RESUMEN
BACKGROUND: A 48-year-old man with a recent diagnosis of multiple myeloma and rapidly progressive oliguric end-stage renal disease requiring hemodialysis, presented with a serum calcium concentration of 3.4 mmol/l (13.6 mg/dl). INVESTIGATIONS: Serum laboratory analysis, electroencephalogram, MRI of the brain and bone marrow, and kidney biopsies. DIAGNOSIS: Hypercalcemia secondary to multiple myeloma. MANAGEMENT: Short-term intravenous disodium pamidronate therapy (30 mg daily) and daily monitoring of serum calcium concentration.
Asunto(s)
Antineoplásicos/uso terapéutico , Difosfonatos/uso terapéutico , Hipercalcemia/tratamiento farmacológico , Fallo Renal Crónico/etiología , Mieloma Múltiple/complicaciones , Diálisis Renal , Humanos , Hipercalcemia/etiología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Mieloma Múltiple/tratamiento farmacológico , PamidronatoRESUMEN
BACKGROUND: The most common complication of hemodialysis (HD) access graft is thrombosis. Clopidogrel, an inhibitor of platelet aggregation, was assessed to prevent this serious complication. METHODS: A prospective study in which 24 patients on chronic HD whose vascular accesses were grafts were divided into two groups: group A (n = 12, 50%) consisted of patients who did not receive antithrombotic therapy after graft creation, and group B (n = 12, 50%) received clopidogrel 75 mg/day from 2 days after surgery onwards. Both groups were not different according to age, gender, cause of renal failure, hematocrit levels, platelet counts and Kt/V. All patients' thrombotic episodes were followed up from the day of graft surgery until thrombosis was diagnosed. Finally, the patient survival difference between both groups was determined. RESULTS: Eleven thrombotic episodes were diagnosed in group A while one event was reported in group B (p < 0.001). Graft access days of patency were significantly longer in group B compared to group A (380.8 +/- 170 vs. 90.1 +/- 57.2, p < 0.001). Time that elapsed from dialysis initiation to graft creation was not different (group A 18 +/- 12 days, group B 20 +/- 10 days). Days on HD were different between both groups (group A 208.9 +/- 97.2 vs. group B 583.2 +/- 287.0, p < 0.001) and all patients from group A (n = 12, 100%) and 2 patients from group B (16.7%) died (p = 0.001). Major bleeding events were not reported. CONCLUSIONS: Clopidogrel significantly decreased thrombotic graft episodes. Patients on clopidogrel had a prolonged vascular access patency, longer time on HD and better survival.
Asunto(s)
Catéteres de Permanencia/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Politetrafluoroetileno , Diálisis Renal , Trombosis/etiología , Trombosis/prevención & control , Ticlopidina/análogos & derivados , Anciano , Clopidogrel , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Ticlopidina/uso terapéuticoRESUMEN
Homocysteine is an independent risk factor for cardiovascular disease in the general population. In addition, it plays a main role in the development of atherogenesis and thrombosis, particularly in end-stage renal disease patients. Therefore, hemodialysis patients are under the burden of homocysteine toxic effects, present in nearly 90% of dialysis patients. Our group found that folic acid is an efficient therapeutic approach to decrease homocysteine levels, and the addition of intravenous methylcobalamin potentiates this effect; however, methylcobalamin alone was unsuccessful to normalize homocysteine levels. With time a group of patients required a higher dose of folic acid to reduce hyperhomocysteinemia. Patients homozygous and, to a lesser extent heterozygous, to the C677T thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) presented a reduced catalytic activity and required a higher folic acid dose. Vascular-access thrombotic events were similar in all patients according to the variants of the enzyme, suggesting that treating hyperhomocysteinemia was the key to lower the risk of thromboses. Noteworthy, hypohomocysteinemia, generally acompanying malnourishment, is associated to higher mortality. Albeit hyper-homocysteinemia is considered a vascular risk factor in renal failure patients, it has not yet been established in this population if its correction is associated with a decrease in the rate of vascular disease and thrombosis. However, given the mentioned evidence about the low risk and good tolerance of vitamin therapy, we believe it useful to know folate, cobalamin and homocysteine blood levels in chronic renal patients and start a prompt treatment, which may proof adequate to maintain homocysteine levels of 10 +/- 5 micromol/l.
Asunto(s)
Aterosclerosis/etiología , Ácido Fólico/uso terapéutico , Hiperhomocisteinemia/complicaciones , Diálisis Renal/efectos adversos , Trombosis/etiología , Complejo Vitamínico B/uso terapéutico , Aterosclerosis/metabolismo , Ácido Fólico/metabolismo , Homocisteína/sangre , Homocisteína/efectos de los fármacos , Humanos , Hiperhomocisteinemia/tratamiento farmacológico , Hiperhomocisteinemia/metabolismo , Fallo Renal Crónico/tratamiento farmacológico , Fallo Renal Crónico/metabolismo , Metilenotetrahidrofolato Reductasa (NADPH2)/metabolismo , Metilenotetrahidrofolato Reductasa (NADPH2)/uso terapéutico , Factores de Riesgo , Trombosis/metabolismo , Vitamina B 12/análogos & derivados , Vitamina B 12/metabolismo , Vitamina B 12/uso terapéutico , Complejo Vitamínico B/metabolismoRESUMEN
Homocysteine is an independent risk factor for cardiovascular disease in the general population. In addition, it plays a main role in the development of atherogenesis and thrombosis, particularly in end-stage renal disease patients. Therefore, hemodialysis patients are under the burden of homocysteine toxic effects, present in nearly 90
of dialysis patients. Our group found that folic acid is an efficient therapeutic approach to decrease homocysteine levels, and the addition of intravenous methylcobalamin potentiates this effect; however, methylcobalamin alone was unsuccessful to normalize homocysteine levels. With time a group of patients required a higher dose of folic acid to reduce hyperhomocysteinemia. Patients homozygous and, to a lesser extent heterozygous, to the C677T thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) presented a reduced catalytic activity and required a higher folic acid dose. Vascular-access thrombotic events were similar in all patients according to the variants of the enzyme, suggesting that treating hyperhomocysteinemia was the key to lower the risk of thromboses. Noteworthy, hypohomocysteinemia, generally acompanying malnourishment, is associated to higher mortality. Albeit hyper-homocysteinemia is considered a vascular risk factor in renal failure patients, it has not yet been established in this population if its correction is associated with a decrease in the rate of vascular disease and thrombosis. However, given the mentioned evidence about the low risk and good tolerance of vitamin therapy, we believe it useful to know folate, cobalamin and homocysteine blood levels in chronic renal patients and start a prompt treatment, which may proof adequate to maintain homocysteine levels of 10 +/- 5 micromol/l.
RESUMEN
Homocysteine is a risk factor for cardiovascular disease. Mutations in a key enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase, may contribute to hyperhomocysteinemia and alter folate and cobalamin levels. After starting hemodialysis, 10 mg oral folate daily and 500 micrograms intravenous methylcobalamin once weekly were prescribed to 27 hemodialysis patients (time on hemodialysis > or = 12 months) and two groups were defined: Group A normal; Group B heterozygous. Initial, third and twelfth month measurements of homocysteine, serum folate and vitamin B12 levels were collected and analyzed. Heterozygous state of methylenetetrahydrofolate reductase prevalence was 48% and homozygozity 4%. Hyperhomocysteinemia was present in both groups. Cobalamin final levels were significantly lower in Group B compared to Group A. Homocysteine, serum folate and cobalamin levels at third and twelfth month were significantly different from baseline levels but non-different between them in both groups. In Group B, vitamin B12 at third month was significantly higher than initial, but final measurements were not different from baseline determinations. In conclusion, the heterozygous prevalence of the enzyme in hemodialysis patients is similar to that reported in the general population; hyperhomocysteinemia is frequent in hemodialysis patients and final levels in heterozygous patients are significantly higher than in normal patients. Cobalamin levels are lower in the heterozygous group. After one year of treatment, homocysteine tends to increase, suggesting a secondary resistance phenomenon to vitamin supplementation in heterozygous patients.
Asunto(s)
Ácido Fólico/sangre , Homocisteína/sangre , Fallo Renal Crónico/enzimología , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Vitamina B 12/análogos & derivados , Vitamina B 12/sangre , Adulto , Distribución de Chi-Cuadrado , Femenino , Ácido Fólico/uso terapéutico , Heterocigoto , Homocisteína/genética , Humanos , Hiperhomocisteinemia/prevención & control , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapia , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2) , Persona de Mediana Edad , Mutación Puntual/genética , Diálisis Renal , Estadísticas no Paramétricas , Vitamina B 12/uso terapéuticoRESUMEN
BACKGROUND: There are no data available on the effects of intravenous (i.v.) methylcobalamin (Me-Cbl), the coenzymatically active form of vitamin B12 that acts as a cofactor for methionine synthase in the conversion of total homocysteine (tHcy) to methionine, with or without oral folic acid (FA) supplementation, on fasting tHcy levels in hemodialysis (HD) patients. METHODS: We performed a prospective randomized trial in which 62 chronic HD patients without previous vitamin supplementation were divided into four groups. Group A received Me-Cbl 500 microg twice/week plus FA 10 mg/day; group B received FA 10 mg/day alone; group C received no vitamin supplementation, and group D was on Me-Cbl 500 microg twice/week alone. Fasting tHcy, vitamin B12, serum (s) FA and erythrocytic (e) FA were measured predialysis before and after 4 months of therapy. RESULTS: Final tHcy levels were significantly lower in group A (10.2 +/- 3.1 micromol/l) compared to groups C (27.3 +/- 9.7 micromol/l, p < 0.001) and group D (24.3 +/- 11.8 micromol/l, p < 0.001) and similar to group B (11.2 +/- 1.9 micromol/l, p = n.s.). Mean tHcy levels showed a significant decrease in group A from 22.5 +/- 15.6 to 10.2 +/- 3.1 micromol/l (p = 0.003) and in group B from 19.9 +/- 4.0 to 11.2 +/- 1.9 micromol/l (p = 0.012), while no significant changes were observed in groups C (25.9 +/- 9.3 vs. 27.3 +/- 9.7 micromol/l, p = n.s.) and D (26.6 +/- 14.3 vs. 24.3 +/- 11.8 micromol/l, p = n.s.). CONCLUSION: Oral FA (10 mg/day) supplementation appears to be an effective approach to normalize plasma tHcy in chronic HD patients; the addition of i.v. Me-Cbl (500 microg twice/week) to this regimen showed no benefit. Separately, FA corrected hyperhomocysteinemia (HtHcy), while Me-Cbl showed no change.
Asunto(s)
Ácido Fólico/farmacología , Homocisteína/sangre , Diálisis Renal , Vitamina B 12/análogos & derivados , Vitamina B 12/farmacología , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Ácido Fólico/sangre , Humanos , Masculino , Metilación , Persona de Mediana Edad , Estudios Prospectivos , Vitamina B 12/sangre , Vitamina B 12/metabolismoRESUMEN
Homocysteine is a risk factor for cardiovascular disease. Mutations in a key enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase, may contribute to hyperhomocysteinemia and alter folate and cobalamin levels. After starting hemodialysis, 10 mg oral folate daily and 500 micrograms intravenous methylcobalamin once weekly were prescribed to 27 hemodialysis patients (time on hemodialysis > or = 12 months) and two groups were defined: Group A normal; Group B heterozygous. Initial, third and twelfth month measurements of homocysteine, serum folate and vitamin B12 levels were collected and analyzed. Heterozygous state of methylenetetrahydrofolate reductase prevalence was 48
and homozygozity 4
. Hyperhomocysteinemia was present in both groups. Cobalamin final levels were significantly lower in Group B compared to Group A. Homocysteine, serum folate and cobalamin levels at third and twelfth month were significantly different from baseline levels but non-different between them in both groups. In Group B, vitamin B12 at third month was significantly higher than initial, but final measurements were not different from baseline determinations. In conclusion, the heterozygous prevalence of the enzyme in hemodialysis patients is similar to that reported in the general population; hyperhomocysteinemia is frequent in hemodialysis patients and final levels in heterozygous patients are significantly higher than in normal patients. Cobalamin levels are lower in the heterozygous group. After one year of treatment, homocysteine tends to increase, suggesting a secondary resistance phenomenon to vitamin supplementation in heterozygous patients.
RESUMEN
Homocysteine is a risk factor for cardiovascular disease. Mutations in a key enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase, may contribute to hyperhomocysteinemia and alter folate and cobalamin levels. After starting hemodialysis, 10 mg oral folate daily and 500 micrograms intravenous methylcobalamin once weekly were prescribed to 27 hemodialysis patients (time on hemodialysis > or = 12 months) and two groups were defined: Group A normal; Group B heterozygous. Initial, third and twelfth month measurements of homocysteine, serum folate and vitamin B12 levels were collected and analyzed. Heterozygous state of methylenetetrahydrofolate reductase prevalence was 48
. Hyperhomocysteinemia was present in both groups. Cobalamin final levels were significantly lower in Group B compared to Group A. Homocysteine, serum folate and cobalamin levels at third and twelfth month were significantly different from baseline levels but non-different between them in both groups. In Group B, vitamin B12 at third month was significantly higher than initial, but final measurements were not different from baseline determinations. In conclusion, the heterozygous prevalence of the enzyme in hemodialysis patients is similar to that reported in the general population; hyperhomocysteinemia is frequent in hemodialysis patients and final levels in heterozygous patients are significantly higher than in normal patients. Cobalamin levels are lower in the heterozygous group. After one year of treatment, homocysteine tends to increase, suggesting a secondary resistance phenomenon to vitamin supplementation in heterozygous patients.
Asunto(s)
Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Vitamina B 12/análogos & derivados , Vitamina B 12/sangre , Ácido Fólico/sangre , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Homocisteína/sangre , Fallo Renal Crónico/enzimología , Vitamina B 12/uso terapéutico , Distribución de Chi-Cuadrado , Diálisis Renal , Mutación Puntual/genética , Estadísticas no Paramétricas , Hiperhomocisteinemia/prevención & control , Metilenotetrahidrofolato Reductasa (NADPH2) , Ácido Fólico/uso terapéutico , Heterocigoto , Homocisteína/genética , Fallo Renal Crónico/sangre , Fallo Renal Crónico/terapiaRESUMEN
La eritrocitosis post-transplante es una entidad caracterizada por un hematocrito superior al 51 por ciento, tiene una prevalencia del 10 al 15 por ciento en los pacientes transplantados renales, y puede manifestarse en cualquier momento post-transplante. La eritrocitosis post-transplante se asocia a hipertensión arterial, por aumento de la volemia, y es un factor predisponente a la trombosis vascular, por aumento de la viscosidad sanguínea. Tanto la angiotensina II como el Insulin Growth Factor I y otros compuestos han sido postulados como posibles mediadores del aumento de la eritropoyesis. La eritropoyetina se encuentra en valores aumentados en esta entidad, aunque existen casos en los cuales la misma se encuentra en valores normales o disminuídos. Independientemente de estos niveles, los inhibidores de la enzima convertidora de angiotensina, o recientemente los inhibidores del receptor de angiotensina II, son las drogas de elección para tratar en forma efectiva y segura la eritrocitosis post-trasnplante. (AU)
Asunto(s)
Humanos , Policitemia/etiología , Policitemia/terapia , Trasplante de Riñón/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina , Angiotensina II/antagonistas & inhibidores , EritropoyetinaRESUMEN
La eritrocitosis post-transplante es una entidad caracterizada por un hematocrito superior al 51 por ciento, tiene una prevalencia del 10 al 15 por ciento en los pacientes transplantados renales, y puede manifestarse en cualquier momento post-transplante. La eritrocitosis post-transplante se asocia a hipertensión arterial, por aumento de la volemia, y es un factor predisponente a la trombosis vascular, por aumento de la viscosidad sanguínea. Tanto la angiotensina II como el Insulin Growth Factor I y otros compuestos han sido postulados como posibles mediadores del aumento de la eritropoyesis. La eritropoyetina se encuentra en valores aumentados en esta entidad, aunque existen casos en los cuales la misma se encuentra en valores normales o disminuídos. Independientemente de estos niveles, los inhibidores de la enzima convertidora de angiotensina, o recientemente los inhibidores del receptor de angiotensina II, son las drogas de elección para tratar en forma efectiva y segura la eritrocitosis post-trasnplante.