN CYCLOSPORINE-TREATED FEMALE KIDNEY TRANSPLANT RECIPIENTS

Outcomes of pregnancies from 115 female kidney transplant recipients maintained on cyclosporine before and during pregnancy were obtained from questionnaires, hospital records, and telephone interviews. The mean age of conception was 29 years with a mean transplant interval of 2.2 years. There were 156 outcomes (2 sets of twins): ectopic 1%, therapeutic abortion 12%, miscarriage 16%, stillborn 2.6%, live birth 68.6%. The incidence of prematurity (< 37 weeks) was 56%, and that of low birthweight (< 2500 g) 49.5%. Complications occurred in 21.7% of newborns, but with only 1 neonatal death. Liveborn infants had a mean gestational age of 35.6 weeks (term 37-42 weeks) and a mean birthweight of 2407 g. The incidence of drug-treated hypertension prior to pregnancy was 51.7%; of diabetes prior to pregnancy, 11.7%; of preeclampsia, 24.8%; and of rejection during pregnancy or within 3 months postdelivery 14.5%. When infants born to women with or without a given risk factor were compared, mothers with pregnancy drug-treated hypertension had significantly lower-birth-weight infants (2250 vs. 2603 g, P = 0.028 by Wilcoxon). Similarly, mothers with prepregnancy creatinine > or = 1.5 mg/dl had smaller infants (2090 vs. 2505 g, P = 0.031 by Wilcoxon). There was a trend toward lower birth-weight in infants of diabetic recipients. Of 107 recipients interviewed, 12(11%) experienced graft loss, 8 associated with graft dysfunction or rejection during pregnancy. There was 1 graft loss during pregnancy due to rejection and 8 grafts were lost within 2 years of the pregnancy. There was one maternal death 4.3 years postpregnancy. For the 8 recipients who lost their graft within 2 years of pregnancy, outcomes included 1 miscarriage and 7 live births. The 7 live births had a mean gestational age of 35.7 weeks and a mean birth-weight of 2194 g. Five of 8 recipients who had graft loss within 2 years of pregnancy were in the drug-treated hypertensive group. Prepregnancy factors that appear to increase the risk to the newborn of a female kidney transplant recipient include maternal drug-treated hypertension, diabetes, and serum creatinine > or = 1.5 mg/dl. More data are needed before specific prepregnancy predictors for maternal graft loss can be determined in this population.

Placental Expression of Vasoactive Agents and Tissue Factor in Pre-Eclamptic and Clyocosporine Treated Kidney Transplant Mothers

We studied the Endothelin-1 (ET-1)/Nitric Oxide Synthase (NOS) balance system,which is one of the most important systems in the regulation of the blood flow in several organs, in the placenta and in the decidua in normal and pre-eclamptic women. Since cyclosporine (CsA) has the potential to affect fetal growth and maternal state, through the modulation of ET-1 and NO synthesis,we compared these data with those obtained from transplanted women. Eleven CsAtreated female kidney transplant recipients (Tx), without fetal growth restriction and/or PE, and 12 PE, non transplanted,women were recruited. Fourteen normal pregnancies served as controls. Placental expression of ET-1 was evaluated by in situ hybridization,NO synthase (NOS) by NADPH-diaphorase staining and in situ hybridization. Both PE and Tx showed a marked reduction of NADPH-diaphorase staining, as weIl as of endothelial constitutive NOS (ecNOS) mRNA, in the syncytiotrophoblast layer of all villi, whereas the expression of inducible NOS was unchanged.Normal placenta showed a strong positive signal of ET-1 along the endothelium of utero-placental arteries within the basal plate which was markedly increased only in the decidua of Tx.Thus,Tx patients showed the mean relevant alteration of ET-1/ecNOS balance, in spite of the Iack of any alteration of fetal growth and maternal renal function.We further explored the state of activation of placental endothelial cells, evaluating Tissue Factor (TF) gene expression.TF was strikingly increased only in PE patients,where it is localized in the endothelial cells, as weII as in the cytotrophoblast invading the basal decidua. The modification of ET-1/ecNOS vasoactive balance, as elicited by CsA, is unable to account for the major features of the preeclamptic state. In the same patients we compared the preceding results with the uterine and umbilical Doppler velocimetry.We found that all Tx patients showed normal umbilical artery blood flow velocimetry, all but one displayed a normal pattern of uterine artery waveforms.Our studies witness that the ET-1/NOS balance is unable to lead to the modifications of Doppler impedance in the umbilical and uterine arteries.