RESUMEN
Ammonia is a major neurotoxic substance associated with the complex pathogenesis of hepatic encephalopathy. Although several primary and secondary conditions have been reported to cause hyperammonemia, in veterinary medicine this condition is considered primarily associated with hepatic disease or portosystemic shunting. Only a few cases of inherited urea cycle enzyme deficiency and organic acid metabolic disorders have been reported in cats with hyperammonemia. To the best of our knowledge, this is the first report of hyperammonemia in a cat caused by accumulation of methylmalonic acid (MMA) secondary to functional cobalamin deficiency. A 2-year-old spayed female Turkish Angora cat exhibited postprandial depression with a 3-month history of hyperammonemia. Serum protein C and bile acid concentrations were normal. Plasma amino acid analysis revealed a deficiency of urea cycle amino acids. Although the serum cobalamin concentration was markedly high, there was no evidence of inflammatory, hepatic, or renal disease or neoplasia on blood, ultrasonographic, and computed tomographic examination. Gas chromatography-mass spectrometry revealed a high MMA concentration in the urine. Based on the results, functional cobalamin deficiency was diagnosed. Following oral amino acid supplementation and initiation of a low-protein diet, the serum ammonia level returned to normal and the postprandial depression improved. Urea cycle amino acid deficiency secondary to functional cobalamin deficiency presumably caused hyperammonemia due to MMA accumulation in this case.
Hyperammoniémie féline associée à un déficit fonctionnel en cobalamine : rapport de cas. L'ammoniac est une substance neurotoxique majeure associée à la pathogenèse complexe de l'encéphalopathie hépatique. Bien que plusieurs affections primaires et secondaires aient été signalées comme étant à l'origine d'une hyperammoniémie, en médecine vétérinaire, cette affection est considérée comme principalement associée à une maladie hépatique ou à un shunt porto-systémique. Seuls quelques cas de déficit héréditaire en enzymes du cycle de l'urée et de troubles métaboliques des acides organiques ont été signalés chez des chats atteints d'hyperammoniémie. À notre connaissance, il s'agit du premier rapport d'hyperammoniémie chez un chat causée par une accumulation d'acide méthylmalonique (MMA) secondaire à un déficit fonctionnel en cobalamine.Une chatte angora turque stérilisée âgée de 2 ans a présenté une dépression postprandiale avec une histoire d'hyperammoniémie depuis 3 mois. Les concentrations sériques de protéine C et d'acides biliaires étaient normales. L'analyse plasmatique des acides aminés a révélé une déficience en acides aminés du cycle de l'urée. Bien que la concentration sérique de cobalamine ait été nettement élevée, il n'y avait aucun signe de maladie inflammatoire, hépatique ou rénale ou de néoplasie à l'examen sanguin, échographique et tomodensitométrique. La chromatographie en phase gazeuse-spectrométrie de masse a révélé une forte concentration de MMA dans l'urine. Sur la base des résultats, un déficit fonctionnel en cobalamine a été diagnostiqué. Après une supplémentation orale en acides aminés et la mise en place d'un régime pauvre en protéines, le taux sérique d'ammoniac est revenu à la normale et la dépression postprandiale s'est améliorée. Une carence en acides aminés du cycle de l'urée secondaire à une carence en cobalamine fonctionnelle a vraisemblablement causé une hyperammoniémie due à l'accumulation de MMA dans ce cas.(Traduit par Dr Serge Messier).
Asunto(s)
Enfermedades de los Gatos , Hiperamonemia , Deficiencia de Vitamina B 12 , Gatos , Animales , Femenino , Hiperamonemia/etiología , Hiperamonemia/veterinaria , Hiperamonemia/diagnóstico , Amoníaco , Deficiencia de Vitamina B 12/complicaciones , Deficiencia de Vitamina B 12/diagnóstico , Deficiencia de Vitamina B 12/veterinaria , Vitamina B 12/uso terapéutico , Ácido Metilmalónico/orina , Aminoácidos , Urea , Enfermedades de los Gatos/diagnóstico , Enfermedades de los Gatos/etiologíaRESUMEN
PURPOSE OF REVIEW: Hyperammonaemia is almost always develops in patients with severe liver failure and this remains the commonest cause of elevated ammonia concentrations in the ICU. Nonhepatic hyperammonaemia in ICU presents diagnostic and management challenges for treating clinicians. Nutritional and metabolic factors play an important role in the cause and management of these complex disorders. RECENT FINDINGS: Nonhepatic hyperammonaemia causes such as drugs, infection and inborn errors of metabolism may be unfamiliar to clinicians and risk being overlooked. Although cirrhotic patients may tolerate marked elevations in ammonia, other causes of acute severe hyperammonaemia may result in fatal cerebral oedema. Any coma of unclear cause should prompt urgent measurement of ammonia and severe elevations warrant immediate protective measures as well as treatments such as renal replacement therapy to avoid life-threatening neurological injury. SUMMARY: The current review explores important clinical considerations, the approach to testing and key treatment principles that may prevent progressive neurological damage and improve outcomes for patients with hyperammonaemia, especially from nonhepatic causes.
Asunto(s)
Hiperamonemia , Terapia Nutricional , Humanos , Hiperamonemia/etiología , Hiperamonemia/terapia , Amoníaco/metabolismo , Enfermedad Crítica/terapia , Apoyo NutricionalRESUMEN
BACKGROUND: Hyperammonaemia is a recognised complication of antiseizure treatment but risk factors leading to individual patient susceptibility and outcome remain unclear. OBJECTIVE: To identify risk factors for hyperammonaemia and investigate the impact of its management on clinical outcomes. METHODS: We carried out a retrospective observational study of adults with epilepsy who had ammonia tested over a 3-year period. Hyperammonaemia was defined as ammonia level > 35 µmol/L. Patients were classified into two groups: hyperammonaemic and non-hyperammonaemic. Association analyses and linear regression analysis were used to identify risk factors for hyperammonaemia. RESULTS: We reviewed 1002 ammonia requests in total and identified 76 people with epilepsy who had ammonia concentration measured, including 26 with repeated measurements. 59/76 (78%) were found to have hyperammonaemia. There was borderline statistical significance of hyperammonaemia being less common in patients with an established monogenic/metabolic condition than in those with structural or cryptogenic epilepsy (P = 0.05). Drug resistance, exposure to stiripentol and oxcarbazepine were identified as risk factors for hyperammonaemia. We found a dose-dependent association between valproate and hyperammonaemia (P = 0.033). Clinical symptoms were reported in 22/59 (37%) of the hyperammonaemic group. Improved clinical outcomes with concurrent decrease in ammonia concentration were seen in 60% of patients following treatment adjustment. CONCLUSIONS: Drug resistance and exposure to stiripentol, oxcarbazepine or high-dose valproate are associated with an increased risk of hyperammonaemia. Clinicians should consider symptoms related to hyperammonaemia in patients on high-dose valproate or multiple antiseizure treatments. Prompt identification of hyperammonaemia and subsequent treatment adjustments can lead to improved clinical outcomes.
Asunto(s)
Epilepsia , Hiperamonemia , Adulto , Humanos , Hiperamonemia/diagnóstico , Hiperamonemia/tratamiento farmacológico , Hiperamonemia/etiología , Ácido Valproico/efectos adversos , Amoníaco/uso terapéutico , Oxcarbazepina/uso terapéutico , Epilepsia/tratamiento farmacológico , Epilepsia/complicaciones , Factores de Riesgo , Estudios Observacionales como AsuntoRESUMEN
Carnitine metabolism and homeostasis is significantly altered in patients receiving maintenance dialysis. Current literature in the adult and pediatric dialysis populations suggest a high prevalence of carnitine deficiency, which may lead to erythropoietin-resistant anemia, cardiomyopathy, and muscle weakness. However, the results of pediatric dialysis studies are limited and have not provided the evidence necessary to support strong recommendations or guidelines pertaining to carnitine management. The characteristics and function of carnitine, the definition and consequences of deficiency, a brief overview of recent adult studies, and current studies on carnitine supplementation in pediatric hemodialysis (HD) and peritoneal dialysis (PD) populations are discussed in this review.
Asunto(s)
Cardiomiopatías , Hiperamonemia , Fallo Renal Crónico , Diálisis Peritoneal , Adulto , Carnitina/uso terapéutico , Niño , Humanos , Hiperamonemia/tratamiento farmacológico , Hiperamonemia/etiología , Fallo Renal Crónico/terapia , Diálisis Peritoneal/efectos adversos , Diálisis Renal/efectos adversosRESUMEN
We investigated the effectiveness of monitoring serum carnitine levels in hemodialysis patients receiving L-carnitine supplementation. One-hundred forty-five hemodialysis patients were divided into three groups. Group 1 consisted of patients (n = 30) who had been receiving supplementation before this study and then discontinued at the beginning. The remaining patients were divided into Group 2 (n = 13) and Group 3 (n = 102) based on their baseline free carnitine (FC) level, <20 or ≥ 20 µmol/L. Group 2 was started on supplementation, and Groups 1 and 3 were observed without any intervention for the first 6 months. FC was measured every 6 months in all three groups up to 18 months. All patients in whom FC was less than 20 µmol/L at 6 and 12 months were prescribed supplementation. After the first 6 months, the mean ± SD of FC changed from 262.5 ± 87.5 µmol/L at baseline to 70.8 ± 33.6 µmol/L (P < 0.001) in Group 1, from 17.4 ± 1.9 to 193.9 ± 43.3 µmol/L (P < 0.001) in Group 2, and from 49.2 ± 24.6 to 44.2 ± 19.8 µmol/L (P < 0.05) in Group 3. The acyl/free carnitine changed from 0.62 to 0.59 in Group 1 (P = 0.287), from 0.76 to 0.66 in Group 2 (P = 0.054) and from 0.57 to 0.60 in Group 3 (P < 0.05). Of the 145 patients, 126 continued follow-up for the full 18 months. FC remained in the normal range (36-74 µmol/L) within the 95% CI. FC was considered a strong predictor of carnitine deficiency after 6 months (AUC: 0.9146, cut-off value: 33.8 µmol/L). FC monitoring is essential for appropriate carnitine supplementation in hemodialysis patients.
Asunto(s)
Cardiomiopatías/prevención & control , Carnitina/administración & dosificación , Carnitina/sangre , Carnitina/deficiencia , Hiperamonemia/prevención & control , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Enfermedades Musculares/prevención & control , Diálisis Renal/métodos , Anciano , Cardiomiopatías/etiología , Suplementos Dietéticos , Femenino , Humanos , Hiperamonemia/etiología , Masculino , Enfermedades Musculares/etiología , Diálisis Renal/efectos adversosRESUMEN
L-carnitine is an important factor in fatty acid metabolism, and carnitine deficiency is common in dialysis patients. This study evaluated whether L-carnitine supplementation improved muscle spasm, cardiac function, and renal anemia in dialysis patients. Eighty Japanese outpatients (62 hemodialysis (HD) patients and 18 peritoneal dialysis (PD) patients) received oral L-carnitine (600 mg/day) for 12 months; the HD patients further received intravenous L-carnitine injections (1000 mg three times/week) for 12 months, amounting to 24 months of treatment. Muscle spasm incidence was assessed using a questionnaire, and cardiac function was assessed using echocardiography. Baseline free carnitine concentrations were relatively low in patients who underwent dialysis for >4 years. Total carnitine serum concentration, free carnitine, and acylcarnitine significantly increased after oral L-carnitine treatment for 12 months, and after intravenous L-carnitine injection. There was no significant improvement in muscle spasms, although decreased muscle cramping after L-carnitine treatment was reported by 31% of patients who had undergone HD for >4 years. Hemoglobin concentrations increased significantly at 12 and 24 months in the HD group. Therefore, L-carnitine may be effective for reducing muscle cramping and improving hemoglobin levels in dialysis patients, especially those who have been undergoing dialysis for >4 years.
Asunto(s)
Carnitina/administración & dosificación , Suplementos Dietéticos , Enfermedades Renales/terapia , Diálisis Peritoneal/efectos adversos , Diálisis Renal/efectos adversos , Anemia/etiología , Anemia/terapia , Cardiomiopatías/etiología , Cardiomiopatías/terapia , Carnitina/deficiencia , Femenino , Corazón/fisiopatología , Humanos , Hiperamonemia/etiología , Hiperamonemia/terapia , Japón , Enfermedades Renales/etiología , Masculino , Persona de Mediana Edad , Enfermedades Musculares/etiología , Enfermedades Musculares/terapia , Estudios Prospectivos , Espasmo/etiología , Espasmo/terapia , Resultado del TratamientoRESUMEN
Objective Rifaximin has become available for treating hyperammonemia in patients with hepatic encephalopathy. This study analyzed the changes in the body composition and nutritional status after long-term rifaximin therapy. Methods Twenty-one patients who underwent rifaximin therapy at 1,200 mg/day for more than 24 weeks were evaluated for the changes in the controlling nutritional status (CONUT) scores for the nutritional assessment, albumin-bilirubin (ALBI) scores for the liver function assessment, and skeletal muscle index (SMI) for the body composition assessment. Results There were 17 men and 4 women, with a mean age of 67.14±8.32 years. Eleven cases had a portosystemic shunt (52.3%), and 10 had hepatocellular carcinoma (47.6%). The Child-Pugh class was A in 9 cases (42.9%), B in 9 cases (42.9%), and C in 3 cases (14.2%). The blood ammonia levels in the rifaximin group improved significantly upon rifaximin therapy, from 124.76±28.68 µg/dL at baseline to 47.00±14.43 µg/dL after 2 weeks (p<0.001) and 49.81±15.02 µg/dL after 24 weeks (p<0.001). The CONUT scores improved significantly during rifaximin therapy, from 6.47±3.25 at baseline to 3.33±2.65 after 24 weeks (p=0.0007). The ALBI scores also improved significantly from -0.39±1.89 at baseline to -2.20±0.55 after 24 weeks (p=0.0002). The SMI scores showed that the body composition had been maintained in response to rifaximin therapy (50.20±7.67 at baseline and 51.29±7.62 after 24 weeks). Conclusion Rifaximin administration for hepatic encephalopathy improved the CONUT and ALBI scores. It may have a secondary effect on the improvement in the nutritional status and hepatic reserve.
Asunto(s)
Composición Corporal/efectos de los fármacos , Encefalopatía Hepática/complicaciones , Hiperamonemia/tratamiento farmacológico , Estado Nutricional/efectos de los fármacos , Rifaximina/uso terapéutico , Anciano , Amoníaco/sangre , Bilirrubina/sangre , Carcinoma Hepatocelular/complicaciones , Femenino , Humanos , Hiperamonemia/etiología , Hiperamonemia/fisiopatología , Japón , Cirrosis Hepática/complicaciones , Pruebas de Función Hepática , Neoplasias Hepáticas/complicaciones , Masculino , Persona de Mediana Edad , Músculo Esquelético/anatomía & histología , Músculo Esquelético/fisiopatología , Estudios Retrospectivos , Rifaximina/farmacología , Albúmina SéricaRESUMEN
Carnitine is a vitamin-like substance that regulates lipid metabolism and energy production. Carnitine homeostasis is mainly regulated by dietary intake and biosynthesis in the organs, including the skeletal muscle and the liver. Therefore, liver cirrhotic patients with reduced food intake, malnutrition, biosynthetic disorder, and poor storage capacity of carnitine in the skeletal muscle and liver are more likely to experience carnitine deficiency. In particular, liver cirrhotic patients with sarcopenia are at a high risk for developing carnitine deficiency. Carnitine deficiency impairs the important metabolic processes of the liver, such as gluconeogenesis, fatty acid metabolism, albumin biosynthesis, and ammonia detoxification by the urea cycle, and causes hypoalbuminemia and hyperammonemia. Carnitine deficiency should be suspected in liver cirrhotic patients with severe malaise, hepatic encephalopathy, sarcopenia, muscle cramps, and so on. Importantly, the blood carnitine level does not always decrease in patients with liver cirrhosis, and it sometimes exceeds the normal level. Therefore, patients with liver cirrhosis should be treated as if they are in a state of relative carnitine deficiency at the liver, skeletal muscle, and mitochondrial levels, even if the blood carnitine level is not decreased. Recent clinical trials have revealed the effectiveness of carnitine supplementation for the complications of liver cirrhosis, such as hepatic encephalopathy, sarcopenia, and muscle cramps. In conclusion, carnitine deficiency is not always rare in liver cirrhosis, and it requires constant attention in the daily medical care of this disease. Carnitine supplementation might be an important strategy for improving the quality of life of patients with liver cirrhosis.
Asunto(s)
Cardiomiopatías/terapia , Carnitina/administración & dosificación , Carnitina/deficiencia , Suplementos Dietéticos , Hiperamonemia/terapia , Cirrosis Hepática/metabolismo , Enfermedades Musculares/terapia , Cardiomiopatías/etiología , Carnitina/metabolismo , Humanos , Hiperamonemia/etiología , Hígado/metabolismo , Cirrosis Hepática/complicaciones , Músculo Esquelético/metabolismo , Enfermedades Musculares/etiologíaRESUMEN
The capacity to metabolize proteins is closely related to the hepatic functional reserve in patients with chronic liver disease, and hypoalbuminemia and hyperammonemia develop along with hepatic disease progression. Zinc deficiency, which is frequently observed in patients with chronic liver disease, significantly affects protein metabolism. Ornithine transcarbamylase is a zinc enzyme involved in the urea cycle. Its activity decreases because of zinc deficiency, thereby reducing hepatic capacity to metabolize ammonia. Because the glutamine-synthesizing system in skeletal muscles compensates for the decrease in ammonia metabolism, hyperammonemia does not develop in the early stages of chronic liver disease. However, branched-chain amino acids (BCAAs) are consumed with the increase in glutamine-synthesizing system reactions, leading to a decreased capacity to synthesize proteins, including albumin, due to amino acid imbalance. Upon further disease progression, skeletal muscle mass decreases because of nutritional deficiency, as well as the further decreased capacity to metabolize ammonia in the liver, whereby the capacity to detoxify ammonia reduces as a whole, resulting in hyperammonemia. BCAA supplementation therapy for nutritional deficiency in liver cirrhosis improves survival by correcting amino acid imbalance via recovery of the capacity to synthesize albumin, while zinc supplementation therapy improves the capacity to metabolize ammonia in the liver. Here, the efficacy of a combination of BCAA and zinc preparation for nutritional deficiency in liver cirrhosis, as well as its theoretical background, was reviewed.
Asunto(s)
Hepatopatías/metabolismo , Proteínas/metabolismo , Zinc/metabolismo , Aminoácidos de Cadena Ramificada/administración & dosificación , Aminoácidos de Cadena Ramificada/metabolismo , Amoníaco/metabolismo , Enfermedad Crónica , Suplementos Dietéticos , Humanos , Hiperamonemia/etiología , Hipoalbuminemia/etiología , Hígado/metabolismo , Cirrosis Hepática/complicaciones , Cirrosis Hepática/metabolismo , Hepatopatías/complicaciones , Hepatopatías/tratamiento farmacológico , Músculo Esquelético/metabolismo , Zinc/administración & dosificación , Zinc/deficienciaRESUMEN
A 44-year-old female, with a background of cerebral palsy, epilepsy and learning disabilities, presented with multiple seizures and a persistently reduced consciousness level secondary to valproate-induced hyperammonaemic encephalopathy (plasma levels >50 µg/dl). Withdrawal of valproate and subsequent infusion of L-carnitine led to full recovery. Nonhepatic hyperammonaemia has been shown to be effectively treated by intravenous L-carnitine therapy by a series of case reports. To date, no randomised controlled trials have demonstrated this. Hyperammonaemic encephalopathy is possibly a more common presentation than expected that is currently underdiagnosed and exacerbated by valproate.
Asunto(s)
Anticonvulsivantes/efectos adversos , Carnitina/administración & dosificación , Hiperamonemia/tratamiento farmacológico , Síndromes de Neurotoxicidad/tratamiento farmacológico , Síndromes de Neurotoxicidad/fisiopatología , Ácido Valproico/efectos adversos , Adulto , Anticonvulsivantes/administración & dosificación , Análisis Químico de la Sangre , Parálisis Cerebral/complicaciones , Parálisis Cerebral/fisiopatología , Suplementos Dietéticos , Epilepsia/complicaciones , Epilepsia/diagnóstico , Epilepsia/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Escala de Coma de Glasgow , Humanos , Hiperamonemia/etiología , Síndromes de Neurotoxicidad/etiología , Medición de Riesgo , Resultado del Tratamiento , Ácido Valproico/administración & dosificaciónRESUMEN
Triplicate groups of juvenile yellow catfish (1.98⯱â¯0.01â¯g) were fed diets supplemented with 0% and 1% alanyl-glutamine dipeptide (AGD) for 56â¯days under three ammonia concentrations (0.01, 5.70 and 11.40â¯mgâ¯L-1 total ammonia nitrogen). The results showed that ammonia poisoning could induce growth (weight gain and specific growth rate) and survival reduction, live ammonia and serum malondialdehyde accumulation, and subsequently lead to blood deterioration (serum total protein, albumin, globulin, alkaline phosphatase and acid phosphatase reduced), oxidative stress (superoxide dismutase and glutathione peroxidase activities declined), and induce down-regulation of antioxidant enzymes (SOD, GPX and GRX) genes transcription. However, dietary supplemented with 1% AGD could mitigate the adverse effect of ammonia poisoning on fish growth performance.
Asunto(s)
Amoníaco/toxicidad , Fenómenos Fisiológicos Nutricionales de los Animales , Bagres/fisiología , Dipéptidos/uso terapéutico , Hiperamonemia/prevención & control , Estrés Oxidativo/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Animales , Antioxidantes/uso terapéutico , Acuicultura , Bagres/sangre , Bagres/crecimiento & desarrollo , China , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Hiperamonemia/etiología , Hiperamonemia/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Malondialdehído/sangre , Concentración Osmolar , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Distribución Aleatoria , Análisis de Supervivencia , Aumento de Peso/efectos de los fármacosRESUMEN
Keto analogues and amino acids (KAAA) supplementation can reduce blood ammonia concentrations in athletes undergoing high-intensity exercise under both ketogenic and thermoneutral conditions. This study evaluated the acute effects of KAAA supplementation on ammonia metabolism during extenuating endurance exercise in rats fed a ketogenic diet. In all, eighty male Fischer rats at 90 d of age were divided into eight groups, and some were trained using a swimming endurance protocol. A ketogenic diet supplemented with keto analogues was administered for 10 d. Administration of the ketogenic diet ended 3 d before the exhaustion test (extenuating endurance exercise). A ketogenic diet plus KAAA supplementation and extenuating endurance exercise (trained ketogenic diet supplemented with KAAA (TKKa)) increased blood ammonia concentrations by approximately 50 % compared with the control diet (trained control diet supplemented with KAAA (TCKa)) and similar training (effect size=1·33; statistical power=0·50). The KAAA supplementation reduced blood urea concentrations by 4 and 18 % in the control and ketogenic diet groups, respectively, compared with the groups fed the same diets without supplementation. The trained groups had 60 % lower blood urate concentrations after TCKa treatment than after TKKa treatment. Our results suggest that KAAA supplementation can reduce blood ammonia concentrations after extenuating endurance exercise in rats fed a balanced diet but not in rats fed a ketogenic diet.
Asunto(s)
Aminoácidos/uso terapéutico , Amoníaco/sangre , Dieta , Suplementos Dietéticos , Hiperamonemia/prevención & control , Cetoácidos/uso terapéutico , Resistencia Física/fisiología , Aminoácidos/farmacología , Animales , Dieta Cetogénica , Hiperamonemia/sangre , Hiperamonemia/etiología , Cetoácidos/farmacología , Masculino , Condicionamiento Físico Animal/fisiología , Ratas Endogámicas F344RESUMEN
BACKGROUND: Carnitine deficiency is a common condition in hemodialysis patients. There have been numerous reports on the efficacy of levocarnitine therapy in hemodialysis patients, including different views. Reported effects of levocarnitine are: (1) improvement of renal anemia, (2) improvement of cardiac functions, (3) effects on muscle spasm and asthenia, (4) anti-atherogenic effects, (5) anti-oxidant and anti-inflammatory effects, and (6) inhibitory effects on dialysis hypotension. SUMMARY: Here, I present the effects of levocarnitine on renal anemia in hemodialysis patients with carnitine deficiency, focusing on the effect on dose reduction in erythropoiesis-stimulating agents and the influence on erythropoiesis resistance index. We also describe the effects on cardiac functions based on changes in cardiac ultrasonography. Key Message: To confirm the efficacy of levocarnitine therapy clinical studies would be required as well as the study of carnitine supplementation therapy for hemodialysis patients with carnitine deficiency.
Asunto(s)
Cardiomiopatías/etiología , Carnitina/deficiencia , Carnitina/farmacología , Hiperamonemia/etiología , Enfermedades Musculares/etiología , Diálisis Renal/efectos adversos , Anemia/tratamiento farmacológico , Cardiomiopatías/tratamiento farmacológico , Carnitina/uso terapéutico , Corazón/diagnóstico por imagen , Corazón/fisiología , Hematínicos/administración & dosificación , Humanos , Hiperamonemia/tratamiento farmacológico , Fallo Renal Crónico/terapia , Enfermedades Musculares/tratamiento farmacológico , UltrasonografíaRESUMEN
We describe the case of a 90-year-old woman who was hospitalized in July 2016 and subsequently experienced a sudden decline in consciousness level resulting in a state of deep coma. Involuntary movements were not observed, and bilateral Babinski signs were inconclusive. Diffusion-weighted MRI (DWI) of the brain showed bilateral hyperintensity in the thalamus and internal capsule, laboratory testing detected high levels of plasma ammonia, and an electroencephalogram showed delta waves and triphasic waves predominantly in the frontal lobe. Based on these results, treatment for hepatic encephalopathy was administered, which led to an improvement in consciousness level, a decrease in plasma ammonia levels, and a normalization in the DWI scan. Abdominal computed tomography scan showed no abnormality in the liver, but revealed an abnormal blood vessel leading from the ileocolic vein to the inferior vena cava; the patient was diagnosed with portal-systemic encephalopathy. In deep coma patients, acute encephalopathy with hyperammonemia is important for differential diagnosis when DWI shows high-density legions in the thalamus and internal capsule.
Asunto(s)
Imagen de Difusión por Resonancia Magnética , Encefalopatía Hepática/diagnóstico por imagen , Cápsula Interna/diagnóstico por imagen , Tálamo/diagnóstico por imagen , Anciano de 80 o más Años , Diagnóstico Diferencial , Electroencefalografía , Femenino , Encefalopatía Hepática/complicaciones , Humanos , Hiperamonemia/etiología , Tomografía Computarizada por Rayos XAsunto(s)
Acidosis/etiología , Encefalopatías Metabólicas/etiología , Hiperamonemia/etiología , Derivación Urinaria/efectos adversos , Acidosis/fisiopatología , Anciano , Amoníaco/farmacocinética , Encefalopatías Metabólicas/fisiopatología , Carcinoma de Células Transicionales/cirugía , Proteínas en la Dieta/administración & dosificación , Proteínas en la Dieta/farmacocinética , Epilepsia Parcial Compleja/etiología , Femenino , Humanos , Concentración de Iones de Hidrógeno , Hiperamonemia/dietoterapia , Hiperamonemia/fisiopatología , Absorción Intestinal , Proteínas de Vegetales Comestibles/administración & dosificación , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
Carnitine deficiency is known to occur in chronic hemodialysis; however, the effect of continuous renal replacement therapy (CRRT) on carnitine homeostasis has not been studied. We hypothesized that children receiving CRRT are at risk for deficiency because of continuous removal, absent intake, decreased production, and comorbidities related to critical illness. Records of patients with acute kidney injury receiving CRRT at Children's National Health System between 2011 and 2014 were reviewed for total carnitine (TC), free carnitine (FC), feeding modality, severity of illness, and survival outcome. The proportion of carnitine-deficient patients at baseline, 1, 2, and ≥3 weeks on CRRT were compared by chi-square, and relationships with other variables assessed by Pearson's correlation and logistic regression. The study group included 42 CRRT patients, age 7.9 + 1.1 years. At baseline, 30.7% and 35.7% of patients were TC and FC deficient. Within 1 week, 64.5% (P = 0.03) and 70% (P = 0.03) were TC and FC deficient, and prevalence of deficiency increased to 80% (P = 0.01) and 90% (P = 0.008) by 2 weeks; 100% of patients were TC and FC deficient after being on CRRT for ≥3 weeks (P = 0.005 and P = 0.01, respectively, vs. baseline). TC and FC levels negatively correlated with days on CRRT (r = -0.39, P = 0.001 and r = -0.35, P = 0.005). Patients with TC and FC deficiency had 5.9 and 4.9 greater odds of death than those with normal levels (P = 0.02 and P = 0.03). Carnitine is significantly and rapidly depleted with longer time on CRRT, and carnitine deficiency is associated with increased mortality. Consequences of deficiency and benefits of supplementation in the pediatric CRRT population should be investigated.
Asunto(s)
Lesión Renal Aguda/terapia , Cardiomiopatías/etiología , Carnitina/deficiencia , Hiperamonemia/etiología , Enfermedades Musculares/etiología , Terapia de Reemplazo Renal/métodos , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Adulto JovenRESUMEN
Fatal hyperammonemia secondary to chemotherapy for hematological malignancies or following bone marrow transplantation has been described in few patients so far. In these, the pathogenesis of hyperammonemia remained unclear and was suggested to be multifactorial. We observed severe hyperammonemia (maximum 475 µmol/L) in a 2-year-old male patient, who underwent high-dose chemotherapy with carboplatin, etoposide and melphalan, and autologous hematopoietic stem cell transplantation for a neuroblastoma stage IV. Despite intensive care treatment, hyperammonemia persisted and the patient died due to cerebral edema. The biochemical profile with elevations of ammonia and glutamine (maximum 1757 µmol/L) suggested urea cycle dysfunction. In liver homogenates, enzymatic activity and protein expression of the urea cycle enzyme carbamoyl phosphate synthetase 1 (CPS1) were virtually absent. However, no mutation was found in CPS1 cDNA from liver and CPS1 mRNA expression was only slightly decreased. We therefore hypothesized that the acute onset of hyperammonemia was due to an acquired, chemotherapy-induced (posttranscriptional) CPS1 deficiency. This was further supported by in vitro experiments in HepG2 cells treated with carboplatin and etoposide showing a dose-dependent decrease in CPS1 protein expression. Due to severe hyperlactatemia, we analysed oxidative phosphorylation complexes in liver tissue and found reduced activities of complexes I and V, which suggested a more general mitochondrial dysfunction. This study adds to the understanding of chemotherapy-induced hyperammonemia as drug-induced CPS1 deficiency is suggested. Moreover, we highlight the need for urgent diagnostic and therapeutic strategies addressing a possible secondary urea cycle failure in future patients with hyperammonemia during chemotherapy and stem cell transplantation.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carbamoil-Fosfato Sintasa (Amoniaco)/deficiencia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Hiperamonemia/etiología , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Edema Encefálico/etiología , Carbamoil-Fosfato Sintasa (Amoniaco)/genética , Carbamoil-Fosfato Sintasa (Amoniaco)/metabolismo , Carbamoil Fosfato/metabolismo , Carboplatino/efectos adversos , Carboplatino/farmacología , Preescolar , Terapia Combinada , Etopósido/efectos adversos , Etopósido/farmacología , Resultado Fatal , Glutamina/sangre , Células Hep G2 , Humanos , Hiperamonemia/inducido químicamente , Hígado/enzimología , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Neuroblastoma/tratamiento farmacológico , Ornitina Carbamoiltransferasa/genética , Fosforilación OxidativaRESUMEN
Transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) are effective treatments for hepatocellular carcinoma (HCC). However, the extent of treatment depends on hepatic functional reserve. L-Carnitine is a vitamin-like substance and several reports have described the usefulness of L-carnitine supplementation in cases of cirrhosis, with confirmed effectiveness against refractory hepatic encephalopathy. On the other hand, we have previously reported that in patients who underwent TACE or RFA, administration of branched-chain amino acids (BCAAs) pre-intervention significantly reduced inflammatory reactions. We first determined serum levels of total, free, and acyl-carnitine before and at 7 d after performing TACE in 10 HCC patients. We administered levocarnitine (L-carnitine chloride, a biologically active form of carnitine) at 900 mg/d to 69 consecutive HCC patients hospitalized to undergo TACE and/or RFA, and compared changes in blood test values with those in 119 consecutive patients not administered this drug. Sixty-seven patients had a history of using BCAAs at the time of admission. We found that after 7 d of TACE, serum levels of total and acyl-carnitine are significantly decreased. On comparing the four groups, the carnitine+BCAA, carnitine-alone, and BCAA-alone groups showed significantly higher values for changes in NH3 when compared with the non-dosed group. The decrease in albumin (Alb) was significantly suppressed in the carnitine+BCAA and BCAA-alone groups. We also conducted the same examinations in a subset of patients classified as Child-Pugh class A, and noted the same trends. Administration of levocarnitine and/or BCAAs during invasive treatments reduced blood NH3 concentrations and suppressed decreases in Alb.
Asunto(s)
Técnicas de Ablación/efectos adversos , Aminoácidos de Cadena Ramificada/uso terapéutico , Carcinoma Hepatocelular/terapia , Carnitina/uso terapéutico , Embolización Terapéutica/efectos adversos , Neoplasias Hepáticas/terapia , Hígado/efectos de los fármacos , Anciano , Anciano de 80 o más Años , Albúminas/metabolismo , Aminoácidos de Cadena Ramificada/farmacología , Amoníaco/sangre , Carcinoma Hepatocelular/sangre , Carnitina/sangre , Carnitina/farmacología , Suplementos Dietéticos , Femenino , Encefalopatía Hepática/sangre , Encefalopatía Hepática/prevención & control , Humanos , Hiperamonemia/etiología , Hiperamonemia/prevención & control , Hígado/patología , Hígado/cirugía , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/sangre , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To our knowledge, no randomized study has shown whether zinc replacement therapy is effective for hyperammonemia in liver cirrhosis; therefore, we performed a double-blind, placebo-controlled trial to examine efficacy and safety of the zinc replacement therapy. METHODS: Patients with liver cirrhosis and hyperammonemia (at or above the institutional reference value) and hypozincemia (≤65 µg/dL) were enrolled in the outpatient units of the participating institutions and were randomly divided to receive placebo (P group) or zinc acetate preparation at a dose of 3 capsules/d for a total zinc content of 150 mg/d (Z group) by the envelope method. Of the 18 enrolled patients, 6 dropped out; thus, the analyses included 12 patients (5 in the P group and 7 in the Z group). Variations in blood concentrations of zinc and ammonia as well as liver function test results were compared. RESULTS: Blood zinc levels significantly increased in the Z group (P = 0.0037; Friedman test) but not the P group. Blood ammonia levels significantly decreased in the Z group (P = 0.0114; Friedman test) but not the P group. The percent change in blood ammonia level also revealed significant reduction at the eighth week in the Z group (P = 0.0188: Mann-Whitney test). No serious adverse events attributable to the zinc preparation were noted. CONCLUSION: Although this study is preliminary and includes a small sample, it is, to our knowledge, the first randomized controlled trial to show that zinc supplementation for 3 mo seems effective and safe for treating hyperammonemia in liver cirrhosis. Studies with a larger sample size are needed to confirm our findings.
Asunto(s)
Amoníaco/sangre , Suplementos Dietéticos , Hiperamonemia/tratamiento farmacológico , Cirrosis Hepática/tratamiento farmacológico , Oligoelementos/uso terapéutico , Zinc/uso terapéutico , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Humanos , Hiperamonemia/sangre , Hiperamonemia/etiología , Cirrosis Hepática/sangre , Cirrosis Hepática/complicaciones , Masculino , Persona de Mediana Edad , Oligoelementos/sangre , Oligoelementos/farmacología , Resultado del Tratamiento , Zinc/sangre , Zinc/deficiencia , Zinc/farmacología , Acetato de Zinc/farmacología , Acetato de Zinc/uso terapéuticoRESUMEN
Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work was to shed light on the mechanisms by which blocking NMDA receptors delays rat's death in ALF. ALF was induced by galactosamine injection. NMDA receptors were blocked by continuous MK-801 administration. Edema and cerebral blood flow were assessed by magnetic resonance. The time course of ammonia levels in brain, muscle, blood, and urine; of glutamine, lactate, and water content in brain; of glomerular filtration rate and kidney damage; and of hepatic encephalopathy (HE) and intracranial pressure was assessed. ALF reduces kidney glomerular filtration rate (GFR) as reflected by reduced inulin clearance. GFR reduction is due to both reduced renal perfusion and kidney tubular damage as reflected by increased Kim-1 in urine and histological analysis. Blocking NMDA receptors delays kidney damage, allowing transient increased GFR and ammonia elimination which delays hyperammonemia and associated changes in brain. Blocking NMDA receptors does not prevent cerebral edema or blood-brain barrier permeability but reduces or prevents changes in cerebral blood flow and brain lactate. The data show that dual protective effects of MK-801 in kidney and brain delay cerebral alterations, HE, intracranial pressure increase and death. NMDA receptors antagonists may increase survival of patients with ALF by providing additional time for liver transplantation or regeneration.