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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 (nâ =â 1123), a decrease in the number of patients on the waiting list (nâ =â 815), and decrease in mortality (nâ =â 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: 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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Suero Antilinfocítico , Trasplante de Riñón , Humanos , Niño , Basiliximab/uso terapéutico , Suero Antilinfocítico/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Prednisona/uso terapéutico , Estudios Retrospectivos , Estudios de Cohortes , Azatioprina , Quimioterapia de Inducción , Rechazo de Injerto/prevención & control , Rechazo de Injerto/epidemiología , Inmunosupresores/uso terapéutico , Proteínas Recombinantes de Fusión/uso terapéutico , Receptores de TrasplantesRESUMEN
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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Diabetes Mellitus Tipo 1 , Trasplante de Riñón , Trasplante de Páncreas , Humanos , Diabetes Mellitus Tipo 1/cirugía , Estudios Retrospectivos , Trasplante de Páncreas/métodos , Medición de Riesgo , Páncreas , Supervivencia de InjertoRESUMEN
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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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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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.
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ABSTRACT Introduction: The clinical impact of vascular calcification is well established in the context of cardiovascular morbidity and mortality, but other clinical syndromes, such as calciphylaxis, although less frequent, have a significant impact on chronic kidney disease. Methods: Case report of a 27-year-old woman, who had complained of bilateral pain in her toes for 3 days, with the presence of small necrotic areas in the referred sites. She had a history of type 1 diabetes (25 years ago), with chronic kidney disease, on peritoneal dialysis, in addition to rheumatoid arthritis. She was admitted to the hospital, which preceded the current condition, due to exacerbation of rheumatoid arthritis, evolving with intracardiac thrombus due to venous catheter complications, when she started using warfarin. Ischemia progressed to her feet, causing the need for bilateral amputations. Her chirodactyls were also affected. Thrombophilia, vasculitis, endocarditis or other embolic sources were investigated and discarded. Her pathology report evidenced skin necrosis and superficial soft parts with recent arterial thrombosis, and Monckeberg's medial calcification. We started treatment with bisphosphonate and sodium thiosulfate, conversion to hemodialysis and replacement of warfarin with unfractionated heparin. Despite all the therapy, the patient died after four months of evolution. Discussion: Calciphylaxis is a rare microvasculature calcification syndrome that results in severe ischemic injuries. It has pathogenesis related to the mineral and bone disorder of chronic kidney disease combined with the imbalance between promoters and inhibitors of vascular calcification, with particular importance to vitamin K antagonism. Conclusion: The preventive strategy is fundamental, since the therapy is complex with poorly validated effectiveness.
RESUMO Introdução: O impacto clínico da calcificação vascular está bem estabelecido no âmbito de morbimortalidade cardiovascular, mas outras síndromes clínicas, como a calcifilaxia, apesar de menos frequente, têm significante impacto na doença renal crônica. Métodos: Relato de caso de mulher, 27 anos, com queixa de dor em pododáctilos bilateralmente havia 3 dias, com presença de pequenas áreas necróticas nos locais referidos. Antecedente pessoal de diabetes tipo 1 (há 25 anos), com doença renal crônica, em diálise peritoneal, além de artrite reumatoide. Teve internação hospitalar, que antecedeu o quadro atual, devido à exacerbação da artrite reumatoide, evoluindo com trombo intracardíaco por complicação de cateter venoso, quando iniciou uso de varfarina. A isquemia progrediu para pés com necessidade de amputações bilaterais. Quirodáctilos também foram acometidos. Trombofilias, vasculites, endocardite ou outras fontes emboligênicas foram pesquisadas e descartadas. Anatomopatológico evidenciou: necrose de pele e partes moles superficiais com trombose arterial recente e calcificação medial de Monckeberg. Tratamento foi instituído com bisfosfonato e tiossulfato de sódio, conversão para hemodiálise e substituição de varfarina por heparina não fracionada. Apesar de toda a terapia, a paciente foi a óbito após quatro meses de evolução. Discussão: A calcifilaxia é uma rara síndrome de calcificação da microvasculatura que resulta em graves lesões isquêmicas. Tem patogênese relacionada ao distúrbio mineral e ósseo da doença renal crônica combinado com o desbalanço entre promotores e inibidores de calcificação vascular, com particular importância ao antagonismo da vitamina K. Conclusão: A estratégia preventiva é fundamental, uma vez que a terapia é complexa e de eficácia pouco validada.
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Humanos , Femenino , Adulto , Calcifilaxia/complicaciones , Fallo Renal Crónico , Heparina , Diálisis , Extremidades , NecrosisRESUMEN
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.
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Humanos , Trasplante de Riñón , COVID-19 , Donadores Vivos , Pandemias , SARS-CoV-2RESUMEN
Abstract Introduction: Infectious complications are common in systemic lupus erythematosus. Although uncommon, central nervous system infections do occur and have significant lethality, with several etiological agents. Methods: We report on the case of a 29-year-old woman recently diagnosed with systemic lupus erythematosus with hematological, cutaneous, serous and renal manifestations (class IV lupus nephritis), who underwent corticosteroid pulse therapy and mycophenolate induction therapy. After 3 months of evolution, she developed headache and altered mental status. Computed tomography showed an area of hypoattenuation in the left frontal white matter and her cerebrospinal fluid examination showed pleocytosis and hyperproteinorrhachia. Peripheral blood and CSF culture identified Listeria monocytogenes. The patient presented deterioration of her neurological status, requiring invasive mechanical ventilation, monitoring of intracranial pressure and, despite all the intensive support, persisted in a comatose state and developed multiple organ failure, evolving to death due to nosocomial bloodstream infection. Discussion: Infection from L. monocytogenes usually occurs after eating contaminated food, manifesting itself with diarrhea and, occasionally, invasively, such as neurolisteriosis. Further investigation with CSF analysis and MRI is necessary, and the diagnosis consists of isolating the bacteria in sterile body fluid. Conclusion: The case presents a patient whose diagnosis of meningoencephalitis became an important differential with neuropsychiatric disorder. The poor outcome reinforces the need to remember this infectious condition as a serious complication in the natural history of SLE.
Resumo Introdução: As complicações infecciosas são frequentes no lúpus eritematoso sistêmico. Apesar de incomum, infecções do sistema nervoso central ocorrem e têm significativa letalidade, apresentando diversos agentes etiológicos. Métodos: Descrevemos aqui o caso de uma mulher de 29 anos recentemente diagnosticada com lúpus eritematoso sistêmico com manifestações hematológica, cutânea, serosa e renal (nefrite lúpica classe IV), submetida a pulsoterapia com corticoide e terapia de indução com micofenolato. Após 3 meses de evolução, apresentou quadro de cefaleia e alteração de estado mental. Tomografia computadorizada evidenciou área de hipoatenuação em substância branca frontal esquerda e exame de líquido cefalorraquidiano mostrava pleocitose e hiperproteinorraquia. Cultura de sangue periférico e do liquor identificaram Listeria monocytogenes. Paciente apresentou deterioração do quadro neurológico, necessitando de ventilação mecânica invasiva, monitorização de pressão intracraniana e, apesar de todo o suporte intensivo, persistiu em estado comatoso e disfunção de múltiplos órgãos, evoluindo a óbito por infecção de corrente sanguínea nosocomial. Discussão: Infecção por L. monocytogenes ocorre geralmente após ingestão de alimentos contaminados, manifestando-se por diarreia e, eventualmente, de forma invasiva como a neurolisteriose. Investigação complementar com análise de liquor e ressonância magnética faz-se necessária, sendo o diagnóstico confirmado por isolamento da bactéria em líquido corporal estéril. Conclusão: O caso representa uma paciente cujo diagnóstico de meningoencefalite tornou-se importante diferencial com atividade de doença neuropsiquiátrica. A evolução insatisfatória reforça a necessidade de se lembrar desta condição infecciosa como complicação grave na história natural do LES.
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Humanos , Femenino , Adulto , Nefritis Lúpica/complicaciones , Listeriosis/complicaciones , Listeria monocytogenes , Lupus Eritematoso Sistémico , Meningoencefalitis/complicaciones , PrednisonaRESUMEN
SUMMARY Acute kidney injury is a very common diagnosis, present in up to 60% of critical patients, and its third main cause is drug toxicity. Nephrotoxicity can be defined as any renal injury caused directly or indirectly by medications, with acute renal failure, tubulopathies, and glomerulopathies as common clinical presentations. Some examples of drugs commonly associated with the acute reduction of glomerular filtration rate are anti-inflammatories, antibiotics, such as vancomycin and aminoglycosides, and chemotherapeutic agents, such as cisplatin and methotrexate. Cases of tubulopathy are very common with amphotericin B, polymyxins, and tenofovir, and cases of glomerulopathies are common with VEGF inhibitors, bisphosphonates, and immunotherapy, and it is also common to have more than one clinical presentation related to a single agent. Early diagnosis is essential for the good evolution of the patient, with a reduction of renal exposure to the toxic agent, which requires knowing the risk factors and biomarkers. General measures such as correcting hydroelectrolytic disorders and hypovolemia, monitoring the serum level, avoiding combinations with the synergy of renal injury, and looking for similar options that are less toxic are the foundations for the treatment of complications that are still common and often preventable.
RESUMO A lesão renal aguda é um diagnóstico muito comum, presente em até 60% dos pacientes críticos, e sua terceira maior causa é a toxicidade de medicamentos. A nefrotoxicidade pode ser definida como qualquer lesão renal causada por medicamentos, direta ou indiretamente, tendo a insuficiência renal aguda, tubulopatias e glomerulopatias como apresentações clínicas comuns. Alguns exemplos de drogas comumente associadas à redução aguda da taxa de filtração glomerular são anti-inflamatórios, antibióticos, como a vancomicina e aminoglicosídeos, e agentes quimioterápicos, tais como cisplatina e metotrexato. Casos de tubulopatia são muito comuns com anfotericina B, polimixinas e tenofovir, já casos de glomerulopatias são comuns com inibidores de VEGF, bisfosfonatos e imunoterapia; também é comum ocorrer mais de uma apresentação clínica relacionada a um único agente. O diagnóstico precoce é essencial para a boa evolução do paciente, com a redução da exposição ao agente tóxico, o que requer conhecimento dos fatores de risco e biomarcadores. Medidas gerais, tais como a correção de distúrbios hidreletrolíticos e da hipovolemia, o monitoramento do nível sérico, evitar combinações com sinergia de lesão renal e procurar opções semelhantes e menos tóxicas são os alicerces do tratamento de complicações que são comuns e, muitas vezes, evitáveis.
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Humanos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Lesión Renal Aguda/inducido químicamente , Factores de Riesgo , Lesión Renal Aguda/epidemiología , Síndrome Nefrótico/inducido químicamente , Síndrome Nefrótico/epidemiologíaRESUMEN
SUMMARY The scenario of infection by the human immunodeficiency virus (HIV) has been undergoing changes in recent years, both in relation to the understanding of HIV infection and regarding the treatments available. As a result, the disease, which before was associated with high morbidity and mortality, is now seen as a chronic disease that can be controlled, regarding both transmission and symptoms. However, even when the virus replication is well controlled, the infected patient remains at high risk of developing renal involvement, either by acute kidney injury not associated with HIV, nephrotoxicity due to antiretroviral drugs, chronic diseases associated with increased survival, or glomerular disease associated to HIV. This review will cover the main aspects of kidney failure associated with HIV.
RESUMO O panorama da infecção pelo vírus da imunodeficiência humana (HIV) vem sofrendo alterações nos últimos anos, tanto em relação ao entendimento da infecção pelo HIV quanto aos tratamentos disponíveis. Como resultado, a doença, que antes estava associada a alta morbimortalidade, é agora considerada uma doença crônica que pode ser controlada, tanto em relação à transmissão quanto aos sintomas. No entanto, mesmo quando a replicação viral é bem controlada, o paciente infectado tem um alto risco de desenvolver complicações renais, seja através de lesão renal aguda não relacionada ao HIV, por nefrotoxicidade causada por drogas antirretrovirais, por doenças crônicas associadas com o aumento da sobrevida ou por doença glomerular associada ao HIV. Esta revisão abordará os principais aspectos da insuficiência renal associada ao HIV.
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Humanos , Infecciones por VIH/complicaciones , Nefropatía Asociada a SIDA/etiología , Lesión Renal Aguda/etiología , Infecciones por VIH/tratamiento farmacológico , Enfermedad Crónica , Factores de Riesgo , Nefropatía Asociada a SIDA/patología , Fármacos Anti-VIH/efectos adversos , Terapia Antirretroviral Altamente Activa/efectos adversos , Lesión Renal Aguda/patología , Tenofovir/efectos adversos , Sulfato de Atazanavir/efectos adversos , Riñón/patologíaRESUMEN
SUMMARY Fabry disease (FD) is a recessive monogenic inheritance disease linked to chromosome X, secondary to mutations in the GLA gene. Its prevalence is estimated between 1:8,454 and 1:117,000 among males and is probably underdiagnosed. Mutations in the GLA gene lead to the progressive accumulation of globotriaosylceramide (Gb3). Gb3 accumulates in lysosomes of different types of cells of the heart, kidneys, skin, eyes, central nervous system, and gastrointestinal system, and may lead to different clinical scenarios. The onset of symptoms occurs during childhood, with acroparesthesia, heat intolerance, and gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, and neuropathic pain. Subsequently, symptoms related to progressive impairment appear, such as angiokeratomas, cornea verticillata, left ventricular hypertrophy, myocardial fibrosis, proteinuria, and renal insufficiency. The latter being the main cause of death in FD. The gold standard for diagnosis is the genetic analysis in search of mutation, in addition to family history. In homozygous patients, the enzyme activity can also be used. Once the diagnosis is confirmed, the patient and their family should receive genetic counseling. The treatment, in turn, currently focuses mainly on replacing the enzyme that is absent or deficient by means of enzyme replacement therapy, with the purpose of avoiding or removing deposits of Gb3. Chaperones can also be used for the treatment of some cases. It is considered that the specific treatment should be initiated as soon as a diagnosis is obtained, which can change the prognosis of the disease.
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Humanos , Masculino , Femenino , Enfermedad de Fabry/patología , Insuficiencia Renal Crónica/patología , Terapia de Reemplazo Enzimático , Riñón/patología , Trihexosilceramidas , Enfermedad de Fabry/complicaciones , Enfermedad de Fabry/genética , Enfermedad de Fabry/terapia , Insuficiencia Renal Crónica/etiologíaRESUMEN
SUMMARY Type 2 diabetes mellitus is an important public health problem, with a significant impact on cardiovascular morbidity and mortality and an important risk factor for chronic kidney disease. Various hypoglycemic therapies have proved to be beneficial to clinical outcomes, while others have failed to provide an improvement in cardiovascular and renal failure, only reducing blood glucose levels. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, represented by the empagliflozin, dapagliflozin, and canagliflozin, have been showing satisfactory and strong results in several clinical trials, especially regarding the reduction of cardiovascular mortality, reduction of hospitalization due to heart failure, reduction of albuminuria, and long-term maintenance of the glomerular filtration rate. The benefit from SGLT2 inhibitors stems from its main mechanism of action, which occurs in the proximal tubule of the nephron, causing glycosuria, and a consequent increase in natriuresis. This leads to increased sodium intake by the juxtaglomerular apparatus, activating the tubule glomerular-feedback and, finally, reducing intraglomerular hypertension, a frequent physiopathological condition in kidney disease caused by diabetes. In addition, this class of medication presents an appropriate safety profile, and its most frequently reported complication is an increase in the incidence of genital infections. Thus, these hypoglycemic agents gained space in practical recommendations for the management of type 2 diabetes mellitus and should be part of the initial therapeutic approach to provide, in addition to glycemic control, cardiovascular outcomes, and the renoprotection in the long term.
Asunto(s)
Humanos , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Transportador 2 de Sodio-Glucosa/farmacología , Inhibidores del Cotransportador de Sodio-Glucosa 2/farmacología , Hipoglucemiantes/farmacología , Enfermedades Renales/prevención & control , Compuestos de Bencidrilo/uso terapéutico , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/prevención & control , Transportador 2 de Sodio-Glucosa/uso terapéutico , Canagliflozina/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Tasa de Filtración Glomerular , Glucosa/metabolismo , Glucósidos/uso terapéutico , Hipoglucemiantes/uso terapéutico , Riñón/efectos de los fármacos , Riñón/fisiopatología , Riñón/metabolismo , Enfermedades Renales/etiología , Enfermedades Renales/metabolismoRESUMEN
ABSTRACT In 2004, a global spread of Chikungunya fever affected most tropical and subtropical regions of the world. In 2016, an outbreak occurred in Northeast Brazil with hundreds of cases documented. Solid organ transplant recipients have a modified immune response to infection and the clinical course is usually different from immunocompetent patients. The diagnosis can be challenging in this population. Most reports describe patients residing in endemic areas, although we must emphasize the importance of differential diagnosis in kidney transplanted travelers who visit endemic regions, such as Northeast Brazil. Here, we reported a case of a kidney transplant recipient that acquired Chikungunya fever after a trip to an endemic region at Northeast Brazil during the outbreak in 2016, with a good clinical evolution. We also present warning recommendations for travelers to endemic areas as additional measures to prevent disease outbreaks.
RESUMO Em 2004, um surto global de Chikungunya afetou a maioria das regiões tropicais e subtropicais do mundo. Em 2016, um surto ocorreu no Nordeste do Brasil com centenas de casos documentados. Receptores de transplantes de órgãos sólidos têm uma resposta imune modificada à infecção, e o curso clínico é geralmente diferente daquele em pacientes imunocompetentes. O diagnóstico pode ser desafiador nessa população. A maioria dos relatos descreve pacientes residentes em áreas endêmicas, embora devamos enfatizar a importância do diagnóstico diferencial em viajantes transplantados renais que visitam regiões endêmicas, como o Nordeste do Brasil. Aqui, nós relatamos o caso de um receptor de transplante renal que adquiriu febre Chikungunya após uma viagem a uma região endêmica no Nordeste do Brasil durante o surto de 2016, com uma boa evolução clínica. Também apresentamos recomendações de alerta para viajantes em áreas endêmicas, como medidas adicionais para prevenir surtos de doenças.