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Background: The discard of expanded criteria donor (ECD) kidneys is unacceptably high, considering the growing demand for transplantation. Using machine perfusion may reduce the discard rate, increase the number of transplants, and reduce mortality on the waiting list. Methods: We developed a 5-y Markov model to simulate incorporating the pulsatile perfusion machine into the current government-funded healthcare system. The model compared the universal use of static cold storage for all kidneys with the selective use of machine perfusion for ECD kidneys. Real-life data were used to compose the cohort characteristics in this model. This pharmacoeconomic analysis aimed to determine the cost-effectiveness and budgetary impact of using machine perfusion to preserve ECD kidneys. Results: Compared with the universal use of static cold storage, the use of machine perfusion for ECD kidneys was associated with an increase in the number of kidney transplants (n = 1123), a decrease in the number of patients on the waiting list (n = 815), and decrease in mortality (n = 120), with a cost difference of US dollar 4 486 009 in the period. The budget impact analysis revealed an additional cost of US dollar 4 453 749 >5 y. The budget impact analysis demonstrated a progressive reduction in costs, becoming cost-saving during the last year of the analysis. Conclusions: This stochastic model showed that incorporating machine perfusion for ECD kidneys is most often a dominant or cost-effective technology associated with an increase in the number of transplants and a reduction in the number of patients on the waiting list, reducing mortality on the waiting list.

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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.

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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.

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BACKGROUND: Mammalian target of rapamycin inhibitors (mTORi), sirolimus (SRL) and everolimus (EVR), have distinct pharmacokinetic/pharmacodynamics properties. There are no studies comparing the efficacy and safety of de novo use of SRL versus EVR in combination with reduced-dose calcineurin inhibitor. METHODS: This single-center prospective, randomized study included first kidney transplant recipients receiving a single 3 mg/kg antithymocyte globulin dose, tacrolimus, and prednisone, without cytomegalovirus (CMV) pharmacological prophylaxis. Patients were randomized into 3 groups: SRL, EVR, or mycophenolate sodium (MPS). Doses of SRL and EVR were adjusted to maintain whole blood concentrations between 4 and 8 ng/mL. The primary endpoint was the 12-mo incidence of the first CMV infection/disease. RESULTS: There were 266 patients (SRL, n = 86; EVR, n = 90; MPS, n = 90). The incidence of the first CMV event was lower in the mTORi versus MPS groups (10.5% versus 7.8% versus 43.3%, P < 0.0001). There were no differences in the incidence of BK polyomavirus viremia (8.2% versus 10.1% versus 15.1%, P = 0.360). There were no differences in survival-free from treatment failure (87.8% versus 88.8% versus 93.3%, P = 0.421) and incidence of donor-specific antibodies. At 12 mo, there were no differences in kidney function (75 ± 23 versus 78 ± 24 versus 77 ± 24 mL/min/1.73 m 2 , P = 0.736), proteinuria, and histology in protocol biopsies. Treatment discontinuation was higher among patients receiving SRL or EVR (18.6% versus 15.6% versus 6.7%, P = 0.054). CONCLUSIONS: De novo use of SRL or EVR, targeting similar therapeutic blood concentrations, shows comparable efficacy and safety. The reduced incidence of CMV infection/disease and distinct safety profile of mTORi versus mycophenolate were confirmed in this study.

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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.

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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.

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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.

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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.

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BACKGROUND: Transplant Renal Artery Stenosis (TRAS) is a recognized vascular complication after kidney transplantation. The overall risk predictors of TRAS are poorly understood. METHODS: Retrospective analysis of patients with suspected TRAS (Doppler ultrasound PSV > 200 cm/s) who underwent angiographic study in a single center between 2007 and 2014. All patients with stenosis > 50% were considered with TRAS. Stenosis restricted in the body of the artery was also analyzed in a subgroup. RESULTS: 274 patients were submitted to a renal angiography and 166 confirmed TRAS. TRAS group featured an older population (46.3 ± 11.0 vs. 40.9 ±14.2 years; p = 0.001), more frequent hypertensive nephropathy (30.1% vs. 15.7%; p = 0.01), higher incidence of Delayed Graft Function (DGF) (52.0% vs. 25.6%; p < 0.001) and longer Cold Ischemia Time (CIT) (21.5 ± 10.6 vs. 15.7 ± 12.9h; p < 0.001). In multivariable analyses, DGF (OR = 3.31; 95% CI 1.78‒6.30; p < 0.0001) was independent risk factors for TRAS. DM and CIT showed a tendency towards TRAS. The compound discriminatory capacity of the multivariable model (AUC = 0.775; 95% CI 0.718‒0.831) is significantly higher than systolic blood pressure and creatinine alone (AUC = 0.62; 95% CI 0.558-0.661). In body artery stenosis subgroup, DGF (OR = 1.86; 95% CI 1.04‒3.36; p = 0.03) and Diabetes Mellitus (DM) (OR = 2.44; 95% CI 1.31‒4.60; p = 0.005) were independent risk factors for TRAS. CONCLUSION: In our transplant population, DGF increased more than 3-fold the risk of TRAS. In the subgroup analysis, both DGF and DM increases the risk of body artery stenosis. The addition of other factors to hypertension and renal dysfunction may increase diagnostic accuracy. TRAS TRIAL REGISTRED: clinicaltrials.gov (n° NCT04225338).

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