Alfaepoetina para o tratamento de pacientes com doença falciforme apresentando declínio da função renal e piora dos níveis de hemoglobina / Epoetin alfa for the treatment of patients with sickle cell disease presenting with declining kidney function and worsening hemoglobin levels

INTRODUÇÃO: A doença falciforme (DF) se refere a um grupo de hemoglobinopatias nas quais a mutação na hemoglobina (Hb) associada à falcização das hemácias é co-herdada com mutações em outras beta globinas. A doença evolui com vaso-oclusão e outras complicações crônicas, graves e multissistêmicas. Uma das principais complicações da DF ­ que ocorre especialmente em pessoas com os genótipos HbSS e HbSbeta0 ­ é a nefropatia falciforme, que pode evoluir desde quadros assintomáticos até doença crônica renal (DRC). Além do tratamento padrão com hidroxiureia e transfusões sanguíneas, diretrizes internacionais recomendam o tratamento com agentes estimulantes da eritropoiese (AEE), como a alfaepoetina para pacientes com comprometimento renal. O uso desse medicamento está consolidado para tratamento da anemia em DRC em pacientes sem DF, estando incorporada ao SUS como pó para solução injetável e em solução injetável para o tratamento desta condição clínica. PERGUNTA: Alfaepoetina em associação ao cuidado-padrão comparada ao cuidado-padrão, é eficaz, efetiva, segura, custo-efetiva e viável economicamente para o tratamento de adultos com DF que apresentam comprometimento renal associado à piora do quadro de anemia? EVIDÊNCIAS CLÍNICAS: Foram incluídos oito estudos observacionais que apresentaram os resultados por meio de análises antes/depois de parâmetros clínicos e hematológicos. O uso de alfaepoetina esteve associado à melhora significativa estatisticamente na concentração de Hb (variação de 4 a 32,8% de aumento nos níveis de Hb comparados aos valores da linha de base, p<0,05), nos níveis percentuais de Hb-F (a diferença variou de 5,2 a 17,1% entre os estudos, p<0,05) e na redução da necessidade de transfusões sanguíneas (resultados quantitativos não reportados). Não houve aumento de crises vaso-oclusivas (CVO) ou tromboembolismo venoso (TEV), sugerindo que o tratamento com alfaepoetina pode ser seguro (resultados quantitativos não reportados). A certeza na evidência pelo GRADE foi muito baixa para todos os desfechos, com preocupações relacionadas ao risco de viés e imprecisão. Ao considerar apenas a evidência para um subgrupo de pacientes (n=4) com comprometimento renal para o desfecho de concentração de Hb (aumento de 29,0%) a certeza na evidência permanece muito baixa, apesar de não haver, neste caso, rebaixamento da qualidade da evidência por evidência indireta. AVALIAÇÃO ECONÔMICA (AE): Foi elaborada uma análise de custo-efetividade/utilidade a partir de modelo de árvore de decisão com horizonte temporal de um ano para avaliar as consequências da alfaepoetina na redução da necessidade de transfusões sanguíneas em termos de custos e ano de vida ajustado por qualidade (QALY). A análise demonstrou que a alfaepoetina + cuidado padrão para o tratamento de adultos com DF apresentando declínio da função renal e piora dos níveis de hemoglobina, quando comparado ao cuidado padrão, apresenta modesto benefício clínico (incremental de 0,033 QALY e redução de custo - R$ 11.564). A alfaepoetina permaneceu como alternativa dominante nas simulações realizadas nas análises de sensibilidade. ANÁLISE DE IMPACTO ORÇAMENTÁRIO (AIO): O tamanho da população elegível foi estimado por demanda aferida combinada à demanda epidemiológica, sendo identificado em média 5.274 pacientes por ano. A taxa de difusão de alfaepoetina variou de 10% a 50% entre primeiro e último anos. O custo direto com aquisição da alfaepoetina variou de R$ 806.129 no primeiro ano a R$ 4.853.242 no quinto ano de incorporação. A AIO construída, atrelada à análise de custoefetividade, sugeriu uma economia de R$ 96.545.791 acumulada em cinco anos. Esta economia é decorrente da efetividade do medicamento em reduzir a necessidade de transfusões frequentes, uma vez que este procedimento está associado a altos custos, como os custos da terapia de quelação de ferro. As análises de sensibilidade reforçaram estes resultados. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Foram identificadas 2 tecnologias para o potencial tratamento de pessoas com doença falciforme, apresentando declínio da função renal e piora dos níveis de hemoglobina. Crizanlizumabe, anti-P selectina, com registro na Anvisa, EMA e FDA. Voxelotor, registrada na EMA e FDA. PERSPECTIVA DO PACIENTE: Foi aberta Chamada Pública nº 35/2023 para inscrição de participantes para a perspectiva do paciente, durante o período de 21 a 27/09/2023, e 11 pessoas se inscreveram, mas nenhuma atendia aos critérios da chamada. A Secretaria-Executiva da Conitec realizou uma busca ativa junto a especialistas, associações de pacientes e Centros de Tratamento para identificar um usuário do SUS que pudesse fazer o relato na reunião da Conitec. Em sua fala, o participante informou que há 10 anos apresentou elevação nas taxas de potássio, necessitando fazer, na época, uso do medicamento denominado "sorcal" (poliestirenossulfonato de cálcio). Há cerca de cinco anos começou a fazer uso da alfaepoetina. O medicamento, segundo ele, mantém a insuficiência renal controlada sem provocar efeitos adversos. Há algum tempo, entretanto, vem apresentando queda nas taxas de hemoglobina, necessitando receber transfusões de sangue a cada dois meses, procedimento que até então não era rotineiro. Não sabe dizer se o declínio das taxas de hemoglobina se deve ao uso da alfaepoetina. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros do Comitê de Medicamentos presentes na 16ª Reunião Extraordinária da Conitec, realizada no dia 01 de novembro de 2023, deliberaram por unanimidade, que a matéria fosse disponibilizada em consulta pública com recomendação preliminar favorável à incorporação ao SUS da alfaepoetina (rHuePO, eritropoietina humana recombinante) para adultos com doença falciforme, com comprometimento renal associado à piora do quadro de anemia. Discutiu-se a necessidade de estabelecer, no contexto da atualização do PCDT, critérios objetivos de declínio da função renal, queda de hemoglobina e níveis de eritropoetina endógena para compor critérios de uso do medicamento. Sugeriu-se o uso de critérios relativos, como queda de 25% ou mais na TFGe em relação ao valor basal. Ademais, frente às incertezas quanto às evidências de benefício, especialmente no longo prazo, recomendou-se que sejam definidos no PCDT da DF, além dos critérios para uso, critérios de interrupção do tratamento na ausência de benefício clínico. CONSULTA PÚBLICA: A consulta pública nº 56 foi realizada entre os dias 26/12/2023 e 15/01/2024 e recebeu uma contribuição técnico-científica e oito contribuições de experiência e opinião. A contribuição técnico-científica foi emitida pela Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular (ABHH), que se posicionou favoravelmente à incorporação, destacando que a tecnologia irá impactar positivamente a qualidade de vida dos pacientes, possibilitando a redução das transfusões de hemácias e da quelação de ferro, e, consequentemente, reduzindo custos associados às complicações. Especialistas participantes do processo de atualização do PCDT da DF contribuíram apresentado critérios de uso e interrupção do tratamento, tendo em vista as discussões realizadas durante a reunião de apresentação da demanda. Em relação às contribuições recebidas pelo formulário de experiência e opinião, observou-se que em uma delas havia um anexo, o qual, por se tratar de artigo científico, foi encaminhado para ser incorporado à análise das contribuições de natureza técnico-científica. Todas as contribuições concordaram com a recomendação preliminar da Conitec, que foi favorável à incorporação da tecnologia avaliada. A eficácia da tecnologia, a melhora da qualidade de vida e a importância do acesso por meio do SUS foram mencionados como pontos a favor da incorporação. Como resultados positivos e facilidades da tecnologia em avaliação, foram mencionadas a eficácia do medicamento e a importância de estar disponível no SUS. Quanto aos efeitos negativos, ao lado da consideração da inexistência de efeitos negativos, foi mencionada a dificuldade de acesso ao medicamento. RECOMENDAÇÃO FINAL DA CONITEC: Após apreciação das contribuições recebidas na Consulta Pública, os membros do Comitê de Medicamentos presentes na 126ª Reunião Ordinária da Conitec deliberaram, por unanimidade, recomendar a incorporação da alfaepoetina para o tratamento de pacientes com doença falciforme apresentando declínio da função renal e piora dos níveis de hemoglobina conforme Protocolo Clínico do Ministério da Saúde. Foi assinado o Registro de Deliberação nº 871/2024. DECISÃO: incorporar, no âmbito do Sistema Único de Saúde - SUS, a alfaepoetina para o tratamento de pacientes com doença falciforme apresentando declínio da função renal e piora dos níveis de hemoglobina, conforme Protocolo Clínico do Ministério da Saúde, publicada no Diário Oficial da União, nº 66, seção 1, página 109, em 05 de abril de 2024.

The high-volume haemodiafiltration vs high-flux haemodialysis registry trial (H4RT): a multi-centre, unblinded, randomised, parallel-group, superiority study to compare the effectiveness and cost-effectiveness of high-volume haemodiafiltration and high-flux haemodialysis in people with kidney failure on maintenance dialysis using linkage to routine healthcare databases for outcomes.

BACKGROUND: More than a third of the 65,000 people living with kidney failure in the UK attend a dialysis unit 2-5 times a week to have their blood cleaned for 3-5 h. In haemodialysis (HD), toxins are removed by diffusion, which can be enhanced using a high-flux dialyser. This can be augmented with convection, as occurs in haemodiafiltration (HDF), and improved outcomes have been reported in people who are able to achieve high volumes of convection. This study compares the clinical- and cost-effectiveness of high-volume HDF compared with high-flux HD in the treatment of kidney failure. METHODS: This is a UK-based, multi-centre, non-blinded randomised controlled trial. Adult patients already receiving HD or HDF will be randomised 1:1 to high-volume HDF (aiming for 21+ L of substitution fluid adjusted for body surface area) or high-flux HD. Exclusion criteria include lack of capacity to consent, life expectancy less than 3 months, on HD/HDF for less than 4 weeks, planned living kidney donor transplant or home dialysis scheduled within 3 months, prior intolerance of HDF and not suitable for high-volume HDF for other clinical reasons. The primary outcome is a composite of non-cancer mortality or hospital admission with a cardiovascular event or infection during follow-up (minimum 32 months, maximum 91 months) determined from routine data. Secondary outcomes include all-cause mortality, cardiovascular- and infection-related morbidity and mortality, health-related quality of life, cost-effectiveness and environmental impact. Baseline data will be collected by research personnel on-site. Follow-up data will be collected by linkage to routine healthcare databases - Hospital Episode Statistics, Civil Registration, Public Health England and the UK Renal Registry (UKRR) in England, and equivalent databases in Scotland and Wales, as necessary - and centrally administered patient-completed questionnaires. In addition, research personnel on-site will monitor for adverse events and collect data on adherence to the protocol (monthly during recruitment and quarterly during follow-up). DISCUSSION: This study will provide evidence of the effectiveness and cost-effectiveness of HD as compared to HDF for adults with kidney failure in-centre HD or HDF. It will inform management for this patient group in the UK and internationally. TRIAL REGISTRATION: ISRCTN10997319 . Registered on 10 October 2017.

Burden of kidney failure from atheroembolic disease and association with survival in people receiving dialysis in Australia and New Zealand: a multi-centre registry study.

BACKGROUND: Cardiovascular disease is a leading cause of mortality in kidney failure (KF). Patients with KF from atheroembolic disease are at higher risk of cardiovascular disease than other causes of KF. This study aimed to determine survival on dialysis for patients with KF from atheroembolic disease compared with other causes of KF. METHODS: All adults (≥ 18 years) with KF initiating dialysis as the first kidney replacement therapy between 1 January 1990 and 31 December 2017 according to the Australia and New Zealand Dialysis and Transplant registry were included. Patients were grouped into either: KF from atheroembolic disease and all other causes of KF. Survival outcomes were assessed by the Kaplan-Meier method and Cox regression analysis adjusted for patient-related characteristics. RESULTS: Among 65,266 people on dialysis during the study period, 334 (0.5%) patients had KF from atheroembolic disease. A decreasing annual incidence of KF from atheroembolic disease was observed from 2008 onwards. Individuals with KF from atheroembolic disease demonstrated worse survival on dialysis compared to those with other causes of KF (HR 1.80, 95% confidence interval [CI] 1.61-2.03). The respective one- and five-year survival rates were 77 and 23% for KF from atheroembolic disease and 88 and 47% for other causes of KF. After adjustment for patient characteristics, KF from atheroembolic disease was not associated with increased patient mortality (adjusted HR 0.93 95% CI 0.82-1.05). CONCLUSIONS: Survival outcomes on dialysis are worse for individuals with KF from atheroembolic disease compared to those with other causes of KF, probably due to patient demographics and higher comorbidity.

Assessment of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker on the split renal function in the patients with primary hypertension.

ABSTRACT: Bilateral kidney damage in hypertensive patients is not parallel. Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), as a commonly used antihypertensive drug, could protect kidney function and delay its deterioration. Most studies focused on overall renal function, but the researches on split renal function (SRF) are rare. We investigated the effects of ACEI/ARB on the SRF in patients with primary hypertension.Patients with primary hypertension (n = 429; male: 213; female: 216) admitted to our department between January 2014 and December 2016 were included in this study. The glomerular filtration rate (GFR) of split and total renal function were determined using diethylenetriaminepentaacetic acid tagged with 99mTc renal dynamic imaging method. For the same patient, the side with high GFR was considered as higher GFR kidney, whereas that with a low GFR was considered as lower GFR kidney. The split function score (Q value) was utilized to evaluate the differences of bilateral renal function. The patients were divided into 3 groups based on the Q values (Group 1, Q value <5%; Group 2, Q value of 5%-10%; Group 3, Q value ≥10%). All the patients received antihypertensive therapy based on ACEI/ARB. The renal dynamic imaging was performed in the 1-year follow-up to investigate the changes of the SRF.Compared with the baseline level, significant decline was noticed in the serum creatinine (Scr) in Group 2 and Group 3 (P < .05). The cystatin C in Group 3 showed significant decline (P < .05). Compared with the baseline, there was significant decline in the Q value in Group 2, whereas the GFR of lower GFR kidney showed significant increase (P < .05). No statistical differences were noticed in the Q value and split GFR in Group 1 and Group 3 (P > .05).In primary hypertension patients, ACEI/ARB therapy could improve the SRF of lower GFR kidney in the presence of certain differences between the SRF. As a result, the SRF difference was reduced. In case of Q value in a range of 5% to 10%, ACEI/ARB could improve the renal function effectively. It may be significant for the design of antihypertensive drugs.

Medicaid Expansion and Incidence of Kidney Failure among Nonelderly Adults.

BACKGROUND: Low-income individuals without health insurance have limited access to health care. Medicaid expansions may reduce kidney failure incidence by improving access to chronic disease care. METHODS: Using a difference-in-differences analysis, we examined the association between Medicaid expansion status under the Affordable Care Act (ACA) and the kidney failure incidence rate among all nonelderly adults, aged 19-64 years, in the United States, from 2012 through 2018. We compared changes in kidney failure incidence in states that implemented Medicaid expansions with concurrent changes in nonexpansion states during pre-expansion, early postexpansion (years 2 and 3 postexpansion), and later postexpansion (years 4 and 5 postexpansion). RESULTS: The unadjusted kidney failure incidence rate increased in the early years of the study period in both expansion and nonexpansion states before stabilizing. After adjustment for population sociodemographic characteristics, Medicaid expansion status was associated with 2.20 fewer incident cases of kidney failure per million adults per quarter in the early postexpansion period (95% CI, -3.89 to -0.51) compared with nonexpansion status, a 3.07% relative reduction (95% CI, -5.43% to -0.72%). In the later postexpansion period, Medicaid expansion status was not associated with a statistically significant change in kidney failure incidence (-0.56 cases per million per quarter; 95% CI, -2.71 to 1.58) compared with nonexpansion status and the pre-expansion time period. CONCLUSIONS: The ACA Medicaid expansion was associated with an initial reduction in kidney failure incidence among the entire, nonelderly, adult population in the United States; but the changes did not persist in the later postexpansion period. Further study is needed to determine the long-term association between Medicaid expansion and changes in kidney failure incidence.

Multiple Myeloma in Hispanics: Incidence, Characteristics, Survival, Results of Discovery, and Validation Using Real-World and Connect MM Registry Data.

BACKGROUND: Multiple myeloma (MM) in Hispanics has never been studied. We therefore sought to determine the clinical characteristics and overall survival in MM of Hispanics compared to non-Hispanic whites (NHW) and non-Hispanic blacks (NHB). PATIENTS AND METHODS: A single-center analysis of 939 patients diagnosed with MM from 2000 to 2017 with a large representation of NHB (n = 489), Hispanics (n = 281), and NHW (n = 169) was conducted to evaluate outcomes and disease characteristics. We used the Connect MM Registry, a large US multicenter prospective observational study with newly diagnosed MM patients, as a validation cohort. RESULTS: Hispanics had a higher incidence of MM compared to NHW. The median age at presentation was 5 years younger (median, 65 years) in Hispanics compared to NHW (median, 70 years), and patients were more likely to present with renal dysfunction (estimated glomerular filtration rate < 30 mL/min). Hispanics had a higher proportion of Revised International Staging System (R-ISS) stage I disease compared to NHW and NHB (P = .03), while there was no difference in cytogenetics between Hispanics and NHB/NHW. In the multivariate analysis, only high-risk disease and response to first-line therapy significantly affected survival. CONCLUSION: In this first and largest analysis of MM in Hispanics, we found that Hispanics present at a younger age, have a higher incidence of renal dysfunction, and have low R-ISS stage disease at presentation. With equal access to therapy, Hispanics have survival similar to NHW/NHB.

Maintaining Equity and Access: Successful Implementation of a Virtual Kidney Transplantation Evaluation.

BACKGROUND: Maintaining access to kidney transplantation during a pandemic is a challenge, particularly for centers that serve a large rural and minority patient population with an additional burden of travel. The aim of this article was to describe our experience with the rollout and use of a virtual pretransplantation evaluation platform to facilitate ongoing transplant waitlisting during the early peak of the COVID-19 pandemic. STUDY DESIGN: This is a retrospective analysis of the process improvement project implemented to continue the evaluation of potential kidney transplantation candidates and ensure waitlist placement during the COVID-19 pandemic. Operational metrics include transplantation volume per month, referral volume per month, pretransplantation patients halted before completing an evaluation per month, evaluations completed per month, and patients waitlisted per month. RESULTS: Between April and September 2020, a total of 1,258 patients completed an evaluation. Two hundred and forty-seven patients were halted during this time period before completing a full evaluation. One hundred and fifty-two patients were presented at selection and 113 were placed on the waitlist. In addition, the number of patients in the active referral phase was able to be reduced by 46%. More evaluations were completed within the virtual platform (n = 930 vs n = 880), yielding similar additions to the waitlist in 2020 (n = 282) vs 2019 (n = 308) despite the COVID-19 pandemic. CONCLUSIONS: The virtual platform allowed continued maintenance of a large kidney transplantation program despite the inability to have in-person visits. The value of this platform will likely transform our approach to the pretransplantation process and provides an additional valuable method to improve patient equity and access to transplantation.

Budget impact analysis for dapagliflozin in type 2 diabetes in Egypt.

Introduction: Type 2 diabetes mellitus (T2DM) is a major health problem in Egypt with a high impact on morbidity, mortality, and healthcare resources. This study evaluated the budget impact and the long-term consequences of dapagliflozin versus other conventional medications, as monotherapy, from both the societal and health insurance perspectives in Egypt.Methods: A static budget impact model was developed to estimate the financial consequences of adopting dapagliflozin on the healthcare payer budget. We measured the direct medical costs of dapagliflozin (new scenario) as monotherapy, compared to metformin, insulin, sulphonylurea, dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinedione, and repaglinide (old scenarios) over a time horizon of 3 years. Myocardial infarction (MI), ischemic stroke, hospitalization for heart failure (HHF), and initiation of renal replacement therapy (RRT) rates were captured from DECLARE TIMI 58 trial. One-way sensitivity analyses were conducted.Results: The budget impact model estimated 2,053,908 patients eligible for treatment with dapagliflozin from a societal perspective and 1,207,698 patients from the health insurance (HI) perspective. The new scenario allows for an initial savings of EGP121 million in the first year, which increased to EGP243 and EGP365 million in the second and third years, respectively. The total cumulative savings from a societal perspective were estimated at EGP731 million. Dapagliflozin allows for savings of EGP71, EGP143, and EGP215 million in the first, second and third years respectively, from the HI perspective, with total cumulative savings of EGP430 million over the 3 years.Conclusion: Treating T2DM patients using dapagliflozin instead of conventional medications, maximizes patients' benefits and decreases total costs due to drug cost offsets from fewer cardiovascular and renal events. The adoption of dapagliflozin is a budget-saving treatment option, resulting in substantial population-level health gains due to reduced event rate and cost savings from the perspective of the national healthcare system.

Sex-Specific Management in Patients With Acute Myocardial Infarction and Cardiogenic Shock: A Substudy of the CULPRIT-SHOCK Trial.

BACKGROUND: Women are more likely to suffer and die from cardiogenic shock (CS) as the most severe complication of acute myocardial infarction. Data concerning optimal management for women with CS are scarce. Aim of this study was to better define characteristics of women experiencing CS and to the influence of sex on different treatment strategies. METHODS: In the CULPRIT-SHOCK trial (The Culprit Lesion Only PCI Versus Multivessel PCI in Cardiogenic Shock), patients with CS complicating acute myocardial infarction and multivessel coronary artery disease were randomly assigned to one of the following revascularization strategies: either percutaneous coronary intervention of the culprit-lesion-only or immediate multivessel percutaneous coronary intervention. Primary end point was composite of death from any cause or severe renal failure leading to renal replacement therapy within 30 days. We investigated sex-specific differences in general and according to the revascularization strategies. RESULTS: Among all 686 randomized patients included in the analysis, 24% were women. Women were older and had more often diabetes mellitus and renal insufficiency, whereas they had less often history of previous acute myocardial infarction and smoking. After 30 days, the primary clinical end point was not significantly different between groups (56% women versus 49% men; odds ratio, 1.29 [95% CI, 0.91-1.84]; P=0.15). There was no interaction between sex and coronary revascularization strategy regarding mortality and renal failure (Pinteraction=0.11). The primary end point occurred in 56% of women treated by the culprit-lesion-only strategy versus 42% men, whereas 55% of women and 55% of men in the multivessel percutaneous coronary intervention group. CONCLUSIONS: Although women presented with a different risk profile, mortality and renal replacement were similar to men. Sex did not influence mortality and renal failure according to the different coronary revascularization strategies. Based on these data, women and men presenting with CS complicating acute myocardial infarction and multivessel coronary artery disease should not be treated differently. However, further randomized trials powered to address potential sex-specific differences in CS are still necessary. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01927549.

[Renal failure in the medicolegal evaluation of civil invalidity and social security disability (INPS)].

After a quick description of the anatomopathology and physiopathology of renal failure, the Authors delve into the problem of assessing its medicolegal aspects in the fields of civil invalidity and social security. In Italy, civil invalidity involves protecting the psychological and physical welfare of the disabled, as sanctioned by law 118 of 1971; this law protects all citizens with a debilitating condition, including those who do not work or are not of working age. A disabled person is someone who, if of working age (between 18 and retirement) has a reduction of more than ⅓ (34%) of their general work capacity; if under or over the retirement age, they have a persistent difficulty in carrying out age-appropriate functions and tasks. In support of an application for being awarded civil invalidity, people can also refer to law no. 104 of 1992, which assesses social, relational and work disadvantages of a disabled person. INPS (Italian Social Security Institute) protection, on the other hand, is a social security protection based on health requirements (having a capacity for work which is reduced by more than ⅓, as established by law no. 222 of 1984), as well as on the following administrative requirement: having paid, as a worker, at least 260 weekly contributions, equivalent to five years of contribution and insurance, of which 156, equal to three years of contribution and insurance, were made in the five-year period preceding the date of submitting the application. If this is the case, the protected person, thus insured, can enjoy protection for their illness by virtue of the stipulations for social security.

Current Status of Simultaneous Liver-Kidney Transplantation in the United States.

On August 10, 2017, a formal policy was enacted in the United States that defined listing criteria for simultaneous liver-kidney transplantation and priority for patients who received a liver transplantation (LT) and subsequently developed significant kidney disease after LT. This article reviews and summarizes the rationale for such policies, the policies themselves, and the potential impact on LT candidates.

Assessment of postoperative renal function after adrenalectomy in patients with primary aldosteronism.

OBJECTIVE: To investigate kidney function change during adrenalectomy in patients with primary aldosteronism and assess predictors of kidney function decline. METHODS: The present study included 90 patients who underwent adrenalectomy for primary aldosteronism between 2004 and 2017. Kidney function was evaluated 1 month after surgery. Predictors associated with a ≥10% decline in the estimated glomerular filtration rate were investigated. Kidney parenchymal volume was compared before and after surgery in 10 patients using volumetric studies. RESULTS: The mean estimated glomerular filtration rate decline in the total cohort at 1 month after surgery was 13.3% (before: 72.9 mL/min/1.73 m2 , after: 64.9 mL/min/1.73 m2 , P < 0.0001). The mean serum plasma aldosterone concentration (before: 373 pg/mL vs after: 78 pg/mL, P < 0.0001) and potassium level (before: 3.7 mEq/L vs after: 3.9 mEq/L, P = 0.0001) were also significantly different after surgery. Age (odds ratio 6.37, P = 0.0006), preoperative plasma aldosterone concentration (odds ratio 3.12, P = 0.0209) and preoperative serum potassium level (odds ratio 2.87, P = 0.0010) were independent predictors of a ≥10% decline in estimated glomerular filtration rate. Volumetric studies in 10 patients showed that mean postoperative parenchymal volume was significantly decreased compared with the preoperative volume (263 cc vs 312 cc, P = 0.0003), with decreases in estimated glomerular filtration rate from 63 to 56 mL/min/1.73 m2 (P = 0.0146). CONCLUSIONS: Kidney function deterioration after adrenalectomy can be detected in patients with primary aldosteronism. Age, preoperative plasma aldosterone concentration and preoperative potassium level are significant predictors of a decrease in the estimated glomerular filtration rate. Normal parenchymal volume decreases in line with renal functional deterioration.

Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate.

Patients with chronic kidney disease and severely decreased glomerular filtration rate (GFR) are at high risk for kidney failure, cardiovascular disease (CVD) and death. Accurate estimates of risk and timing of these clinical outcomes could guide patient counseling and therapy. Therefore, we developed models using data of 264,296 individuals in 30 countries participating in the international Chronic Kidney Disease Prognosis Consortium with estimated GFR (eGFR)s under 30 ml/min/1.73m2. Median participant eGFR and urine albumin-to-creatinine ratio were 24 ml/min/1.73m2 and 168 mg/g, respectively. Using competing-risk regression, random-effect meta-analysis, and Markov processes with Monte Carlo simulations, we developed two- and four-year models of the probability and timing of kidney failure requiring kidney replacement therapy (KRT), a non-fatal CVD event, and death according to age, sex, race, eGFR, albumin-to-creatinine ratio, systolic blood pressure, smoking status, diabetes mellitus, and history of CVD. Hypothetically applied to a 60-year-old white male with a history of CVD, a systolic blood pressure of 140 mmHg, an eGFR of 25 ml/min/1.73m2 and a urine albumin-to-creatinine ratio of 1000 mg/g, the four-year model predicted a 17% chance of survival after KRT, a 17% chance of survival after a CVD event, a 4% chance of survival after both, and a 28% chance of death (9% as a first event, and 19% after another CVD event or KRT). Risk predictions for KRT showed good overall agreement with the published kidney failure risk equation, and both models were well calibrated with observed risk. Thus, commonly-measured clinical characteristics can predict the timing and occurrence of clinical outcomes in patients with severely decreased GFR.

Assessment of Glomerular Filtration Rate and End-Stage Kidney Disease Risk in Living Kidney Donor Candidates: A Paradigm for Evaluation, Selection, and Counseling.

Living donor kidney transplantation is the preferred treatment option for ESRD. However, recent data suggest a small increase in the long-term risk of kidney failure in living kidney donors when compared to healthy nondonors. These data have led to a need for reconsideration of how donor candidates are evaluated and selected for donation. A Kidney Disease: Improving Global Outcomes (KDIGO) work group completed a comprehensive clinical practice guideline for evaluation of living kidney donor candidates in 2017, based on systematic evidence review, de novo evidence generation, and expert opinion. Central to the evaluation framework is assessment of glomerular filtration rate (GFR), which is used to screen for kidney disease and aid the prediction of long-term kidney failure risk after donation. Accurate estimation of the level of GFR and risk of kidney failure, and communication of estimated risks, can support evidence-based donor selection and shared decision-making. In this review, we discuss approaches to optimal GFR estimation in the donor evaluation process, long-term risk projection, and risk communication to donor candidates, integrating recommendations from the new KDIGO guideline, other recent literature, and experience from our own research and practice. We conclude by highlighting topics for further research in this important area of transplant medicine.

Comparison of Endovascular Stent Grafts for Abdominal Aortic Aneurysm Repair in Medicare Beneficiaries.

BACKGROUND: Increased renal complications have been suggested with suprarenal stent grafts, but long-term analyses have been limited. Therefore, the purpose of this study was to evaluate the effect of endograft choice on perioperative and long-term outcomes. METHODS: We compared Medicare beneficiaries undergoing endovascular abdominal aortic aneurysms repair from 2005 to 2008 with endografts with infrarenal fixation and a single docking limb (AneuRx, Excluder) to those with suprarenal fixation and 2 docking limbs (Zenith), or a unibody configuration (Powerlink). Propensity score weighting accounted for differences in patient characteristics among the different graft formations, and perioperative mortality, complications, and length of stay and 4-year rates of survival, rupture, and reintervention were compared. RESULTS: Forty-six thousand one hundred seventy-one Medicare beneficiaries were identified including 11,002 (24%) with suprarenal fixation, 32,909 (71%) with infrarenal fixation, and 2,260 (5%) with a unibody graft. After propensity score weighting, there were no significant differences in patients' baseline clinical and demographic characteristics. The suprarenal fixation patients had higher rates of perioperative mortality (1.7% vs. 1.3%, P < 0.01), renal failure (6.0% vs. 4.7%, P < 0.001), and mesenteric ischemia (0.7% vs. 0.4%, P < 0.01) and longer length of stay (3.4 days vs. 3.0 days, P < 0.001) compared with patients with infrarenal fixation. Unibody grafts had higher rates of renal failure (5.9% vs. 4.7%, P < 0.001), mesenteric ischemia (1.0% vs. 0.4%, P < 0.001), and conversion to open repair (0.7% vs. 0.1%, P < 0.001) compared to those with infrarenal fixation and single docking limbs. At 4 years, mortality remained slightly higher with suprarenal compared to infrarenal fixation (30% vs. 29%, P = 0.047), although these patients had fewer conversions to open repair (0.6% vs. 0.9%, P = 0.03) and aneurysm-related reinterventions (10% vs. 12%, P < 0.01). At 4 years, unibody grafts had more aneurysm-related interventions compared to infrarenal fixation grafts (15% vs. 12%, P < 0.01) but fewer conversions to open repair (0.4% vs. 0.9%, P = 0.02). Late rupture did not differ among the groups. CONCLUSIONS: Compared to infrarenal fixation devices, patients who underwent EVAR with suprarenal fixation had higher perioperative mortality and renal complications but fewer reinterventions including conversion, while the unibody graft had more perioperative complications and aneurysm-related reinterventions, but fewer conversions to open repair. Although these differences could be explained by selection bias, these data suggest that further comparative effectiveness analyses should be performed to understand the outcomes following EVAR with suprarenal fixation and unibody grafts.

High prevalence of diabetes in patients with rheumatoid arthritis: results from a questionnaire survey linked to claims data.

Objectives: To investigate the prevalence of diabetes in patients with RA and the impact of diabetes on self-reported outcomes and health care. Methods: RA patients between the ages of 18 and 79 years were randomly selected from a nationwide statutory health insurance fund and were surveyed about rheumatological care and disease burden. Comorbid diabetes (E10-14) was analysed regarding age, sex, BMI and socioeconomic status. Disease burden, comorbidity and prescriptions were compared in RA patients with and without diabetes. Predictors of rheumatological care were identified by multivariate regression. Results: Of the 2535 RA patients, 498 (20%) had diabetes. Diabetes was more frequent in males, in older patients, in patients with a higher BMI and in those with a lower socioeconomic status. All disease outcomes were poorer in RA-diabetes patients and were mainly attributable to a higher BMI. RA-diabetes patients received less DMARDs (40% vs 48%) and had more hospital stays (41% vs 30%) than patients without diabetes (all P < 0.05). Rates of cardiovascular disease (35% vs 15%), depression (39% vs 26%) and renal failure (23% vs 8%) were higher in RA-diabetes patients (all P < 0.0001). They were less frequently treated by rheumatology specialists: 57% vs 67%; odds ratio = 0.64 (95% CI: 0.45, 0.92), after controlling for confounders. Conclusion: The prevalence of diabetes in patients with RA is high and is associated with known sociodemographic factors. More than 40% of patients with RA and diabetes were not under rheumatological care even though they reported a high disease burden, were frequently hospitalized and often presented with further comorbidities.

Five-Year Outcomes after Off-Pump or On-Pump Coronary-Artery Bypass Grafting.

BACKGROUND: We previously reported that there was no significant difference at 30 days or at 1 year in the rate of the composite outcome of death, stroke, myocardial infarction, or renal failure between patients who underwent coronary-artery bypass grafting (CABG) performed with a beating-heart technique (off-pump) and those who underwent CABG performed with cardiopulmonary bypass (on-pump). We now report the results at 5 years (the end of the trial). METHODS: A total of 4752 patients (from 19 countries) who had coronary artery disease were randomly assigned to undergo off-pump or on-pump CABG. For this report, we analyzed a composite outcome of death, stroke, myocardial infarction, renal failure, or repeat coronary revascularization (either CABG or percutaneous coronary intervention). The mean follow-up period was 4.8 years. RESULTS: There were no significant differences between the off-pump group and the on-pump group in the rate of the composite outcome (23.1% and 23.6%, respectively; hazard ratio with off-pump CABG, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P=0.72) or in the rates of the components of the outcome, including repeat coronary revascularization, which was performed in 2.8% of the patients in the off-pump group and in 2.3% of the patients in the on-pump group (hazard ratio, 1.21; 95% CI, 0.85 to 1.73; P=0.29). The secondary outcome for the overall period of the trial - the mean cost in U.S. dollars per patient - also did not differ significantly between the off-pump group and the on-pump group ($15,107 and $14,992, respectively; between-group difference, $115; 95% CI, -$697 to $927). There were no significant between-group differences in quality-of-life measures. CONCLUSIONS: In our trial, the rate of the composite outcome of death, stroke, myocardial infarction, renal failure, or repeat revascularization at 5 years of follow-up was similar among patients who underwent off-pump CABG and those who underwent on-pump CABG. (Funded by the Canadian Institutes of Health Research; CORONARY ClinicalTrials.gov number, NCT00463294 .).

Cost of nosocomial pneumonia: the example of vancomycin versus linezolid-shorter stay or fewer complications?

Hospital and national committees often focus on drug acquisition costs when taking decisions on the use of new drugs, but antimicrobial agent costs represent a minor part of the bill compared with the indirect costs of hospitalization or loss in days of productivity in working people. Although reducing the length of stay should be a main priority in the USA due to the indirect costs associated with hospitalization, adverse events, such as renal failure, have a major impact on healthcare resource use and costs. However, where hospital reimbursement is based on closed budgets, the paradox is that treating more patients due to reductions in length of stay may not be attractive to administrators, because the cost of discharging patients earlier is not compensated by the increase in severity in replacing stays of newer patient admissions. Furthermore, neuropsychological, physical, and immune impairment caused by sepsis has an extreme impact on long-term quality of patient life and health care resource consumption. Future research is warranted to further explore the potential impact of newer therapies for infections and sepsis, taking into account the costs of complications, effects on long-term quality of life, and particularly an international perspective, which requires customization for each national payer's system.

Cumulative Effects of Several Target Organ Damages in Risk Assessment in Hypertension.

BACKGROUND: The prognostic value of screening multiple target organ damages (TODs) in hypertensive subjects has not been extensively studied. We estimated the prognostic value of considering 3 TODs in estimating the 10-year survival in hypertensive subjects. METHODS: At baseline 1,848 out of a cohort of 1,963 hypertensive patients had a previous cardiovascular disease (CVD) or assessments of 3 TODs: Modification in Diet in Renal Disease (MDRD) <60ml/min or albuminuria >300mg/day, Sokolow index >3.5 mV, and advanced hypertensive retinopathy (grades 3 and 4 of Keith-Wagener-Barker classification). The cohort was divided into 5 groups: 0 TOD (N = 978), 1 TOD (N = 308), 2 TODs (N = 94), 3 TODs (N = 30), and previous CVD (N = 438). RESULTS: After 10 years of follow-up, we observed 418 deaths of which 254 from cardiovascular cause. The adjusted hazard ratios for the major cardiovascular risk factors showed a progressive risk associated with the number of TODs. For all-cause death, the hazard ratios [95% confidence intervals] vs. 0 TOD of the other 4 groups were 1.91 [1.39-2.63], 1.99 [1.28-3.10], 4.33 [2.42-7.72], and 3.09 [2.35-4.05], respectively. For cardiovascular death, the hazard ratios [95% confidence intervals] were of the same order of magnitude: 2.14 [1.38-3.32], 2.12 [1.15-3.89], 4.22 [1.83-9.72], and 4.24 [2.95-6.11], respectively. CONCLUSIONS: Our results indicate that hypertensive patients with several TODs had a worst outcome. Thus, it seems important to screen for multiple TODs in hypertension; especially check for severe hypertensive retinopathy in patients with left ventricular hypertrophy (LVH) and renal damage.