RESUMO
RATIONALE & OBJECTIVE: The national kidney allocation system (KAS) implemented in December 2014 in the United States redefined the start of waiting time from the time of waitlisting to the time of kidney failure. Waitlisting has declined post-KAS, but it is unknown if this is due to transplant center practices or changes in dialysis facility referral and evaluation. The purpose of this study was to assess the impact of the 2014 KAS policy change on referral and evaluation for transplantation among a population of incident and prevalent patients with kidney failure. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 37,676 incident (2012-2016) patients in Georgia, North Carolina, and South Carolina identified within the US Renal Data System at 9 transplant centers and followed through December 2017. A prevalent population of 6,079 patients from the same centers receiving maintenance dialysis in 2012 but not referred for transplantation in 2012. EXPOSURE: KAS era (pre-KAS vs post-KAS). OUTCOME: Referral for transplantation, start of transplant evaluation, and waitlisting. ANALYTICAL APPROACH: Multivariable time-dependent Cox models for the incident and prevalent population. RESULTS: Among incident patients, KAS was associated with increased referrals (adjusted HR, 1.16 [95% CI, 1.12-1.20]) and evaluation starts among those referred (adjusted HR, 1.16 [95% CI, 1.10-1.21]), decreased overall waitlisting (adjusted HR, 0.70 [95% CI, 0.65-0.76]), and lower rates of active waitlisting among those evaluated compared to the pre-KAS era (adjusted HR, 0.81 [95% CI, 0.74-0.90]). Among the prevalent population, KAS was associated with increases in overall waitlisting (adjusted HR, 1.74 [95% CI, 1.15-2.63]) and active waitlisting among those evaluated (adjusted HR, 2.01 [95% CI, 1.16-3.49]), but had no significant impact on referral or evaluation starts among those referred. LIMITATIONS: Limited to 3 states, residual confounding. CONCLUSIONS: In the southeastern United States, the impact of KAS on steps to transplantation was different among incident and prevalent patients with kidney failure. Dialysis facilities referred more incident patients and transplant centers evaluated more incident patients after implementation of KAS, but fewer evaluated patients were placed onto the waitlist. Changes in dialysis facility and transplant center behaviors after KAS implementation may have influenced the observed changes in access to transplantation.
Assuntos
Falência Renal Crônica , Transplante de Rim , Humanos , Estados Unidos/epidemiologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/cirurgia , Estudos de Coortes , Listas de Espera , Encaminhamento e Consulta , RimRESUMO
Although research shows that minorities exhibit higher levels of medical mistrust, perceived racism, and discrimination in healthcare settings, the degree to which these underlying sociocultural factors preclude end-stage renal disease (ESRD) patients from initiating kidney transplant evaluation is unknown. We telephone surveyed 528 adult ESRD patients of black or white race referred for evaluation to a Georgia transplant center (N = 3) in 2014-2016. We used multivariable logistic regression to examine associations between sociocultural factors and evaluation initiation, adjusting for demographic, clinical, and socioeconomic characteristics. Despite blacks (n = 407) reporting higher levels of medical mistrust (40.0% vs 26.4%, P < .01), perceived racism (55.5% vs 18.2%, P < .01), and experienced discrimination (29.0% vs 15.7%, P < .01) than whites (n = 121), blacks were only slightly less likely than whites to initiate evaluation (49.6% vs 57.9%, P = .11). However, after adjustment, medical mistrust (odds ratio [OR]: 0.59; 95% confidence interval [CI]: 0.39, 0.91), experienced discrimination (OR: 0.62, 95% CI: 0.41, 0.95), and perceived racism (OR: 0.61; 95% CI: 0.40, 0.92) were associated with lower evaluation initiation. Results suggest that sociocultural disparities exist in early kidney transplant access and occur despite the absence of a significant racial disparity in evaluation initiation. Interventions to reduce disparities in transplantation access should target underlying sociocultural factors, not just race.
Assuntos
Etnicidade/psicologia , Disparidades em Assistência à Saúde , Falência Renal Crônica/diagnóstico , Transplante de Rim/estatística & dados numéricos , Fatores Socioeconômicos , Confiança , Estudos Transversais , Estudos de Avaliação como Assunto , Feminino , Seguimentos , Humanos , Falência Renal Crônica/psicologia , Falência Renal Crônica/cirurgia , Transplante de Rim/psicologia , Masculino , Pessoa de Meia-Idade , Prognóstico , TelefoneRESUMO
Variability in transplant access exists, but barriers to referral and evaluation are underexplored due to lack of national surveillance data. We examined referral for kidney transplantation evaluation and start of the evaluation among 34 857 incident, adult (18-79 years) end-stage kidney disease patients from 690 dialysis facilities in the United States Renal Data System from January 1, 2012 through August 31, 2016, followed through February 2018 and linked data to referral and evaluation data from nine transplant centers in Georgia, North Carolina, and South Carolina. Multivariable-adjusted competing risk analysis examined each outcome. The median within-facility cumulative percentage of patients referred for kidney transplantation within 1 year of dialysis at the 690 dialysis facilities in Network 6 was 33.7% (interquartile range [IQR]: 25.3%-43.1%). Only 48.3% of referred patients started the transplant evaluation within 6 months of referral. In multivariable analyses, factors associated with referral vs evaluation start among those referred at any time differed. For example, black, non-Hispanic patients had a higher rate of referral (hazard ratio [HR]: 1.22; 95% confidence interval [CI]: 1.18-1.27), but lower evaluation start among those referred (HR: 0.93; 95% CI: 0.88-0.98), vs white non-Hispanic patients. Barriers to transplant varied by step, and national surveillance data should be collected on early transplant steps to improve transplant access.
Assuntos
Falência Renal Crônica , Transplante de Rim , Adulto , Humanos , Falência Renal Crônica/cirurgia , North Carolina/epidemiologia , Encaminhamento e Consulta , Diálise Renal , Estados UnidosRESUMO
Human leukocyte antigen G (HLA-G), a nonclassic HLA class Ib molecule involved in the maintenance of maternal tolerance to semiallogeneic fetal tissues during pregnancy, has emerged as a potential therapeutic target to control allograft rejection. We demonstrate here that the level of soluble HLA-G dimer was higher in a group of 90 patients with a functioning renal allograft compared with 40 patients who rejected (RJ) their transplants. The HLA-G dimer level was not affected by demographic status. One of the potential mechanisms in tissue-organ allograft rejection involves the induction of granzymes and perforin, which are the main effector molecules expressed by CD8+ cytotoxic T lymphocytes and function to destroy allogeneic transplants. Using genomics and molecular and cellular analyses of cells from T-cell-mediated RJ and nonrejected kidney transplant patients, cells from leukocyte Ig-like receptor B1 (LILRB1) transgenic mice, humanized mice, and genetically engineered HLA-G dimer, we demonstrated a novel mechanism by which HLA-G dimer inhibits activation and cytotoxic capabilities of human CD8+ T cells. This mechanism implicated the down-regulation of Granzyme B expression and the essential involvement of LILRB1. Thus, HLA-G dimer has the potential to be a specific and effective therapy for prevention of allograft rejection and prolongation of graft survival.-Ajith, A., Portik-Dobos, V., Nguyen-Lefebvre, A. T., Callaway, C., Horuzsko, D. D., Kapoor, R., Zayas, C., Maenaka, K., Mulloy, L. L., Horuzsko, A. HLA-G dimer targets Granzyme B pathway to prolong human renal allograft survival.
Assuntos
Granzimas/metabolismo , Antígenos HLA-G/metabolismo , Adulto , Animais , Antígenos CD/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Concanavalina A/farmacologia , Feminino , Citometria de Fluxo , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Transplante de Rim , Receptor B1 de Leucócitos Semelhante a Imunoglobulina/antagonistas & inibidores , Receptor B1 de Leucócitos Semelhante a Imunoglobulina/metabolismo , Camundongos , Reação em Cadeia da Polimerase em Tempo Real , Linfócitos T/metabolismoRESUMO
BACKGROUND: Racial disparities persist in access to kidney transplantation. Racial differences in preemptive referral, or referral prior to dialysis start, may explain this discrepancy. METHODS: Patient-level data on kidney transplant referrals (2005-2012) from all Georgia transplant centers were linked to the United States Renal Data System to examine racial disparities in preemptive referral, waitlisting, and living donor transplant. Adjusted logistic regression and Cox proportional hazard models determined the associations between race (African American vs white) and preemptive referral, and placement on the waitlist and receipt of a living donor kidney, respectively. RESULTS: Among 7752 adults referred for transplant evaluation, 20.38% (n = 1580) were preemptively referred. The odds of African Americans being preemptively referred for transplant evaluation were 37% (OR = 0.63; [95% CI: 0.55 0.71]) lower than white patients. Among preemptively referred patients, there was no racial difference (African Americans compared to white patients. HR = 0.96; [95% CI: 0.88, 1.04]) in waitlisting. However, African Americans were 70% less likely than white patients to receive a living donor transplant (HR = 0.30; [95% CI: 0.21, 0.42]). CONCLUSION: Racial disparities in transplant receipt may be partially explained by disparities in preemptive referral. Interventions to reduce racial disparities in kidney transplant access may need to be targeted earlier in the disease process.
Assuntos
Acessibilidade aos Serviços de Saúde , Disparidades em Assistência à Saúde , Falência Renal Crônica/cirurgia , Transplante de Rim/estatística & dados numéricos , Doadores Vivos/provisão & distribuição , Encaminhamento e Consulta/estatística & dados numéricos , Listas de Espera , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Diálise Renal , Obtenção de Tecidos e Órgãos , Adulto JovemRESUMO
Clinical outcomes are generally worse for black vs nonblack renal allograft recipients. In BENEFIT and BENEFIT-EXT, recipients were randomized to belatacept more intense-based, belatacept less intense-based, or cyclosporine-based immunosuppression. At year 7, belatacept was associated with superior graft survival vs cyclosporine in BENEFIT (recipients of living or standard criteria deceased donor kidneys); belatacept was associated with similar graft survival vs cyclosporine in BENEFIT-EXT (recipients of extended criteria donor kidneys). In both studies, renal function was superior for belatacept-treated vs cyclosporine-treated patients. Seven-year outcomes were examined by race post hoc in each study. The effect of race and treatment on time to death or graft loss was compared using Cox regression. The interaction between treatment and race was also considered. Glomerular filtration rate (GFR) was estimated from months 1 to 84 using a repeated-measures model. In total, 8.3% (55/666) and 13.1% (71/543) of patients in BENEFIT and BENEFIT-EXT, respectively, were black. Time to death or graft loss was similar in blacks and nonblacks. For both subgroups, estimated mean GFR increased over 7 years for belatacept, but declined for cyclosporine. Outcomes were similar in belatacept-treated black and nonblack patients. Due to the small number of black patients, these results must be interpreted with caution.
Assuntos
Abatacepte/administração & dosagem , Ciclosporina/administração & dosagem , Etnicidade/estatística & dados numéricos , Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/administração & dosagem , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Negro ou Afro-Americano/estatística & dados numéricos , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Incidência , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Transplantados/estatística & dados numéricosRESUMO
BACKGROUND: The Reducing Disparities in Access to kidNey Transplantation Community Study (RaDIANT) was an End-Stage Renal Disease (ESRD) Network 6-developed, dialysis facility-level randomized trial testing the effectiveness of a 1-year multicomponent education and quality improvement intervention in increasing referral for kidney transplant evaluation among selected Georgia dialysis facilities. METHODS: To assess implementation of the RaDIANT intervention, we conducted a process evaluation at the conclusion of the intervention period (January-December 2014). We administered a 20-item survey to the staff involved with transplant education in 67 dialysis facilities randomized to participate in intervention activities. Survey items assessed facility participation in the intervention (fidelity and reach), helpfulness and willingness to continue intervention activities (sustainability), suggestions for improving intervention components (sustainability), and factors that may have influenced participation and study outcomes (context). We defined high fidelity to the intervention as completing 11 or more activities, and high participation in an activity as having at least 75% participation across intervention facilities. RESULTS: Staff from 65 of the 67 dialysis facilities completed the questionnaire, and more than half (50.8%) reported high adherence (fidelity) to RaDIANT intervention requirements. Nearly two-thirds (63.1%) of facilities reported that RaDIANT intervention activities were helpful or very helpful, with 90.8% of facilities willing to continue at least one intervention component beyond the study period. Intervention components with high participation emphasized staff and patient-level education, including in-service staff orientations, patient and family education programs, and patient educational materials. Suggested improvements for intervention activities emphasized addressing financial barriers to transplantation, with financial education materials perceived as most helpful among RaDIANT educational materials. Variation in facility-level fidelity of the RADIANT intervention did not significantly influence the mean difference in proportion of patients referred pre- (2013) and post-intervention (2014). CONCLUSIONS: We found high fidelity to the RaDIANT multicomponent intervention at the majority of intervention facilities, with sustainability of select intervention components at intervention facilities and feasibility for dissemination across ESRD Networks. Future modification of the intervention should emphasize financial education regarding kidney transplantation and amend intervention components that facilities perceive as time-intensive or non-sustainable. TRIAL REGISTRATION: Clinicaltrials.gov number NCT02092727 . Registered 13 Mar 2014 (retrospectively registered).
Assuntos
Instituições de Assistência Ambulatorial/normas , Disparidades em Assistência à Saúde/normas , Falência Renal Crônica/terapia , Transplante de Rim/normas , Encaminhamento e Consulta/normas , Diálise Renal/normas , Idoso , Instituições de Assistência Ambulatorial/tendências , Serviços de Saúde Comunitária/normas , Serviços de Saúde Comunitária/tendências , Feminino , Pessoal de Saúde/normas , Pessoal de Saúde/tendências , Disparidades em Assistência à Saúde/tendências , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Transplante de Rim/tendências , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta/tendências , Diálise Renal/tendênciasRESUMO
Georgia has the lowest kidney transplant rates in the United States and substantial racial disparities in transplantation. We determined the effectiveness of a multicomponent intervention to increase referral of patients on dialysis for transplant evaluation in the Reducing Disparities in Access to kidNey Transplantation Community Study (RaDIANT), a randomized, dialysis facility-based, controlled trial involving >9000 patients receiving dialysis from 134 dialysis facilities in Georgia. In December of 2013, we selected dialysis facilities with either low transplant referral or racial disparity in referral. The intervention consisted of transplant education and engagement activities targeting dialysis facility leadership, staff, and patients conducted from January to December of 2014. We examined the proportion of patients with prevalent ESRD in each facility referred for transplant within 1 year as the primary outcome, and disparity in the referral of black and white patients as a secondary outcome. Compared with control facilities, intervention facilities referred a higher proportion of patients for transplant at 12 months (adjusted mean difference [aMD], 7.3%; 95% confidence interval [95% CI], 5.5% to 9.2%; odds ratio, 1.75; 95% CI, 1.36 to 2.26). The difference between intervention and control facilities in the proportion of patients referred for transplant was higher among black patients (aMD, 6.4%; 95% CI, 4.3% to 8.6%) than white patients (aMD, 3.7%; 95% CI, 1.6% to 5.9%; P<0.05). In conclusion, this intervention increased referral and improved equity in kidney transplant referral for patients on dialysis in Georgia; long-term follow-up is needed to determine whether these effects led to more transplants.
Assuntos
Disparidades em Assistência à Saúde/estatística & dados numéricos , Transplante de Rim , Seleção de Pacientes , Encaminhamento e Consulta/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Estados UnidosRESUMO
BACKGROUND: Dialysis facility performance measures to improve access to kidney transplantation are being considered. Referral of patients for kidney transplantation evaluation by the dialysis facility is one potential indicator, but limited data exist to evaluate whether referral is associated with existing dialysis facility quality indicators. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 12,926 incident (July 2005 to September 2011) adult (aged 18-69 years) patients treated at 241 dialysis facilities with complete quality indicator information from US national registry data linked to transplantation referral data from all 3 Georgia kidney transplantation centers. FACTORS: Facility performance on dialysis quality indicators (high, intermediate, and low tertiles). OUTCOME: Percentages of patients referred within 1 year of dialysis therapy initiation at dialysis facility. RESULTS: Overall, a median of 25.4% of patients were referred for kidney transplantation within 1 year of dialysis therapy initiation. Higher facility-level referral was associated with better performance with respect to standardized transplantation ratio (high, 28.6%; intermediate, 25.1%; and low, 22.9%; P=0.001) and percentage waitlisted (high, 30.7%; intermediate, 26.8%; and low, 19.2%; P<0.001). Facility-level referral was not associated with indicators of quality of care associated with dialysis therapy initiation, including percentage of incident patients being informed of transplantation options. For most non-transplantation-related indicators of high-quality care, including those capturing mortality, morbidity, and anemia management, better performance was not associated with higher facility-level transplantation referral. LIMITATIONS: Potential ecologic fallacy and residual confounding. CONCLUSIONS: Transplantation referral among patients at dialysis facilities does not appear to be associated with overall quality of dialysis care at the facility. Quality indicators related to kidney transplantation were positively associated with, but not entirely correspondent with, higher percentages of patients referred for kidney transplantation evaluation from dialysis facilities. These results suggest that facility-level referral, which is within the control of the dialysis facility, may provide information about the quality of dialysis care beyond current indicators.
Assuntos
Transplante de Rim , Indicadores de Qualidade em Assistência à Saúde , Diálise Renal/normas , Adolescente , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta , Adulto JovemRESUMO
IMPORTANCE: Dialysis facilities in the United States are required to educate patients with end-stage renal disease about all treatment options, including kidney transplantation. Patients receiving dialysis typically require a referral for kidney transplant evaluation at a transplant center from a dialysis facility to start the transplantation process, but the proportion of patients referred for transplantation is unknown. OBJECTIVE: To describe variation in dialysis facility-level referral for kidney transplant evaluation and factors associated with referral among patients initiating dialysis in Georgia, the US state with the lowest kidney transplantation rates. DESIGN, SETTING, AND PARTICIPANTS: Examination of United States Renal Data System data from a cohort of 15,279 incident, adult (18-69 years) patients with end-stage renal disease from 308 Georgia dialysis facilities from January 2005 to September 2011, followed up through September 2012, linked to kidney transplant referral data collected from adult transplant centers in Georgia in the same period. MAIN OUTCOMES AND MEASURES: Referral for kidney transplant evaluation within 1 year of starting dialysis at any of the 3 Georgia transplant centers was the primary outcome; placement on the deceased donor waiting list was also examined. RESULTS: The median within-facility percentage of patients referred within 1 year of starting dialysis was 24.4% (interquartile range, 16.7%-33.3%) and varied from 0% to 75.0%. Facilities in the lowest tertile of referral (<19.2%) were more likely to treat patients living in high-poverty neighborhoods (absolute difference, 21.8% [95% CI, 14.1%-29.4%]), had a higher patient to social worker ratio (difference, 22.5 [95% CI, 9.7-35.2]), and were more likely nonprofit (difference, 17.6% [95% CI, 7.7%-27.4%]) compared with facilities in the highest tertile of referral (>31.3%). In multivariable, multilevel analyses, factors associated with lower referral for transplantation, such as older age, white race, and nonprofit facility status, were not always consistent with the factors associated with lower waitlisting. CONCLUSIONS AND RELEVANCE: In Georgia overall, a limited proportion of patients treated with dialysis were referred for kidney transplant evaluation between 2005 and 2011, but there was substantial variability in referral among facilities. Variables associated with referral were not always associated with waitlisting, suggesting that different factors may account for disparities in referral.
Assuntos
Falência Renal Crônica/terapia , Transplante de Rim , Encaminhamento e Consulta/estatística & dados numéricos , Diálise Renal , Adolescente , Adulto , Idoso , Instituições de Assistência Ambulatorial/economia , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Estudos de Coortes , Feminino , Georgia , Humanos , Masculino , Pessoa de Meia-Idade , Pobreza , Listas de Espera , Adulto JovemRESUMO
BACKGROUND: The Southeastern United States has the lowest kidney transplant rates in the nation, and racial disparities in kidney transplant access are concentrated in this region. The Southeastern Kidney Transplant Coalition (SEKTC) of Georgia, North Carolina, and South Carolina is an academic and community partnership that was formed with the mission to improve access to kidney transplantation and reduce disparities among African American (AA) end stage renal disease (ESRD) patients in the Southeastern United States. METHODS/DESIGN: We describe the community-based participatory research (CBPR) process utilized in planning the Reducing Disparities In Access to kidNey Transplantation (RaDIANT) Community Study, a trial developed by the SEKTC to reduce health disparities in access to kidney transplantation among AA ESRD patients in Georgia, the state with the lowest kidney transplant rates in the nation. The SEKTC Coalition conducted a needs assessment of the ESRD population in the Southeast and used results to develop a multicomponent, dialysis facility-randomized, quality improvement intervention to improve transplant access among dialysis facilities in GA. A total of 134 dialysis facilities are randomized to receive either: (1) standard of care or "usual" transplant education, or (2) the multicomponent intervention consisting of transplant education and engagement activities targeting dialysis facility leadership, staff, and patients within dialysis facilities. The primary outcome is change in facility-level referral for kidney transplantation from baseline to 12 months; the secondary outcome is reduction in racial disparity in transplant referral. DISCUSSION: The RaDIANT Community Study aims to improve equity in access to kidney transplantation for ESRD patients in the Southeast. TRIAL REGISTRATION: Clinicaltrials.gov number NCT02092727.
Assuntos
População Negra/estatística & dados numéricos , Pesquisa Participativa Baseada na Comunidade , Disparidades em Assistência à Saúde , Transplante de Rim , Encaminhamento e Consulta/estatística & dados numéricos , População Branca/estatística & dados numéricos , Instituições de Assistência Ambulatorial/estatística & dados numéricos , Atitude do Pessoal de Saúde , Pesquisa Participativa Baseada na Comunidade/organização & administração , Georgia , Pessoal de Saúde/psicologia , Acessibilidade aos Serviços de Saúde , Necessidades e Demandas de Serviços de Saúde , Disparidades em Assistência à Saúde/etnologia , Humanos , Cobertura do Seguro , Internet , Falência Renal Crônica/cirurgia , Falência Renal Crônica/terapia , Transplante de Rim/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde , Educação de Pacientes como Assunto , Melhoria de Qualidade , Diálise Renal , Padrão de CuidadoRESUMO
Despite the growing interest in the role of regulatory B cells (Bregs) in autoimmunity, their distinct role and function in kidney transplant outcomes remain elusive. Here, we retrospectively analyzed the proportion of Bregs, transitional Bregs (tBregs) and memory Bregs (mBregs) and their capacity to produce IL-10 in non-rejected (NR) versus rejected (RJ) kidney transplant recipients. In the NR group, we observed a significant increase in the proportion of mBregs (CD19+CD24hiCD27+) but no difference in tBregs (CD19+CD24hiCD38+), as compared to the RJ group. We also observed a significant increase in IL-10-producing mBregs (CD19+CD24hiCD27+IL-10+) in the NR group. As our group and others have previously reported a potential role of the human leukocyte antigen G (HLA-G) in human renal allograft survival, notably through IL-10, we then investigated possible crosstalk between HLA-G and IL-10+ mBregs. Our ex vivo data suggest a role of HLA-G in enhancing IL-10+ mBreg expansion upon stimulation, which further decreased CD3+ T cell proliferation capability. Using RNA-sequencing (RNA-seq), we identified potential key signaling pathways involved in HLA-G-driven IL-10+ mBreg expansion, such as the MAPK, TNF and chemokine signaling pathways. Together, our study highlights a novel HLA-G-mediated IL-10-producing mBreg pathway that may serve as a therapeutic target to improve kidney allograft survival.
Assuntos
Linfócitos B Reguladores , Transplante de Rim , Humanos , Antígenos HLA-G/metabolismo , Interleucina-10/metabolismo , Estudos Retrospectivos , Rim , AloenxertosRESUMO
Hypercalcemia and weight loss in a renal transplant patient especially with history of parathyroidectomy raises concern for an underlying malignancy, fungal infections or granulomatous disease. We present a case of 45-year-old male with history of subtotal parathyroidectomy presented with severe persistent hypercalcemia, acute kidney injury (AKI) and significant weight loss. An extensive workup revealed disseminated histoplasmosis. Hypercalcemia (which was refractory to initial medical management) and other symptoms resolved after a few weeks of initiating the antifungal treatment.
Assuntos
Injúria Renal Aguda/etiologia , Histoplasmose/diagnóstico , Hipercalcemia/etiologia , Transplante de Rim/efeitos adversos , Paratireoidectomia/efeitos adversos , Redução de Peso , Injúria Renal Aguda/diagnóstico , Diagnóstico Diferencial , Histoplasmose/complicações , Histoplasmose/diagnóstico por imagem , Humanos , Hipercalcemia/diagnóstico , Masculino , Pessoa de Meia-IdadeRESUMO
A 52-year-old African-American male patient with end-stage renal disease due to hypertension underwent deceased donor kidney transplant procedure with no immediate complications. The postprocedure complications, interventions, and course were abstracted by chart review. The ureteric stent was removed with flexible cystoscopy on postoperative day (POD) 24. 24 hours later, the patient presented with abdominal pain and inability to urinate. An urgent ultrasound and noncontrast CT scan showed grade 4 hydronephrosis of the transplanted kidney. A percutaneous nephrostomy stent was placed for urinary diversion. A large ureteric hematoma filling the lumen of the mid to distal ureter was identified on the nephrostogram and was evacuated. A follow-up nephrostogram on POD 44 revealed a distal ureter stricture and persistent well-formed midureter filling defect. A repeat nephrostogram performed at POD 72 was done with stricture dilatation, internalization of stents, and removal of a percutaneous nephrostomy tube. The patient was maintained on antibiotics for UTI prophylaxis throughout the course.
RESUMO
The outcome of organ transplantation is largely dictated by selection of a well-matched donor, which results in less chance of graft rejection. An allogeneic immune response is the main immunological barrier for successful organ transplantation. Donor and recipient human leukocyte antigen (HLA) mismatching diminishes outcomes after solid organ transplantation. The current evaluation of HLA incompatibility does not provide information on the immunogenicity of individual HLA mismatches and impact of non-HLA-related alloantigens, especially in vivo. Here we demonstrate a new method for analysis of alloimmune responsiveness between donor and recipient in vivo by introducing a humanized mouse model. Using molecular, cellular, and genomic analyses, we demonstrated that a recipient's personalized humanized mouse provided the most sensitive assessment of allogeneic responsiveness to potential donors. In our study, HLA typing provided a better recipient-donor match for one donor among two related donors. In contrast, assessment of an allogeneic response by mixed lymphocyte reaction (MLR) was indistinguishable between these donors. We determined that, in the recipient's humanized mouse model, the donor selected by HLA typing induced the strongest allogeneic response with markedly increased allograft rejection markers, including activated cytotoxic Granzyme B-expressing CD8+ T cells. Moreover, the same donor induced stronger upregulation of genes involved in the allograft rejection pathway as determined by transcriptome analysis of isolated human CD45+cells. Thus, the humanized mouse model determined the lowest degree of recipient-donor alloimmune response, allowing for better selection of donor and minimized immunological risk of allograft rejection in organ transplantation. In addition, this approach could be used to evaluate the level of alloresponse in allogeneic cell-based therapies that include cell products derived from pluripotent embryonic stem cells or adult stem cells, both undifferentiated and differentiated, all of which will produce allogeneic immune responses.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Rejeição de Enxerto/prevenção & controle , Antígenos HLA/imunologia , Teste de Histocompatibilidade , Histocompatibilidade , Leucócitos Mononucleares/transplante , Transplante de Órgãos , Baço/imunologia , Tolerância ao Transplante , Animais , Linfócitos T CD8-Positivos/metabolismo , Células Cultivadas , Bases de Dados Genéticas , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Sobrevivência de Enxerto , Antígenos HLA/genética , Humanos , Isoanticorpos/metabolismo , Leucócitos Mononucleares/imunologia , Teste de Cultura Mista de Linfócitos , Camundongos Endogâmicos NOD , Camundongos SCID , Transplante de Órgãos/efeitos adversos , Fenótipo , Valor Preditivo dos Testes , Baço/metabolismo , Transcriptoma , Transplante HomólogoRESUMO
Purpose of review: The purpose of this review is to describe the Southeastern Kidney Transplant Coalition's mission, vision, goals, and Early Transplant Access registry as an example of a community/academic collaboration dedicated to improving access to transplantation and reducing inequities in transplant access. Recent findings: The barriers and facilitators to referral and evaluation for kidney transplantation are not necessarily the same as for waitlisting and transplantation. Recent findings suggest that inequities in transplant access are multilevel and multifactorial and require continued community engagement to improve access to kidney transplantation across patients, health systems, and populations. Summary: Community-engaged approaches are critical to ensuring that inequities in transplant access - which may vary across regions -- are not only described but are addressed in practice in a sustainable manner.
RESUMO
Collapsing focal segmental glomerulosclerosis (FSGS) is classically seen in HIV-infected patients and carries a dismal prognosis. It can also occur in HIV-negative patients in which case, early aggressive treatment with glucocorticoids may be helpful with improvement in both proteinuria and renal function.
RESUMO
Nocardia transvalensis is a rare species of Nocardia and is known to be a drug-resistant organism. Multiple cases have been reported of Nocardia species causing opportunistic infections in immunocompromised hosts. To our knowledge, we report the first case of successfully treated drug-resistant Nocardia transvalensis causing pulmonary nocardiosis in a renal transplant patient. Our case validates the importance of prompt identification of Nocardia species and their drug sensitivities to improve clinical outcomes and reduce mortality.
Assuntos
Transplante de Rim , Nocardiose/microbiologia , Nocardia/isolamento & purificação , Infecções Oportunistas/complicações , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla , Humanos , Hospedeiro Imunocomprometido , Nocardiose/tratamento farmacológicoRESUMO
Critically ill patients with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop respiratory failure and septic shock. Extracorporeal blood purification is proposed as an adjuvant therapy for sepsis and aims at controlling the dysregulated autoimmune system. We describe our experience in treating COVID-19 patients with the oXiris® hemofilter which adsorbs both cytokines and endotoxins, provides renal replacement therapy and has anti-thrombogenic properties. It was approved by the US Food and Drug Administration (FDA) under emergency use authorization for COVID-19 patients in April 2020. In our study, the use of the oXiris® filter decreased levels of inflammatory markers including interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), and improved clinical outcomes in two out of three patients.
RESUMO
Calcinosis cutis refers to the deposition of calcium salts in the cutaneous and subcutaneous tissue and is frequently associated with inflammation. Gastric calcinosis can be classified into metastatic, dystrophic, and idiopathic; metastatic calcinosis is the most common type. In metastatic calcification, calcium salts are deposited in normal soft tissues in the setting of altered metabolism of serum calcium and phosphorus and is a rare and serious complication of chronic renal failure. The important factors contributing to the development of metastatic calcinosis are hypercalcemia, hyperphosphatemia, and an elevated calcium-phosphate product. The most striking feature of this diagnosis is the calcification around the large joints. While it mostly involves dermis of small and medium-sized vessels, it can rarely affect the mucosal layers of the gastrointestinal (GI) tract. Calcinosis presents as a marker for the presence of calcifications in other organs, such as heart or lung, which can be life-threatening. Patients rarely present with clinical symptoms of GI upset, dyspepsia, or epigastric pain that are attributed to calcinosis. If patients present with GI symptoms, infectious causes remain to be higher on the differential. We present a case of incidental finding of gastric mucosal calcinosis during the workup and treatment of dysphagia.