Multifaceted Control Interventions for Healthcare-associated Infections in a Kidney Transplant Intensive Care Unit: Clinical Outcome Improvement and Bundle Adherence.

Background: Healthcare-associated infections (HAIs) are preventable complications that overwhelm the healthcare system. The implementation of multifaceted control intervention actions in the intensive care setting modifies clinical outcomes, but its effectiveness has not been specifically investigated for high-risk patients, such as kidney transplant recipients (KTRs). Methods: This observational retrospective natural experiment evaluated the effectiveness of multifaceted control interventions (bundles) in reducing HAIs in a KTR intensive care unit. We also measured the bundle adherence rate during 16 mo in the after era. Results: We included 1257 KTRs, 684 before and 573 in the postintervention period. After the bundle implementation, the incidence density of device-associated HAIs decreased from 8.5 to 3.9 per 1000 patient-days (relative risk [RR] = 0.46; 95% confidence interval [CI], 0.25-0.85; P = 0.01), primarily because of the reduction in central line-associated bloodstream infection from 8.0 to 3.4 events per 1000 catheter-days (RR = 0.43; 95% CI, 0.22-0.83; P = 0.012). Reductions in catheter-associated urinary tract infection (2.5 versus 0.6 per 1000 catheter-days; RR = 0.22; 95% CI, 0.03-1.92; P = 0.17) and ventilator-associated pneumonia (3.4 versus 1.0 per 1000 ventilator-days; RR = 0.29; 95% CI, 0.03-2.63; P = 0.27) were not significant. Central venous (P = 0.53) and urinary catheter (P = 0.47) insertion adherence were stable during 16 mo, whereas central venous (P < 0.001) and urinary catheter (P = 0.004) maintenance gradually increased. Finally, ventilator-associated pneumonia prevention bundle adherence slightly decreased over time (P = 0.06). Conclusions: The implementation of comprehensive multifaceted control intervention actions in an intensive care unit dedicated to KTR care was effective in significantly reducing device-associated infections. The impact was in line with the reductions observed in populations that have not undergone transplantation, underscoring the effectiveness of these interventions across different patient groups.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Transition from antigenemia to quantitative nucleic acid amplification testing in cytomegalovirus-seropositive kidney transplant recipients receiving preemptive therapy for cytomegalovirus infection.

Due to the high costs, the strategy to reduce the impact of cytomegalovirus (CMV) after kidney transplant (KT) involves preemptive treatment in low and middle-income countries. Thus, this retrospective cohort study compared the performance of antigenemia transitioned to quantitative nucleic acid amplification testing, RT-PCR, in CMV-seropositive KT recipients receiving preemptive treatment as a strategy to prevent CMV infection. Between 2016 and 2018, 363 patients were enrolled and received preemptive treatment based on antigenemia (n = 177) or RT-PCR (n = 186). The primary outcome was CMV disease. Secondarily, the CMV-related events were composed of CMV-infection and disease, which occurred first. There were no differences in 1-year cumulative incidence of CMV-disease (23.7% vs. 19.1%, p = 0.41), CMV-related events (50.8% vs. 44.1%, p = 0.20), neither in time to diagnosis (47.0 vs. 47.0 days) among patients conducted by antigenemia vs. RT-PCR, respectively. The length of CMV first treatment was longer with RT-PCR (20.0 vs. 27.5 days, p < 0.001), while the rate of retreatment was not different (14.7% vs. 11.8%, p = 0.48). In the Cox regression, acute rejection within 30 days was associated with an increased the risk (HR = 2.34; 95% CI = 1.12-4.89; p = 0.024), while each increase of 1 mL/min/1.73 m2 of 30-day eGFR was associated with a 2% reduction risk of CMV-disease (HR = 0.98; 95% CI = 0.97-0.99; p = 0.001). In conclusion, acute rejection and glomerular filtration rate are risk factors for CMV disease, showing comparable performance in the impact of CMV-related events between antigenemia and RT-PCR for preemptive treatment.

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.

The Mycophenolate-based Immunosuppressive Regimen Is Associated With Increased Mortality in Kidney Transplant Patients With COVID-19.

BACKGROUND: The chronic use of immunosuppressive drugs is a key risk factor of death because of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTRs), although no evident association between the class of immunosuppressive and outcomes has been observed. Thus, we aimed to compare COVID-19-associated outcomes among KTRs receiving 3 different immunosuppressive maintenance regimes. METHODS: This study included data from 1833 KTRs with COVID-19 diagnosed between March 20 and April 21 extracted from the national registry before immunization. All patients were taking calcineurin inhibitor associated with mycophenolate acid (MPA, n = 1258), azathioprine (AZA, n = 389), or mammalian targets of rapamycin inhibitors (mTORi, n = 186). Outcomes within 30 and 90 d were assessed. RESULTS: Compared with patients receiving MPA, the 30-d (79.9% versus 87.9% versus 89.2%; P < 0.0001) and 90-d (75% versus 83.5% versus 88.2%; P < 0.0001) unadjusted patient survivals were higher in those receiving AZA or mTORi, respectively. Using adjusted multivariable Cox regression, compared with patients receiving AZA, the use of MPA was associated with a higher risk of death within 30 d (adjusted hazard ratio [aHR], 1.70; 95% confidence interval [CI], 1.21-2.40; P = 0.003), which was not observed in patients using mTORi (aHR, 0.78; 95% CI, 0.45-1.35; P = 0.365). At 90 d, although higher risk of death was confirmed in patients receiving MPA (aHR, 1.46; 95% CI, 1.09-1.98; P = 0.013), a reduced risk was observed in patients receiving mTORi (aHR, 0.59; 95% CI, 0.35-0.97; P = 0.04) compared with AZA. CONCLUSIONS: This national cohort data suggest that, in KTRs receiving calcineurin inhibitor and diagnosed with COVID-19, the use of MPA was associated with higher risk of death, whereas mTORi use was associated with lower risk of death.

Paired kidney donation: are we going beyond reasonable limits in living-donor transplantation?

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.

Inactivated Whole-virus Vaccine Triggers Low Response Against SARS-CoV-2 Infection Among Renal Transplant Patients: Prospective Phase 4 Study Results.

BACKGROUND: Anti-severe acute respiratory syndrome coronavirus 2 mRNA vaccines elicit lower humoral responses in solid-organ transplant recipients. This is the first prospective trial investigating the effect of an inactivated whole-virion vaccine in kidney transplant recipients. METHODS: Prospective, single-center, phase 4, interventional study. Kidney transplant recipients aged 30-69 y with >30 d of transplantation received two 3 µg intramuscular doses of CoronaVac 28 d apart and are being followed for 6 mo. Primary outcomes: (1) reactogenicity after first dose; (2) antibody responses 28 d after each dose; and (3) incidence/severity of confirmed coronavirus disease 2019 (COVID-19) and 28-d lethality rate. For this analysis, clinical effectiveness was assessed for 3 mo, starting 15 d after the second dose, and compared with 3-mo period before vaccination. RESULTS: Of the 3371 individuals who received the first dose, 99% completed vaccination schedule. Mild/local adverse reactions were reported by 33% of the patients. In the immunogenicity cohort (n = 942), the proportion of patients with IgG antibodies to severe acute respiratory syndrome coronavirus 2 increased from 15.2% after first dose to 43% after second dose. Increase in antibody values after second dose was associated with higher proportion of patients with detected neutralizing antibodies. A significant reduction in the incidence of COVID-19 was observed (6.4% versus 4.2%; P < 0.0001), although the 28-d lethality rate remained unchanged (25% versus 22%; P = 0.534). In 45 patients from the immunogenicity cohort who developed COVID-19, all the 6 deaths occurred among those without antibody response (n = 22; 49%). CONCLUSIONS: CoronaVac vaccine was associated with low reactogenicity, low immunogenicity but reduced incidence of COVID-19 among kidney transplant recipients. The lack of reduction in lethality rates is perhaps associated with the low percentage of patients developing humoral response after the second dose.