Pregnancy in renal transplant recipients: report of two successful pregnancies in a patient with impaired renal function.

Pregnancy in renal transplant recipients is common and, in spite of several potential problems, overall maternal and fetal outcome has been good in patients with transplants that are functioning well. The presence of renal impairment or hypertension, or both, usually leads to complications, especially in the mother. A patient is described who had a baseline creatinine clearance of about 35 mL/min-1.73 m2 and two successful pregnancies. Renal function deteriorated in the 3rd trimester of the first pregnancy but was reversible; permanent loss of function occurred in the 3rd trimester of the second pregnancy. The potential fetal and maternal risks and details of management of pregnant transplant recipients are reviewed.     

Acute undernutrition is not associated with excess of females at birth in humans: the Dutch hunger winter

It has been suggested that maternal undernutrition results in adjustment of the sex ratio at birth, favouring females. We tested this hypothesis using births during the Dutch Hunger Winter of 1944-1945, an acute severe famine of seven months' duration. There was no evidence of an excess of female births among deliveries of human infants exposed to famine in any period in gestation. Indeed, among deliveries to women maximally exposed to famine prior to conception, there was an excess (odds ratio = 1.31, 95% CI 1.09-1.58; p = 0.004) of male offspring. Our data do not provide any support for acute and severe maternal undernutrition as a trigger for an increase in female conceptions or in male foetal deaths in human populations.     

A Shift towards Pro-Inflammatory CD16+ Monocyte Subsets with Preserved Cytokine Production Potential after Kidney Transplantation

Background

The presence of monocyte-macrophage lineage cells in rejecting kidney transplants is associated with worse graft outcome. At present, it is still unclear how the monocyte-macrophage related responses develop after transplantation. Here, we studied the dynamics, phenotypic and functional characteristics of circulating monocytes during the first 6 months after transplantation and aimed to establish the differences between kidney transplant recipients and healthy individuals.

Methods

Phenotype, activation status and cytokine production capacity of classical (CD14++CD16−), intermediate (CD14++CD16+) and non-classical (CD14+CD16++), monocytes were determined by flow cytometry in a cohort of 33 healthy individuals, 30 renal transplant recipients at transplantation, 19 recipients at 3 months and 16 recipients at 6 months after transplantation using a cross-sectional approach.

Results

The percentage of both CD16+ monocyte subsets was significantly increased in transplant recipients compared to healthy individuals, indicative of triggered innate immunity (p≤0.039). Enhanced production capacity of tumor necrosis factor-α, interferon-γ and interleukin-1β was observed by monocytes at transplantation compared to healthy individuals. Remarkably, three months post-transplant, in presence of potent immunosuppressive drugs and despite improved kidney function, interferon-γ, tumor necrosis factor-α and interleukin-10 production capacity still remained significantly increased.

Conclusion

Our data demonstrate a skewed balance towards pro-inflammatory CD16+ monocytes that is present at the time of transplantation and retained for at least 6 months after transplantation. This shift could be one of the important drivers of early post-transplant cellular immunity.     

Chronic maternal dietary iodine deficiency but not thiocyanate feeding affects maternal reproduction and postnatal performance of the rat

Iodine deficiency disorders affect reproductive performance in the afflicted populations. Environmental iodine deficiency (ID) and goitrogens are important in their aetiology. We observed earlier that chronic maternal dietary ID but not goitrogen feeding altered the blood-brain barrier nutrient transport in adult rats. Whether similar differences exist in their effects on reproduction of dams and postnatal performance of the offspring has been assessed. Inbred, female, weaning WNIN rats were rendered hypothyroid by feeding for 8-12 weeks, a low iodine test diet or a control diet with added potassium thiocyanate (KSCN) (@ 25 mg/rat/day). Following mating with control males, they continued on their respective diets till their pups were weaned. Indices of reproductive performance such as percentage of conception, mortality of dams during pregnancy and parturition, litter size, and survival of pups till weaning were affected markedly by ID but not thiocyanate feeding. Neither ID nor thiocyanate feeding from conception or parturition affected their reproductive performance. Nevertheless, postnatal weight gain of pups was less in all the three ID groups but not thiocyanate fed dams. Rehabilitation of chronically ID pregnant dams from conception or parturition did not improve their pregnancy weight gain, litter size or birth weight of pups but decreased abortion and mortality of mothers during pregnancy and parturition. Rehabilitation improved the pups' postnatal weight gain but the effect was only moderate. Based on the results of the present study it may be suggested that maternal ID but not thiocyanate feeding affects reproductive performance and postnatal performance of their offspring.     

The incidence and clinical relevance of anti-HLA and/or MICA antibodies in patients with long-term survival renal allo-grafts

The purpose of this study was to analyze the incidence and clinical relevance of anti-HLA and/or MICA antibodies in renal allo-grafts transplant recipients with long-term renal survival (> 5 years). This retrospective study collected post-transplant serum samples from a total of 110 patients which were used to detect the incidence of anti-HLA and/or MICA antibodies as well as anti-HLA donor specific antibodies. Among these 110 patients, 72 patients had antibodies against HLA and/or MICA at the time of test, 61 had only anti-HLA antibodies, 31 had anti-MICA antibodies, and 38 were antibody negative. There was no difference in the number of patients developing antibodies against non-donor specific antibodies, donor specific antibodies, Class I donor specific antibodies, Class II donor specific antibodies or MICA antibodies between normal function group (serum creatinine level < 2.0 mg/dL) and dysfunction group (serum creatinine level > 2.0 mg/dL). For the serum creatinine level, estimated glomerular filtration rate and blood urea nitrogen level, patients with different antibodies were not statistically different to antibody-negative patients. Cox regression analysis showed that the type of transplantation and HLA mismatch number were significant negative risk factors for the development of anti-HLA (P < 0.05). Our results suggested that the anti-HLA antibody status has little impact on the renal graft function in the long-term survival allo-graft renal recipients.     

Pre-Transplant Depression Is Associated with Length of Hospitalization,Discharge Disposition,and Survival after Liver Transplantation

Depression after liver transplantation has been associated with decreased survival, but the effects of pre-transplant depression on early and late post-transplant outcomes remain incompletely evaluated. We assessed all patients who had undergone single-organ liver transplantation at a single center over the prior 10 years. A diagnosis of pre-transplant depression, covariates, and the outcomes of interest were extracted from the electronic medical record. Potential covariates included demographics, etiology and severity of liver disease, comorbidities, donor age, graft type, immunosuppression, and ischemic times. In multivariable models adjusting for these factors, we evaluated the effect of pre-transplant depression on transplant length of stay (LOS), discharge disposition (home vs. facility) and long-term survival. Among 1115 transplant recipients with a median follow-up time of 5 years, the average age was 56±11 and MELD was 12±9. Nineteen percent of the study population had a history of pre-transplant depression. Pre-transplant depression was associated with longer LOS (median = 19 vs. 14 days, IRR = 1.25, CI = 1.13,1.39), discharge to a facility (36% vs. 25%, OR 1.70,CI = 1.18,2.45), and decreased survival (HR = 1.54,CI = 1.14,2.08) in this cohort, accounting for other potential confounders. In conclusion, pre-transplant depression was significantly associated with longer transplant length of stay, discharge to a facility, and mortality in this cohort.     

肾移植受者生活质量和健康素养现状调查及影响因素分析

目的:调查肾移植受者生活质量(QOL)、健康素养(HL)现状,并分析其QOL、HL的影响因素。方法:选择我院2015年1月～2016年1月收治的369例肾移植受者为研究对象,采用自制问卷结合病历信息的方式收集入选患者的临床资料,分别采用健康状况调查简表(SF-36)、中文版成人快速健康素养评估量表(REALAM-T)对肾移植受者的QOL、HL的现状进行调查,并分析肾移植受者QOL、HL的影响因素。结果:369例肾移植受者QOL评分为(561.08±54.95)分,HL评分为(62.75±5.26)分,其中288例(78.05%)患者处于HL充足水平,56例(15.18%)患者处于HL临界水平,25例(6.78%)患者处于HL缺乏水平。单因素分析结果显示,不同婚姻状况、家庭人均月收入、文化程度、费用支付方式、移植肾来源、移植术后时间的肾移植受者QOL评分比较差异有统计学意义(P0.05);不同家庭人均月收入、文化程度、费用支付方式、移植肾来源、移植术后时间的肾移植受者HL评分比较差异有统计学意义(P0.05)。多元线性回归分析显示,家庭人均月收入、费用支付方式、移植肾来源、移植术后时间是肾移植受者QOL的影响因素(P0.05),文化程度、移植肾来源、移植术后时间是肾移植受者HL的影响因素(P0.05)。结论:肾移植受者QOL较差,HL整体不高,家庭人均月收入、费用支付方式、移植肾来源、移植术后时间是肾移植受者QOL的影响因素,文化程度、移植肾来源、移植术后时间是肾移植受者HL的影响因素,临床应根据以上因素采取针对性的措施,以提高肾移植受者的QOL和HL。     

Longitudinal Analysis of T and B Cell Phenotype and Function in Renal Transplant Recipients with or without Rituximab Induction Therapy

Background

Prevention of rejection after renal transplantation requires treatment with immunosuppressive drugs. Data on their in vivo effects on T- and B-cell phenotype and function are limited.

Methods

In a randomized double-blind placebo-controlled study to prevent renal allograft rejection, patients were treated with tacrolimus, mycophenolate mofetil (MMF), steroids, and a single dose of rituximab or placebo during transplant surgery. In a subset of patients, we analyzed the number and phenotype of peripheral T and B cells by multiparameter flow cytometry before transplantation, and at 3, 6, 12, and 24 months after transplantation.

Results

In patients treated with tacrolimus/MMF/steroids the proportion of central memory CD4⁺ and CD8⁺ T cells was higher at 3 months post-transplant compared to pre-transplant levels. In addition, the ratio between the percentage of central memory CD4⁺ and CD4⁺ regulatory T cells was significantly higher up to 24 months post-transplant compared to pre-transplant levels. Interestingly, treatment with tacrolimus/MMF/steroids resulted in a shift toward a more memory-like B-cell phenotype post-transplant. Addition of a single dose of rituximab resulted in a long-lasting B-cell depletion. At 12 months post-transplant, the small fraction of repopulated B cells consisted of a high percentage of transitional B cells. Rituximab treatment had no effect on the T-cell phenotype and function post-transplant.

Conclusions

Renal transplant recipients treated with tacrolimus/MMF/steroids show an altered memory T and B-cell compartment post-transplant. Additional B-cell depletion by rituximab leads to a relative increase of transitional and memory-like B cells, without affecting T-cell phenotype and function.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00565331","term_id":"NCT00565331"}}NCT00565331     

Maternal exposure to exogenous sex hormones in relation to birth weight of offspring

Birth weight was analyzed among singleton live births (N = 665) in Upstate New York in 1974 to women who used oral contraceptives (OC) in comparison to live births to women who used no contraceptives (N = 716), within 11 months prior to last menstrual period (LMP). In addition, birth weight was examined among live births to women who received hormone support therapy (N = 97) and hormone pregnancy tests (N = 75) during pregnancy. There was no evidence for a reduction in mean birth weight, or an increase in frequency of lower weights, among births to OC users, including those who stopped using OC within 2 months of LMP. Generally similar findings held within three maternal age groups (less than 25, 25-29, and 30-39 years). There was no evidence for a reduction in birth weight among offspring of women who received hormone pregnancy tests. Mean birth weight was relatively low among male and female births to women who received hormone therapy for "threatened abortion," but this may reflect the selection of women for such treatment rather than an effect of exogenous hormones on fetal growth.     

Sunshine,fertility and racial disparities

This research investigates the effect of sun exposure on fertility, with a special focus on how its effects and consequences for birth outcomes may differ by race. Sun exposure is a key mechanism for obtaining Vitamin D, but this process is inhibited by skin pigmentation. Vitamin D has been linked to male and female fertility and risk of miscarriage, and Vitamin D deficiency is more prevalent among blacks than whites. Using 1989–2004 individual live births data from the Natality Detail Files, county-level, monthly conceptions are estimated as a function of monthly solar insolation, temperature and humidity, as well as month, time and location fixed effects and controls. Insolation has positive, statistically significant effects on fertility for both non-Hispanic blacks and whites, but the effects are stronger and the pattern of effect different for black mothers than white mothers. Poisson estimates from the main model suggest that a 1 kWh increase in average daily insolation in the conception month – approximately the difference in sunshine experienced in the typical September vs. October – increases non-Hispanic black conceptions by 1% and non-Hispanic white conceptions by 0.6%. Allowing insolation's effect to differ by maternal characteristic suggests that the racial differences are not being driven by differences in socioeconomic status (SES). Models that allow for more complicated timing of insolation's effect further suggest that insolation pushes black (white) conceptions into the unfavorable (favorable) season of birth. These estimated effects and our decomposition analyses suggest that insolation – and the implied Vitamin D deficiency underlying its effect–helps explain why black conceptions are more likely to display a seasonal pattern that is disadvantageous to birth outcomes.     

Seasonal variation in conception and various pregnancy outcomes

Abstract

U.S. vital registration data on live births and data on abortions and ectopic pregnancies from a national hospital discharge survey were used to examine the seasonality of conceptions and the influence the conception pattern has on the monthly incidence of abortions and ectopic pregnancies. We found that in the United States conceptions follow a consistent seasonal pattern with the peak in November and December. However, when the pattern for conceptions is controlled, the monthly variation for abortions and ectopic pregnancies is not significant. Therefore, we find no monthly excess for any of these outcomes of pregnancy over that expected as a consequence of the seasonality of conception. We suggest the monthly variation for the number of each of these pregnancy outcomes will best be explained when the seasonal variation in conceptions is understood.     

BK antibody and virus-specific IgM responses in renal transplant recipients,patients with malignant disease,and healthy people.

Haemagglutination-inhibition (HAI) antibodies to BK virus, including BK-virus-specific IgM, were determined before and after renal transplantation in 20 patients, in 57 patients with malignant disease, and in 66 healthy controls, Before transplantation 11 of the renal transplant recipients were seronegative, but eight later serocconverted, two before and six after transplantation. Twenty of the patients with malignant disease and 22 controls were also seronegative. The geometric mean titre of BK HAI antibodies was significantly higher among transplanted patients (1/180) than among controls (1/90). BK-virus-specific IgM antibody was detected in seven renal transplant recipients, six patients with malignant disease, and 13 healthy controls. In transplant recipients BK-virus-specific IgM antibody usually persisted throughout the duration of the study, and studies on controls from whom second serum samples were available suggested that they too had persistent BK-virus-specific IgM responses. The geometric mean titre of BK-virus-specific IgM HAI antibody was significantly greater in post-transplantation sera (1/223) than in control sera (1/28). The specificity of the detection of BK-virus-specific IgM HAI antibody was confirmed by direct visualisation of antibody by immune electron microscopy. The persistence of BK-virus-specific IgM suggested that BK virus continued to provide an antigenic stimulus. Nevertheless, there was no obvious association between the serological findings and any clinical features, and prospective studies will be needed to elucidate any such association.     

Molecular origin of female meiotic aneuploidies

Chromosome aneuploidy is a major cause of pregnancy loss, abnormal pregnancy and live births following both natural conception and in vitro fertilisation (IVF) and increases exponentially with maternal age in the decade preceding the menopause. Molecular genetic analysis has shown that these are predominantly maternal in origin and trisomies most frequently occur through errors in the first meiotic division. Analysis of chromosome copy number in the three products of female meiosis, the first and second polar bodies and the corresponding zygote by microarray comparative genomic hybridisation (array CGH), in women of advanced maternal age undergoing IVF, has recently revealed a pattern of frequent multiple meiotic errors, caused by premature predivision of sister chromatids in meiosis I and a high incidence of errors in meiosis II. This pattern is similar to those observed in various mouse models which implicate the gradual depletion of cohesins, which are essential for cohesion of sister chromatids, as the primary cause of age related aneuploidy in female meiosis. However, defects in other aspects of meiosis including the formation and stabilisation of chiasmata and the spindle assembly checkpoint (SAC) may also contribute. The challenge remains to explain the molecular basis of ‘physiological’ rather than ‘chronological’ female ageing and the contribution of multifactorial causes from the fetal to adult ovary. This article is part of a Special Issue entitled: Molecular Genetics of Human Reproductive Failure.     

Maternal and neonatal factors influencing premature birth and low birth weight in Australia

This study identified the influences of neonatal and maternal factors on premature birth and low birth weight in New South Wales, Australia. Bivariate and multivariate analyses were used to explore the association of selected neonatal and maternal characteristics with premature birth and low birth weight. The findings of this study showed that premature birth and low birth weight rate significantly varied by infant sex, maternal age, marital status, Aboriginality, parity, maternal smoking behaviour during pregnancy and maternal hypertension. First-born infants, and infants born to mothers aged less than 20 years, or who were single, separated/divorced, Aboriginal or who smoked during the pregnancy, were at increased risk of being premature or of low birth weight. This study also found that risk factors for premature births and low birth weight were similar in both singleton and multiple births. Gestational age was confirmed to be the single most important risk factor for low birth weight. The findings of this study suggest that in order to reduce the incidence of low birth weight and premature births, health improvement strategies should focus on anti-smoking campaigns during pregnancy and other healthcare programmes targeted at the socially disadvantaged populations identified in the study.     

The presence of antibodies against the AD2 epitope of cytomegalovirus glycoprotein B is associated with acute rejection after renal transplantation

The aim of this study was to evaluate the association between antibodies against cytomegalovirus (CMV) glycoprotein B (gB) and acute rejection after transplantation. Seventy‐seven consecutive renal transplant recipients in a D + /R+ setting were studied. Biopsy‐proven rejection occurred in 35% of the recipients. Among these recipients, 85% had antibodies against CMV gB. The rate of acute rejection was significantly higher in recipients with antibodies against gB than in those without them. Antibodies against gB can be a useful predictor of acute rejection in renal transplant recipients in a D + /R+ setting.     

Cellular senescence in pretransplant renal biopsies predicts postoperative organ function

Older and marginal donors have been used to meet the shortfall in available organs for renal transplantation. Post-transplant renal function and outcome from these donors are often poorer than chronologically younger donors. Some organs, however, function adequately for many years. We have hypothesized that such organs are biologically younger than poorer performing counterparts. We have tested this hypothesis in a cohort of pre-implantation human renal allograft biopsies ( n  = 75) that have been assayed by real-time polymerase chain reaction for the expression of known markers of cellular damage and biological aging, including CDKN2A, CDKN1A, SIRT2 and POT1. These have been investigated for any associations with traditional factors affecting transplant outcome (donor age, cold ischaemic time) and organ function post-transplant (serum creatinine levels). Linear regression analyses indicated a strong association for serum creatinine with pre-transplant CDKN2A levels ( p  = 0.001) and donor age ( p  = 0.004) at 6 months post-transplant. Both these markers correlated significantly with urinary protein to creatinine ratios ( p  = 0.002 and p  = 0.005 respectively), an informative marker for subsequent graft dysfunction. POT1 expression also showed a significant association with this parameter ( p  = 0.05). Multiple linear regression analyses for CDKN2A and donor age accounted for 24.6% ( p  = 0.001) of observed variability in serum creatinine levels at 6 months and 23.7% ( p  = 0.001) at 1 year post-transplant. Thus, these data indicate that allograft biological age is an important novel prognostic determinant for renal transplant outcome.     

Reproductive Seasonality in Female Capuchins (<Emphasis Type="Italic">Cebus capucinus</Emphasis>) in Santa Rosa (Area de Conservación Guanacaste), Costa Rica

The income-capital breeding model was developed to explain birth seasonality and reproductive strategies in female animals in relation to the abundance of food energy in the environment. An income breeder uses currently available energy and acts so as to maximize either maternal survival or weanling survival, depending on the relationship between timing of births and abundance of food energy. A capital breeder stores energy reserves for future reproductive use. Here we examined energetic influences on reproductive seasonality in a population of female white-faced capuchins (Cebus capucinus) living in a seasonal dry forest in Costa Rica. Our objectives were to determine: 1) the degree of fruiting seasonality in capuchin food trees and 2) the temporal relationship between capuchin births/conceptions and fruit abundance. Our sample included 25 yr of birth data (N = 100 births), 4 yr of capuchin fruit tree phenology data, and 18 mo of ovarian hormone data, which we used to calculate gestation lengths and estimate conception dates. Using circular statistics, we found that the mean peak in fruit abundance occurs in June, and that this population of capuchins reproduces seasonally, with 44% of births occurring within a 3-mo period (May to July, mean month = May). We propose that white-faced capuchins can be generally classified as income breeders that maximize maternal survival instead of weanling survival and that they time infant births such that the most energy expensive period of reproduction, mid-to-late lactation, occurs during the mean peak in fruit abundance.     

Diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome after renal transplantation in the United States

BACKGROUND: The incidence and risk factors for diabetic ketoacidosis (diabetic ketoacidosis) and hyperglycemic hyperosmolar syndrome (hyperglycemic hyperosmolar syndrome, previously called non-ketotic hyperosmolar coma) have not been reported in a national population of renal transplant (renal transplantation) recipients. METHODS: We performed a historical cohort study of 39,628 renal transplantation recipients in the United States Renal Data System between 1 July 1994 and 30 June 1998, followed until 31 Dec 1999. Outcomes were hospitalizations for a primary diagnosis of diabetic ketoacidosis (ICD-9 code 250.1x) and hyperglycemic hyperosmolar syndrome (code 250.2x). Cox Regression analysis was used to calculate adjusted hazard ratios for time to hospitalization for diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome. RESULTS: The incidence of diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome were 33.2/1000 person years (PY) and 2.7/1000 PY respectively for recipients with a prior diagnosis of diabetes mellitus (DM), and 2.0/1000 PY and 1.1/1000 PY in patients without DM. In Cox Regression analysis, African Americans (AHR, 2.71, 95 %CI, 1.96-3.75), females, recipients of cadaver kidneys, patients age 33-44 (vs. >55), more recent year of transplant, and patients with maintenance TAC (tacrolimus, vs. cyclosporine) had significantly higher risk of diabetic ketoacidosis. However, the rate of diabetic ketoacidosis decreased more over time in TAC users than overall. Risk factors for hyperglycemic hyperosmolar syndrome were similar except for the significance of positive recipient hepatitis C serology and non-significance of female gender. Both diabetic ketoacidosis (AHR, 2.44, 95% CI, 2.10-2.85, p < 0.0001) and hyperglycemic hyperosmolar syndrome (AHR 1.87, 95% CI, 1.22-2.88, p = 0.004) were independently associated with increased mortality. CONCLUSIONS: We conclude that diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome were associated with increased risk of mortality and were not uncommon after renal transplantation. High-risk groups were identified.     

Identification of Molecular Markers of Delayed Graft Function Based on the Regulation of Biological Ageing

IntroductionDelayed graft function is a prevalent clinical problem in renal transplantation for which there is no objective system to predict occurrence in advance. It can result in a significant increase in the necessity for hospitalisation post-transplant and is a significant risk factor for other post-transplant complications.MethodologyThe importance of microRNAs (miRNAs), a specific subclass of small RNA, have been clearly demonstrated to influence many pathways in health and disease. To investigate the influence of miRNAs on renal allograft performance post-transplant, the expression of a panel of miRNAs in pre-transplant renal biopsies was measured using qPCR. Expression was then related to clinical parameters and outcomes in two independent renal transplant cohorts.ResultsHere we demonstrate, in two independent cohorts of pre-implantation human renal allograft biopsies, that a novel pre-transplant renal performance scoring system (GRPSS), can determine the occurrence of DGF with a high sensitivity (>90%) and specificity (>60%) for donor allografts pre-transplant, using just three senescence associated microRNAs combined with donor age and type of organ donation.ConclusionThese results demonstrate a relationship between pre-transplant microRNA expression levels, cellular biological ageing pathways and clinical outcomes for renal transplantation. They provide for a simple, rapid quantitative molecular pre-transplant assay to determine post-transplant allograft function and scope for future intervention. Furthermore, these results demonstrate the involvement of senescence pathways in ischaemic injury during the organ transplantation process and an indication of accelerated bio-ageing as a consequence of both warm and cold ischaemia.     

Renal transplant patients treated with total lymphoid irradiation show specific unresponsiveness to donor antigens the mixed leukocyte reaction (MLR)

A group of 25 cadaveric renal transplant recipients received total lymphoid irradiation (TLI) before transplantation, rabbit anti-thymocyte globulin on alternate days for 10 days after transplantation, and low dose prednisone (5 to 10 mg/day) as the sole maintenance immunosuppressive therapy. Allograft function and the mixed leukocyte reaction (MLR) were monitored serially. After 18 to 30 mo, nine patients were selected on the basis of a return of the MLR such that the mean stimulation index to a panel of normal stimulator cells was greater than or equal to 5, a stable serum creatinine level which was less than or equal to 2 mg/dl, and a history of no more than one rejection episode. The MLR of these patients' post-transplant peripheral blood mononuclear leukocytes (PBML) against cryopreserved donor cells was compared with that against cryopreserved normal third-party cells. In control experiments, the MLR of cryopreserved pre-TLI recipient PBML or fresh normal PBML were tested against the same panel of donor and third-party stimulator cells. Seven of the nine recipients showed a pattern of specific unresponsiveness to the donor cells more than 18 mo after transplantation. Preliminary attempts to identify antigen specific suppressor cells were unsuccessful. The pattern of unresponsiveness may indicate a state of specific immune tolerance to the allogeneic graft.