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Dialysis treatment has improved the survival of patients with kidney failure. However, the hospitalization and mortality rates remain alarmingly high, primarily due to incomplete uremic toxin elimination. High-volume hemodiafiltration (HDF) has emerged as a promising approach that significantly improves patient outcomes by effectively eliminating medium and large uremic toxins, which explains its increasing adoption, particularly in Europe and Japan. Interest in this therapy has grown following the findings of the recently published CONVINCE study, as well as the need to understand the mechanisms behind the benefits. This comprehensive review aims to enhance the scientific understanding by explaining the underlying physiological mechanisms that contribute to the positive effects of HDF in terms of short-term benefits, like hemodynamic tolerance and cardiovascular disease. Additionally, it explores the rationale behind the medium-term clinical benefits, including phosphorus removal, the modulation of inflammation and oxidative stress, anemia management, immune response modulation, nutritional effects, the mitigation of bone disorders, neuropathy relief, and amyloidosis reduction. This review also analyzes the impact of HDF on patient-reported outcomes and mortality. Considering the importance of applying personalized uremic toxin removal strategies tailored to the unique needs of each patient, high-volume HDF appears to be the most effective treatment to date for patients with renal failure. This justifies the need to prioritize its application in clinical practice, initially focusing on the groups with the greatest potential benefits and subsequently extending its use to a larger number of patients.
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OBJETIVOS Determinar la prevalencia de déficit de vitamina D, así como evaluar la seguridad y efectividad de un nuevo método de carga con colecalciferol en pacientes adultos con fractura de tibia. MATERIALES Y MÉTODOS Se reclutaron a 56 pacientes consecutivos con edades entre 18 y 65 años con fractura de tibia ingresados en nuestro hospital durante 1 año. Se determinó el nivel de 25-hidroxivitamina D ([25(OH)-D]) al ingreso y tras suplementación con 100.000 UI semanales de colecalciferol, durante 3 o 5 semanas, en casos de insuficiencia ([25(OH)-D] entre 20 ng/mL y 29,9 ng/mL) o deficiencia ([25(OH)-D] < 20 ng/mL), respectivamente. Se determinó la prevalencia de hipovitaminosis D, el porcentaje de normalización de [25(OH)-D], y los efectos adversos. RESULTADOS Se evaluaron 56 pacientes; 98,2% presentó hipovitaminosis D, y 28 (73,7%) y 10 (26,3%) presentaron déficit e insuficiencia, respectivamente. Tras la suplementación, 92,1% alcanzaron niveles [25(OH)-D] normales. Ningún paciente presentó efectos adversos. DISCUSIÓN La prevalencia de deficiencia de vitamina D en nuestra población fue mayor a la reportada en la literatura. Comprobamos que un esquema de suplementación en altas dosis de vitamina D es seguro, y más efectivo que los previamente recomendados. Este esquema de suplementación puede ser implementado en futuros estudios randomizados. CONCLUSIÓN La prevalencia de hipovitaminosis D en pacientes adultos chilenos con fractura de tibia fue alta (98,2%). El esquema de suplementación con vitamina D propuesto fue efectivo y seguro.
OBJETIVOS Determinar la prevalencia de déficit de vitamina D, así como evaluar la seguridad y efectividad de un nuevo método de carga con colecalciferol en pacientes adultos con fractura de tibia. MATERIALES Y MÉTODOS Se reclutaron a 56 pacientes consecutivos con edades entre 18 y 65 años con fractura de tibia ingresados en nuestro hospital durante 1 año. Se determinó el nivel de 25-hidroxivitamina D ([25(OH)-D]) al ingreso y tras suplementación con 100.000 UI semanales de colecalciferol, durante 3 o 5 semanas, en casos de insuficiencia ([25(OH)-D] entre 20 ng/mL y 29,9 ng/mL) o deficiencia ([25(OH)-D] < 20 ng/mL), respectivamente. Se determinó la prevalencia de hipovitaminosis D, el porcentaje de normalización de [25(OH)-D], y los efectos adversos. RESULTADOS Se evaluaron 56 pacientes; 98,2% presentó hipovitaminosis D, y 28 (73,7%) y 10 (26,3%) presentaron déficit e insuficiencia, respectivamente. Tras la suplementación, 92,1% alcanzaron niveles [25(OH)-D] normales. Ningún paciente presentó efectos adversos. DISCUSIÓN La prevalencia de deficiencia de vitamina D en nuestra población fue mayor a la reportada en la literatura. Comprobamos que un esquema de suplementación en altas dosis de vitamina D es seguro, y más efectivo que los previamente recomendados. Este esquema de suplementación puede ser implementado en futuros estudios randomizados. CONCLUSIÓN La prevalencia de hipovitaminosis D en pacientes adultos chilenos con fractura de tibia fue alta (98,2%). El esquema de suplementación con vitamina D propuesto fue efectivo y seguro.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Fraturas da Tíbia/tratamento farmacológico , Deficiência de Vitamina D/epidemiologia , Colecalciferol/uso terapêutico , Hormônios e Agentes Reguladores de Cálcio , Chile/epidemiologia , Incidência , PrevalênciaRESUMO
Background: Solid-organ transplant (SOT) recipients have worse COVID-19 outcomes than general population and effective immunisation in these patients is essential but more difficult to reach. We aimed to determine the immunogenicity of an mRNA SARS-CoV-2 vaccine booster in SOT recipients previously immunised with either inactivated or homologous SARS-CoV-2 mRNA vaccine. Methods: Prospective cohort study of SOT recipients under medical care at Red de Salud UC-CHRISTUS, Chile, previously vaccinated with either CoronaVac or BNT162b2. All participants received a BNT162b2 vaccine booster. The primary study end point was anti-SARS-CoV-2 total IgG antibodies (TAb) seropositivity at 8-12 weeks (56-84 days) post booster. Secondary end points included neutralising antibodies (NAb) and specific T-cell responses. Findings: A total of 140 (50% kidney, 38% liver, 6% heart) SOT recipients (mean age 54 [13.6] years; 64 [46%] women) were included. Of them, 62 had homologous (three doses of BNT162b2) and 78 heterologous vaccine schedules (two doses of CoronaVac followed by BNT162b2 booster). Boosters were received at a median of 21.3 weeks after primary vaccination. The proportion achieving TAb seropositivity (82.3% vs 65.4%, P = 0.035) and NAb positivity (77.4% vs 55.1%, P = 0.007) were higher for the homologous versus the heterologous group. On the other hand, the number of IFN-γ and IL-2 secreting SARS-CoV-2-specific T-cells did not differ significantly between groups. Interpretation: This cohort study shows that homologous mRNA vaccine priming plus boosting in SOT recipients, reaches a significantly higher humoral immune response than inactivated SARS-CoV-2 vaccine priming followed by heterologous mRNA booster. Funding: School of Medicine, UC-Chile and ANID.ClinicalTrials.gov ID: NCT05124509.
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BACKGROUND: IgG4-related disease (IgG4 RD) is an immune-mediated fibro-inflammatory disorder, with tissue infiltration of IgG4+ plasma cells. It causes pseudotumors, tumors, and a wide spectrum of clinical manifestations. AIM: To report the clinical, laboratory, histopathological and treatment characteristics of a group of Chilean patients with IgG4 RD. MATERIAL AND METHODS: Review of medical records of 52 patients aged 18 to 76 years with IgG4 RD seen at six medical centers. RESULTS: Elevated IgG4 serum levels (> 135 mg/dl) were found in 18 of 44 (41%) patients. There was histological confirmation of the disease in 46 patients. The most common sites of involvement were lungs, eyes and kidneys. Eighteen (35%) patients had only one organ involved, 34 (65%) patients had two organs and 13 (25%) patients had three or more organs. The involvement of two organs was significantly more common in men (p < 0.05). In patients with only one organ involvement, the most frequent location was orbital and meningeal. All patients with kidney or lung disease had multiorgan involvement. All patients received corticosteroid therapy, 67% synthetic immunosuppressants, and 16% rituximab. CONCLUSIONS: ER-IgG4 can affect any tissue. Multiorgan involvement was more common in this series, with preference for lungs, eyes and kidneys. An excellent response to steroids is characteristic of the disease, but with a high relapse rate that requires additional immunosuppression.
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Humanos , Masculino , Doenças Autoimunes/tratamento farmacológico , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Imunoglobulina G , Rituximab/uso terapêutico , Imunossupressores/uso terapêutico , Rim/patologiaRESUMO
BACKGROUND: IgG4-related disease (IgG4 RD) is an immune-mediated fibro-inflammatory disorder, with tissue infiltration of IgG4+ plasma cells. It causes pseudotumors, tumors, and a wide spectrum of clinical manifestations. AIM: To report the clinical, laboratory, histopathological and treatment characteristics of a group of Chilean patients with IgG4 RD. MATERIAL AND METHODS: Review of medical records of 52 patients aged 18 to 76 years with IgG4 RD seen at six medical centers. RESULTS: Elevated IgG4 serum levels (> 135 mg/dl) were found in 18 of 44 (41%) patients. There was histological confirmation of the disease in 46 patients. The most common sites of involvement were lungs, eyes and kidneys. Eighteen (35%) patients had only one organ involved, 34 (65%) patients had two organs and 13 (25%) patients had three or more organs. The involvement of two organs was significantly more common in men (p < 0.05). In patients with only one organ involvement, the most frequent location was orbital and meningeal. All patients with kidney or lung disease had multiorgan involvement. All patients received corticosteroid therapy, 67% synthetic immunosuppressants, and 16% rituximab. CONCLUSIONS: ER-IgG4 can affect any tissue. Multiorgan involvement was more common in this series, with preference for lungs, eyes and kidneys. An excellent response to steroids is characteristic of the disease, but with a high relapse rate that requires additional immunosuppression.
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Doenças Autoimunes , Doença Relacionada a Imunoglobulina G4 , Masculino , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Imunossupressores/uso terapêutico , Imunoglobulina G , Rituximab/uso terapêutico , Rim/patologia , Doenças Autoimunes/tratamento farmacológicoRESUMO
BACKGROUND: Excessive sodium intake is associated with increased cardiovascular morbidity and mortality. Daily sodium intake is usually inferred from sodium excretion in a 24-hour urine collection, which is cumbersome and prone to errors. Different formulas have attempted to estimate 24-hour urinary sodium from a spot urine sample. Unfortunately, their concordances are insufficient and have not been tested in our population. AIM: To develop an equation to predict 24-hour urine sodium from parameters in plasma and spot urine samples. To validate the equation and compare it with other formulas in Chilean population. MATERIAL AND METHODS: Analysis of 24-hour urine collections, plasma sample and spot urine sample from 174 adult outpatients (81% females) with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2. These were collected between 2015 and 2019 using standardized methods and educating patients about the correct method to collect 24 h urine samples. In all these patients, creatinine and electrolytes were measured in plasma and urine. A new equation was developed using a multiple linear regression model. RESULTS: Twenty-four-hour urine sodium excretion was significantly correlated with age, weight, height, eGFR, plasma osmolarity, urine electrolytes and parameters obtained from spot urine sample, among others. The new equation had a linear correlation with 24-hour natriuresis of 0.91 and the concordance was 0.9. The predictive capacity of the new equation was better than the existing formulas. CONCLUSIONS: We developed a formula to accurately predict daily natriuresis in the Chilean population.
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Natriurese , Sódio , Adulto , Creatinina , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , UrináliseRESUMO
Background: Excessive sodium intake is associated with increased cardiovascular morbidity and mortality. Daily sodium intake is usually inferred from sodium excretion in a 24-hour urine collection, which is cumbersome and prone to errors. Different formulas have attempted to estimate 24-hour urinary sodium from a spot urine sample. Unfortunately, their concordances are insufficient and have not been tested in our population. Aim: To develop an equation to predict 24-hour urine sodium from parameters in plasma and spot urine samples. To validate the equation and compare it with other formulas in Chilean population. Material and Methods: Analysis of 24-hour urine collections, plasma sample and spot urine sample from 174 adult outpatients (81% females) with an estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73m2. These were collected between 2015 and 2019 using standardized methods and educating patients about the correct method to collect 24 h urine samples. In all these patients, creatinine and electrolytes were measured in plasma and urine. A new equation was developed using a multiple linear regression model. Results: Twenty-four-hour urine sodium excretion was significantly correlated with age, weight, height, eGFR, plasma osmolarity, urine electrolytes and parameters obtained from spot urine sample, among others. The new equation had a linear correlation with 24-hour natriuresis of 0.91 and the concordance was 0.9. The predictive capacity of the new equation was better than the existing formulas. Conclusions: We developed a formula to accurately predict daily natriuresis in the Chilean population.
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Humanos , Masculino , Feminino , Adulto , Sódio , Natriurese , Urinálise , Creatinina , Taxa de Filtração GlomerularRESUMO
Background: Renal replacement therapies, especially hemodialysis (HD) in end-stage kidney disease, avoid an inevitable death caused by the disease. However, in elderly patients with multiple comorbidities, this therapy could derive in a comparable survival than conservative management. Considering that HD represents a high cost for the health system, it is worth analyzing the effects of HD on survival. Aim: To analyze the survival and mortality of all national health security system's patients (FONASA) admitted to HD in Chile from 2013 to 2019. Material and Methods: We requested to the Ministry of Health information about all patients affiliated to the public health insurance system that started dialysis between 2013 and 2019. We evaluated the influence of age when starting HD, sex, presence of hypertension, presence of diabetes mellitus (DM), the region of residence, and year of admission on mortality. Results: A total of 24,113 patients aged 61 ± 15 years (45% women) were analyzed. Forty five percent of patients were aged > 65 years. After 5 years of follow-up, the median survival in this age group was 36.1 months. Among patients who started HD at age > 85 years, the median survival was 14.8 months. Diabetic patients had a median survival of 52.3 months. Advanced age and DM were associated with higher annual mortality. Also, the region of residence and year of admission were associated with higher mortality at 3 and 12 months. Conclusions: The median survival of patients on HD is dependent on age and the presence of comorbidities, among other factors. We performed an analysis to determine if starting HD in older patients with comorbidities has a real benefit over conservative management in terms of survival.
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Idoso , Idoso de 80 Anos ou mais , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diabetes Mellitus , Falência Renal Crônica , Análise de Sobrevida , Chile/epidemiologia , Diálise Renal , Diabetes Mellitus/epidemiologia , Falência Renal Crônica/terapiaRESUMO
Methemoglobinemia is a rare condition with serious consequences if not diagnosed. We report the case of a 64-year-old woman with a history of allergy to sulfa drugs and a recent diagnosis of a small vessel vasculitis (ANCA-p) who started induction therapy with corticosteroids and rituximab. Due to the need for infectious prophylaxis, and considering her history, dapsone was administered instead of cotrimoxazole after ruling out glucose-6-phosphate dehydrogenase deficiency. During the admission to the hospital for her second dose of rituximab, and while being asymptomatic, she persistently presented a pulse oximetry ≪ 90% despite the administration of O2. Therefore, the infusion was postponed to study the patient. The arterial gasometric study by direct potentiometry revealed an O2 saturation of 98%, with a saturation gap > 5%. Considering the use of dapsone, a methemoglobinemia was suspected and confirmed by co-oximetry (methemoglobinemia 9%). Dapsone was suspended and one week later, her methemoglobinemia was absent.
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Feminino , Humanos , Pessoa de Meia-Idade , Dapsona , Metemoglobinemia , Combinação Trimetoprima e Sulfametoxazol , Dapsona/efeitos adversos , Rituximab , Metemoglobinemia/diagnóstico , Metemoglobinemia/induzido quimicamente , Metemoglobinemia/tratamento farmacológicoRESUMO
BACKGROUND: Renal replacement therapies, especially hemodialysis (HD) in end-stage kidney disease, avoid an inevitable death caused by the disease. However, in elderly patients with multiple comorbidities, this therapy could derive in a comparable survival than conservative management. Considering that HD represents a high cost for the health system, it is worth analyzing the effects of HD on survival. AIM: To analyze the survival and mortality of all national health security system's patients (FONASA) admitted to HD in Chile from 2013 to 2019. MATERIAL AND METHODS: We requested to the Ministry of Health information about all patients affiliated to the public health insurance system that started dialysis between 2013 and 2019. We evaluated the influence of age when starting HD, sex, presence of hypertension, presence of diabetes mellitus (DM), the region of residence, and year of admission on mortality. RESULTS: A total of 24,113 patients aged 61 ± 15 years (45% women) were analyzed. Forty five percent of patients were aged > 65 years. After 5 years of follow-up, the median survival in this age group was 36.1 months. Among patients who started HD at age > 85 years, the median survival was 14.8 months. Diabetic patients had a median survival of 52.3 months. Advanced age and DM were associated with higher annual mortality. Also, the region of residence and year of admission were associated with higher mortality at 3 and 12 months. CONCLUSIONS: The median survival of patients on HD is dependent on age and the presence of comorbidities, among other factors. We performed an analysis to determine if starting HD in older patients with comorbidities has a real benefit over conservative management in terms of survival.
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Diabetes Mellitus , Falência Renal Crônica , Idoso , Idoso de 80 Anos ou mais , Pré-Escolar , Chile/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Diálise Renal , Análise de SobrevidaRESUMO
Methemoglobinemia is a rare condition with serious consequences if not diagnosed. We report the case of a 64-year-old woman with a history of allergy to sulfa drugs and a recent diagnosis of a small vessel vasculitis (ANCA-p) who started induction therapy with corticosteroids and rituximab. Due to the need for infectious prophylaxis, and considering her history, dapsone was administered instead of cotrimoxazole after ruling out glucose-6-phosphate dehydrogenase deficiency. During the admission to the hospital for her second dose of rituximab, and while being asymptomatic, she persistently presented a pulse oximetry ⪠90% despite the administration of O2. Therefore, the infusion was postponed to study the patient. The arterial gasometric study by direct potentiometry revealed an O2 saturation of 98%, with a saturation gap > 5%. Considering the use of dapsone, a methemoglobinemia was suspected and confirmed by co-oximetry (methemoglobinemia 9%). Dapsone was suspended and one week later, her methemoglobinemia was absent.
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Dapsona , Metemoglobinemia , Dapsona/efeitos adversos , Feminino , Humanos , Metemoglobinemia/induzido quimicamente , Metemoglobinemia/diagnóstico , Metemoglobinemia/tratamento farmacológico , Pessoa de Meia-Idade , Rituximab , Combinação Trimetoprima e SulfametoxazolAssuntos
Injúria Renal Aguda/etiologia , Hipercalcemia/etiologia , Rabdomiólise/complicações , Injúria Renal Aguda/terapia , Adulto , Cálcio/sangue , Creatina Quinase/sangue , Humanos , Hipercalcemia/diagnóstico por imagem , Hipocalcemia/etiologia , Masculino , Cintilografia/métodos , Diálise Renal/métodosRESUMO
Rhabdomyolysis (RD) is the process that leads to cell destruction of striated muscle. Causes include inherited metabolic defects or acquired disorders. RD is frequently associated with acute kidney injury (AKI) and disorders of calcium metabolism. We report a 33 year old man that after amphetamine consumption and an uninterrupted 3,000 km driving presented vomiting, muscle pain and dark urine. He had elevated creatinkinase levels, severe hypocalcemia and an acute renal failure. He was treated with hemodialysis and calcitriol. He was transferred to our hospital and on admission a serum calcium of 18 mg/dl was detected. He continued on hemodialysis, recovering renal function and with normalization of creatinkinase levels and serum calcium level.
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Humanos , Masculino , Adulto , Rabdomiólise/complicações , Injúria Renal Aguda/etiologia , Hipercalcemia/etiologia , Cintilografia/métodos , Cálcio/sangue , Diálise Renal/métodos , Creatina Quinase/sangue , Injúria Renal Aguda/terapia , Hipercalcemia/diagnóstico por imagem , Hipocalcemia/etiologiaRESUMO
Acetylsalicylic acid (ASA) intoxication is potentially lethal. After ingestion, AAS is rapidly transformed into salicylic acid that dissociates into an hydrogen ion plus salicylate. Salicylate is the main form of AAS in the body and produces multiple alterations. Initially, the stimulation of the ventilatory center promotes a respiratory alkalosis. Then, the mitochondrial dysfunction induced by salicylate, will generate a progressive metabolic acidosis due to the accumulation of ketoacids, lactic acid and dicarboxylic acids among others. Another alterations include hydro electrolytic disorders, gastrointestinal lesions, neurological involvement, ototoxicity and coagulopathy. The correct handling of acetylsalicylic acid intoxication requires an thorough knowledge of its pharmacokinetics and pharmacodynamics. Treatment consists in life support measures, gastric lavage, activated charcoal and urinary alkalization to promote the excretion of salicylates. In some occasions, it will be necessary to start renal replacement therapy as soon as possible.
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Humanos , Aspirina/intoxicação , Aspirina/metabolismo , Fibrinolíticos/intoxicação , Fibrinolíticos/metabolismo , Overdose de Drogas/fisiopatologia , Overdose de Drogas/terapia , Acidose/induzido quimicamente , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Aspirina/administração & dosagem , Overdose de Drogas/metabolismo , Hipoglicemia/induzido quimicamente , Hipotensão/induzido quimicamente , Mitocôndrias/efeitos dos fármacosRESUMO
Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy, characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal involvement. It causes end stage renal disease requiring dialysis in most affected patients. It mainly affects young adults (contrary to what was thought years ago). When aHUS is primary, the cause is a genetic mutation in the alternative complement pathway. Instead, secondary aHUS is caused by external factors that trigger the disease by themselves or in combination with a genetic vulnerability. The type of mutation determines the severity of the disease, prognosis, response to therapy and renal transplantation. Advances in the understanding of renal diseases associated with complement defects and the development of specific biologic therapies changed the course of this disease. Eculizumab is internationally approved for the treatment of primary aHUS. Its inhibitory action on the complement cascade leads to hematologic remission and restoration of renal function. We present a review of aHUS detailing its etiology, pathogenesis, clinical presentation, diagnosis and treatment.
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Síndrome Hemolítico-Urêmica Atípica/etiologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , Humanos , Transplante de Rim , MutaçãoRESUMO
Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy, characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal involvement. It causes end stage renal disease requiring dialysis in most affected patients. It mainly affects young adults (contrary to what was thought years ago). When aHUS is primary, the cause is a genetic mutation in the alternative complement pathway. Instead, secondary aHUS is caused by external factors that trigger the disease by themselves or in combination with a genetic vulnerability. The type of mutation determines the severity of the disease, prognosis, response to therapy and renal transplantation. Advances in the understanding of renal diseases associated with complement defects and the development of specific biologic therapies changed the course of this disease. Eculizumab is internationally approved for the treatment of primary aHUS. Its inhibitory action on the complement cascade leads to hematologic remission and restoration of renal function. We present a review of aHUS detailing its etiology, pathogenesis, clinical presentation, diagnosis and treatment.
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Humanos , Síndrome Hemolítico-Urêmica Atípica/etiologia , Síndrome Hemolítico-Urêmica Atípica/terapia , Transplante de Rim , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/diagnóstico , MutaçãoAssuntos
Aspirina/metabolismo , Aspirina/intoxicação , Overdose de Drogas/fisiopatologia , Overdose de Drogas/terapia , Fibrinolíticos/metabolismo , Fibrinolíticos/intoxicação , Acidose/induzido quimicamente , Aspirina/administração & dosagem , Overdose de Drogas/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Hipotensão/induzido quimicamente , Mitocôndrias/efeitos dos fármacos , Equilíbrio Hidroeletrolítico/efeitos dos fármacosRESUMO
BACKGROUND: Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is a condition of dialysis patients associated with both morbidity and mortality. Management is based on clinical guidelines with goals that are hard to comply with. AIM: To describe and compare biochemical variables associated with this disorder in two different time periods. MATERIAL AND METHODS: Revision of medical records of 814 patients (49% females) dialyzed during 2009 and 1018 patients (48% females), dialyzed during 2012 in Southern Metropolitan Santiago. Information about serum calcium, phosphorus, parathyroid hormone (PTH) and albumin was retrieved. RESULTS: Median PTH values in 2009 and 2012 were 222.5 and 353.5 pg/ml respectively (p < 0.05). The figures for serum calcium corrected by albumin were 9.0 and 8.5 mg/dl respectively (p < 0.05). The figures for phosphorus were 4.7 and 5.0 mg/dl respectively (p < 0.05). The Calcium x Phosphorus product was 41.4 and 42.5 mg²/dl² (p < 0.05). Of note, the proportion patients with serum calcium below recommended levels (< 8.4 mg/dl) increased from 16% to 40% from 2009 to 2012. The proportion of patients with biochemical variables within recommended ranges was lower in 2012 than in 2009. CONCLUSIONS: There was a low proportion of patients with bone metabolism parameters within ranges recommended by clinical guidelines. These parameters were worst in 2012.
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Osso e Ossos/metabolismo , Diálise Renal , Insuficiência Renal Crônica/metabolismo , Idoso , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/metabolismo , Cálcio/sangue , Chile , Estudos de Coortes , Feminino , Fidelidade a Diretrizes , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fósforo/sangue , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Albumina Sérica/análise , Fatores de TempoRESUMO
Background: Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is a condition of dialysis patients associated with both morbidity and mortality. Management is based on clinical guidelines with goals that are hard to comply with. Aim: To describe and compare biochemical variables associated with this disorder in two different time periods. Material and Methods: Revision of medical records of 814 patients (49% females) dialyzed during 2009 and 1018 patients (48% females), dialyzed during 2012 in Southern Metropolitan Santiago. Information about serum calcium, phosphorus, parathyroid hormone (PTH) and albumin was retrieved. Results: Median PTH values in 2009 and 2012 were 222.5 and 353.5 pg/ml respectively (p < 0.05). The figures for serum calcium corrected by albumin were 9.0 and 8.5 mg/dl respectively (p < 0.05). The figures for phosphorus were 4.7 and 5.0 mg/dl respectively (p < 0.05). The Calcium x Phosphorus product was 41.4 and 42.5 mg²/dl² (p < 0.05). Of note, the proportion patients with serum calcium below recommended levels (< 8.4 mg/dl) increased from 16% to 40% from 2009 to 2012. The proportion of patients with biochemical variables within recommended ranges was lower in 2012 than in 2009. Conclusions: There was a low proportion of patients with bone metabolism parameters within ranges recommended by clinical guidelines. These parameters were worst in 2012.
Assuntos
Animais , Feminino , Masculino , Camundongos , Gravidez , Adiposidade/fisiologia , Animais Lactentes/metabolismo , Doenças Cardiovasculares/metabolismo , Privação Materna , Síndrome Metabólica/metabolismo , Fatores Etários , Animais Lactentes/psicologia , Pressão Sanguínea/fisiologia , Peso Corporal/fisiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/psicologia , Intolerância à Glucose/etiologia , Intolerância à Glucose/metabolismo , Intolerância à Glucose/psicologia , Síndrome Metabólica/etiologia , Síndrome Metabólica/fisiopatologia , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/psicologia , FenótipoRESUMO
BACKGROUND: Vascular calcification has been widely recognized as a significant contributor to cardiovascular risk in patients with chronic kidney disease. Recent evidence suggests that BMP-7 decreases the vascular calcification observed in uraemic rats, while BMP-2 could also be participating in this process. Gremlin, a bone morphogenetic protein antagonist, has been detected in rat aortic vascular smooth muscle cells (VSMCs), and since the role of the VSMCs into vascular calcification in uraemia is considered critical in this process, we hypothesized that gremlin could be participating in its pathogenesis. With this aim, we studied its expression in aorta from uraemic rats with calcitriol-induced vascular calcification and in 16-vessel biopsies of uraemic patients undergoing kidney transplantation. METHODS: Gremlin was detected by in situ hybridization (ISH) and immunohistochemistry (IMH). BMP-7, BMP-2 and BMP-2 receptor (BMPR2) were detected by IMH. Vascular calcification was assessed by the von Kossa staining method. Sham-operated and 5/6 nephrectomized rats (NFX) (1.2%P) were treated with vehicle or calcitriol (80 ng/kg, intraperitoneally every other day). Rats were killed after 4 weeks of treatment, and abdominal aorta was dissected for assessment of gremlin expression and vascular calcification. Epigastric arteries were obtained from dialysis patients during kidney transplantation procedure. Arteries from kidney donors were also studied. RESULTS: NFX rats developed a mild vascular calcification, whereas NFX-calcitriol rats developed a severe vascular and tissue calcification. A marked overexpression of gremlin was observed in the vascular media of aorta from NFX-calcitriol rats as compared with NFX and sham-calcitriol groups (4.8 +/- 1.3 versus 0.59 +/- 0.17 versus 0.19 +/- 0.07 percentage/mm(2), P < 0.01), and correlated with the BMP-2 and BMPR2 expression. Sham rats showed minimal or null gremlin expression. BMP-7 was not found in sham or calcified arteries. In human studies, we observed strong expression of gremlin mRNA and protein in the media layer of vessels from uraemic patients as compared with those from normal humans (staining score 3.72 +/- 0.95 versus 0.91 +/- 0.08 percentage/mm(2), P < 0.05). CONCLUSION: We observed a marked gremlin overexpression in the media layer of vessels in uraemic rats and patients in association with vascular calcification and BMP-2 expression. We postulate that gremlin may play a role in the vascular calcification process in uraemia, and its interaction with BMP-7 or BMP-2 remains to be elucidated.