Use of Machine Perfusion to Increase the Number of Expanded Criteria Deceased Donor Kidney Transplants: A Pharmacoeconomic Analysis.

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.

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.

The impact of universal induction therapy on early hospital readmission of kidney transplant recipients / O impacto da terapia de indução universal na readmissão hospitalar precoce de receptores de transplante renal

ABSTRACT Background: Early hospital readmission (EHR) is associated with worse outcomes. The use of anti-thymocyte globulin (rATG) induction therapy is associated with increased efficacy in preventing acute rejection, although safety concerns still exist. Methods: This retrospective single-center study compared the incidence, causes of EHR, and one-year clinical outcomes of patients receiving a kidney transplant between August 18, 2011 and December 31, 2012 (old era), in which only high-risk patients received 5 mg/kg rATG, with those transplanted between August 18, 2014 and December 31, 2015 (new era), in which all patients received a single 3 mg/kg dose of rATG. Results: There were 788 patients from the Old Era and 800 from the New Era. The EHR incidence in the old era patients was 26.4% and in the new era patients, 22.5% (p = 0.071). The main cause of EHR in both eras was infection (67% vs. 68%). The incidence of acute rejection episodes was lower (22.7% vs 3.5%, p < 0.001) and the one-year patient survival was higher (95.6% vs. 98.1%, vs. p = 0.004) in new era patients. Conclusion: The universal use of 3 mg/kg rATG single-dose induction therapy in the new era was associated with a trend towards reduced EHR and a reduction in the incidence of acute rejection and mortality.

Resumo Histórico: A Readmissão Hospitalar Precoce (RHP) está associada a piores desfechos. O uso de terapia de indução com globulina antitimócito (rATG, por sua sigla em inglês) está associado ao aumento da eficácia na prevenção de rejeição aguda, embora ainda existam preocupações quanto à segurança. Métodos: Este estudo retrospectivo de centro único comparou a incidência, as causas da RHP e os desfechos clínicos de um ano de pacientes que receberam transplante renal entre 18 de Agosto de 2011 e 31 de Dezembro de 2012 (Antiga Era), em que apenas pacientes de alto risco receberam 5 mg/kg de rATG, com aqueles transplantados entre 18 de Agosto de 2014 e 31 de Dezembro de 2015 (Nova Era), em que todos os pacientes receberam uma única dose de 3 mg/kg de rATG. Resultados: Houve 788 pacientes da Antiga Era e 800 da Nova Era. A incidência de RHP nos pacientes da antiga era foi de 26,4% e nos pacientes da nova era, 22,5% (p = 0,071). A principal causa de RHP em ambas as eras foi infecção (67% vs. 68%). A incidência de episódios de rejeição aguda foi menor (22,7% vs. 3,5%; p < 0,001) e a sobrevida do paciente em um ano foi maior (95,6% vs. 98,1%; vs. p = 0,004) em pacientes da nova era. Conclusão: O uso universal de terapia de indução de 3 mg/kg de rATG em dose única na nova era foi associado a uma tendência à redução da RHP e a uma redução na incidência de rejeição aguda e mortalidade.

Time from kidney failure onset to transplantation and its impact on growth in pediatric patients.

BACKGROUND: In children with kidney failure, the longer the duration of dialysis the greater the impact on growth deficit, quality of life, and life expectancy. The aim of this research is to test whether there was a shortening of treatment time from kidney failure to transplantation in pediatric patients and whether this time interval impacted height. METHODS: Observational retrospective cohort study from 2005 to 2018. The first outcome variable was time to transplantation in years, while the second was height/age standard deviation score (SDS) at transplantation. Cox regression models were used to analyze time from disease to transplantation and linear regression was employed to test the association of the year of kidney failure onset with height. RESULTS: A total of 780 children were evaluated and 517 underwent kidney transplantation after a median time of 1.9 years (IQR = 1.0-4.0). The variables significantly associated with time to transplant were: year of kidney failure onset (HR = 1.07; 95% CI: 1.05-1.10; p < .001), age at kidney failure onset <12 years (HR = 0.59; 95% CI: 0.49-0.71; p < .001), living in different state as transplant center (HR = 0.63; 95% CI: 0.53-0.77; p < .001), and undergoing blood transfusion before transplantation (HR = 0.63; 95% CI: 0.53-0.75; p < .001). Regarding growth, for each 1-year increase in the epoch of kidney failure onset, a 0.05 SDS raise in height/age is expected (p < .001). CONCLUSION: Children with recent kidney failure onset had significantly lower time to the outcome and this reduction was associated with a less severe growth deficit.

The impact of universal induction therapy on early hospital readmission of kidney transplant recipients.

BACKGROUND: Early hospital readmission (EHR) is associated with worse outcomes. The use of anti-thymocyte globulin (rATG) induction therapy is associated with increased efficacy in preventing acute rejection, although safety concerns still exist. METHODS: This retrospective single-center study compared the incidence, causes of EHR, and one-year clinical outcomes of patients receiving a kidney transplant between August 18, 2011 and December 31, 2012 (old era), in which only high-risk patients received 5 mg/kg rATG, with those transplanted between August 18, 2014 and December 31, 2015 (new era), in which all patients received a single 3 mg/kg dose of rATG. RESULTS: There were 788 patients from the Old Era and 800 from the New Era. The EHR incidence in the old era patients was 26.4% and in the new era patients, 22.5% (p = 0.071). The main cause of EHR in both eras was infection (67% vs. 68%). The incidence of acute rejection episodes was lower (22.7% vs 3.5%, p < 0.001) and the one-year patient survival was higher (95.6% vs. 98.1%, vs. p = 0.004) in new era patients. CONCLUSION: The universal use of 3 mg/kg rATG single-dose induction therapy in the new era was associated with a trend towards reduced EHR and a reduction in the incidence of acute rejection and mortality.

Presumed cytomegalovirus retinitis late after kidney transplant / Retinite presumida por citomegalovírus tardiamente após um transplante renal

Abstract Cytomegalovirus (CMV) retinitis is a rare manifestation of CMV invasive disease and potentially threatening to vision in immunocompromised individuals. Clinical suspicion is fundamental since it is an unusual entity with a progressive and often asymptomatic installation over a long period. The authors report a 70-year-old man with diabetic nephropathy who underwent a kidney transplant (KT) in August 2014 with good clinical evolution. No previous CMV infection or episodes of acute rejection were reported. Five years after transplant, he was admitted due to a reduced visual acuity of the left eye with seven days of evolution with associated hyperemia, without exudate. The ophthalmologic evaluation was compatible with acute necrosis of the retina and presumed associated with CMV infection. He had a progressive improvement after ganciclovir initiation. CMV retinitis is one of the most serious ocular complications in immune-suppressed individuals and can lead to irreversible blindness, and because of that, early diagnosis and treatment remains crucial in obtaining the best visual prognosis in affected patients. Secondary prophylaxis with ganciclovir is not consensual, neither is the safety of reintroducing the antimetabolite in these cases.

Resumo A retinite por citomegalovírus (CMV) é uma manifestação rara de doença invasiva por CMV e potencialmente ameaçadora para a visão em indivíduos imunocomprometidos. A suspeita clínica é fundamental, uma vez que se trata de uma entidade incomum, com uma instalação progressiva e frequentemente assintomática durante um longo período. Os autores relatam um homem de 70 anos de idade com doença renal do diabetes que foi submetido a um transplante renal (KT) em Agosto de 2014 com boa evolução clínica. Nenhuma infecção anterior por CMV ou episódios de rejeição aguda foram relatados. Cinco anos após o transplante, ele foi internado devido a uma acuidade visual reduzida do olho esquerdo com sete dias de evolução com hiperemia associada, sem exsudato. A avaliação oftalmológica foi compatível com a necrose aguda da retina e presumivelmente associada à infecção por CMV. Ele teve uma melhora progressiva após o início do ganciclovir. A retinite por CMV é uma das complicações oculares mais graves em indivíduos imunossuprimidos e pode levar à cegueira irreversível e, por isso, o diagnóstico e o tratamento precoces continuam sendo cruciais para obter o melhor prognóstico visual em pacientes afetados. A profilaxia secundária com ganciclovir não é consensual, tampouco a segurança de reintroduzir o antimetabólito nestes casos.

Risk factors of transplant renal artery stenosis in kidney transplant recipients.

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).

Presumed cytomegalovirus retinitis late after kidney transplant.

Cytomegalovirus (CMV) retinitis is a rare manifestation of CMV invasive disease and potentially threatening to vision in immunocompromised individuals. Clinical suspicion is fundamental since it is an unusual entity with a progressive and often asymptomatic installation over a long period. The authors report a 70-year-old man with diabetic nephropathy who underwent a kidney transplant (KT) in August 2014 with good clinical evolution. No previous CMV infection or episodes of acute rejection were reported. Five years after transplant, he was admitted due to a reduced visual acuity of the left eye with seven days of evolution with associated hyperemia, without exudate. The ophthalmologic evaluation was compatible with acute necrosis of the retina and presumed associated with CMV infection. He had a progressive improvement after ganciclovir initiation. CMV retinitis is one of the most serious ocular complications in immune-suppressed individuals and can lead to irreversible blindness, and because of that, early diagnosis and treatment remains crucial in obtaining the best visual prognosis in affected patients. Secondary prophylaxis with ganciclovir is not consensual, neither is the safety of reintroducing the antimetabolite in these cases.

Risk factors of transplant renal artery stenosis in kidney transplant recipients

Abstract 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.

Cholecystectomy-Associated Complications in Kidney Transplant Recipients Compared With the General Population.

Cholelithiasis is one of the most prevalent diseases in the general population. Among kidney transplant (KT) recipients, atypical clinical presentation may delay the diagnosis and proper treatment. This single-center retrospective cohort study compared cholelithiasis clinical presentation and cholecystectomy-associated complications in 230 KT recipients and in 172 members of the general population. KT recipients had a higher proportion of men, comorbidities, biliary pancreatitis, choledocholithiasis, and acute cholecystitis clinical presentations than the general population. KT recipients presented higher American Society of Anesthesiologists scores and higher rates of emergency surgeries (15.7% vs 9.9%, P = .091), conversion (5.7% vs 1.2%, P = .019), drainage (7.8% vs 2.3%, P = .016), postoperative complications (10% vs 4.7%, P = .047), and longer hospital length of stay (1 vs 1 days, interquartile range, 2 vs 0 days; P < .001). There were 5 deaths, all of which occurred in KT recipients. History of diabetes mellitus, renal function, and surgical conversion were independent risk factors associated with postoperative complications. Male sex and level of renal function were independent risk factors associated with postoperative acute cholecystitis. KT was an independent risk factor associated with postoperative choledocholithiasis (adjusted odds ratio, 5.89; 95% confidence interval, 3.03-15.66) and pancreatitis (adjusted odds ratio, 6.89; 95% confidence interval, 2.99-11.61). In conclusion, KT recipients with cholelithiasis have an increased risk for clinical and surgical complications compared with the general population.

Strategies to keep kidney transplant alive amid the SARS-CoV-2 pandemic.

OBJECTIVE: This study aims to describe the result of the strategies adopted to maintain the transplant program amid the COVID-19 pandemic. METHODS: Since March 2020, several measures have been adopted sequentially, including the compulsory use of personal protective equipment and the real-time polymerase chain reaction testing of collaborators, symptomatic patients, potential deceased donors, candidates for recipients, and in-hospital readmissions, regardless of symptoms. The living-donor transplantation was restricted to exceptional cases. RESULTS: Among 1013 health professionals, 201 cases of COVID-19 were confirmed between March and August 2020, with no severe cases reported. In this period, we observed a 19% institutional increase in the number of transplants from deceased donors compared with that observed in the same period in 2019. There was no donor-derived severe acute respiratory syndrome virus (SARS-CoV-2) infection. Four COVID-19-positive patients underwent transplantation; after 28 days, all were alive and with functioning allograft. Among the 11,875 already transplanted patients being followed up, there were 546 individuals with confirmed diagnosis, 372 who required hospitalization, and 167 on mechanical ventilation, resulting in a 27% mortality rate. CONCLUSIONS: These data confirm that the adoption of sequential and coordinated measures amid the pandemic was able to successfully maintain the transplant program and ensure the safety of health professionals and transplanted patients who were already in follow-up.

Strategies to keep kidney transplant alive amid the SARS-CoV-2 pandemic

SUMMARY OBJECTIVE: This study aims to describe the result of the strategies adopted to maintain the transplant program amid the COVID-19 pandemic. METHODS: Since March 2020, several measures have been adopted sequentially, including the compulsory use of personal protective equipment and the real-time polymerase chain reaction testing of collaborators, symptomatic patients, potential deceased donors, candidates for recipients, and in-hospital readmissions, regardless of symptoms. The living-donor transplantation was restricted to exceptional cases. RESULTS: Among 1013 health professionals, 201 cases of COVID-19 were confirmed between March and August 2020, with no severe cases reported. In this period, we observed a 19% institutional increase in the number of transplants from deceased donors compared with that observed in the same period in 2019. There was no donor-derived severe acute respiratory syndrome virus (SARS-CoV-2) infection. Four COVID-19-positive patients underwent transplantation; after 28 days, all were alive and with functioning allograft. Among the 11,875 already transplanted patients being followed up, there were 546 individuals with confirmed diagnosis, 372 who required hospitalization, and 167 on mechanical ventilation, resulting in a 27% mortality rate. CONCLUSIONS: These data confirm that the adoption of sequential and coordinated measures amid the pandemic was able to successfully maintain the transplant program and ensure the safety of health professionals and transplanted patients who were already in follow-up.

Iron Overload in Renal Transplant Patients: The Role of Hepcidin and Erythropoietin.

Renal transplant patients may present important serum iron overload (IO), which can persist for long periods after transplantation, but its mechanisms are not fully understood. We raised the hypothesis that post-transplant hypererythropoietinemia might induce reduction in serum hepcidin, favoring iron absorption. The aims of this study were to determine the prevalence of IO and associated factors in transplant patients and to evaluate erythropoietin and hepcidin levels in patients with and without IO. A total of 168 patients were included, with a median time of dialysis and transplantation of 28 and 65 months, respectively. Most patients (85%) received large amounts of parenteral iron (3600 mg iron) during the dialysis period. Median ferritin was 427 ng/mL, and transferrin saturation was 33%. IO was present in 26 patients (15%). A comparison of patients with and without IO showed a predominance of male and nonwhite patients in the former group (P < .001 and .002, respectively). The total amount of iron used before transplantation and hemoglobin levels were higher in the group with IO (P = .023 and .046, respectively). Hepcidin was higher in the group with IO (P < .0001), whereas erythropoietin did not differ between groups. There was no correlation between serum levels of hepcidin and erythropoietin (r = -0.001). In conclusion, factors associated with IO were male sex, higher hemoglobin levels, and the amount of iron received before transplantation. IO was not the result of reduction in hepcidin secondary to hypererythropoietinemia. The elevated levels of serum hepcidin were possibly secondary to IO, mediated by mechanisms that are independent of the hepcidin-erythropoietin axis.

Budd-Chiari Syndrome after Bilateral Nephrectomy for Polycystic Kidney Disease in a Kidney Transplant Recipient.

We report a rare case of Budd-Chiari syndrome (BCS) as a postoperative complication after bilateral nephrectomy in a kidney transplant recipient with polycystic liver and kidneys. Contrast-enhanced computed tomography of the abdomen showed a narrowed inferior vena cava, compressed by the polycystic liver that moved downwards after nephrectomy. A stenting angioplasty was performed, resulting in remarkable clinical improvement. This case highlights the need for careful evaluation of polycystic kidneys and their anatomic relationship with the liver before nephrectomy, as well as for considering BCS as a differential diagnosis in similar cases.