Aportes de la biotecnología al diagnóstico y tratamiento de la enfermedad renal crónica y comorbilidades frecuentes / Biotechnology contribution to the diagnosis and treatment of chronic kidney disease and frequent comorbidities

Este trabajo tiene como objetivo revisar las contribuciones de la biotecnología, en relación con el tratamiento, diagnóstico y la monitorización de la enfermedad renal crónica (ERC) y sus comorbilidades más frecuentes, especialmente la anemia. En relación con los tratamientos, enfocamos el desarrollo de productos biofarmacéuticos como los agentes estimulantes de la eritropoyesis (ESA), que fueron los primeros biofármacos utilizados para el tratamiento de la anemia asociada a la ERC; analizamos sus características y utilización actual después de varios años de experiencia clínica, así como también otras alternativas en desarrollo. Revisamos distintos tipos de bioterapias, la utilización de las células estromales mesenquimales de médula ósea (MSC) y tratamientos alternativos con modificaciones dietarias, que se basan en la asociación entre la microbiota intestinal de los pacientes renales crónicos y sus condiciones fisiopatológicas. Finalmente, en relación con el diagnóstico y monitorización, nos referimos al estudio y validación de biomarcadores diagnósticos, predictivos y terapéuticos que han permitido optimizar los resultados clínicos en este tipo de pacientes. (AU)

The aim of this work is to review the contributions of biotechnology, in relation to the treatment, diagnosis and monitoring of chronic kidney disease (CKD) and its most frequent comorbidities, especially anemia. Regarding the treatment, we focus on the development of biopharmaceutical products such as erythropoiesis stimulating agents (ESA), which were the first biopharmaceuticals used to treat anemia associated with chronic kidney disease (CKD). We analyzed their characteristics and their current use after several years of clinical experience, as well as other alternatives in development. We also review different types of biotherapies, the use of bone marrow mesenchymal stromal cells (MSC) and alternative treatments with dietary modifications, which are based on the association between the intestinal microbiota of chronic kidney patients and their pathophysiological conditions. Finally, in relation to diagnosis and monitoring, we refer to the study and validation of diagnostic, predictive and therapeutic biomarkers that have made clinical results possible to be optimized in this type of patient. (AU)

Epoetin alfa resistance in hemodialysis patients with chronic kidney disease: a longitudinal study

Anemia is an inevitable complication of hemodialysis, and the primary cause is erythropoietin deficiency. After diagnosis, treatment begins with an erythropoiesis-stimulating agent (ESA). However, some patients remain anemic even after receiving this medication. This study aimed to investigate the factors associated with resistance to recombinant human erythropoietin therapy with epoetin alfa (αEPO). We performed a prospective, longitudinal study of hemodialysis patients receiving treatment with αEPO at our reference hospital from July 2015 to June 2016. Clinical data was collected, and the response to αEPO treatment was evaluated using the erythropoietin resistance index (ERI). The ERI was defined as the weekly weight-adjusted αEPO dose (U/kg per week)/hemoglobin level (g/dL). A longitudinal linear regression model was fitted with random effects to verify the relationships between clinical and laboratory data and ERI. We enrolled 99 patients (average age, 45.7 (±17.6) years; male, 51.5%; 86.8% with hypertension). The ERI showed a significant positive association with serum ferritin and C-reactive protein, percentage interdialytic weight gain, and continuous usage of angiotensin receptor blocker (ARB) hypertension medication. The ERI was negatively associated with serum iron and albumin, age, urea reduction ratio, and body mass index. Our findings indicate that resistance to αEPO was related to a low serum iron reserve, an inflammatory state, poor nutritional status, and continuous usage of ARBs.

Validade do autorrelato de anemia e do uso terapêutico de sais de ferro durante a gestação: coorte de nascimentos de 2015 de Pelotas, Rio Grande do Sul, Brasil / Validity of patient-reported anemia and therapeutic use of iron supplements during pregnancy: 2015 Pelotas (Brazil) birth cohort / Validez del autoinforme de anemia y uso terapéutico de sales de hierro durante la gestación: cohorte de nacimientos de 2015 en Pelotas, Río Grande do Sul, Brasil

O objetivo deste estudo é investigar a validade do autorrelato de anemia e de uso terapêutico de sais de ferro, frente à informação de hemoglobina da carteira da gestante. O estudo utiliza dados da coorte de nascimentos de 2015 de Pelotas, Rio Grande do Sul, Brasil. Para a validação do autorrelato de anemia, foram incluídas todas as mães que tinham registro de hemoglobina na carteira da gestante (N = 3.419), ao passo que, para a validação do autorrelato de uso terapêutico de sais de ferro, foram incluídas as que tinham registro de exames de hemoglobina na carteira da gestante e que relataram haver utilizado algum medicamento com sulfato ferroso em sua composição durante a gestação. Anemia foi definida como, pelo menos, um registro de hemoglobina ≤ 11g/dL na carteira da gestante (padrão-ouro). A prevalência de anemia conforme padrão-ouro foi 35,9% (34,3-37,5), ao passo que a de anemia autorrelatada foi 42,2% (40,8-43,7), e o autorrelato de uso terapêutico de sais de ferro, 43,2% (41,3-45,1). A sensibilidade do autorrelato de anemia foi 75,2% (72,8-77,6) e a especificidade, 75,1% (73,3-76,9). Para o autorrelato de uso terapêutico de sais de ferro, a sensibilidade foi 66,4% (63,5-69,2) e a especificidade, 71,9% (69,7-74,0). A especificidade do autorrelato de anemia e do autorrelato de uso terapêutico de sais de ferro entre mães com ≥ 12 anos de escolaridade foi 78,4% (75,4-81,4) e 79,5% (76,1-82,9). Na população estudada, com alta prevalência de anemia, de cada cinco puérperas que relataram anemia ou uso terapêutico de sais de ferro, três relatavam a verdade. A especificidade de ambos os autorrelatos foi mais elevada entre mães com ≥ 12 anos de escolaridade.

This study aimed to investigate the validity of patient-reported anemia and therapeutic use of iron supplements, compared to hemoglobin values recorded on the patient's prenatal card. The study used data from the 2015 Pelotas (Brazil) birth cohort. For validation of self-reported anemia, we included all mothers with hemoglobin values recorded on their prenatal card (N = 3,419), while validation of self-reported therapeutic use of iron supplements included those who had hemoglobin values recorded on their prenatal care and who reported having used medicines containing ferrous sulfate during pregnancy. Anemia was defined as at least one record of hemoglobin ≤ 11g/dL on the prenatal card (gold standard). Prevalence of anemia according to the gold standard was 35.9% (34.3-37.5), while patient-reported anemia was 42.2% (40.8-43.7), and patient-reported therapeutic use of iron supplements was 43.2% (41.3-45.1). Sensitivity of patient-reported anemia was 75.2% (72.8-77.6) and specificity was 75.1% (73.3-76.9). For patient-reported therapeutic use of iron supplements, sensitivity was 66.4% (63.5-69.2) and specificity was 71.9% (69.7-74.0). Specificity of patient-reported anemia and patient-reported therapeutic use of iron supplements in mothers with ≥ 12 years of schooling was 78.4% (75.4-81.4) and 79.5% (76.1-82.9), respectively. In the study population, for every five postpartum women that reported anemia or therapeutic use of iron supplements, three were telling the truth. The specificity of both self-reports was high in mothers with ≥ 12 years of schooling.

El objetivo de este estudio es investigar la validez del autoinforme de anemia y uso terapéutico de sales de hierro, respecto a la información sobre la hemoglobina, presente la cartilla de la embarazada. El estudio utiliza datos de la cohorte de nacimientos en Pelotas, Rio Grande ddo Sul, Brasil, 2015. Para la validación del autoinforme de anemia, se incluyeron a todas las madres que tenían un registro de hemoglobina en la cartilla de la embarazada (N = 3.419), al mismo tiempo que, para la validación del autoinforme del uso terapéutico de sales de hierro, se incluyeron a quienes tenían registro de exámenes de hemoglobina en la cartilla de la embarazada, y que informaron haber utilizado algún medicamento con sulfato ferroso en su composición durante la gestación. La anemia se definió como, por lo menos, un registro de hemoglobina ≤ 11g/dL en la cartilla de la embarazada (patrón ideal). La prevalencia de anemia, según el patrón ideal, fue de un 35,9% (34,3-37,5), mientras que la de la anemia autoinformada fue de un 42,2% (40,8-43,7), y el autoinforme de uso terapéutico de sales de hierro, 43,2% (41,3-45,1). La sensibilidad del autoinforme de anemia fue de un 75,2% (72,8-77,6) y la especificidad, 75,1% (73,3-76,9). Para el autoinforme de uso terapéutico de sales de hierro, la sensibilidad fue 66,4% (63,5-69,2) y la especificidad, 71,9% (69,7-74,0). La especificidad del autoinforme de anemia y del autoinforme de uso terapéutico de sales de hierro entre madres con ≥ 12 años de escolaridad fue 78,4% (75,4-81,4) y 79,5% (76,1-82,9). En la población estudiada, con una alta prevalencia de anemia, de cada cinco puérperas que informaron anemia o uso terapéutico de sales de hierro, tres relataban la verdad. La especificidad de ambos autoinformes fue más elevada entre madres con ≥ 12 años de escolaridad.

Inflamação e má resposta ao uso de eritropoetina na doença renal crônica / Inflammation and poor response to treatment with erythropoietin in chronic kidney disease

Resumo A prevalência da doença renal crônica (DRC) tem aumentado nos últimos anos e vários fatores estão associados à instalação e progressão da DRC, tais como obesidade, hipertensão arterial e diabetes mellitus. Uma das complicações da DRC é a anemia causada principalmente pela deficiência de ferro e de eritropoetina (EPO). Um dos tratamentos para este tipo de anemia é uso de eritropoetina exógena. O paciente com DRC submetido à diálise apresenta um estado inflamatório crônico, provocando uma situação de má resposta à ação medular da EPO, causando anemia, desnutrição, agravamento da aterosclerose e aumento da mortalidade. O objetivo deste artigo foi revisar as evidências científicas referentes à associação da má resposta clínica ao uso de EPO e a presença de inflamação na DRC.

Abstract The prevalence of kidney chronic disease (CKD) has increased in recent years and several risk factors have been associated with the onset and progression of CDK, such as obesity, hypertension and diabetes mellitus. In addition, anemia is one of the complications of CRD, mainly by iron and erythropoietin (EPO) deficiency and the management of this situation is with exogenous erythropoietin, but patients undergoing dialysis present chronic inflammatory process followed by EPO resistance and anemia, malnutrition, worse of atherosclerosis and increased mortality ratio. The aim of this study was to review the association of erythropoietin resistance and chronic inflammatory process in patients with chronic renal disease.

Erythropoietin resistance in end-stage renal disease patient with gastric antral vascular ectasia / Resistência à eritropoetina em paciente com IRC e ectasia vascular gástrica

Abstract We observed a case of recombinant human erythropoietin resistance caused by Gastric Antral Vascular Ectasia in a 40-year-old female with ESRD on hemodialysis. Some associated factors such as autoimmune disease, hemolysis, heart and liver disease were discarded on physical examination and complementary tests. The diagnosis is based on the clinical history and endoscopic appearance of watermelon stomach. The histologic findings are fibromuscular proliferation and capillary ectasia with microvascular thrombosis of the lamina propria. However, these histologic findings are not necessary to confirm the diagnosis. Gastric Antral Vascular Ectasia is a serious condition and should be considered in ESRD patients on hemodialysis with anemia and resistance to recombinant human erythropoietin because GAVE is potentially curable with specific endoscopic treatment method or through surgical procedure.

Resumo Observou-se um caso de resistência à eritropoetina recombinante humana causada por Ectasia Vascular Antral Gástrica em uma mulher de 40 anos de idade, com doença renal terminal em hemodiálise. Alguns fatores associados, tais como a doença autoimune, hemólise, doenças cardíacas e hepáticas foram descartados no exame físico e exames complementares. O diagnóstico é baseado na história clínica e aspecto endoscópico de estômago em melancia. Os achados histológicos são proliferação fibromuscular e ectasia capilar com trombose microvascular da lâmina própria. No entanto, esses achados histológicos não são necessários para confirmar o diagnóstico. Ectasia Vascular Antral Gástrica é uma condição séria e deve ser considerada em pacientes com insuficiência renal terminal em hemodiálise com anemia refratária e resistência à eritropoetina humana recombinante porque é potencialmente curável com o método de tratamento endoscópico específico ou através de procedimento cirúrgico.

Randomized double-blind clinical trial of a new human epoetin versus a commercially available formula for anemia control in patients on hemodialysis

OBJECTIVES: Anemia is a common complication among chronic kidney disease patients on hemodialysis, occurring mostly due to erythropoietin deficiency. This randomized noninferiority trial sought to compare the efficacy and safety of a new epoetin formulation developed by Bio-Manguinhos, a biologics manufacturer affiliated with the Brazilian government, with those of a commercially available product currently used in Brazil (a biosimilar epoetin formulation). METHODS: The sample size needed to enable demonstration of noninferiority with a statistical power of 85% for a between-group difference in hemoglobin levels of no more than 1.5 g/dL was calculated. In total, 74 patients were randomly assigned to receive the epoetin formulation from Bio-Manguinhos (n = 36) or the biosimilar epoetin formulation (n = 38) in a double-blind fashion. The inclusion criteria were current epoetin therapy and stable hemoglobin levels for at least 3 months prior to the study. The primary and secondary outcomes were mean monthly hemoglobin levels and safety, respectively. The dose was calculated according to international criteria and adjusted monthly in both groups according to hemoglobin levels and at the assistant physicians' discretion. Iron storage was estimated at baseline and once monthly. Clinicaltrials.gov: NCT01184495. RESULTS: The study was conducted for 6 months after randomization. The mean baseline hemoglobin levels were 10.9±1.2 and 10.96±1.2 g/dL (p = 0.89) in the Bio-Manguinhos epoetin and biosimilar epoetin groups, respectively. During the study period, there was no significant change in hemoglobin levels in either group (p = 0.055, ANOVA). The epoetin from Bio-Manguinhos was slightly superior in the last 3 months of follow-up. The adverse event profiles of the two formulations were also similar. CONCLUSIONS: The epoetin formulations tested in this study are equivalent in efficacy ...

Efeitos do levosimendan sobre TNF-alfa, PNB e MMP-1 em pacientes com insuficiência cardíaca com anemia / Effects of levosimendan on TNF-alpha, BNP and MMP-1 in patients with heart failure with anemia

FUNDAMENTO: O levosimendan é conhecido pelo seu efeito bilateral de fortalecimento contração das miofibrilas sem aumentar a demanda de oxigênio no miocárdio. A anemia é uma deterioração que causa aumento da dosagem de fármacos em pacientes com insuficiência cardíaca. OBJETIVO: No presente estudo comparamos a eficácia do tratamento com levosimendan em pacientes com insuficiência cardíaca descompensada com ou sem anemia. MÉTODOS: Foram incluídos no estudo 23 pacientes anêmicos com insuficiência cardíaca classe 3 ou 4, segundo a New York Heart Association (NYHA) e fração de ejeção abaixo de 35%. Outros 23 pacientes com o mesmo diagnóstico cardíaco, mas sem anemia, serviu como grupo controle. Ao tratamento da insuficiência cardíaca tradicional desses pacientes foi acrescido um tratamento de 24 horas de levosimendan. Amostras foram tomadas para dosar os níveis séricos do fator de necrose tumoral alfa sérico (TNF-alfa), peptídeo natriurético cerebral aminoterminal (NT-proPNB) e metaloproteinase da matriz 1 (MMP-1), antes e após a administração. RESULTADOS: Não houve diferença significativa entre os níveis séricos de TNF-alfa e MMP-1, antes e depois do tratamento (p > 0,05). Embora o nível de NT-proBNP tenha diminuído em ambos os grupos após o tratamento, não foi estatisticamente significativo (p = 0,531 e p = 0,913 para os grupos de anemia e de controle, respectivamente). Uma restauração significativa da capacidade funcional foi observada em ambos os grupos avaliados, de acordo com a NYHA (p < 0,001 e p = 0,001 para os grupos de anemia e controle, respectivamente). CONCLUSÃO: O tratamento com levosimendan apresenta efeitos semelhantes em pacientes com insuficiência cardíaca, com anemia e sem anemia. No entanto, o efeito precoce desse tratamento sobre os níveis de TNF-alfa, NT-proPNB e MMP-1 não é evidente. Ele oferece uma melhora significativa na capacidade funcional, sem a influência da anemia.

BACKGROUND: Levosimendan is known with its two-sided effects of strengthening myofibril contraction without increasing myocardial oxygen demand. Anemia is a deteriorating situation that causes increase of drug dosing in patients with heart failure. OBJECTIVES: In this study, we compared the effectiveness of levosimendan treatment in decompensated heart failure patients with or without anemia. METHODS: Twenty-three anemic patients having class 3 or 4 heart failure according to New York Heart Association (NYHA) and an ejection fraction of below 35% were included to the study. Another 23 patients with the same cardiac diagnosis but without anemia served as control group. Twenty-four hours levosimendan treatment was added to the traditional heart failure treatment of these patients. Samples were taken to measure serum tumor necrotizing factor alpha (TNF-alpha), aminoterminal pro-brain natriuretic peptide (NT-proBNP) and matrix metalloproteinase-1 (MMP-1) levels before and after the administration. RESULTS: There was no significant difference between serum TNF-alpha and MMP-1 levels before and after the treatment (p>0.05). Although NT-proBNP level decreased in both groups after the treatment this was not statistically significant (p=0.531 and p=0.913 for anemia and control groups respectively). Significant restoration of functional capacity was seen in both groups assessed according to NYHA (p<0.001 and p=0.001 for anemia and control groups respectively). CONCLUSION: Levosimendan treatment shows similar effects in heart failure patients with anemia to that of patients without anemia. However, the early effect of this treatment on TNF-alpha, NT-proBNP and MMP-1 levels is not evident. It provides significant improvement in functional capacity without influence from anemia.

Utilização de eritropoetina por pacientes incidentes em hemodiálise no Sistema Único de Saúde, Brasil, 2002-2003 / Erythropoietin use by incident hemodialysis patients in the Brazilian Unified National Health System, 2002-2003

Este estudo visa a descrever o perfil demográfico e epidemiológico de pacientes incidentes em hemodiálise, que utilizaram eritropoetina em 2002 e 2003, no Brasil, e identificar fatores associados ao uso desse medicamento. Foram analisados dados demográficos, clínicos e relacionados à unidade de diálise de 32.136 pacientes, identificados por pareamento determinístico-probabilístico de dados do subsistema de autorização de procedimentos de alto custo e do Sistema de Informações sobre Mortalidade. Um modelo de regressão de Poisson foi usado para identificar fatores associados ao uso de eritropoetina. Sexo masculino; idade inferior a 65 anos; nefropatia diabética; fístula arteriovenosa ao iniciar hemodiálise e residir em outras Unidades Federativas diferentes do Mato Grosso foram fatores associados ao uso de eritropoetina. A política de atenção ao doente renal, a alocação de recursos para estados e municípios e o manejo da anemia, segundo o perfil farmacoterapêutico dos pacientes, devem ser revistos, a fim de reduzir as iniquidades observadas na utilização da eritropoetina.

This study aimed to describe the demographic and epidemiological profile of Brazilian patients entering hemodialysis from 2002 to 2003 and identify predictors of erythropoietin use. The study analyzed demographic and clinical characteristics and dialysis facility-related variables from 32,136 patients identified by deterministic-probabilistic matching in the database of authorizations for high-cost procedures and the Mortality Information System. Poisson regression was used to identify predictors of erythropoietin use. Male gender, age < 65 years, diabetic renal failure, arteriovenous fistula at the beginning of hemodialysis, and living in States of Brazil other than Mato Grosso were predictors of erythropoietin use. The policy of care for chronic kidney disease, resource allocation for States and municipalities, and anemia management according to the patient's drug therapy profile need to be revised in order to reduce observed inequities in erythropoietin use.

Hemodiálisis y embarazo: aspectos técnicos / Hemodialysis and pregnancy: technical aspects

La hemodiálisis es el método de primera elección para sustituir la función renal en mujeres con insuficiencia renal crónica o aguda durante el embarazo o posparto. Las complicaciones perinatales son frecuentes, sin embargo, el conocimiento de la adecuación de la técnica en el tratamiento médico de las pacientes puede contribuir a la reducción de su presentación y mejorar los resultados perinatales. El objetivo de esta investigación fue revisar la técnica y prescripción médica de la hemodiálisis en la mujer durante el embarazo o posparto. Este tipo de enfermas debe atenderse en un centro de alta especialidad. Se recomienda la hemodiálisis intensa incrementando la frecuencia y duración de las sesiones, utilizar aparatos que manejan altos flujos de sangre y líquido de diálisis, filtros nuevos, microdosis de heparina y limitar la ultrafiltración para evitar cambios hemodinámicos, hidroelectrolíticos, metabólicos, hemorragia obstétrica o parto pretérmino. El objetivo es mantener un estado clínico satisfactorio y niveles sanguíneos maternos de nitrógeno de la urea ≤ 80 mg/dl y creatinina 5 a 7 mg/dl para favorecer el crecimiento y desarrollo fetales. El tratamiento farmacológico rutinario debe continuarse, ajustando el número de medicamentos y su dosis de manera individual. El conocimiento de la técnica de hemodiálisis y su prescripción pueden contribuir a lograr mejores resultados perinatales.

Hemodialysis is the gold standard for substitution of renal function in women with chronic or acute renal insufficiency during pregnancy or during the postpartum period. Perinatal complications are frequent. Recognition of appropriate techniques in medical treatment of patients will contribute to decrease its incidence and allow better perinatal results. We undertook this study to review the techniques and medical indications of hemodialysis in pregnant and postpartum patients. This condition requires care in a high-specialty medical center. We recommend incremental increases in intensity and frequency and duration of treatments, use of equipment to manage fluctuations in blood and dialysis fluids, new filters, microdose of heparin and limiting ultrafiltration to avoid hemodynamic, electrolytic, and metabolic alterations, obstetrical hemorrhage or premature delivery. The objective is to maintain a satisfactory clinical status and maternal blood, urea, nitrogen (BUN) levels =80 mg/dl and creatinine 5-7 mg/dl for opportune fetal development and birth. Routine pharmacological treatment should continually be individually adjusted as to number of medications and dosage. Recognition of hemodialysis techniques and indications will contribute to obtaining improved perinatal results.

Variação dos níveis de hemoglobina de pacientes em hemodiálise tratados com eritropoetina: uma experiência brasileira / Hemoglobin levels in hemodialysis patients treated with epoetin: a Brazilian experience

OBJETIVO: Avaliar a variabilidade dos níveis de hemoglobina (Hb) em pacientes em hemodiálise (HD) tratados com eritropoetina. MÉTODOS: Foram coletados dados retrospectivos de 249 pacientes que estavam em HD e apresentavam, nos três meses anteriores, média de Hb entre 10,5 g/dL e 12,5 g/dL. O período de observação total foi de 36 meses. A cada mês de coleta, classificaram-se os valores de Hb em: < 10,5g/dL, 10,5g/dL< Hb< 12,5g/dL (intervalo alvo), ou Hb >12,5g/dL. Além disto, os pacientes foram divididos em seis categorias de variabilidade da Hb: baixo persistente (<10,5g/dL), alvo persistente (10,5 a 12,5 g/dL), alto persistente (>12,5g/dL), flutuação de baixa amplitude com Hb baixo, flutuações de baixa amplitude com Hb alto e flutuações de alta amplitude. RESULTADOS: Mês a mês, a média da proporção de pacientes com Hb dentro da faixa alvo foi de 50 por cento (variação, 42 por cento a 61 por cento). A proporção de valores de Hb médios acima da faixa alvo (30 por cento) foi mais frequente que a proporção abaixo do alvo (20 por cento). Durante os períodos de seis, 12, e 36 meses, a proporção de pacientes com Hb baixa persistente se reduziu de 3,6 por cento para 0 por cento; de 31,7 por cento para 2,8 por cento naqueles com Hb alta persistente; de 7,6 por cento para 0 por cento naqueles com baixa amplitude com Hb baixo; e de 41,3 por cento para 8,3 por cento nos pacientes com baixa amplitude com Hb alto. Entretanto, houve aumento na proporção de pacientes (de 21,5 por cento a 88,9 por cento) com alta amplitude de Hb. Portanto, à medida que o tempo de observação se alongou observou-se maior variabilidade dos valores de hemoglobina. Nenhum paciente manteve os níveis de Hb dentro do alvo durante todo o período do estudo. CONCLUSÃO: A manutenção da Hb dentro da faixa alvo é difícil, especialmente em períodos longos e a variabilidade ocorre mais frequentemente para valores mais elevados de Hb.

OBJECTIVE: Correction of anemia using epoetin decreases morbidity and increases survival and quality of life in end-stage renal disease. Maintaining hemoglobin levels within the range proposed by guidelines has become a major challenge, with hemoglobin cycling affecting more than 90 percent of patients undergoing hemodialysis. The variability of hemoglobin levels over time was assessed in our patients. METHODS: Data were retrospectively collected on 249 patients undergoing hemodialysis over a 3-year period at seven centers in Brazil. Hemoglobin was measured at least monthly, and target levels were those between 10.5 g/dL and 12.5 g/dL. Patients were grouped into six categories of variability consistently low (<10.5g/dL), consistently target range (10.5 to 12.5 g/dL), consistently high (>12.5g/dL), low amplitude fluctuation with low hemoglobin levels, low amplitude fluctuation with high hemoglobin levels and high amplitude fluctuation. None of the patients maintained stable hemoglobin levels for the entire 36-month period. RESULTS: The mean monthly proportion of patients that had hemoglobin levels within the target range was 50 percent (range, 42 percent to 61 percent). Mean levels above the target (30 percent) were more frequent than those below it (20 percent). During 6, 12, and 36 months, proportions of patients with consistently low levels of hemoglobin decreased from 3.6 percent to 0 percent, from 31.7 percent to 2.8 percent for those with consistently high, from 7.6 percent to 0 percent for those with low amplitude fluctuation with low hemoglobin levels and from 41.3 percent to 8.3 percent for those with low amplitude fluctuation with high hemoglobin levels. However, the proportions of patients with high amplitude fluctuation increased from 21.5 percent to 88.9 percent. CONCLUSION: Maintaining hemoglobin levels within the target range is difficult, especially for longer periods of time. Missing the target seems more often due to ...

Tratamiento de la anemia con eritropoyetina humana recombinante en la insuficiencia renal crónica terminal / Treatment of the anemia with human erythropoietin recombinant in the kidney failure, chronic

El principal factor etiológico de la anemia en los pacientes con enfermedad renal crónica es la insuficiencia en la producción de eritropoyetina por parte del riñon. Tratamos a 33 pacientes renales crónicos con eritropoyetina humana recombinante y le dimos un seguimiento durante un año. Además de mejorar el hematocrito, mejoró la calidad de los pacientes y no requirieron de transfusiones sanguíneas. Se encontró mejor respuesta cuando se administró por vía subcutánea. El único efecto secundario que se presentó fue un incremento de la hipertensión arterial, en dos pacientes. El tratamiento ideal de la anemia del paciente con enfermedad renal crónica requiere de eritropoyetina humana recombinante.

Eritropoietina y transfusiones en la anemia del insuficiente renal crónico: visión actualizada / Erytropoietin and tranfusions in anemia of chronic renal failure: update view

Aiming to know the factors that influenced the use of erythropoietin (EPO) in chronic hemodialysis patients, we retrospectively studied 82 patients (41 male), of whom 15 received EPO. No differences, between patients receiving or not receiving EPO, were found in age (46.9ñ25 and 57ñ13 years respectively), male/female ratio (9/6 and 32/35 respectively), time on dialysis (36.4ñ25.6 and 36.8ñ31.8 months respectively), dialysis hours (3.19ñ0.6 and 3.33ñ0.39 h respectively) and proportion of diabetics (6.6 and 20.8 percent respectively). Prior to EPO use and compared to untreated patients, treated patients were transfused with a higher frequency (60 vs 22 percent) and with more units/patients/years (0.12 vs 0.08). Hemoglobin levels at the start of the treatment was similar in treated and untreated patients (8.4ñ1.46 vs 8.78ñ1.97 g/dl). Epo was indicated in 11 patients due to general symptomatology associated to anemia and in 4 due to cardiac failure or angina. We conclude that EPO treatment is indicated in approximately 18 percent of patients in dialysis. An adequate dialytic treatment may achieve optimal hemoglobin levels with minimal transfusion requirements and without need of EPO, thus reducing costs

Tratamiento de niños con insuficiencia renal crónica terminal con eritropoyetina recombinante humana / Treatment with recombinant human erythropoietin (rHuEPO) of children with terminal chronic renal failure (TRF)

Con el propósito de evaluar los efectos de la eritropoyetina recombinante humana (EPOrHu) sobre la anemia en niños con insuficiencia renal crónica terminal (I.R.C.T.), 10 pacientes con edad promedio de 10,55 +/- 5,20 años (rango: 3 a 16), todos en diálisis peritoneal ambulatoria continua (D.P.A.C.), recibieron tratamiento durante 16 semanas. Previo a la terapia, presentaban: hemoglobina: promedio 6,08 +/- 0,41 (rango 5,5 a 6,6) g/dl, hematócrito: promedio 18,4 +/- 2,01 por ciento (rango: 15 a 21). La dosis inicial de EPOrHu fue de 25 unidades/kg peso, administrada por vía subcutánea, ajustándola según el incremento porcentual del hematócrito y fijándose como objetivo un hematócrito de 30 por ciento. La respuesta al tratamiento se valoró a través del incremento de los valores de hemoglobina y hematócrito, analizándose estadísticamente los resultados por t de Student. Previo a la terapia, y periódicamente, se determinó hierro sérico, ferritina, creatinina y recuento de reticulocitos. Al final de la terapia se obtuvo una hemoglobina promedio de 8,08 +/- 1,18 g/dl (p < 0,001) y un hematócrito promedio de 24,9 +/- 4,33 por ciento (rango 17-30) (p < 0,001). La hipertensión arterial fue el efecto adverso más comúnmente observado. Se concluye que la EPOrHu constituye una terapia efectiva para coregir de manera importante la anemia en niños con I.R.C.T., para evitar el uso de transfusiones sanguíneas y mejorar la calidad de vida de los pacientes. El control adecuado de la tensión arterial preterapia y el ajuste de la medicación hipotensora obvia este efecto adverso