RESUMO
Kidney transplantation is the most successful kidney replacement therapy available, resulting in improved recipient survival and societal cost savings. Yet, nearly 70 years after the first successful kidney transplant, there are still numerous barriers and untapped opportunities that constrain the access to transplant. The literature describing these barriers is extensive, but the practices and processes to solve them are less clear. Solutions must be multidisciplinary and be the product of strong partnerships among patients, their networks, health care providers, and transplant programs. Transparency in the referral, evaluation, and listing process as well as organ selection are paramount to build such partnerships. Providing early culturally congruent and patient-centered education as well as maximizing the use of local resources to facilitate the transplant work up should be prioritized. Every opportunity to facilitate pre-emptive kidney transplantation and living donation must be taken. Promoting the use of telemedicine and kidney paired donation as standards of care can positively impact the work up completion and maximize the chances of a living donor kidney transplant.
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Acessibilidade aos Serviços de Saúde , Falência Renal Crônica , Transplante de Rim , Obtenção de Tecidos e Órgãos , Humanos , Obtenção de Tecidos e Órgãos/métodos , Falência Renal Crônica/cirurgia , Doadores Vivos/provisão & distribuição , Listas de EsperaRESUMO
BACKGROUND: Standard-of-care biomarkers for renal allograft rejection are lagging indicators, signaling existing organ injury. This precludes early intervention, when immunological cascades leading to rejection are most susceptible. Donor-derived cell-free DNA (dd-cfDNA) shows promise as an early indicator of rejection, allowing earlier and possibly more effective treatment. This analysis was designed to assess this promise using real-world dd-cfDNA testing evidence. METHODS: This retrospective analysis of the prospective, observational ProActive registry study (NCT04091984) assessed dd-cfDNA and serum creatinine levels before biopsy in 424 patients with ≥1 dd-cfDNA test (nâ =â 1013) in the 6 mo before biopsy. RESULTS: Of 4667 enrolled patients, 1631 patients had ≥18 mo of follow-up data, of which 424 had a biopsy and were included in this analysis. Twenty-six biopsies showed antibody-mediated rejection (ABMR), 62 showed T cell-mediated rejection, and 336 showed nonrejection; each from a unique patient. dd-cfDNA fractions were significantly elevated 5 mo before ABMR biopsies, and 2 mo before T cell-mediated rejection biopsies, compared with nonrejection biopsies. In contrast, serum creatinine did not discriminate between rejection and nonrejection in advance, or concurrent with biopsy. Among patients with nonrejection biopsies, estimated glomerular filtration rate was significantly lower in cases with ≥2 increased dd-cfDNA results (≥1%), compared with those with 0 or 1 increased dd-cfDNA result. CONCLUSIONS: These data indicate that dd-cfDNA is an early indicator of biopsy-proven rejection, especially ABMR, suggesting a greater role for dd-cfDNA in surveillance to identify patients at high risk of ongoing or future rejection, thus requiring closer monitoring, biopsy, or other management changes.
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The objective of this study was to validate the performance of Tutivia, a peripheral blood gene expression signature, in predicting early acute rejection (AR) post-kidney transplant. Recipients of living or deceased donor kidney transplants were enrolled in a nonrandomized, prospective, global, and observational study (NCT04727788). The main outcome was validation of the area under the curve (AUC) of Tutivia vs serum creatinine at biopsy alone, or Tutivia + serum creatinine at biopsy. Of the 151 kidney transplant recipients, the mean cohort age was 53 years old, and 64% were male. There were 71% (107/151) surveillance/protocol biopsies and 29% (44/151) for-cause biopsies, with a 31% (47/151) overall rejection rate. Tutivia (AUC 0.69 [95% CI: 0.59-0.77]) and AUC of Tutivia + creatinine at biopsy (0.68 [95% CI: 0.59-0.77]) were greater than the AUC of creatinine at biopsy alone (0.51.4 [95% CI: 0.43-0.60]). Applying a model cut-off of 50 (scale 0-100) generated a high- and low-risk category for AR with a negative predictive value of 0.79 (95% CI: 0.71-0.86), a positive predictive value of 0.60 (95% CI: 0.45-0.74), and an odds ratio of 5.74 (95% CI: 2.63-12.54). Tutivia represents a validated noninvasive approach for clinicians to accurately predict early AR, beyond the current standard of care.
Assuntos
Transplante de Rim , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Transplante de Rim/efeitos adversos , Estudos Prospectivos , Creatinina , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Biomarcadores/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , RNARESUMO
BACKGROUND AND OBJECTIVES: There are no standardized benchmarks to measure productivity and compensation of transplant nephrologists in the United States, and consequently, criteria set for general nephrologists are often used. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A web-based survey was sent to 809 nephrologists who were members of the American Society of Transplantation to gather data on measures of productivity, compensation, and job satisfaction. Factors associated with higher total compensation and job satisfaction were examined. RESULTS: Of 365 respondents, 260 were actively practicing in the United States and provided data on compensation. Clinical productivity was assessed variably, and although 194 (76%) had their work relative value units (wRVUs) reported to them, only 107 (44%) had an established RVU target. Two hundred thirty-four respondents (90%) had fixed base compensation, and 172 (66%) received a bonus on the basis of clinical workload (68%), academic productivity (31%), service (32%), and/or teaching responsibility (31%). Only 127 respondents (49%) filled out time studies, and 92 (35%) received some compensation for nonbillable transplant activity. Mean total compensation (base salary and bonus) was $274,460±$91,509. The unadjusted mean total compensation was higher with older age and was higher for men; Hispanic and White respondents; adult care transplant nephrologists; residents of the western United States; US medical school graduates; nonuniversity hospital employees; and those with an administrative title, higher academic rank, and a higher number of years in practice. Two hundred and nine respondents (80%) thought their compensation was unfair, and 180 (70%) lacked a clear understanding of how they were compensated. One hundred forty-five respondents (55%) reported being satisfied or highly satisfied with their job. Job satisfaction was greater among those with higher amounts of compensation and US medical school graduates. CONCLUSIONS: We report significant heterogeneity in the assessment of productivity and compensation for transplant nephrologists and the association of compensation with job satisfaction.
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Satisfação no Emprego , Nefrologistas , Adulto , Masculino , Humanos , Estados Unidos , Inquéritos e Questionários , Carga de Trabalho , Salários e BenefíciosRESUMO
Acute kidney injury (AKI) in the setting of cirrhosis (hepatorenal syndrome [HRS]-AKI) is a severe and often fatal complication of end-stage liver disease. The goals of treatment are to reverse renal failure and prolong survival in patients who are critically ill. However, interventions have limited efficacy, and mortality rates remain high. In the United States, the mainstay of pharmacologic therapy consists of the off-label use of vasoconstrictive agents in combination with plasma expanders, a strategy that produces modest effects. Liver transplantation is the ultimate solution but is only an option in a minority of patients because contraindications to transplantation are common and organ availability is limited. Renal replacement therapy is a temporary option but is known to confer an extremely poor short-term prognosis in patients with HRS-AKI and at best serves as a bridge to liver transplantation for the minority of patients who are transplantation candidates. The high mortality rate associated with HRS-AKI in the United States is a reflection of the suboptimal standard of care. Improved therapeutic options to treat HRS-AKI are sought. Terlipressin is a drug approved in Europe for treatment of HRS-AKI and supported by recommendations for first-line therapy by some liver societies and experts around the world. This review article will discuss the substantial unmet medical need associated with HRS-AKI and the potential benefits if terlipressin was approved in the United States.
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Injúria Renal Aguda , Síndrome Hepatorrenal , Transplante de Fígado , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/tratamento farmacológico , Síndrome Hepatorrenal/diagnóstico , Síndrome Hepatorrenal/tratamento farmacológico , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Transplante de Fígado/efeitos adversos , Terlipressina , Estados Unidos/epidemiologia , Vasoconstritores/uso terapêuticoRESUMO
INTRODUCTION: Pulmonary hypertension is common among patients with end-stage renal disease, although data regarding the impact of right ventricular (RV) failure on postoperative outcomes remain limited. We hypothesized that echocardiographic findings of RV dilation and dysfunction are associated with adverse clinical outcomes after renal transplant. METHODS: A retrospective review of adult renal transplant recipients at a single institution from January 2008 to June 2010 was conducted. Patients with transthoracic echocardiograms (TTEs) within 1 year leading up to transplant were included. The primary end point was a composite of delayed graft function, graft failure, and all-cause mortality. RESULTS: Eighty patients were included. Mean follow-up time was 9.4 ± 0.8 years. Eight patients (100%) with qualitative RV dysfunction met the primary end point, while 39/65 patients (60.0%) without RV dysfunction met the end point (p = 0.026). Qualitative RV dilation was associated with a significantly shorter time to all-cause graft failure (p = 0.03) and death (p = 0.048). RV systolic pressure was not measurable in 45/80 patients (56%) and was not associated with outcomes in the remaining patients. CONCLUSION: RV dilation and dysfunction are associated with adverse outcomes after renal transplant. TTE assessment of RV size and function should be a standard part of the pre-kidney transplant cardiovascular risk assessment.
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Hipertensão Pulmonar , Transplante de Rim , Disfunção Ventricular Direita , Ecocardiografia , Humanos , Hipertensão Pulmonar/complicações , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Disfunção Ventricular Direita/etiologiaRESUMO
BACKGROUND: Reducing immunosuppression can effectively treat BK viremia (BKV) and BK nephropathy, but has been associated with increased risks for acute rejection and development of donor-specific antibodies (DSA). To date there have been no systematic evaluations of re-escalating immunosuppression in transplant patients with resolving BKV. Importantly, the safety of this approach and impact on graft survival is unclear. METHODS: We performed a single-center retrospective review of kidney transplant recipients between July 2011 and June 2013 who had immunosuppression reduction after developing BKV (plasma PCR ≥ 1000 copies/ml). Changes in immunosuppression and patient outcomes were tracked until occurrence of a complication event: biopsy-proven acute rejection (BPAR), detection of de novo DSA, or recurrent BKV. Patients were grouped according to whether or not net immunosuppression was eventually increased. RESULTS: Out of 88 patients with BKV, 44 (50%) had net immunosuppression increased while the other 44 did not. Duration of viremia, peak viremia, induction, and sensitization status were similar between the two groups. In a Kaplan-Meier analysis, increasing immunosuppression was associated with less BPAR (P = .001) and a trend toward less de novo DSA development (P = .06). Death-censored graft survival (P = .27) was not different between the two groups. In the net immunosuppression increase group, recurrent BKV occurred in 22.7% without any BKV-related graft losses. CONCLUSION: These findings support potential benefits of increasing immunosuppression in patients with low-level or resolved BKV, but prospective trials are needed to better understand such an approach.
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Vírus BK , Infecções por Polyomavirus , Humanos , Terapia de Imunossupressão , Imunossupressores , Transplante de Rim , Estudos Prospectivos , Estudos Retrospectivos , Infecções Tumorais por VírusAssuntos
COVID-19 , Transplante de Rim , Transplante de Pâncreas , Idoso , Nefropatias Diabéticas/cirurgia , Feminino , HumanosRESUMO
Solid organ transplant recipients (SOTr) with coronavirus disease 2019 (COVID-19) are expected to have poorer outcomes compared to nontransplant patients because of immunosuppression and comorbidities. The clinical characteristics of 47 SOTr (38 kidneys and 9 nonkidney organs) were compared to 100 consecutive hospitalized nontransplant controls. Twelve of 47 SOTr managed as outpatients were subsequently excluded from the outcome analyses to avoid potential selection bias. Chronic kidney disease (89% vs 57% P = .0007), diabetes (66% vs 33% P = .0007), and hypertension (94% vs 72% P = .006) were more common in the 35 hospitalized SOTr compared to controls. Diarrhea (54% vs 17%, P < .0001) was more frequent in SOTr. Primary composite outcome (escalation to intensive care unit, mechanical ventilation, or in-hospital all-cause mortality) was comparable between SOTr and controls (40% vs 48%, odds ratio [OR] 0.72 confidence interval [CI] [0.33-1.58] P = .42), despite more comorbidities in SOTr. Acute kidney injury requiring renal replacement therapy occurred in 20% of SOTr compared to 4% of controls (OR 6 CI [1.64-22] P = .007). Multivariate analysis demonstrated that increasing age and clinical severity were associated with mortality. Transplant status itself was not associated with mortality.
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COVID-19/epidemiologia , Rejeição de Enxerto/prevenção & controle , Terapia de Imunossupressão/métodos , Transplante de Órgãos , Pandemias , SARS-CoV-2 , Transplantados , Idoso , Comorbidade , Feminino , Rejeição de Enxerto/epidemiologia , Humanos , Incidência , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Despite the increased use, comparative safety and efficacy of direct-acting oral anticoagulants (DOACs) against warfarin have not been well studied in kidney transplant recipients. In this single-center retrospective study, we evaluated 197 adult kidney transplant recipients on DOAC or warfarin between January 1, 2011, and June 30, 2018. The primary outcome was incidence of major bleeding defined as a hemoglobin decrease ≥2 g/dl, blood transfusion ≥2 units, or symptomatic bleeding in a critical area or organ. Patients were initiated on anticoagulation therapy at a median of 6.5 years post-transplant and followed for a median of 12.3 months. The rates of major bleeding were 7.2% per year with DOACs vs. 11.4% per year with warfarin (Mantel-Cox P = 0.15). No difference was found in composite bleeding, clinically relevant nonmajor bleeding, or thromboembolic events between the groups. There was a lower incidence of major bleeding with apixaban compared to all other anticoagulants (6.7% vs. 19.0%, P = 0.027). After controlling for potential confounders, DOAC use was not associated with an increased risk of major bleeding (HR 0.73, 95% CI 0.27-1.95). Further research is warranted to definitively determine whether DOACs are effective and safe alternatives to warfarin for anticoagulation in kidney transplant recipients.
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Transplante de Rim , Varfarina , Administração Oral , Adulto , Anticoagulantes/efeitos adversos , Estudos de Coortes , Inibidores do Fator Xa , Humanos , Estudos Retrospectivos , Varfarina/efeitos adversosRESUMO
We aimed to evaluate patient factors including nonadherence and viral infection and de novo donor-specific antibody (dnDSA) characteristics [total immunoglobulin G (IgG), C1q, IgG3, and IgG4] as predictors of renal allograft failure in a multicenter cohort with dnDSA. We performed a retrospective observational study of 113 kidney transplant recipients with dnDSA and stored sera for analysis. Predictors of death-censored allograft loss were assessed by Cox proportional modeling. Death-censored allograft survival was 77.0% (87/113) during a median follow-up of 2.2 (IQR 1.2-3.7) years after dnDSA detection. Predictors of allograft failure included medication nonadherence [HR 6.5 (95% CI 2.6-15.9)], prior viral infection requiring immunosuppression reduction [HR 5.3 (95% CI 2.1-13.5)], IgG3 positivity [HR 3.8 (95% CI 1.5, 9.3)], and time post-transplant (years) until donor-specific antibody (DSA) detection [HR 1.2 (95% CI 1.0, 1.3)]. In the 67 patients who were biopsied at dnDSA detection, chronic antibody-mediated rejection [HR 11.4 (95% CI 2.3, 56.0)] and mixed rejection [HR 7.4 (95% CI 2.2, 24.8)] were associated with allograft failure. We conclude that patient factors, including a history of viral infection requiring immunosuppression reduction or medication nonadherence, combined with DSA and histologic parameters must be considered to understand the risk of allograft failure in patients with dnDSA.
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Anticorpos/imunologia , Falência Renal Crônica/imunologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Adulto , Aloenxertos , Biópsia , Feminino , Glomerulonefrite/cirurgia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto , Antígenos HLA/imunologia , Humanos , Imunoglobulina G/imunologia , Imunossupressores , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Transplantados , Transplante HomólogoRESUMO
High hemodialysis ultrafiltration rate (UFR) is increasingly recognized as an important and modifiable risk factor for mortality among patients receiving maintenance hemodialysis. Recently, the Kidney Care Quality Alliance (KCQA) developed a UFR measure to assess dialysis unit care quality. The UFR measure was defined as UFR≥13mL/kg/h for patients with dialysis session length less than 240 minutes and was endorsed by the National Quality Forum as a quality measure in December 2015. Despite this, implementation of a UFR threshold remains controversial. In this NKF-KDOQI (National Kidney Foundation-Kidney Disease Outcomes Quality Initiative) Controversies Report, we discuss the concept of the UFR, which is governed by patients' interdialytic weight gain, body weight, and dialysis treatment time. We also examine the potential benefits and pitfalls of adopting a UFR threshold as a clinical performance measure and outline several aspects of UFR thresholds that require further research.
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Falência Renal Crônica/terapia , Diálise Renal , Insuficiência Cardíaca/etiologia , Humanos , Hipertensão/etiologia , Guias de Prática Clínica como Assunto , Diálise Renal/efeitos adversos , Diálise Renal/métodos , Ultrafiltração/estatística & dados numéricosRESUMO
BACKGROUND: The impact of pretransplant body mass index (BMI) on long-term allograft outcomes after kidney transplantation remains controversial. The conventional approach of using Kaplan-Meier method to calculate the cumulative risk of death-censored allograft failure may overestimate the risk of failure especially when competing failure risks are present. METHOD: A retrospective cohort of adult first-time kidney transplant recipients was drawn from the Organ Procurement and Transplantation Network database (2001 to 2009). Based on World Health Organization obesity classification, BMI was categorized as: less than 18.5, 18.5 to <25, 25 to < 30, 30 to < 35, 35 to <40 and ≥40 kg/m. Both unadjusted and adjusted risk models were used to assess for risk of allograft failure in the presence of death as a competing event. RESULTS: A total of 108 654 recipients were studied. In both unadjusted and adjusted models, increasing BMI level was associated with increased risk of long-term allograft failure. In the adjusted model with BMI 18.5 to less than 25 as the reference, the subhazards ratios (SHRs) for BMI were: less than 18.5: SHR, 0.96; P = 0.41; 25 to less than 30: SHR, 1.05; P = 0.01; 30 to less than 35: SHR, 1.15; P = <0.001; 35 to less than 40: SHR, 1.21; P < 0.001; and greater than 40: SHR, 1.13; P = 0.002. CONCLUSIONS: Handling of death as a competing event demonstrates a graded, detrimental impact of increasing pretransplant BMI on the risk of graft failure after kidney transplantation in both unadjusted and adjusted models. Compared with previous studies, a lower BMI was not associated with an increased risk of graft loss in a competing risk model.
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Sobrevivência de Enxerto , Transplante de Rim/efeitos adversos , Obesidade/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Aloenxertos , Índice de Massa Corporal , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/diagnóstico , Obesidade/mortalidade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/mortalidade , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Obtenção de Tecidos e Órgãos , Falha de Tratamento , Estados UnidosRESUMO
Concerns about adverse effects of calcineurin inhibitors (CNIs) have prompted development of protocols that minimize their use. Whereas previous CNI withdrawal trials in heterogeneous cohorts showed unacceptable rates of acute rejection (AR), we hypothesized that we could identify individuals capable of tolerating CNI withdrawal by targeting immunologically quiescent kidney transplant recipients. The Clinical Trials in Organ Transplantation-09 Trial was a randomized, prospective study of nonsensitized primary recipients of living donor kidney transplants. Subjects received rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil, and prednisone. Six months post-transplantation, subjects without de novo donor-specific antibodies (DSAs), AR, or inflammation at protocol biopsy were randomized to wean off or remain on tacrolimus. The intended primary end point was the change in interstitial fibrosis/tubular atrophy score between implantation and 24-month protocol biopsies. Serially collected urine CXCL9 ELISA results were correlated with outcomes. The study was terminated prematurely because of unacceptable rates of AR (4 of 14) and/or de novo DSAs (5 of 14) in the tacrolimus withdrawal arm. Positive urinary CXCL9 predated clinical detection of AR by a median of 15 days. Analyses showed that >16 HLA-DQ epitope mismatches and pretransplant, peripheral blood, donor-reactive IFN-γ ELISPOT assay results correlated with development of DSAs and/or AR on tacrolimus withdrawal. Although data indicate that urinary CXCL9 monitoring, epitope mismatches, and ELISPOT assays are potentially informative, complete CNI withdrawal must be strongly discouraged in kidney transplant recipients who are receiving standard-of-care immunosuppression, including those who are deemed to be immunologically quiescent on the basis of current clinical and laboratory criteria.
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Inibidores de Calcineurina/administração & dosagem , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Antígenos HLA-DQ/imunologia , Rim/patologia , Tacrolimo/administração & dosagem , Suspensão de Tratamento , Adulto , Idoso , Anticorpos/sangue , Atrofia , Quimiocina CXCL9/urina , Término Precoce de Ensaios Clínicos , Feminino , Fibrose , Rejeição de Enxerto/patologia , Rejeição de Enxerto/urina , Teste de Histocompatibilidade , Humanos , Terapia de Imunossupressão/métodos , Interferon gama/sangue , Transplante de Rim , Túbulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Nefrite/patologia , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Urological complications, namely ureteral leak and obstruction, remain a major source of morbidity after renal transplantation. Given that the existing literature on ureteral complications pertains mostly to deceased as opposed to living donors, we aimed to assess the risk factors for ureteral complications solely after living donor nephrectomy. METHODS: We identified 480 consecutive cases of renal transplantation after hand-assisted laparoscopic living donor nephrectomy at our institution from January 2008 to February 2013. We determined the incidence of ureteral complications and assessed the association with a number of perioperative factors, including age, sex, race, and body mass index of both the donor and recipient; arterial and ureteral anatomy; procurement by transplant surgeon versus urologist; history of previous renal transplantations; technique of ureteral anastomosis; use of ureteral stent; total ischemia time; serum creatinine on discharge; and need for temporary posttransplant hemodialysis. RESULTS: Among 480 renal transplantations after living donor nephrectomy, ureteral complications occurred in 18 (3.7%), including ureteral leak in 10 (2.1%) and ureteral stricture in 8 (1.6%). Only two factors were significantly associated with ureteral complications on multivariate analysis: increased donor age and no placement of ureteral stent. CONCLUSIONS: Ureteral complications of renal transplants after living donor nephrectomy are uncommon. The use of a ureteral stent is protective against ureteral complications and increased donor age is associated with an increased incidence of ureteral complications.
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Transplante de Rim/efeitos adversos , Laparoscopia/efeitos adversos , Doadores Vivos , Nefrectomia , Obstrução Ureteral/etiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , StentsRESUMO
A new clinical diagnostic schema is needed for the diagnosis of antibody-mediated rejection (AMR) in kidney transplant recipients due to the limited utility of C4d staining, lack of standardized quantitative tests for donor specific antibodies, and potential new diagnostic markers. The treatment of AMR remains controversial because previous studies included heterogeneous treatment modalities, small sample sizes, and short follow-up time. At the University of Michigan Transplant Center, 26 patients were diagnosed with AMR based on our diagnostic protocol including C4d-negative AMR in thesetting of graft dysfunction and Banff tissue injury type II (capillaritis) or type III (arteritis). After diagnosis, these patients received six sessions of plasmapheresis (PP) and IVIG (100 mg/kg after the first to fifth PP and 500 mg/kg with the last PP). Our novel finding in this analysis was the association between persistent C1q detection and graft loss. We confirmed that C4d positivity at diagnosis is associated with worse outcomes. Also, we found that response to our treatment protocol is dependent on C4d staining and Banff tissue injury type.
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Dessensibilização Imunológica/normas , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Antígenos HLA/imunologia , Histocompatibilidade , Isoanticorpos/sangue , Transplante de Rim , Adulto , Biomarcadores/sangue , Biópsia , Complemento C4b/análise , Dessensibilização Imunológica/efeitos adversos , Dessensibilização Imunológica/métodos , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/imunologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imuno-Histoquímica , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Masculino , Michigan , Pessoa de Meia-Idade , Monitorização Imunológica , Fragmentos de Peptídeos/análise , Plasmaferese/normas , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: There is little information on chronic kidney disease (CKD) stage progression rates and outcomes in liver transplant recipients. Identifying modifiable risk factors may help prevent CKD progression in liver transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a retrospective review of 1151 adult, deceased-donor, single-organ primary liver transplants between July 1984 and December 2007 and analyzed kidney outcomes and risk factors for CKD stage progression. Seven hundred twenty-nine patients had an available estimated GFR at 1 year posttransplant to establish a baseline stage. The primary end point was the CKD progression from one stage to a higher stage (lower GFR). RESULTS: Kaplan-Meier estimates of patient survival were 91%, 74%, and 64% at 5, 10, and 15 years, respectively. Estimates of liver allograft survival were 89%, 71%, and 60% at the same time points. At 1 year, 7%, 34%, 56%, 3%, and 1% of patients were in CKD stages 1, 2, 3, 4, and 5. The incidence of stage progression was 28%, 40%, and 53% at 3, 5, and 10 years. The incidence of ESRD was 2.6%, 7.5%, and 18% at 5, 10, and 20 years. Multivariable Cox regression analyses demonstrated that CKD stage at 1 year, pretransplant diabetes and urinary tract infections/hypercholesterolemia in the first year proved to be independent risk factors for stage progression (hazard ratio 1.9, 0.28, 1.39, and 1.46, respectively, P < 0.05). CONCLUSIONS: Future studies will determine whether treatment of risk factors in the first posttransplant year prevent CKD progression in liver transplant recipients.
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Nefropatias/epidemiologia , Falência Renal Crônica/epidemiologia , Transplante de Fígado/efeitos adversos , Adulto , Doença Crônica , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Incidência , Estimativa de Kaplan-Meier , Rim/fisiopatologia , Nefropatias/mortalidade , Nefropatias/fisiopatologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Wisconsin/epidemiologiaRESUMO
BACKGROUND: We have demonstrated that immunodominant donor-specific antibody (DSA) more than 100 mean fluorescence intensity (MFI) at the time of transplant is associated with a significantly higher risk of rejection. We now present short-term outcomes of DSA-based desensitization (DSZ) strategies in patients with a negative complement-dependent cytotoxicity crossmatch. METHODS: Between January 1, 2009, and January 1, 2010, live-donor kidney transplant recipients were divided into three protocols based on their immunodominant DSA MFI pretransplant (D1: 100-500, D2: 501-1000, and D3: 1001-3000). Deceased donor kidney transplant recipients were stratified into two protocols (D4: 501-1000 and D5: 1001-3000). The intensity of the conditioning treatment increased with DSA levels and included thymoglobulin induction, plasmapheresis, and intravenous immunoglobulin in the highest risk groups. We compared outcomes between desensitized patients (DSZ) and those undergoing no DSZ (or D0) during the same interval. RESULTS: Forty-eight of 249 (23%) kidney transplants underwent DSZ (n=20, 4, 3, 4, and 17 in D1-D5 protocols, respectively). There was more retransplantation (50% vs. 18%, P<0.001) and live donor transplantation (56% vs. 30%, P<0.001) in the DSZ group. In this group, mean peak panel reactive antibody and MFI at transplant were 51% ± 7% and 960 ± 136, respectively. The incidence of antibody-mediated rejection (25% vs. 12.5%, P=0.008) and acute cellular rejection (23% vs. 14%, P=0.02) was greater in the DSZ group. However, mixed rejection (8%), graft loss (0 vs. 6), patient death (0 vs. 3), cytomegalovirus infection (15% vs. 12%), and 1-year serum creatinine (1.4 ± 0.5 and 1.4 ± 0.4 mg/dL) were similar between DSZ and no-DSZ groups. CONCLUSION.: Long-term follow-up is needed to determine the role of Luminex-based strategies in current preconditioning regimens.
Assuntos
Transplante de Rim/imunologia , Transplante de Rim/métodos , Condicionamento Pré-Transplante/métodos , Adulto , Soro Antilinfocitário/uso terapêutico , Protocolos Clínicos , Feminino , Teste de Histocompatibilidade , Hospitais Universitários , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Isoanticorpos/sangue , Isoanticorpos/isolamento & purificação , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Plasmaferese , Estudos Retrospectivos , Doadores de Tecidos , Resultado do Tratamento , WisconsinRESUMO
BACKGROUND: The best induction agent for simultaneous pancreas-kidney transplantation (SPKT) remains the subject of debate. Alemtuzumab is effective in preventing acute cellular rejection (ACR) in SPK recipients and has been used to prevent antibody-mediated rejection (AMR) in sensitized kidney transplant candidates. METHODS: A retrospective cohort study was performed including 136 SPK recipients receiving maintenance immunosuppression with tacrolimus, mycophenolic acid prodrugs, and prednisone. Two groups were compared: those who received induction with alemtuzumab (n=97) and those induced with basiliximab (n=39). RESULTS: Kidney ACR was more frequent in SPKT induced with basiliximab (2-year 12.8% vs. 3.1%, P=0.04), but the incidence of AMR was similar (2-year 18% with basiliximab vs. 13.8% with alemtuzumab, P=NS). Kidney rejection was associated with clinical pancreas rejection in 70% of cases, without differences between the groups. Postrejection kidney graft survival was similar in both groups (2-year basiliximab/alemtuzumab 94.7%/91.2%), but death-censored kidney graft survival was lower with alemtuzumab (100%/91.2%, P=0.056). In the basiliximab group, the predominant cause of kidney loss was death-with-function, whereas in the alemtuzumab group AMR accounted for all losses. Pancreas graft survival was similar in both groups, yet more pancreas losses due to acute rejection occurred in alemtuzumab-treated patients (4 vs. 1). CONCLUSIONS: Kidney AMR is more common than ACR in SPKT recipients treated with alemtuzumab, tacrolimus, mycophenolic acid, and steroids. ACR is better prevented by alemtuzumab than basiliximab, but no relevant difference is found in prevention of AMR. Despite the high incidence of AMR, survival rates are excellent in both groups.