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1.
Transplantation ; 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38499511

RESUMEN

BACKGROUND: The outcomes after kidney transplantation (KT), including access, wait time, and other issues around the globe, have been studied. However, issues do vary from one country to another. METHODS: We obtained data from several countries from North America, South America, Europe, Asia, and Australia, including the number of patients awaiting KT from 2015, transplant rate per million population (pmp), proportion of living donor and deceased donor (LD/DD) KT, and posttransplant survival. We also sought opinions on key difficulties faced by each of these countries with respect to KT and long-term survival. RESULTS: Variation in access to KT across the globe was noted. Countries with the highest rates of KT pmp included the United States (79%) and Spain (71%). A higher proportion of LD transplants was noted in Japan (93%), India (85%), Singapore (63%), and South Korea (63%). A higher proportion of DD KTs was noted in Spain (90%), Brazil (90%), France (85%), Italy (85%), Finland (85%), Australia-New Zealand (80%), and the United States (77%). The 5-y graft survival for LD was highest in South Korea (95%), Singapore (94%), Italy (93%), Finland (93%), and Japan (93%), whereas for DD, it was South Korea (93%), Italy (88%), Japan (86%), and Singapore (86%). The common issues surrounding KTs are access and a limited number of LDs and DDs. Key issues identified for long-term survival were increasing age of donors and recipients, higher recipient comorbidity, and posttransplant events, such as alloimmune injury to the kidney, infection, cancer, and suboptimal adherence to therapy. CONCLUSIONS: A unified approach is necessary to improve issues surrounding KT as the demand continues to increase.

2.
Am J Clin Pathol ; 161(6): 543-552, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38340346

RESUMEN

OBJECTIVES: Pathologists interpreting kidney allograft biopsies using the Banff system usually start by recording component scores (eg, i, t, cg) using histopathologic criteria committed to memory. Component scores are then melded into diagnoses using the same manual/mental processes. This approach to complex Banff rules during routine sign-out produces a lack of fidelity and needs improvement. METHODS: We constructed a web-based "smart template" (software-assisted sign-out) system that uniquely starts with upstream Banff-defined additional diagnostic parameters (eg, infection) and histopathologic criteria (eg, percent interstitial inflammation) collectively referred to as feeder data that is then translated into component scores and integrated into final diagnoses using software-encoded decision trees. RESULTS: Software-assisted sign-out enables pathologists to (1) accurately and uniformly apply Banff rules, thereby eliminating human inconsistencies (present in 25% of the cohort); (2) document areas of improvement; (3) show improved correlation with function; (4) examine t-Distributed Stochastic Neighbor Embedding clustering for diagnosis stratification; and (5) ready upstream incorporation of artificial intelligence-assisted scoring of biopsies. CONCLUSIONS: Compared with the legacy approach, software-assisted sign-out improves Banff accuracy and fidelity, more closely correlates with kidney function, is practical for routine clinical work and translational research studies, facilitates downstream integration with nonpathology data, and readies biopsy scoring for artificial intelligence algorithms.


Asunto(s)
Trasplante de Riñón , Programas Informáticos , Humanos , Biopsia , Riñón/patología , Aloinjertos/patología , Rechazo de Injerto/patología , Rechazo de Injerto/diagnóstico
3.
Am J Transplant ; 24(5): 781-794, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38307416

RESUMEN

We analyzed whether there is an interaction between the Kidney Donor Profile Index (KDPI) and cold ischemia time (CIT) in recipients of deceased donor kidney transplant (KTs). Adults who underwent KTs in the United States between 2014 and 2020 were included and divided into 3 KDPI groups (≤20%, 21%-85%, >85%) and 4 CIT strata (<12, 12-17.9, 18-23.9, ≥24 hours). Multivariate analyses were used to test the interaction between KDPI and CIT for the following outcomes: primary graft nonfunction (PGNF), delayed graft function (DGF), estimated glomerular filtration rate (eGFR) at 6 and 12 months, patient survival, graft survival, and death-censored graft survival (DCGS). A total of 69,490 recipients were analyzed: 18,241 (26.3%) received a graft with KDPI ≤20%, 46,953 (67.6%) with KDPI 21%-85%, and 4,296 (6.2%) with KDPI >85%. Increasing KDPI and CIT were associated with worse post-KT outcomes. Contrary to our hypothesis, howerver, the interaction between KDPI and CIT was statistically significant only for PGNF and DGF and eGFR at 6 months. Paradoxically, the negative coefficient of the interaction suggested that increasing duration of CIT was more detrimental for low and intermediate-KDPI organs relative to high-KDPI grafts. Conversely, for mortality, graft survival, and DCGS, we found that the interaction between CIT and KDPI was not statistically significant. We conclude that, high KDPI and prolonged CIT are independent risk factors for inferior outcomes after KT. Their interaction, however, is statistically significant only for the short-term outcomes and more pronounced on low and intermediate-KDPI grafts than high-KDPI kidneys.


Asunto(s)
Isquemia Fría , Funcionamiento Retardado del Injerto , Tasa de Filtración Glomerular , Supervivencia de Injerto , Trasplante de Riñón , Donantes de Tejidos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Donantes de Tejidos/provisión & distribución , Factores de Riesgo , Adulto , Estudios de Seguimiento , Funcionamiento Retardado del Injerto/etiología , Pronóstico , Tasa de Supervivencia , Estudios Retrospectivos , Fallo Renal Crónico/cirugía , Rechazo de Injerto/etiología , Pruebas de Función Renal , Obtención de Tejidos y Órganos , Complicaciones Posoperatorias
4.
Clin Transplant ; 38(1): e15157, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37792310

RESUMEN

INTRODUCTION: Self-reported measures of immunosuppression adherence have been largely examined in research settings. METHODS: In this single center study of 610 kidney transplant recipients, we examined if a voluntary, non-anonymous self-report measure could identify non-adherence in a routine clinic setting and how patients perceived such a measure. Non-adherence was measured using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) and patient perception was elicited using a customized questionnaire. RESULTS: Non-responders to the survey (15%) were younger, more likely to be black, and less likely to have had a pre-emptive transplant. Among complete responders (n = 485), 38% reported non-adherence with non-adherent patients being younger (54 y vs. 60 y; p = .01), less likely to have been on dialysis pre-transplant (59% vs. 68%; p = .04), further out from transplant (37 vs. 22 months; p < .001) and had more rejections in the preceding year (8% vs. 3%; p = .02). Self-reported non-adherence was associated with higher calcineurin inhibitor intra-patient variability (27.4% vs. 24.5%; p = .02), but not with donor-specific antibody detection (27.8% vs. 21.2%, p = .15). Of patients providing feedback (n = 500), the majority of patients felt comfortable reporting adherence (92%), that the survey was relevant to their visit (71%), and that the survey did not interfere with their clinic visit (88%). CONCLUSION: In summary, a self-reported questionnaire during clinic visits identified immunosuppression non-adherence in a significant proportion of patients and was well received by patients. Integrating self-report measures into routine post-transplant care may enable early identification of non-adherence.


Asunto(s)
Trasplante de Riñón , Humanos , Autoinforme , Inmunosupresores/uso terapéutico , Encuestas y Cuestionarios , Terapia de Inmunosupresión , Receptores de Trasplantes , Cumplimiento de la Medicación
5.
J Am Soc Nephrol ; 34(1): 26-39, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36302599

RESUMEN

BACKGROUND: In March 2021, the United States implemented a new kidney allocation system (KAS250) for deceased donor kidney transplantation (DDKT), which eliminated the donation service area-based allocation and replaced it with a system on the basis of distance from donor hospital to transplant center within/outside a radius of 250 nautical miles. The effect of this policy on kidney discards and logistics is unknown. METHODS: We examined discards, donor-recipient characteristics, cold ischemia time (CIT), and delayed graft function (DGF) during the first 9 months of KAS250 compared with a pre-KAS250 cohort from the preceding 2 years. Changes in discards and CIT after the onset of COVID-19 and the implementation of KAS250 were evaluated using an interrupted time-series model. Changes in allocation practices (biopsy, machine perfusion, and virtual cross-match) were also evaluated. RESULTS: Post-KAS250 saw a two-fold increase in kidneys imported from nonlocal organ procurement organizations (OPO) and a higher proportion of recipients with calculated panel reactive antibody (cPRA) 81%-98% (12% versus 8%; P <0.001) and those with >5 years of pretransplant dialysis (35% versus 33%; P <0.001). CIT increased (mean 2 hours), including among local OPO kidneys. DGF was similar on adjusted analysis. Discards after KAS250 did not immediately change, but we observed a statistically significant increase over time that was independent of donor quality. Machine perfusion use decreased, whereas reliance on virtual cross-match increased, which was associated with shorter CIT. CONCLUSIONS: Early trends after KAS250 show an increase in transplant access to patients with cPRA>80% and those with longer dialysis duration, but this was accompanied by an increase in CIT and a suggestion of worsening kidney discards.


Asunto(s)
COVID-19 , Trasplante de Riñón , Obtención de Tejidos y Órganos , Humanos , Estados Unidos , Riñón , Donantes de Tejidos , Anticuerpos , Supervivencia de Injerto , Funcionamiento Retardado del Injerto/epidemiología
6.
Kidney Int ; 103(4): 749-761, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36436679

RESUMEN

Borderline rejection (BL) in renal transplantation is associated with decreased allograft survival, yet many patients with BL maintain stable graft function. Identifying patients with early BL at risk for shortened allograft survival would allow for timely targeted therapeutic intervention aimed at improving outcomes. 851/1187 patients transplanted between 2013-18 underwent early biopsy (0-4 mos). 217/851 (25%) had BL and were compared to 387/851 without significant inflammation (NI). Serial surveillance and for-cause biopsies and seven-year follow-up were used to evaluate histological and clinical progression. To identify high-risk patients, we examined clinical/histological parameters using regression and non-linear dimensionality reduction (tSNE) and a biomarker based on peripheral blood transitional-1 B cell (T1B) IL-10/TNFα ratio. Compared to NI, early BL was associated with increased progression to late acute rejection (AR; 5-12 mos), premature interstitial fibrosis and tubular atrophy (IFTA) and decreased seven-year graft survival. However, decreased graft survival was limited to BL patients who progressed to late AR or IFTA, and was not influenced by treatment. Although tSNE clustered patients into groups based on clinical factors, the ability of these factors to risk stratify BL patients was modest. In contrast, a low T1B IL-10/TNFα ratio at 3 months identified BL patients at high risk for progression to AR (ROC AUC 0.87) and poor 7-yr graft survival (52% vs. 92%, p=0.003), while BL patients with a high ratio had similar graft survival to patients with NI (91%, p=NS). Thus, progressive early allograft inflammation manifested as BL that progresses to late AR in the first post-transplant year represents a high-risk clinical state for poor allograft outcomes. Such high-risk status can be predicted by the T1B IL-10/TNFα ratio before irreversible scarring sets in, thus allowing timely risk stratification.


Asunto(s)
Enfermedades Renales , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Factor de Necrosis Tumoral alfa , Interleucina-10 , Citocinas , Células Precursoras de Linfocitos B/patología , Fibrosis , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/prevención & control , Rechazo de Injerto/etiología , Enfermedades Renales/patología , Inflamación/patología , Supervivencia de Injerto , Biopsia
7.
Hum Immunol ; 84(3): 214-223, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36581507

RESUMEN

Virtual crossmatch (VXM) is used as an alternative to or in conjunction with a cell-based physical crossmatch (PXM) for assessing HLA (human leukocyte antigen) compatibility prior to deceased donor kidney transplantation (DDKT). Data on practice patterns and perceptions regarding VXM use in the US are limited. We performed a survey of US HLA directors and transplant surgeons regarding HLA testing and crossmatch strategies. 53 (56 %) HLA directors and 68 surgeons (representing âˆ¼ 23 % of US transplant centers) completed the survey. Both groups agreed that VXM could reduce cold ischemia time (CIT), costs and improve allocation efficiency. VXM use increased following the 2021 kidney allocation change. Reducing CIT was the primary reason for favoring VXM over PXM. Preference for VXM reduced as candidates' panel reactive antibodies increased. Regulations, program policies and limitations of HLA technology were cited as important reasons for preferring PXM over VXM. Surgeons reported similar perceptions, but findings are limited by the low response rate. Finally, half the labs reported lacking specific protocols for VXM use. In conclusion, improved HLA technology and protocols along with changes to institutional procedures and policy regulations are needed for safer expansion of VXM in DDKT.


Asunto(s)
Trasplante de Riñón , Humanos , Estados Unidos , Trasplante de Riñón/métodos , Tipificación y Pruebas Cruzadas Sanguíneas , Prueba de Histocompatibilidad/métodos , Riñón , Antígenos HLA , Histocompatibilidad , Rechazo de Injerto
8.
Kidney Int ; 102(6): 1371-1381, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36049641

RESUMEN

The long-term impact of early subclinical inflammation (SCI) through surveillance biopsy has not been well studied. To do this, we recruited a prospective observational cohort that included 1000 sequential patients who received a kidney transplant from 2013-2017 at our center. A total of 586 patients who underwent a surveillance biopsy in their first year post-transplant were included after excluding those with clinical rejections, and those who were unable to undergo a surveillance biopsy. Patients were classified based on their biopsy findings: 282 with NSI (No Significant Inflammation) and 304 with SCI-T (SCI and Tubulitis) which was further subdivided into 182 with SC-BLR (Subclinical Borderline Changes) and 122 with SC-TCMR (Subclinical T Cell Mediated Rejection, Banff 2019 classification of 1A or more). We followed the clinical and immunological events including Clinical Biopsy Proven Acute Rejection [C-BPAR], long-term kidney function and death-censored graft loss over a median follow-up of five years. Episodes of C-BPAR were noted at a median of two years post-transplant. Adjusted odds of having a subsequent C-BPAR was significantly higher in the SCI-T group [SC-BLR and SC-TCMR] compared to NSI 3.8 (2.1-7.5). The adjusted hazard for death-censored graft loss was significantly higher with SCI-T compared to NSI [1.99 (1.04-3.84)]. Overall, SCI detected through surveillance biopsy within the first year post-transplant is a harbinger for subsequent immunological events and is associated with a significantly greater hazard for subsequent C-BPAR and death-censored graft loss. Thus, our study highlights the need for identifying patients with SCI through surveillance biopsy and develop strategies to prevent further alloimmune injuries.


Asunto(s)
Rechazo de Injerto , Supervivencia de Injerto , Humanos , Factores de Riesgo , Biopsia , Inflamación/patología , Aloinjertos/patología , Riñón/patología
9.
Clin Transplant ; 36(9): e14759, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35778369

RESUMEN

BACKGROUND: High kidney-donor profile index (KDPI) kidneys have a shorter survival than grafts with lower KDPI values. It is still unclear, however, whether their shorter longevity depends on an inferior baseline function, faster functional decline, or the combination of both. METHODS: We analyzed the estimated glomerular filtration rate (eGFR) of 605 consecutive recipients of deceased donor kidney transplants (KT) at 1, 3, 6, 12, 18, 24, 36, 48, and 60 months. Comparisons were performed among four groups based on KDPI quartile: Group I-KDPI ≤ 25% (n = 151), Group II-KDPI 26-50% (n = 182), Group III-KDPI 51-75% (n = 176), and Group IV-KDPI 〉 75% (n = 96). Linear mixed model analysis was subsequently used to assess whether KDPI was independently associated with the decline in eGFR during the first 5-years after KT. We also analyzed the incidence of delayed graft function (DGF), rejection within the first year after KT, patient survival, graft survival, and death censored graft survival based on KDPI group. FINDINGS: High-KDPI grafts had lower eGFR immediately after KT, had a higher incidence of DGF and rejection. However, there were no signifcant differences in the adjusted rate (slope) of decline in eGFR among the four KDPI groups (P = .06). Although patient survival was signigicantly lower for recipients of high-KDPI grafts, death-censored graft survival was similar among the four KDPI groups (P = .33). CONCLUSIONS: The shorter functional survival of high-KDPI grafts seems to be due to their lower baseline eGFR rather than a more rapid functional decline after KT.


Asunto(s)
Trasplante de Riñón , Donantes de Tejidos , Tasa de Filtración Glomerular , Supervivencia de Injerto , Humanos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Factores de Riesgo
10.
Clin Transplant ; 36(9): e14776, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35821617

RESUMEN

BACKGROUND: In kidney transplantation, delayed graft function (DGF) is associated with increased morbidity and a higher risk of graft failure. Prior research suggests that chronic hypotension increases DGF risk, but the relationship of preoperative blood pressure to DGF is unclear. METHODS: In this single center study of adult deceased donor kidney transplant recipients transplanted between 2015 and 2019, we evaluated the question of whether preoperative mean arterial pressure (MAP) affected DGF risk. Additionally, we investigated whether the risk of DGF was moderated by certain donor and recipient characteristics. For recipient characteristics associated with increased DGF risk and preoperative MAP, we performed a mediation analysis to estimate the proportion of DGF risk mediated through preoperative MAP. RESULTS: Among 562 deceased donor kidney recipients, DGF risk decreased as preoperative MAP increased, with a 2% lower risk per 1 mm Hg increase in MAP. This increased risk was similar, with no statistically significant interaction effect between preoperative MAP and donor (donation after circulatory death) and recipient characteristics (diabetes, body mass index, and use of anti-hypertensive medications). Preoperative MAP was negativity correlated with recipient BMI and duration of pre transplant dialysis. On mediation analysis, MAP accounted for 12% and 16% of the DGF risk associated with recipient BMI and pre-transplant dialysis duration, respectively. CONCLUSION: In deceased donor kidney transplantation, each 1 mm Hg increase in preoperative MAP was associated with 2% lower DGF risk. Preoperative MAP was influenced by recipient BMI and dialysis duration, and likely contributes to some of the high DGF risk from obesity and long dialysis vintage.


Asunto(s)
Funcionamiento Retardado del Injerto , Trasplante de Riñón , Adulto , Antihipertensivos , Presión Sanguínea , Funcionamiento Retardado del Injerto/etiología , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Riñón , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Donantes de Tejidos
11.
Transpl Int ; 35: 10253, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35572466

RESUMEN

Transplantation of kidneys from shorter donors into taller recipients may lead to suboptimal allograft survival. The effect of discrepancy in donor and recipient heights (ΔHeight) on long term transplant outcomes is not known. Adult patients ≥18 years undergoing living or deceased donor (LD or DD) kidney transplants alone from donors ≥18 years between 2000 and 2016 in the United States were included in this observational study. The cohort was divided into three groups based on ΔHeight of 5 inches as 1) Recipient < Donor (DD: 31,688, LD: 12,384), 2) Recipient = Donor (DD: 84,711, LD: 54,709), and 3) Recipient > Donor (DD: 21,741, LD: 18,753). Univariate analysis showed a higher risk of DCGL and mortality in both DD and LD (p < 0.001 for both). The absolute difference in graft and patient survival between the two extremes of ΔHeight was 5.7% and 5.7% for DD, and 0.4% and 1.4% for LD. On multivariate analysis, the HR of DCGL for Recipient < Donor and Recipient > Donor was 0.95 (p = 0.05) and 1.07 (p = 0.01) in DD and 0.98 (p = 0.55) and 1.14 (p < 0.001) in LD. Similarly, the corresponding HR of mortality were 0.97 (p = 0.07) and 1.07 (p = 0.003) for DD and 1.01 (p < 0.001) and 1.05 (p = 0.13) for LD. For DGF, the HR were 1.04 (p = 0.1) and 1.01 (p = 0.7) for DD and 1.07 (p = 0.45) and 0.89 (p = 0.13) for LD. Height mismatch between the donor and recipient influences kidney transplant outcomes.


Asunto(s)
Trasplante de Riñón , Adulto , Estudios de Cohortes , Supervivencia de Injerto , Humanos , Riñón , Donadores Vivos , Donantes de Tejidos , Estados Unidos/epidemiología
12.
Transpl Int ; 35: 10094, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35368641

RESUMEN

Anti-HLA Donor Specific Antibody (DSA) detection post kidney transplant has been associated with adverse outcomes, though the impact of early DSA screening on stable patients remain unclear. We analyzed impact of DSA detection through screening in 1st year stable patients (n = 736) on subsequent estimated glomerular filtration rate (eGFR), death censored graft survival (DCGS), and graft failure (graft loss including return to dialysis or re-transplant, patient death, or eGFR < 20 ml/min at last follow up). Patients were grouped using 1st year screening into DSA+ (Class I, II; n = 131) or DSA- (n = 605). DSA+ group were more DR mismatched (p = 0.02), more sensitized (cPRA ≥90%, p = 0.002), less Caucasian (p = 0.04), and had less pre-emptive (p = 0.04) and more deceased donor transplants (p = 0.03). DSA+ patients had similar eGFR (54.8 vs. 53.8 ml/min/1.73 m2, p = 0.56), DCGS (91% vs. 94%, p = 0.30), and graft failure free survival (76% vs. 82%, p = 0.11). DSA timing and type did not impact survival. Among those with a protocol biopsy (n = 515), DSA detected on 1st year screening was a predictor for graft failure on multivariate analysis (1.91, 95% CI 1.03-3.55, p = 0.04). Overall, early DSA detection in stable patients was an independent risk factor for graft failure, though only among those who underwent a protocol biopsy.


Asunto(s)
Trasplante de Riñón , Rechazo de Injerto , Antígenos HLA , Humanos , Trasplante de Riñón/efectos adversos , Donantes de Tejidos , Receptores de Trasplantes
13.
Transplantation ; 106(4): e219-e233, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35135973

RESUMEN

BACKGROUND: Racial/ethnic minorities face known disparities in likelihood of kidney transplantation. These disparities may be exacerbated when coupled with ongoing substance use, a factor also reducing likelihood of transplantation. We examined whether race/ethnicity in combination with ongoing substance use predicted incidence of transplantation. METHODS: Patients were enrolled between March 2010 and October 2012 at the time of transplant evaluation. Substance use data were retrieved from transplant evaluations. Following descriptive analyses, the primary multivariable analyses evaluated whether, relative to the referent group (White patients with no substance use), racial/ethnic minority patients using any substances at the time of evaluation were less likely to receive transplants by the end of study follow-up (August 2020). RESULTS: Among 1152 patients, 69% were non-Hispanic White, 23% non-Hispanic Black, and 8% Other racial/ethnic minorities. White, Black, and Other patients differed in percentages of current tobacco smoking (15%, 26%, and 18%, respectively; P = 0.002) and illicit substance use (3%, 8%, and 9%; P < 0.001) but not heavy alcohol consumption (2%, 4%, and 1%; P = 0.346). Black and Other minority patients using substances were each less likely to receive transplants than the referent group (hazard ratios ≤0.45, P ≤ 0.021). Neither White patients using substances nor racial/ethnic minority nonusers differed from the referent group in transplant rates. Additional analyses indicated that these effects reflected differences in waitlisting rates; once waitlisted, study groups did not differ in transplant rates. CONCLUSIONS: The combination of minority race/ethnicity and substance use may lead to unique disparities in likelihood of transplantation. To facilitate equity, strategies should be considered to remove any barriers to referral for and receipt of substance use care in racial/ethnic minorities.


Asunto(s)
Trasplante de Riñón , Trastornos Relacionados con Sustancias , Minorías Étnicas y Raciales , Etnicidad , Disparidades en Atención de Salud , Humanos , Grupos Minoritarios , Estados Unidos/epidemiología
15.
Clin Infect Dis ; 75(1): e630-e644, 2022 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-35179197

RESUMEN

BACKGROUND: We studied humoral responses after coronavirus disease 2019 (COVID-19) vaccination across varying causes of immunodeficiency. METHODS: Prospective study of fully vaccinated immunocompromised adults (solid organ transplant [SOT], hematologic malignancy, solid cancers, autoimmune conditions, human immunodeficiency virus [HIV]) versus nonimmunocompromised healthcare workers (HCWs). The primary outcome was the proportion with a reactive test (seropositive) for immunoglobulin G to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain. Secondary outcomes were comparisons of antibody levels and their correlation with pseudovirus neutralization titers. Stepwise logistic regression was used to identify factors associated with seropositivity. RESULTS: A total of 1271 participants enrolled: 1099 immunocompromised and 172 HCW. Compared with HCW (92.4% seropositive), seropositivity was lower among participants with SOT (30.7%), hematological malignancies (50.0%), autoimmune conditions (79.1%), solid tumors (78.7%), and HIV (79.8%) (P < .01). Factors associated with poor seropositivity included age, greater immunosuppression, time since vaccination, anti-CD20 monoclonal antibodies, and vaccination with BNT162b2 (Pfizer) or adenovirus vector vaccines versus messenger RNA (mRNA)-1273 (Moderna). mRNA-1273 was associated with higher antibody levels than BNT162b2 or adenovirus vector vaccines after adjusting for time since vaccination, age, and underlying condition. Antibody levels were strongly correlated with pseudovirus neutralization titers (Spearman r = 0.89, P < .0001), but in seropositive participants with intermediate antibody levels, neutralization titers were significantly lower in immunocompromised individuals versus HCW. CONCLUSIONS: Antibody responses to COVID-19 vaccines were lowest among SOT and anti-CD20 monoclonal recipients, and recipients of vaccines other than mRNA-1273. Among those with intermediate antibody levels, pseudovirus neutralization titers were lower in immunocompromised patients than HCWs. Additional SARS-CoV-2 preventive approaches are needed for immunocompromised persons, which may need to be tailored to the cause of immunodeficiency.


Asunto(s)
COVID-19 , Infecciones por VIH , Adulto , Anticuerpos Antivirales , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19 , Infecciones por VIH/complicaciones , Humanos , Huésped Inmunocomprometido , Estudios Prospectivos , SARS-CoV-2 , Vacunación
16.
Clin Transplant ; 36(4): e14582, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35000234

RESUMEN

Antithymocyte globulin (ATG) is a commonly used induction agent in kidney transplant recipients. However, the optimal dosing has not been well defined. Our protocol aims for a 5-6 mg/kg cumulative dose. It is unclear if a dose lower than 5 mg/kg is associated with more rejection. We performed a retrospective cohort study of patients who received a kidney transplant at our center between January 1, 2013 and December 31, 2016. Primary outcome was biopsy proven acute rejection (clinical and subclinical) in the first 6 months after kidney transplant. CMV viremia in high risk (D+/R-) recipients and BK viremia was compared as a secondary endpoint. Of the 543 patients, the Low Dose (LD) group (n = 56) received <5 mg/kg ATG and Regular Dose (RD) group (n = 487) received ≧5 mg/kg. Patients in RD were more sensitized (higher PRA and CPRA). LD received a dose of 4 ± 1.1 mg/kg ATG whereas RD received 5.6 ± .3 mg/kg ATG (P < .001). TCMR (Banff 1A or greater) was present in 34% of patients in LD versus 22% in RD (P = .04) (OR 2.1; 95%CI 1.12-3.81; P = .019). There was no difference in the incidence of CMV or BK viremia. ATG doses lower than 5 mg/kg may be associated with a heightened risk of rejection despite a low degree of sensitization.


Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Riñón , Suero Antilinfocítico , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Citomegalovirus/etiología , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/etiología , Humanos , Inmunosupresores , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Estudios Retrospectivos , Viremia/complicaciones
18.
PLoS One ; 16(8): e0254115, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34437548

RESUMEN

Due to shortage of donor, kidney transplants (KTs) from donors with acute kidney injury (AKI) are expanding. Although previous studies comparing clinical outcomes between AKI and non-AKI donors in KTs have shown comparable results, data on high-volume analysis of KTs outcomes with AKI donors are limited. This study aimed to analyze the selection trends of AKI donors and investigate the impact of AKI on graft failure using the United states cohort data. We analyzed a total 52,757 KTs collected in the Scientific Registry of Transplant Recipient (SRTR) from 2010 to 2015. The sample included 4,962 (9.4%) cases of KTs with AKI donors (creatinine ≥ 2 mg/dL). Clinical characteristics of AKI and non-AKI donors were analyzed and outcomes of both groups were compared. We also analyzed risk factors for graft failure in AKI donor KTs. Although the incidence of delayed graft function was higher in recipients of AKI donors compared to non-AKI donors, graft and patient survival were not significantly different between the two groups. We found donor hypertension, cold ischemic time, the proportion of African American donors, and high KDPI were risk factors for graft failure in AKI donor KTs. KTs from deceased donor with AKI showed comparable outcomes. Thus, donors with AKI need to be considered more actively to expand donor pool. Caution is still needed when donors have additional risk factors of graft failure.


Asunto(s)
Lesión Renal Aguda , Selección de Donante , Rechazo de Injerto/mortalidad , Trasplante de Riñón/mortalidad , Sistema de Registros , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/cirugía , Adulto , Femenino , Humanos , Masculino , Estudios Retrospectivos , Gestión de Riesgos
19.
Clin Transplant ; 35(9): e14399, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34176169

RESUMEN

AIM: The use of kidneys donated after circulatory death (DCD) provides an invaluable expansion of the organ supply for transplantation. Here, we investigated the effect of DCD on fibrotic changes on 1 1-year post 1-transplant surveillance kidney allograft biopsy. METHODS: Recipients of a deceased donor kidney transplant between 2013 and 2017 at a single institution, who survived 1 year and underwent surveillance biopsy, were included in the analysis (n = 333: 87 DCD kidneys, 246 kidneys donated after brain death [DBD]). Banff scores for interstitial fibrosis and tubular atrophy were summed as IFTA and compared between the groups. RESULTS: DCD and DBD groups were comparable for baseline characteristics. Delayed graft function was 39% in DCD versus 19% in DBD, P = .0002. Patient and graft survival were comparable for DCD and DBD cohorts. IFTA scores were higher in DCD compared to DBD (2.43±..13 vs. 2.01±..08, P = .0054). On multivariate analysis, the odds of IFTA > 2 in the DCD group was 2.5× higher (95%CI: 1.354.63) than in the DBD group. Within the DCD group, kidneys with IFTA > 2 had inferior 5-year graft survival (P = .037). CONCLUSION: Compared to DBD kidneys, DCD kidneys developed a greater degree of fibrotic changes on 1-year post-transplant surveillance biopsy, which affected graft longevity within the DCD cohort.


Asunto(s)
Trasplante de Riñón , Obtención de Tejidos y Órganos , Aloinjertos , Biopsia , Muerte Encefálica , Muerte , Fibrosis , Supervivencia de Injerto , Humanos , Riñón , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Donantes de Tejidos
20.
Transplant Direct ; 7(7): e706, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34124342

RESUMEN

Early acute kidney rejection remains an important clinical issue. METHODS: The current study included 552 recipients who had 1-2 surveillance or indication biopsy within the 1 y posttransplant. We evaluated the impact of type of allograft inflammation on allograft outcome. They were divided into 5 groups: no inflammation (NI: 95), subclinical inflammation (SCI: 244), subclinical T cell-mediated rejection (TCMR) (SC-TCMR: 110), clinical TCMR (C-TCMR: 83), and antibody-mediated rejection (AMR: 20). Estimated glomerular filtration rate (eGFR) over time using linear mixed model, cumulative chronic allograft scores/interstitial fibrosis and tubular atrophy (IFTA) ≥2 at 12 mo, and survival estimates were compared between groups. RESULTS: The common types of rejections were C-TCMR (15%), SC-TCMR (19.9%), and AMR (3.6%) of patients. Eighteen of 20 patients with AMR had mixed rejection with TCMR. Key findings were as follows: (i) posttransplant renal function: eGFR was lower for patients with C-TCMR and AMR (P < 0.0001) compared with NI, SCI, and SC-TCMR groups. There was an increase in delta-creatinine from 3 to 12 mo and cumulative allograft chronicity scores at 12 mo (P < 0.001) according to the type of allograft inflammation. (ii) Allograft histology: the odds of IFTA ≥2 was higher for SC-TCMR (3.7 [1.3-10.4]; P = 0.04) but was not significant for C-TCMR (3.1 [1.0-9.4]; P = 0.26), and AMR (2.5 [0.5-12.8]; P = 0.84) compared with NI group, and (iii) graft loss: C-TCMR accounted for the largest number of graft losses and impending graft losses on long-term follow-up. Graft loss among patient with AMR was numerically higher but was not statistically significant. CONCLUSIONS: The type of kidney allograft inflammation predicted posttransplant eGFR, cumulative chronic allograft score/IFTA ≥2 at 12 mo, and graft loss.

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