Assessing the influence of graft loss on 4-year patient survival after simultaneous pancreas-kidney transplantation: Kaplan-Meier versus Competing Risk Analysis model.

BACKGROUND: Graft loss increases the risk of patient death after simultaneous pancreas-kidney (SPK) transplantation. The relative risk of each graft failure is complex due to the influence of several competing events. METHODS: This retrospective, single-center study compared 4-year patient survival according to the graft status using Kaplan-Meier (KM) and Competing Risk Analysis (CRA). Patient survival was also assessed according to five eras (Era 1: 2001-2003; Era 2: 2004-2006; Era 3: 2007-2009; Era 4: 2010-2012; Era 5: 2012-2015). RESULTS: Between 2000 and 2015, 432 SPK transplants were performed. Using KM, patient survival was 86.5% for patients without graft loss (n = 333), 93.4% for patients with pancreas graft loss (n = 46), 43.7% for patients with kidney graft loss (n = 16), and 25.4% for patients with pancreas and kidney graft loss (n = 37). Patient survival was underestimated using KM versus CRA methods in patients with pancreas and kidney graft losses (25.4% vs. 36.2%), respectively. Induction with lymphocyte depleting antibodies was associated with 81% reduced risk (HR.19, 95% CI.38-.98, p = .0048), while delayed kidney function (HR 2.94, 95% CI 1.09-7.95, p = .033) and surgical complications (HR 2.94, 95% CI 1.22-7.08, p = .016) were associated with higher risk of death. Four-year patient survival increased from Era 1 to Era 5 (79% vs. 87.9%, p = .047). CONCLUSION: In this cohort of patients, kidney graft loss, with or without pancreas graft loss, was associated with higher mortality after SPK transplantation. Compared to CRA, the KM model underestimated survival only among patients with pancreas and kidney graft losses. Patient survival increased over time.

Efficacy and safety of single-dose anti-thymocyte globulin versus basiliximab induction therapy in pediatric kidney transplant recipients: A retrospective comparative cohort study.

BACKGROUND: This study aimed to compare the efficacy and safety of basiliximab (BAS) versus a single dose of anti-thymocyte globulin (r-ATG) induction therapy in pediatric kidney transplant recipients (KTRs). METHODS: This single-center retrospective comparative cohort study included all pediatric KTRs from May 2013 to April 2018 and followed up to 12 months. In the first period, all recipients received BAS, while from May 2016, a single 3 mg/kg dose of r-ATG was instituted. Maintenance therapy consisted of a calcineurin inhibitor plus prednisone plus azathioprine or mycophenolate. RESULTS: A total of 227 patients were included (BAS, n = 113; r-ATG, n = 114). The main combination of immunosuppressive drugs was tacrolimus, prednisone, and azathioprine in both groups (87% vs. 88%, p = .718). Patients receiving r-ATG showed superior survival-free of the composite endpoint (acute rejection, graft loss, or death; 76% vs. 61%, p = .003; HR 2.08, 1.29-3.34, p = .003) and lower incidence of biopsy-proven acute rejection (10% vs. 21%, p = .015). There was no difference in the overall incidence of CMV infection (33% vs. 37%, p = .457), PTLD (1% vs. 3%, p = .309), 30-day hospital readmissions (24% vs. 23%, p = .847), and kidney function at 12 months (86 ± 29 vs. 84 ± 30 mL/min/1.73m2, p = .614). CONCLUSIONS: These data suggest that induction therapy with a single 3 mg/kg dose of r-ATG is associated with higher efficacy for preventing acute rejection and similar safety profile compared to BAS.

Long-term Kidney Transplant Survival Across the Globe.

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.

Excess mortality among kidney transplant recipients: Impact of COVID-19-related deaths during the pandemic.

BACKGROUND: Because COVID-19 has been associated with high lethality rates among kidney transplant recipients (KTR), but also with a severe disruption and delays in overall healthcare, this study aims to evaluate the excess mortality in the pandemic era among KTR in a high-volume Brazilian transplant center. METHODS: This study used data from a single center that provides follow-up on all its transplant recipients. The population of interest included all the patients who were transplanted between August 31, 1983 and December 31, 2022 and who were live from January 1, 2014. Using the "AutoRegressive Integrated Moving Average" forecasting algorithm, the expected mortality for the pandemic era (2020-2022) was modeled from the pre-pandemic era (2014-2019). RESULTS: There were 12 077 KTRs at risk of dying in the entire observation period. In the pre-pandemic era, there were 21 deaths per 1000 patients at risk. In the pandemic era, there were 1429 observed deaths (rate of 47 deaths per 1000 patients at risk) versus the expected 587 deaths, resulting in an absolute number of 842 excess deaths, or an observed-to-expected ratio of 2.4, or an absolute rate of 26 deaths in excess per 1000 patients at risk. The excess deaths exhibited a temporal pattern mirroring that of the surges in new cases and lethality rates of COVID-19. COVID-19-related deaths drove 94% of excess mortality in the pandemic era. CONCLUSION: In this large cohort of KTR under centralized follow-up, more than twofold excess mortality was primarily driven by COVID-19-related deaths, highlighting the vulnerability of this population to the most severe presentation of SARS-CoV-2 infection.

Long COVID Among Kidney Transplant Recipients Appears to Be Attenuated During the Omicron Predominance.

BACKGROUND: Omicron variant has been associated with milder cases of COVID-19 among kidney transplant recipients. However, little is known about postacute sequelae, referred to as Long COVID. METHODS: Prospective, single-center cohort study investigating prevalence and risk factors for Long COVID among kidney transplant recipients during the omicron predominance in Brazil. The analysis included adult patients with confirmed SARS-CoV-2 infection between January 5, 2022, and July 18, 2022, were alive, had a functioning kidney transplant 3 mo after symptom onset, and answered a telephonic survey about physical complains of Long COVID. RESULTS: From the 1529 eligible, 602 (39%) patients responded the survey. Sixteen percent reported a previous SARS-CoV-2 infection, and 85% had been fully vaccinated. The prevalence of Long COVID was 52%, with the most common complaints being weakness (46%), myalgia (41%), dizziness (33%), and headache (31%). Among employed patients, 94% were able to resume their normal work activities. In multivariable analysis, female gender (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.51-3.02; P < 0.0001), previous SARS-CoV-2 infection (HR, 3.55; 95% CI, 1.91-6.60; P < 0.0001), fatigue (HR, 2.32; 95% CI, 1.18-4.55; P = 0.014), myalgia (HR, 1.48; 95% CI, 1.03-2.15; P = 0.036) during the acute phase, and hospitalization because of COVID-19 (HR, 1.71; 95% CI, 1.06-2.76; P = 0.028) were independently associated with Long COVID. CONCLUSIONS: In the "omicron era," Long COVID among kidney transplant recipients exhibited milder characteristics and had a less significant impact on their ability to resume normal life activities. The risk factors for persistent symptoms were similar to those observed in the general population except for the vaccination status, underscoring the importance of closer monitoring in special subgroups.

Patterns of Circulating Cytokines and Vascular Markers' Response in the Presence of COVID-19 in Kidney Transplant Recipients Compared with Non-Transplanted Patients.

COVID-19's severity has been associated with a possible imbalance in the cross-regulation of cytokines and vascular mediators. Since the beginning of the pandemic, kidney transplant recipients (KTRs) have been identified as patients of high vulnerability to more severe diseases. Thus, aiming to describe the patterns of cytokines and vascular mediators and to trace patients' differences according to their KTR status, this prospective study enrolled 67 COVID-19 patients (20 KTRs) and 29 non-COVID-19 controls before vaccination. A panel comprising 17 circulating cytokines and vascular mediators was run on samples collected at different time points. The cytokine and mediator patterns were investigated via principal component analysis (PCA) and correlation-based network (CBN). In both groups, compared to their respective controls, COVID-19 was associated with higher levels of cytokines and vascular mediators. Differentiating between the KTRs and non-KTRs, the number of correlations was much higher in the non-KTRs (44 vs. 14), and the node analysis showed the highest interactions of NGAL and sVCAM-1 in the non-KTRs and KTRs (9 vs. 4), respectively. In the PCA, while the non-KTRs with COVID-19 were differentiated from their controls in their IL-10, IFN-α, and TNF-α, this pattern was marked in the NGAL, sVCAM-1, and IL-8 of the KTRs.

Preemptive kidney transplantation: why, when, and how? / Transplante renal preemptivo: por que, quando e como?

ABSTRACT Among renal replacement therapies, preemptive kidney transplantation (PKT) presents the best clinical, social, and economic results. However, it is still infrequently chosen as first therapy for patients with irreversible kidney failure. Initiatives in different parts of the world were developed to identify the reasons why PKT is still not widely used and to facilitate the access of patients with end-stage kidney disease to the advantages associated with it. This article addresses the main advantages and difficulties of PKT and discusses when it should be indicated and how to prepare potential recipients for PKT.

Resumo Entre as terapias renais substitutivas, o transplante renal preemptivo (TRP) apresenta os melhores resultados clínicos, sociais e econômicos. No entanto, ainda é raramente escolhido como primeira terapia para pacientes com falência renal irreversível. Foram desenvolvidas iniciativas em diferentes partes do mundo para identificar as razões pelas quais o TRP ainda não é amplamente utilizado e para facilitar o acesso de pacientes com doença renal em estágio terminal às vantagens associadas ao mesmo. Este artigo aborda as principais vantagens e dificuldades do TRP e discute quando ele deve ser indicado e como preparar potenciais receptores para o TRP.

The Association Between Kidney Donor Profile Index and 1-y Graft Function.

The association between Kidney Donor Profile Index (KDPI) and 1-y estimated glomerular filtration rate (eGFR) with long-term kidney graft survival is well known. Yet, the association between KDPI and 1-y eGFR remains uncertain considering the several concurrent competing risk factors. Methods: This single-center, retrospective cohort study analyzed data from 3059 consecutive deceased donor kidney transplant recipients with a 1-y follow-up from January 2013 to December 2017. The aim was to determine the association between the KDPI strata (0%-35%, 36%-50%, 51%-85%, 86%-100%) and 1-y eGFR estimated by the CKD-EPI equation. Results: The incidence of delayed graft function (50.6% versus 59.3% versus 62.7% versus 62.0%; P < 0.001) and cytomegalovirus infection (36.7% versus 36.6% versus 43.3% versus 57.8%; P < 0.001) increased with increasing KDPI strata but not biopsy-proven acute rejection (9.1% versus 9.8% versus 8.4% versus 9.1%; P = 0.736). The median 1-y eGFR decreased with increasing KDPI strata (64.8 versus 53.5 versus 46.9 versus 39.1 mL/min/1.73 m2; P < 0.001). In the Cox regression, the higher the KDPI was, the lower the probability of a lower 1-y eGFR was. Assuming the 0%-35% strata as the reference, the likelihood of eGFR <50 mL/min/1.73 m2 was increased by 76.6% (hazard ratio [HR] = 1.767, 95% confidence interval [CI] = 1.406-2.220), 2.24- and 2.87-fold higher for KDPI higher >35%-50% (HR = 2.239, 95% CI = 1.862-2.691), and >51%-85% (HR = 2.871, 95% CI = 2.361-3.491), respectively. Other variables associated with a lower graft function were donor sex (HR male versus female = 0.896, 95% CI = 0.813-0.989) and cold ischemia time (HR for each hour = 1.011, 95% CI = 1.004-1.019). This association was sustained after the Poisson mediation analysis, including delayed graft function, cytomegalovirus, and acute rejection as mediators. Conclusions: In this cohort of deceased donor kidney recipients, KDPI, and cold ischemia time were the major independent risk factors associated with lower 1-y kidney function.

Conversion to mTOR Inhibitor to Reduce the Incidence of Cytomegalovirus Recurrence in Kidney Transplant Recipients Receiving Preemptive Treatment: A Prospective, Randomized Trial.

BACKGROUND: Although mammalian target of rapamycin inhibitors (mTORi) are associated with a lower incidence of the first episode of cytomegalovirus (CMV) infection/disease in kidney transplant recipients receiving calcineurin inhibitors (CNIs), the efficacy and safety of the conversion from the antimetabolite to an mTORi for the prevention of CMV recurrence are unknown. METHODS: In this single-center prospective randomized trial, low-immunological-risk, CMV-positive kidney transplant recipients receiving preemptive therapy were randomized to be converted (sirolimus [SRL]) or not (control [CTR]) immediately after the treatment of the first episode of CMV infection/disease and were followed for 12 mo. A sample size of 72 patients was calculated to demonstrate a 75% reduction in the incidence of CMV recurrence (80% power, 95% confidence level). RESULTS: Of 3247 adult kidney transplants performed between September 13, 2015, and May 7, 2019, 1309 (40%) were treated for the first CMV infection/disease, and 72 were randomized (35 SRL and 37 CTR). In the SRL group, there were no episodes of CMV recurrence, compared with 16 patients in the CTR group (0% versus 43%; P < 0.0001). Four patients had a second and 1 a third recurrent CMV event. Three of them were converted to SRL and did not develop any further CMV events. There were no differences in the incidence of acute rejection, drug discontinuation, kidney function, and patient and graft survival at 12 mo. CONCLUSIONS: These data suggest that, in CMV-positive kidney transplant recipients, the conversion from an antiproliferative drug to SRL after the first CMV episode is an effective and safe strategy for recurrent episodes.

Challenges of Multidrug-resistant New Delhi Metallo-beta-Lactamase (NDM-1)-producing Enterobacteriaceae in Kidney Transplant Patients / Desafios da Enterobacteriaceae produtora de New Delhi Metalo-beta-Lactamase (NDM-1) multirresistente em pacientes com transplante renal

Abstract Background: The emergence of multidrug-resistant NDM-1-producing enterobacteriaceae strains has become a threat to inpatients, especially to immunosuppressed ones, such as kidney transplant recipients. NDM-1 is a carbapenemase that makes gram-negative bacteria resistant to many types of antibiotics. The incidence of carbapenemase-producing enterobacteria infection in solid organ transplant recipients is around 3 to 10%, with a mortality rate of up to 30%. Methods: We present a case series of 4 patients with NDM-1-producing enterobacteria isolated in urine cultures or rectal swabs. We also conducted a cross-sectional study 30 days after patient identification, collecting surveillance cultures (rectal swab) from all inpatients to assess the extent of spread of this resistance mechanism; a total of 101 patients were included. Results: Two patients were adequately treated with negative control cultures. The other two patients were not treated because they were asymptomatic and had subsequent negative urine cultures. No new colonization was identified in the cross-sectional screening, and no new cases of urinary NDM-1 infection were recorded after a 4-year follow-up. Conclusion: Surveillance for infections caused by multidrug-resistant strains in hospitals treating immunosuppressed patients should be continued and prompt action should be taken in cases of outbreaks of multidrug-resistant infections.

Resumo Histórico: O surgimento de cepas multirresistentes de enterobacteriaceae produtoras de NDM-1 tornou-se uma ameaça para pacientes hospitalizados, especialmente para os imunossuprimidos, como os receptores de transplante renal. NDM-1 é uma carbapenemase que torna as bactérias gram-negativas resistentes a muitos tipos de antibióticos. A incidência de infecção por enterobactérias produtoras de carbapenemas em receptores de transplante de órgãos sólidos é de cerca de 3 a 10%, com uma taxa de mortalidade de até 30%. Métodos: Apresentamos uma série de casos de 4 pacientes com enterobactérias produtoras de NDM-1 isoladas em culturas de urina ou esfregaços retais. Também realizamos um estudo transversal 30 dias após a identificação do paciente, coletando culturas de vigilância (esfregaço retal) de todos os pacientes internados para avaliar a extensão de disseminação deste mecanismo de resistência; foram incluídos um total de 101 pacientes. Resultados: Dois pacientes foram tratados adequadamente com culturas de controle negativo. Os outros dois pacientes não foram tratados porque eram assintomáticos e tiveram culturas de urina negativas subsequentes. Não foi identificada nenhuma nova colonização na triagem transversal, e não foram registrados novos casos de infecção urinária por NDM-1 após um acompanhamento de 4 anos. Conclusão: A vigilância de infecções causadas por cepas multirresistentes em hospitais que tratam pacientes imunossuprimidos deve ser continuada e devem ser tomadas medidas imediatas em casos de surtos desses tipos de infecções.

Challenges of Multidrug-resistant New Delhi Metallo-beta-Lactamase (NDM-1)-producing Enterobacteriaceae in Kidney Transplant Patients.

BACKGROUND: The emergence of multidrug-resistant NDM-1-producing enterobacteriaceae strains has become a threat to inpatients, especially to immunosuppressed ones, such as kidney transplant recipients. NDM-1 is a carbapenemase that makes gram-negative bacteria resistant to many types of antibiotics. The incidence of carbapenemase-producing enterobacteria infection in solid organ transplant recipients is around 3 to 10%, with a mortality rate of up to 30%. METHODS: We present a case series of 4 patients with NDM-1-producing enterobacteria isolated in urine cultures or rectal swabs. We also conducted a cross-sectional study 30 days after patient identification, collecting surveillance cultures (rectal swab) from all inpatients to assess the extent of spread of this resistance mechanism; a total of 101 patients were included. RESULTS: Two patients were adequately treated with negative control cultures. The other two patients were not treated because they were asymptomatic and had subsequent negative urine cultures. No new colonization was identified in the cross-sectional screening, and no new cases of urinary NDM-1 infection were recorded after a 4-year follow-up. CONCLUSION: Surveillance for infections caused by multidrug-resistant strains in hospitals treating immunosuppressed patients should be continued and prompt action should be taken in cases of outbreaks of multidrug-resistant infections.

Preemptive kidney transplantation: why, when, and how?

Among renal replacement therapies, preemptive kidney transplantation (PKT) presents the best clinical, social, and economic results. However, it is still infrequently chosen as first therapy for patients with irreversible kidney failure. Initiatives in different parts of the world were developed to identify the reasons why PKT is still not widely used and to facilitate the access of patients with end-stage kidney disease to the advantages associated with it. This article addresses the main advantages and difficulties of PKT and discusses when it should be indicated and how to prepare potential recipients for PKT.

HLA-DPB1 molecular mismatches are risk factors for acute rejection and low 5-year graft function in first kidney transplants.

The study aimed to investigate the impact of HLA-DPB1 allelic and molecular mismatches on the occurrence of acute rejection (AR) and low 5-year graft function (5Y-GF) in first kidney transplant (KT) recipients. This is a single center retrospective study of 130 deceased donor KT recipients transplanted between 2014 and 2016. HLA-DPB1 allelic MM and the following molecular MM (mMM) were analyzed: expression MM with the high expression G allele in the donor; T cell epitope MM (TCE MM); epitope MM (EMM), considering all six hypervariable regions (EMM-ABCDEF HVR), or only ABEF regions (EMM-ABEF HVR); eplet MM (EpMM); antibody-verified eplet MM (AbVer EpMM); and solvent accessible amino acid MM (SAMM). There was no association of allelic MM with AR or 5Y-GF. The variables independently associated (Cox regression analyses) with AR were high donor final creatinine, nonpermissive TCE MM, ABCDEF EMM load ≥6, EpMM load ≥6; SAMM load ≥5, and AbVer EpMM load ≥3. No association between any HLA-DPB1 mMM and 5Y-GF was observed when all 130 transplant recipients were considered. However, when transplants from expanded criteria donors were excluded, independent associations were detected (logistic regression analyses) with AbVerEpMM load ≥2, SAMM load ≥7, cerebro-vascular death, donor age, and AR. To our knowledge, this is the first study that shows that some HLA-DPB1 mMM are associated with AR and low 5Y-GF in a population of exclusively first kidney transplant recipients.

Migratory pattern of the coronavirus disease 2019 and high fatality rates among kidney transplant recipients: report from the Brazilian Multicenter Cohort Study / Padrão migratório da doença coronavírus 2019 e altas taxas de mortalidade entre receptores de transplante renal: relatório do Estudo de Coorte Multicêntrico Brasileiro

Abstract Introduction: The unprecedented coronavirus disease 2019 (COVID-19) pandemic has affected kidney transplant (KT) recipients, with worldwide fatality rates around 25%. Considering the well-known Brazilian socio-demographic disparities, this report describes for the first time the main outcomes of COVID-19 in KT recipients according to Brazilian geographic regions. Methods: This multicenter national retrospective analysis included data from KT recipients with confirmed COVID-19 between March and November 2020. Results: Thirty-five of the 81 centers (57% of KT activity in Brazil) reported 1,680 patients with COVID-19. The Northeast was the first to reach the peak in the number of infections. The Southeast, due to its population density, contributed with the largest number of patients. Patients had a median age of 52 years, 76% had hypertension and 34% diabetes, 75% were recipients of a deceased donor, and the time interval between diagnosis and transplantation was 5.9 years. In 53% of patients, immunosuppression was adjusted, and clinical support varied according to geographic region. Hospitalization was required for 65% of the patients, 35% of them needed intensive care, 25% mechanical ventilation, and 23% renal replacement therapy. The 90-day overall fatality was 21%, being 23% in the Southeast, 16% in the Northeast, and 19% in the Central-west and South regions. Conclusion: The migratory pattern of the pandemic among KT recipients followed that of the general population and the outcomes were influenced by regional features. COVID-19 in KT recipients was associated with high utilization of health-care resources and higher fatality rates than those reported in the general population.

Resumo Introdução: A pandemia da COVID-19 afetou receptores de transplante renal (TR), com taxas de mortalidade mundial em torno de 25%. Considerando as notórias disparidades sócio-demográficas brasileiras, este relatório descreve pela primeira vez principais características e desfechos da doença em receptores de TR, segundo as regiões geográficas. Métodos: Esta análise retrospectiva multicêntrica nacional incluiu dados de receptores de TR com COVID-19 confirmada entre Março/Novembro de 2020. Resultados: Trinta e cinco dos 81 centros (57% da atividade de transplante renal brasileira) relataram 1.680 pacientes com COVID-19. O Nordeste foi o primeiro a atingir o pico no número de infecções. O Sudeste, por sua densidade populacional, contribuiu com maior número de pacientes. Pacientes tinham em média 52 anos, 76% apresentavam hipertensão e 34% diabetes, 75% receptores de doador falecido e o tempo entre diagnóstico e transplante foi de 5,9 anos. Em 53% dos pacientes, os imunossupressores foram ajustados, e o tratamento variou segundo a região. Hospitalização foi necessária para 65% dos pacientes, 35% necessitaram de cuidados intensivos, 25% ventilação mecânica, e 23% terapia renal substitutiva. A mortalidade geral em 90 dias foi 21%, sendo 23% no Sudeste, 16% no Nordeste, e 19% nas regiões Centro-Oeste e Sul. Conclusão: O padrão migratório da pandemia entre os receptores de TR seguiu o da população em geral e os desfechos foram influenciados por características regionais. A COVID-19 em receptores de TR foi associada à alta utilização de recursos de saúde e taxas de mortalidade mais altas do que as relatadas na população em geral.

Predictive ability of severity scores and outcomes for mortality in kidney transplant recipients with coronavirus disease 2019 admitted to the intensive care unit: results from a Brazilian single-center cohort study / Capacidade preditiva de escores de gravidade e desfechos para mortalidade em receptores de transplante renal com COVID-2019 admitidos em unidade de terapia intensiva: resultados de um estudo de coorte brasileiro de um único centro

Abstract Background: the predictive ability of severity scores for mortality in patients admitted to intensive care units is not well-known among kidney transplanted (KT) patients, especially those diagnosed with coronavirus disease 2019 (COVID-19). The purpose of the present study was to evaluate the predictive ability of severity scores for mortality in KT recipients. Methods: 51 KT recipients with COVID-19 diagnosis were enrolled. The performance of the SOFA, SAPS 3, and APACHE IV tools in predicting mortality after COVID-19 was compared by the area under the ROC curve (AUC-ROC) and univariate Cox regression analysis was performed. Results: The 90-day cumulative incidence of death was 63.4%. Only APACHE IV score differed between survivors and nonsurvivors: 91.2±18.3 vs. 106.5±26.3, P = 0.03. The AUC- ROC of APACHE IV for predicting death was 0.706 (P = 0.04) and 0.656 (P = 0.06) at 7 and 90 days, respectively. Receiving a kidney from a deceased donor (HR = 3.16; P = 0.03), troponin levels at admission (HR for each ng/mL = 1.001; P = 0.03), APACHE IV score (HR for each 1 point = 1.02; P = 0.01), mechanical ventilation (MV) requirement (HR = 3.04; P = 0.002) and vasopressor use on the first day after ICU admission (HR = 3.85; P < 0.001) were associated with the 90-day mortality in the univariate analysis. Conclusion: KT recipients had high mortality, which was associated with type of donor, troponin levels, early use of vasopressors, and MV requirement. The other traditional severity scores investigated could not predict mortality.

RESUMO Introdução: a capacidade preditiva dos escores de gravidade para mortalidade em pacientes admitidos em unidades de terapia intensiva não é bem conhecida entre pacientes transplantados renais (TR), especialmente aqueles diagnosticados com doença coronavírus 2019 (COVID-19). Este estudo avaliou a capacidade preditiva dos escores de gravidade para mortalidade em receptores de TR. Métodos: Foram inscritos 51 receptores de TR diagnosticados com COVID-19. O desempenho das ferramentas SOFA, SAPS 3, APACHE IV em predizer mortalidade após COVID-19 foi comparado pela área sob a curva ROC (AUC-ROC) e realizou-se análise de regressão univariada de Cox. Resultados: A incidência cumulativa de óbito em 90 dias foi 63,4%. Somente APACHE IV diferiu entre sobreviventes e não-sobreviventes: 91,2±18,3 vs. 106,5±26,3; P = 0,03. A AUC-ROC do APACHE IV para predizer óbito foi 0,706 (P = 0,04) e 0,656 (P = 0,06) aos 7 e 90 dias, respectivamente. Receber rim de doador falecido (HR = 3,16; P = 0,03), níveis de troponina na admissão (HR para cada ng/mL = 1,001; P = 0,03), escore APACHE IV (HR para cada 1 ponto = 1,02; P = 0,01), necessidade de ventilação mecânica (VM) (HR = 3,04; P = 0,002), uso de vasopressor no primeiro dia após admissão na UTI (HR = 3,85; P < 0,001) foram associados à mortalidade em 90 dias na análise univariada. Conclusão: Receptores de TR apresentaram alta mortalidade, associada ao tipo de doador, níveis de troponina, uso precoce de vasopressores e necessidade de VM. Os outros escores tradicionais de gravidade investigados não puderam predizer mortalidade.

Paired kidney donation: are we going beyond reasonable limits in living-donor transplantation? / Doação renal pareada: estamos passando dos limites razoáveis no transplante entre vivos?

Abstract The growing demand for transplant kidneys requires strategies to increase organ supply and avoid long waiting periods on the list. The increase in the number of transplants from living donors involves the growth in the use of unrelated donors and paired kidney donation. Most of these transplants are performed in the USA, where they already represent, respectively, 34% and 16% of total transplants from living donors. In Latin America, and especially in Brazil, there is no collective enthusiasm for these modalities, either at the request of transplanters or that of the community, with the region's priority being to increase transplants from deceased donors, which growth can be up to three-fold. Concerning transplants from matched donors, the possible conflicting results between donors can generate public challenges and they risk compromise the concepts of equal opportunities for transplant candidates, with the possibility of generating resistance to organ donation, especially in regions with socioeconomic limitations and disparities in access to qualified health care and education. This donation model involves challenging ethical and logistical issues, which are subject to questionings, starting with an act of exchange between two pairs until reaching embarrassing proposals, which can compromise the altruistic character of organ donation, and thus not be universally incorporated.

Resumo A demanda crescente por rins para transplante requer estratégias para aumentar a oferta de órgãos e evitar longos períodos de espera em lista. O aumento no número de transplantes com doador vivo envolve o crescimento da utilização de doadores não aparentados e a doação renal pareada. A maior parte desses transplantes são realizados nos EUA, onde já representam, respectivamente, 34% e 16% do total de transplantes com doador vivo. Na América Latina, e especialmente no Brasil, não existe entusiasmo coletivo por essas modalidades, quer por demanda dos transplantadores ou da comunidade, sendo prioridade da região incrementar o transplante com doador falecido, cujo crescimento pode ser de até três vezes. Na modalidade de transplantes com doadores pareados, os possíveis resultados conflitantes entre doadores podem gerar questionamentos públicos e riscos que comprometem os conceitos de equidade de oportunidades para os candidatos a transplante, com possibilidade de gerar resistência à doação de órgãos, especialmente em regiões com limitações socioeconômicas e disparidades de acesso aos atendimentos de saúde e educação qualificados. Esse modelo de doação envolve questões éticas e logísticas desafiadoras, que estão sujeitas a questionamentos, começando por um ato de troca entre dois pares até alcançar propostas constrangedoras, o que pode comprometer o caráter altruístico da doação de órgãos, e assim não ser universalmente incorporado.

Immunogenicity After a Heterologous BNT262b2 Versus Homologous Booster in Kidney Transplant Recipients Receiving 2 Doses of CoronaVac Vaccine: A Prospective Cohort Study.

BACKGROUND: Comparative studies of third heterologous doses following the CoronaVac vaccine against coronavirus disease 2019 (COVID-19) in kidney transplant recipients are lacking. METHODS: This prospective, single-center cohort study included kidney transplant recipients without previous COVID-19. Patients received a third heterologous (BNT162b2 mRNA) or homologous dose at least 4 wk after 2 doses of the CoronaVac vaccine. Immunoglobulin G antibody response and seroprevalence for neutralizing anti-severe acute respiratory syndrome coronavirus 2 antibodies immediately before and 28 d after third doses were compared between the groups. RESULTS: There were 307 patients in the heterologous group and 777 in the homologous group. Patients in the heterologous group were older (54 versus 50 y; P < 0.0001), with a longer time since transplant (11 versus 6 y; P < 0.0001). Immediately before the third dose, immunoglobulin G seroprevalence (36% versus 34%; P = 0.597) and antibody titers (246 versus 268 AU/mL; P = 0.279) were similar. After booster, seroconversion was higher in the heterologous group (49% versus 32%; P < 0.0001), resulting in a higher seroprevalence (67% versus 55%; P = 0.0003); however, 42% of all patients remained seronegative. Antibody titers after booster in seropositive patients were higher in the heterologous group (7771 versus 599 AU/mL; P < 0.0001). These results persisted after adjusting for confounding variables. Lastly, a similar proportion of patients became seropositive for neutralizing antibodies (98% versus 94%; P = 0.098). CONCLUSIONS: In kidney transplant recipients fully vaccinated with CoronaVac, a third dose with an mRNA vaccine produced a higher seroconversion rate and antibody titers than a third homologous dose. However, both boosters achieved equivalent seroprevalence for neutralizing antibodies. The high proportion of still seronegative patients indicates the need for alternative strategies of protection.

Vascular Calcification Is Associated with Fetuin-A and Cortical Bone Porosity in Stone Formers.

Background: Nephrolithiasis has been associated with bone loss and vascular calcification (VC), reflecting abnormal extraosseous calcium deposition. Fetuin-A (Fet-A) acts as a potent inhibitor of ectopic mineralization. The aim of the present study was to evaluate the prevalence of VC in stone formers (SF) and non-stone formers (NSF) and to investigate potential determinants of VC among SF, including circulating levels of Fet-A and bone microarchitecture parameters. Methods: Abdominal aortic calcification (AAC) was assessed using available computed tomography in SF and in age-, sex-, and BMI-matched NSF (potential living kidney donors). Serum Fet-A was measured in stored blood samples from SF. Bone microarchitecture parameters were obtained as a post hoc analysis of a cross-sectional cohort from young SF evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Results: A total of 62 SF (38.0 [28.0−45.3] years old) and 80 NSF (40.0 [37.0−45.8] years old) were included. There was no significant difference in AAC scores between SF and NSF. However, when dividing SF according to mean AAC score, below <5.8% (n = 33) or above ≥5.8% (n = 29), SF with higher AAC presented significantly higher BMI and tibial cortical porosity (Ct.Po) and significantly lower serum HDL, klotho, Fet-A, and eGFR. Urinary calcium did not differ between groups, but fractional excretion of phosphate was higher in the former. Upon multivariate regression, BMI, serum Fet-A, and tibial Ct.Po remained independently associated with AAC. Conclusions: This study suggests an association between reduced circulating Fet-A levels and increased bone Ct.Po with VC in SF.