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BACKGROUND: Persistent rejection is an increasingly recognized barrier to long-term kidney allograft survival. A noninvasive method to help identify patients with persistent rejection in need of biopsy would be valuable. METHODS: This was a post-hoc analysis of a multicenter observational study. Subjects that had a biopsy-proven acute rejection and had another biopsy within 9 months (270 days) and had a biopsy-paired biomarker sample were included. RESULTS: A total of 64 "index" rejections in 58 subjects with repeat biopsies were identified with a median time to repeat biopsy of 100 days. Persistent rejection was present in 61%; 69% of follow-up biopsies were performed in clinically stable patients. Peripheral blood gene expression profile (GEP) demonstrated 59% sensitivity, 76% specificity, PPV of 79%, and NPV of 54%. Donor-derived cell-free DNA (dd-cfDNA) demonstrated sensitivity of 62%, specificity of 86%, PPV of 88%, and NPV of 56%. For repeat biopsies within 90 days of rejection in clinically stable patients (63% of repeat biopsies), both GEP and dd-cfDNA had specificities and PPVs of 100%. GEP was more likely to be positive in TCMR, while dd-cfDNA was more likely to be positive in AMR. CONCLUSIONS: Both GEP and dd-cfDNA may have utility at identifying clinically stable patients with persistent rejection in need of biopsy, however they identify different types of rejection.
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BACKGROUND: Alternate complement dysregulation postrenal transplantation can result in thrombotic microangiopathy (TMA). There is a scarcity of data regarding outcomes based on the timing of TMA post-transplant, coupled with a lack of follow-up biopsy findings post TMA diagnosis. This study aims to assess allograft and patient outcomes in individuals developing early TMA, defined within 4 months post-transplantation, and explore any differences in follow-up surveillance biopsies compared to a non-TMA group. DESIGN: This is a single center retrospective study between January 1, 2002 and October 10, 2019. Patients who developed TMA within 4 months post-transplantation were compared to a propensity matched non-TMA group. RESULTS: Thirty-one patients developed TMA within 4 months of renal transplantation. Index TMA biopsy featured noticeable glomerular, and vascular lesions along with acute tubular injury. Four-month surveillance biopsy showed significant glomerulitis, transplant glomerulopathy and chronic interstitial fibrosis as compared to non-TMA group. However, at 1 year, these differences were no longer significant. There was no significant difference in patient survival (TMA vs. non-TMA, p = 0.083); however, death censored graft survival was significantly lower in the TMA group (p < 0.001). TMA patients had a significantly lower estimated glomerular filtration rate at 4 months and at 1 year as compared to the non-TMA group. CONCLUSION: Early onset TMA post renal transplant leads to decreased renal function and lower graft survival. Early recognition and prompt treatment may help in reducing the adverse outcomes.
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Rechazo de Injerto , Supervivencia de Injerto , Trasplante de Riñón , Complicaciones Posoperatorias , Microangiopatías Trombóticas , Humanos , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/patología , Trasplante de Riñón/efectos adversos , Femenino , Masculino , Estudios Retrospectivos , Persona de Mediana Edad , Estudios de Seguimiento , Pronóstico , Complicaciones Posoperatorias/etiología , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Adulto , Tasa de Filtración Glomerular , Factores de Riesgo , Pruebas de Función Renal , Tasa de Supervivencia , Fallo Renal Crónico/cirugíaRESUMEN
Introduction: The impact of renal allograft rejection treatment on infection development has not been formally defined in the literature. Methods: We conducted a retrospective cohort study of 185 rejection (case) and 185 nonrejection (control) kidney transplant patients treated at our institution from 2014 to 2020 to understand the impact of rejection on infection development. Propensity scoring was used to match cohorts. We collected data for infections within 6 months of rejection for the cases and 18 months posttransplant for controls. Results: In 370 patients, we identified 466 infections, 297 in the controls, and 169 in the cases. Urinary tract infections (38.9%) and cytomegalovirus viremia (13.7%) were most common. Cumulative incidence of infection between the case and controls was 2.17 (CI 1.54-3.05); p < 0.001. There was no difference in overall survival (HR 0.90, CI 0.49-1.66) or graft survival (HR 1.27, CI 0.74-2.20) between the groups. There was a significant difference in overall survival (HR 2.28, CI 1.14-4.55; p = 0.019) and graft survival (HR 1.98, CI 1.10-3.56; p = 0.023) when patients with infection were compared to those without. Conclusions: As previously understood, rejection treatment is a risk factor for subsequent infection development. Our data have defined this relationship more clearly. This study is unique, however, in that we found that infections, but not rejection, negatively impacted both overall patient survival and allograft survival, likely due to our institution's robust post-rejection protocols. Clinicians should monitor patients closely for infections in the post-rejection period and have a low threshold to treat these infections while also restarting appropriate prophylaxis.
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BACKGROUND: Acute kidney injury (AKI) kidneys, including those from donors on dialysis, are often underutilized, although there is increasing data available demonstrating good transplant outcomes. To date, data on the duration of donor dialysis and transplant outcomes are limited. STUDY DESIGN: This was a single-center study of deceased donor kidney transplants from 2010 to 2022. The study cohort consisted of recipients of deceased donor kidney transplants from donors with AKI and on dialysis. Three groups were identified based on the predetermined interquartile range of donor dialysis duration: 1 to 2 dialysis days, 3 to 4 dialysis days, and 5 or more dialysis days. RESULTS: During this period, 765 AKI deceased donor transplants were performed, of which 230 were from donors on dialysis. The median dialysis duration was 2 days with a maximum of 13 days. Across the 3 groups, there were no differences in recipient age (p = 0.23) or dialysis vintage (p = 0.70). Donor age (p = 0.86) and kidney donor profile index (p = 0.57) were comparable between the groups. Recipients of deceased donor kidney transplants from donors on dialysis 5 or more days had lower terminal creatinine levels (p = 0.003) and longer cold ischemia times (p = 0.04). Posttransplant, the median length of hospital stay was 3 days for all groups (p = 0.75). There were no differences in delayed graft function occurrence (94.4% vs 86.8% vs 92.1%, p = 0.19), duration of delayed graft function (p = 0.56), or readmissions (p = 0.99). At 1 year posttransplant, the estimated glomerular filtration rate (p = 0.76), patient survival (p = 0.82), or death-censored graft survival (p = 0.28) were comparable. CONCLUSIONS: Excellent outcomes have been observed in AKI deceased donor kidney transplants, including those coming from donors on dialysis. In this small cohort, the duration of donor dialysis did not adversely affect outcomes. Cautious expansion of the donor pool, including donors on dialysis, should be considered given the ongoing organ shortage.
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Lesión Renal Aguda , Trasplante de Riñón , Humanos , Funcionamiento Retardado del Injerto/etiología , Funcionamiento Retardado del Injerto/epidemiología , Diálisis Renal , Donantes de Tejidos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Supervivencia de Injerto , Riñón , Estudios RetrospectivosRESUMEN
BACKGROUND: Urinary Tract Infections are the most common post-transplant infection and can have varied presentations. This study aimed to describe the outcomes of kidney transplant recipients with asymptomatic histologic pyelonephritis on allograft biopsy. Histologic Pyelonephritis was defined as neutrophil cast or neutrophilic tubulitis, interstitial infiltrates with predominant neutrophils, and no evidence of rejection or glomerulonephritis on biopsy. METHODS: The study included 123 kidney transplant recipients, of whom 95 underwent protocol biopsies, and 28 had biopsies for elevated creatinine within the first 2 years of a kidney transplant. RESULTS: The mean age of the cohort was 55.3 years, with 52% females and 78% deceased donor transplants. The risk factors for asymptomatic histologic pyelonephritis were recipient female sex (OR 1.89, 1.3-2.7, diabetes mellitus (OR 2.479, 1.687-3.645), and deceased donation (OR 1.69, 1.098-2.63). The incidence of asymptomatic pyelonephritis on protocol biopsy was 1.7%, with 52% having positive urine cultures and Escherichia coli being the most common bacteria. Subjects with asymptomatic pyelonephritis had inferior graft survival compared to the matched cohort HR 1.88 (1.06-3.35), p = .0281. In addition, of these 123 subjects, 68 (55%) subsequently developed pyelonephritis, and 34 subjects had pyelonephritis within 6 months after this episode. Subjects with recurrent infections exhibited lower survival HR 2.86 (1.36-6.02) and a trend toward higher rejection risk. CONCLUSION: Asymptomatic histologic pyelonephritis can occur in kidney transplant recipients and is associated with inferior graft survival.
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Trasplante de Riñón , Pielonefritis , Infecciones Urinarias , Humanos , Femenino , Persona de Mediana Edad , Masculino , Trasplante de Riñón/efectos adversos , Pielonefritis/etiología , Pielonefritis/patología , Infecciones Urinarias/etiología , Trasplante Homólogo , Bacterias , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/etiología , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Riñón/patologíaRESUMEN
The objective of this study was to compare the long-term outcomes of Hispanic versus white recipients who underwent simultaneous pancreas kidney transplantation (SPKT). This single-center study, conducted from 2003 to 2022, had a median follow-up of 7.5 years. The study included 91 Hispanic and 202 white SPKT recipients. The mean age (44 vs. 46 years), percentage of males (67% vs. 58%), and body mass index (BMI) (25.6 vs. 25.3 kg/m2 ) were similar between the Hispanic and white groups. The Hispanic group had more recipients with type 2 diabetes (38%) compared to the white group (5%, p < .001). The duration of dialysis was longer in Hispanics (640 vs. 473 days, p = .02), and fewer patients received preemptive transplants (10% vs. 29%, p < .01) compared to whites. Hospital length of stay, rates of BK Viremia, and acute rejection episodes within 1 year were similar between the groups. The estimated 5-year kidney, pancreas, and patient survival rates were also similar between the groups, 94%, 81%, and 95% in Hispanics, compared to 90%, 79%, and 90% in whites. Increasing age and longer duration of dialysis were risk factors for death. Although Hispanic recipients had a longer duration on dialysis and fewer preemptive transplants, the survival rates were similar to those of white recipients. However, referring providers and many transplant centers continue to overlook pancreas transplants for appropriately selected patients with type 2 diabetes, particularly among minority populations. As a transplant community, it is crucial that we make efforts to comprehend and tackle these obstacles to transplantation.
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Diabetes Mellitus Tipo 2 , Trasplante de Riñón , Trasplante de Páncreas , Humanos , Masculino , Diabetes Mellitus Tipo 2/cirugía , Diabetes Mellitus Tipo 2/etiología , Supervivencia de Injerto , Hispánicos o Latinos , Páncreas , Femenino , Adulto , Persona de Mediana EdadRESUMEN
BACKGROUND: The aim of this study was to correlate peripheral blood gene expression profile (GEP) results during the first post-transplant year with outcomes after kidney transplantation. METHODS: We conducted a prospective, multicenter observational study of obtaining peripheral blood at five timepoints during the first post-transplant year to perform a GEP assay. The cohort was stratified based on the pattern of the peripheral blood GEP results: Tx-all GEP results normal, 1 Not-TX had one GEP result abnormal and >1 Not-TX two or more abnormal GEP results. We correlated the GEP results with outcomes after transplantation. RESULTS: We enrolled 240 kidney transplant recipients. The cohort was stratified into the three groups: TX n = 117 (47%), 1 Not-TX n = 59 (25%) and >1 Not-TX n = 64 (27%). Compared to the TX group, the >1 Not-TX group had lower eGFR (p < .001) and more chronic changes on 1-year surveillance biopsy (p = .007). Death censored graft survival showed inferior graft survival in the >1 Not-TX group (p < .001) but not in the 1 Not-TX group. All graft losses in the >1 Not-TX group occurred after 1-year post-transplant. CONCLUSIONS: We conclude that a pattern of persistently Not-TX GEP assay correlates with inferior graft survival.
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Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Estudios Prospectivos , Expresión Génica , Supervivencia de Injerto , Rechazo de Injerto/etiología , Rechazo de Injerto/genéticaRESUMEN
There is a lower incidence of antibody-mediated rejection (AMR) after simultaneous liver-kidney transplantation (SLKT) than after kidney-only transplantation. It has been suggested that soluble human leukocyte antigen (sHLA) produced by the liver protects the kidney from AMR. However, this hypothesis has not been tested after SLKT. We present a case of SLKT with 2 donor-specific antibodies (DSAs) (DR53, 12,364 mean fluorescence intensity [MFI]; DQ7, 1253 MFI) that displayed a decrease by day 7 (DR53, 2747 MFI; DQ7, 107 MFI). On day 351, the patient was diagnosed with kidney AMR associated with high levels of DSA (DR53, 18,542 MFI; DQ7, 22,007 MFI) that persisted until day 531. High levels of sHLA-DR/DQ and HLA-DR/DQ-containing exosomes were also detected on day 398. Consequently, the patient underwent treatment with plasmapheresis, intravenous immunoglobulin, prednisone, and rituximab. On day 752, biopsy results were negative for AMR. Moderate levels of DSA (DR53, 9798 MFI; DQ7, 1271 MFI), and baseline levels of sHLA-DR/DQ and HLA-DR/DQ-containing exosomes were observed. Increases in CD4+CD25+FOXP3+ regulatory T cell marker-containing exosomes (CD73, programmed death-ligand 1) were observed on day 752 compared to day 398. These data show a direct correlation between sHLA and HLA-containing exosomes and an inverse correlation between tolerance marker-containing exosomes and kidney AMR after SLKT.
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Exosomas , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Isoanticuerpos , Rechazo de Injerto , Prueba de Histocompatibilidad , Antígenos HLA , Riñón , Antígenos HLA-DR , HígadoRESUMEN
The objective of this study was to compare the long-term outcomes of older (50-65 y) type 1 diabetics with body mass index <35 kg/m2 and type 2 diabetics with body mass index <30 kg/m2 who received simultaneous pancreas kidney transplantation (SPKT) versus living donor kidney transplants (LDKTs). All subjects had insulin-dependent diabetes. Methods: This is a retrospective single-center study from July 2003 to March 2021 with a median follow-up of 7.5 y. Results: There were 104 recipients in the SPKT and 80 in the LDKT group. The mean age was 56 y in SPKT and 58 y in LDKT. There were 55% male recipients in the SPKT group versus 75% in LDKT. The duration of diabetes was 32 y in SPKT versus 25 y in LDKT. The number of preemptive transplants and length of dialysis were similar. However, the wait time was shorter for LDKT (269 versus 460 d). Forty-nine percent of the LDKT recipients received the organ within 6 mo of being waitlisted compared with 28% of SPKT recipients (P = 0.001). Donor age was lower in the SPKT group (27 versus 41 y). The estimated 5-y death censored kidney survival was 92% versus 98%, and 5-y patient survival was 86% versus 89% for SPKT versus LDKT. Death censored kidney and patient survival, acute kidney rejection by 1 y, and BK viremia were similar between the 2 groups. There were 17 pancreas graft losses within 1 y of transplant, the majority related to surgical complications, and it was not associated with increased mortality. Conclusions: SPKT in selected recipients aged 50 and above can have excellent outcomes similar to LDKT recipients.
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INTRODUCTION: Infections are known complications of solid-organ transplant. Treatment for rejection may increase risk of infection. We aimed to study frequency of infection and identify the risk factors for infections in solid organ transplant (SOT) (liver and kidney) recipients treated for rejection. METHODS: This is a retrospective chart review of all liver and kidney transplant recipients treated for rejection at our institution from 2014 to 2020. We collected information on episodes of acute rejection in the first year of transplant and infections within 6 months following rejection treatment. RESULTS: We identified 257 transplant patients treated for rejection. One hundred twelve (43.6%) developed infections, with a total of 226 infections. Urinary tracts infections were the most common, 72 (31.9%), followed by cytomegalovirus viremia in 37 (16.4%), bacteremia in 24 (10.6%), and BK virus in 14 (6.2%). Female sex (p = .047), elevated neutrophil count at rejection (p = .002), and increased number of rejection episodes (p = .022) were predictors of infection in kidney and simultaneous liver-kidney recipients. No specific type of induction or rejection therapy was identified as a risk factor for infection, likely due to the prophylaxis protocols at our institution. Infection post rejection treatment was associated with higher graft loss (p = .021) and mortality (p = .031) in kidney transplant recipients. CONCLUSIONS: Infections are common complications after treatment of SOT rejection. Female gender, higher neutrophil at time of rejection, and increased numbers of rejection episodes were predictors of infections after rejection in simultaneous liver-kidney and kidney transplant patients. Infections were predictors of graft loss at 6 months and mortality at any point in follow-up in kidney transplant patients.
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Trasplante de Hígado , Trasplante de Órganos , Humanos , Femenino , Inmunosupresores/uso terapéutico , Estudios Retrospectivos , Trasplante de Hígado/efectos adversos , Trasplante de Órganos/efectos adversos , Riñón , Rechazo de Injerto/prevención & control , Rechazo de Injerto/tratamiento farmacológico , Receptores de TrasplantesRESUMEN
The Banff classification scheme provides a framework for interpreting transplant kidney biopsies and has undergone various updates in the past 2 decades especially related to antibody-mediated rejection. The clinical significance of early glomerulitis seen within 4 mo on protocol biopsies has received limited attention. We hypothesized that early glomerulitis seen on protocol biopsies will lead to significant adverse outcomes as assessed by histopathology and allograft outcome. Methods: A single-center retrospective study of a cohort of patients who underwent protocol biopsies within 4 mo after transplantation with timely follow-up protocol biopsies were assessed. Patients with recurrent glomerulonephritis were excluded. Results: We calculated glomerulitis (g) scores for 2212 biopsy specimens and identified 186 patients with glomerulitis (g > 0) and 2026 patients without glomerulitis (g = 0). The progression to chronic transplant glomerulopathy at 1 and 2 y was higher in patients with g > 0 as compared with g = 0 (year 1, 10.7% versus 2.3% [P < 0.001]' respectively; year 2, 17.2% versus 4.3% [P < 0.001], respectively) with no difference in other chronic lesions. The death-censored graft failure rate was higher in patients with g > 0 as compared with g = 0 (hazard ratio, 1.68 [95% CI, 1.07-2.65]; P = 0.02). We did not find any difference in outcomes in glomerulitis group based on donor-specific antibody. Conclusion: Our findings suggest that early glomerulitis (seen within 4 mo after transplantation) may lead to clinically significant long-term changes and thus could be a target for early intervention therapies.
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BACKGROUND: The pleiotropic effects of statin therapy on inflammation and coagulation may reduce the risk of venous thromboembolism. This study evaluated whether statin therapy is associated with decreased venous thromboembolic (VTE) events following kidney transplantation. METHODS: We performed a retrospective analysis of all primary kidney transplants performed between January 2014 and December 2019 at Mayo Clinic Arizona. Patients were divided into two groups depending on sustained statin therapy during the first year following transplantation. Recipient and donor clinical and demographic data were collected. The primary outcome was admission for symptomatic VTE events (deep vein thrombosis [DVT] or pulmonary embolism [PE]). RESULTS: Sustained statin therapy in the first year following transplant was observed in 16.1% (n = 223) of 1384 kidney transplants. The overall incidence of VTE events in the year following kidney transplant was 3.8%. VTE occurred in 4.1% of recipients treated with statins and 3.8% of the controls - (hazard ratio [HR] .92, 95% confidence interval [95% CI] .39, 2.21, p = .86). However, there were significant differences between the groups in terms of age, sex, race/ethnicity, body mass index, indication for transplant, diagnosis of diabetes and discharge antiplatelet or anticoagulant therapy. Following sensitivity analysis in which cohort matching was performed to account for these differences, there was no difference in VTE event-free survival (HR .89, 95% CI .41, 1.96, p = .78) or overall survival (HR .54, 95% CI .15, 1.94, p = .35) between patients treated with statins compared to controls. CONCLUSION: Statin therapy in the year following successful kidney transplant was not associated with a reduction in risk of VTE.
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Inhibidores de Hidroximetilglutaril-CoA Reductasas , Trasplante de Riñón , Embolia Pulmonar , Tromboembolia Venosa , Trombosis de la Vena , Humanos , Tromboembolia Venosa/tratamiento farmacológico , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Estudios Retrospectivos , Incidencia , Trasplante de Riñón/efectos adversos , Factores de Riesgo , Trombosis de la Vena/complicaciones , Embolia Pulmonar/tratamiento farmacológico , Embolia Pulmonar/epidemiología , Embolia Pulmonar/etiologíaRESUMEN
We used the Bayesian model to show the relationship between prevalence and the test's negative and positive predictive value. We used the above principle to understand the utility of biomarkers for acute rejection under different pretest probability of rejection. Given the test's sensitivity and specificity, the disease prevalence affects the predictive value of the test; the clinical decision to get any test should be considered while understanding the prevalence of disease and cost, risks, benefits of the tests, and available alternatives.
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Prevalencia , Humanos , Teorema de Bayes , Sensibilidad y Especificidad , Valor Predictivo de las Pruebas , ProbabilidadRESUMEN
BACKGROUND: There is controversy regarding the impact of delayed graft function (DGF) on kidney transplant outcomes. We hypothesize that the duration of DGF, rather than DGF itself, is associated with long-term kidney graft function. METHODS: We analyzed all deceased donor kidney transplants (DDKT) done at our center between 2008 to 2020. We determined factors associated with DGF duration. DGF duration was assessed at three 14-day intervals: < 14 DGF days, 14-27 DGF days, > 28 DGF days. We studied the impact of DGF duration on survival and graft function and resource utilization, including hospital length of stay and readmissions. RESULTS: 1714 DDKT recipients were included, 59.4% (n = 1018) had DGF. The median DGF duration was 10 days IQR (6,15). The majority of recipients (95%) had resolution of DGF within 28 days. Donor factors associated with DGF days were longer cold ischemia time, donor on inotropes, older age, donation after circulatory death, higher terminal creatinine, and hypertension. Recipient factors associated with increased DGF duration included male sex, length on dialysis before transplant, and higher body mass index. There were no differences in acute rejection events or interstitial fibrosis progression by 4 months when comparing DGF days. The median length of stay was 3 days. However, readmissions increased with increasing DGF duration. Death-censored graft survival was not associated with the length of DGF except when DGF lasted > 28 days. CONCLUSIONS: Inferior graft survival was observed only in recipients of DDKT with DGF lasting beyond 28 days. DGF lasting < 28 days had no impact on graft survival. Duration of DGF, rather than DGF itself, is associated with graft survival. TRIAL REGISTRATION: Retrospective study approved by Mayo Clinic IRB number ID: 20-011561.
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Funcionamiento Retardado del Injerto , Trasplante de Riñón , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Riñón , Masculino , Diálisis Renal , Estudios Retrospectivos , Factores de Riesgo , Donantes de TejidosRESUMEN
BACKGROUND: Centers discard high kidney donor profile index (KDPI) allografts, potentially related to delayed graft function and prolonged hospital use by kidney transplant recipients (KTR). We sought to determine whether high KDPI KTRs have excess health care utilization. METHODS: We conducted a retrospective cohort study from a high-volume center analyzing KTRs from January 3, 2011 to April 12, 2015 (n = 652). We measured differences in hospital use, emergency visits, and outpatient visits within the first 90 days between low (≤85%) versus high KDPI (>85%) KTRs, as well as long-term graft function and patient survival. RESULTS: High (n = 107) and low KDPI (n = 545) KTRs had similar length of stay (median = 3 days, P = .66), and readmission rates at 7, 30, and 90 days after surgery (all, P > .05). High KDPI kidneys were not associated with excess utilization of the hospital, emergency services, outpatient transplant clinics, or ambulatory infusion visits on univariate or multivariate analysis (all, P > .05). Low KDPI KTRs had significantly better eGFR at 2 years (Low vs. High KDPI: 60.35 vs. 41.54 ml/min, P < .001), but similar 3-year patient and graft survival (both, P > .09). CONCLUSIONS: High and low KDPI KTRs demonstrated similar 90-day risk-adjusted health care utilization, which should encourage use of high KDPI kidneys.
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Trasplante de Riñón , Obtención de Tejidos y Órganos , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Aceptación de la Atención de Salud , Estudios Retrospectivos , Donantes de TejidosRESUMEN
Simultaneous liver-kidney transplant (SLKT) in the presence of antihuman leukocyte antigen (HLA) donor-specific antibodies (DSA) is a well-accepted practice. Herein, we describe the evolution of alloantibodies in a patient who received an SLKT. The pre-SLKT serum sample showed multiple strong DSA. As expected, all DSA cleared in a sample collected 4 days after the SLKT. Because of the primary nonfunction of the liver in the SLKT, the patient had a second liver transplant 4 days later. An abrupt increase in DSA levels against the kidney was detected 10 days after the second liver transplant. These DSA were refractory to treatment, and the transplanted kidney was lost due to antibody-mediated rejection (AMR). A detailed study of the HLA epitopes recognized by DSA and, after normalization with third-party alloantibodies to address the effect of multiple transfusions and liver allograft neutralization, showed that the elimination of these antibodies depended on the HLA antigens expressed by the transplanted liver cells. The return of DSA after removal of the first transplanted liver was associated with AMR in the transplanted kidney.
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Trasplante de Riñón , Trasplante de Hígado , Rechazo de Injerto , Supervivencia de Injerto , Antígenos HLA , Humanos , Isoanticuerpos , Riñón , Trasplante de Riñón/efectos adversos , Hígado , Trasplante de Hígado/efectos adversos , ReoperaciónRESUMEN
CONTEXT.: It is unclear if preimplantation frozen section biopsy correlates with outcomes after deceased donor kidney transplantation. OBJECTIVE.: To assess if chronic histologic changes on the preimplant frozen section correlates with graft loss and estimated glomerular filtration rate independently of kidney donor profile index (KDPI). DESIGN.: Seven hundred three preimplantation biopsies were reviewed and a Banff sum score was calculated using glomerular sclerosis, interstitial fibrosis, vascular intimal thickening, and arteriolar hyalinosis. The posttransplant outcomes were compared for preimplantation biopsy Banff sum 0-1, 2-3, and 4-9. The cohort was also stratified by KDPI 85 or less versus more than 85. RESULTS.: For the entire biopsy cohort, graft survival, estimated glomerular filtration rate at 1 year, and chronic changes on a 1-year posttransplant biopsy were superior in the group with preimplantation Banff sum 0-1. After stratifying by KDPI, the Banff sum no longer correlated with graft survival. In a univariate mode, using the Banff sum score as a continuous variable, a higher Banff sum score was significantly associated with graft failure (P = .03); however, after adjusting the KDPI, the Banff sum score no longer correlated with graft failure (P = .45). The 1-year estimated glomerular filtration rate and 1-year biopsy changes were superior in the group with Banff sum 0-1 only in the cohort with KDPI 85 or less. CONCLUSIONS.: In donor kidneys used for transplant, preimplantation biopsy chronic changes correlate with estimated glomerular filtration rate and biopsy findings at 1 year, but biopsies with mostly mild chronicity and Banff sum scores less than or equal to 5 did not impact graft survival beyond KDPI.
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Trasplante de Riñón , Biopsia , Secciones por Congelación , Humanos , Riñón/patología , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Estudios Retrospectivos , Donantes de TejidosRESUMEN
BACKGROUND AND OBJECTIVES: Subclinical acute rejection is associated with poor outcomes in kidney transplant recipients. As an alternative to surveillance biopsies, noninvasive screening has been established with a blood gene expression profile. Donor-derived cellfree DNA (cfDNA) has been used to detect rejection in patients with allograft dysfunction but not tested extensively in stable patients. We hypothesized that we could complement noninvasive diagnostic performance for subclinical rejection by combining a donor-derived cfDNA and a gene expression profile assay. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a post hoc analysis of simultaneous blood gene expression profile and donor-derived cfDNA assays in 428 samples paired with surveillance biopsies from 208 subjects enrolled in an observational clinical trial (Clinical Trials in Organ Transplantation-08). Assay results were analyzed as binary variables, and then, their continuous scores were combined using logistic regression. The performance of each assay alone and in combination was compared. RESULTS: For diagnosing subclinical rejection, the gene expression profile demonstrated a negative predictive value of 82%, a positive predictive value of 47%, a balanced accuracy of 64%, and an area under the receiver operating curve of 0.75. The donor-derived cfDNA assay showed similar negative predictive value (84%), positive predictive value (56%), balanced accuracy (68%), and area under the receiver operating curve (0.72). When both assays were negative, negative predictive value increased to 88%. When both assays were positive, positive predictive value increased to 81%. Combining assays using multivariable logistic regression, area under the receiver operating curve was 0.81, significantly higher than the gene expression profile (P<0.001) or donor-derived cfDNA alone (P=0.006). Notably, when cases were separated on the basis of rejection type, the gene expression profile was significantly better at detecting cellular rejection (area under the receiver operating curve, 0.80 versus 0.62; P=0.001), whereas the donor-derived cfDNA was significantly better at detecting antibody-mediated rejection (area under the receiver operating curve, 0.84 versus 0.71; P=0.003). CONCLUSIONS: A combination of blood-based biomarkers can improve detection and provide less invasive monitoring for subclinical rejection. In this study, the gene expression profile detected more cellular rejection, whereas donor-derived cfDNA detected more antibody-mediated rejection.
Asunto(s)
Ácidos Nucleicos Libres de Células/sangre , ADN/sangre , Perfilación de la Expresión Génica , Rechazo de Injerto/diagnóstico , Trasplante de Riñón/efectos adversos , Donantes de Tejidos , Transcriptoma , Adulto , Enfermedades Asintomáticas , Biomarcadores/sangre , Biopsia , Ácidos Nucleicos Libres de Células/genética , ADN/genética , Femenino , Rechazo de Injerto/sangre , Rechazo de Injerto/genética , Rechazo de Injerto/inmunología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Resultado del Tratamiento , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: We aimed to determine outcomes with transplanting kidneys from deceased donors with severe acute kidney injury requiring acute renal replacement therapy (RRT). MATERIALS AND METHODS: A total of 172 recipients received a kidney from donors with acute kidney injury stage 3 (AKIN3) requiring RRT. We compared the study group to 528 recipients who received a kidney from donors with AKIN stage 3 not on RRT and 463 recipients who received < 85% Kidney Donor Profile Index (KDPI) AKIN stage 0 kidney. RESULTS: The study group donors were younger compared to the 2 control groups. Despite higher DGF in the study group, the length of hospital stay and acute rejection were similar. Death censored graft survival (96% AKIN3-RRT vs. 97%AKIN3 no RRT vs. 96% KDPI < 85% AKIN0, P = 0.26) and patient survival with functioning graft at 1 year (95% across all groups, P = 0.402) were similar. The estimated glomerular filtration rate were similar across the 3 groups after first month. Interstitial fibrosis and tubular atrophy score ≥ 2 on protocol biopsy at time 0, 4 and 12 months were similar. Primary nonfunction was rare and associated with high KDPI. CONCLUSIONS: Transplanting selected kidneys from deceased donors with AKIN3 requiring RRT is safe and has good outcomes.