RESUMEN
The relationship between blood pressure (BP) and clinical outcomes among hemodialysis patients is complex and incompletely understood. This study sought to assess the relationship between blood pressure changes with hemodialysis and clinical outcomes during a 6-month period. This study is a secondary analysis of the Crit-Line Intradialytic Monitoring Benefit Study, a randomized trial of 443 hemodialysis subjects, designed to determine whether blood volume monitoring reduced hospitalization. Logistic regression was used to estimate the association between BP changes with hemodialysis (Deltasystolic blood pressure=postdialysis-predialysis systoic BP (SBP) and the primary outcome of non-access-related hospitalization and death. Subjects whose systolic blood pressure fell with dialysis were younger, took fewer blood pressure medications, had higher serum creatinine, and higher dry weights. After controlling for baseline characteristics, lab variables, and treatment group, subjects whose SBP remained unchanged with hemodialysis (N=150, DeltaSBP -10 to 10 mm Hg) or whose SBP rose with hemodialysis (N=58, DeltaSBP > or =10 mm Hg) had a higher odds of hospitalization or death compared to subjects whose SBP fell with hemodialysis (N=230, DeltaSBP < or =-10 mm Hg) (odds ratio: 1.85, confidence interval: 1.15-2.98; and odds ratio: 2.17, confidence interval: 1.13-4.15). Subjects whose systolic blood pressure fell with hemodialysis had a significantly decreased risk of hospitalization or death at 6 months, suggesting that hemodynamic responses to dialysis are associated with short-term outcomes among a group of prevalent hemodialysis subjects. Further research should attempt to elucidate the mechanisms behind these findings.
Asunto(s)
Presión Sanguínea , Hospitalización , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Adulto , Anciano , Femenino , Humanos , Hipertensión/diagnóstico , Hipertensión/etiología , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico , Hipotonía Muscular/diagnóstico , Hipotonía Muscular/etiología , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: We conducted a case control study to determine risk factors and mortality associated with calciphylaxis in end-stage renal disease. METHODS: Cases of calciphylaxis diagnosed between December 1989 and January 2000 were identified. Three controls were identified for each hemodialysis patient, with calciphylaxis matched to the date of initiation of hemodialysis. Laboratory data and medication doses were recorded during the 12 months prior to the date of diagnosis and at the time of diagnosis of calciphylaxis. Conditional logistic regression was used to identify risk factors for calciphylaxis. Cox proportional hazards models were used to estimate the risk of death associated with calciphylaxis. RESULTS: Nineteen cases and 54 controls were identified. Eighteen patients were hemodialysis patients, and one had a functioning renal allograft. Diagnosis was confirmed by skin biopsy in 16 cases. Women were at a sixfold higher risk of developing calciphylaxis (OR = 6.04, 95% CI 1.62 to 22.6, P = 0.007). There was a 21% lower risk of calciphylaxis associated with each 0.1 g/dL increase in the mean serum albumin during the year prior to diagnosis and at the time of diagnosis of calciphylaxis (OR = 0.79, 95% CI, 0.64 to 0.99, P = 0.037, and OR = 0.80, 95% CI, 0.67 to 0.96, P = 0.019, respectively). There was a 3.51-fold increase in the risk of calciphylaxis associated with each mg/dL increase in the mean serum phosphate during the year prior to diagnosis (95% CI, 0.99 to 12.5, P = 0.052). At the time of diagnosis of calciphylaxis, for each 10 IU/L increment in alkaline phosphatase, the risk of calciphylaxis increased by 19% (OR = 1.19, 95% CI, 1.00 to 1.40, P = 0.045). Body mass index, diabetes, blood pressure, aluminum, and higher dosage of erythropoietin and iron dextran were not independent predictors of calciphylaxis. Calciphylaxis independently increased the risk of death by eightfold (OR = 8.58, 95% CI, 3.26 to 22.6, P < 0.001). CONCLUSIONS: Female gender, hyperphosphatemia, high alkaline phosphatase, and low serum albumin are risk factors for calciphylaxis. Calciphylaxis is associated with a very high mortality.
Asunto(s)
Calcifilaxia/etiología , Calcifilaxia/mortalidad , Fallo Renal Crónico/complicaciones , Fosfatasa Alcalina/sangre , Calcifilaxia/epidemiología , Estudios de Casos y Controles , Humanos , Fosfatos/sangre , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Albúmina Sérica/análisis , Distribución por SexoRESUMEN
The role of anaemia in the pathogenesis of abnormal cognitive function in haemodialysis patients is only partly understood. Several contemporary studies have assessed cognitive function in haemodialysis patients using neuropsychological and neurophysiological tests, comparing the results obtained over a wide range of haematocrits before and after treatment with epoetin. Of the neurophysiological tests, which measure electrical impulses from the brain in the presence or absence of specific stimuli, the cognitive event-related potential (ERP) has been particularly useful in evaluating this issue. Changes in amplitude (increase) and latency (decrease) of a specific wave form (P300) seen in the ERP correlate with improved cognitive function in haemodialysis patients following initiation of dialysis therapy. Similar effects are also evident when haematocrit is increased. Marsh et al. (Kidney Int 1991; 39: 155 163) examined the effect of increasing haematocrit with epoetin therapy on the P300 amplitude and latency, and noted that after increasing haematocrit to 23.7 36% over 12 months with epoetin, P300 amplitude increased (P<0.025), and several neuropsychological test scores were significantly improved. Grimm et al. (Kidney Int 1990; 38: 480 486) found a significant decrease in P300 latency and statistically nonsignificant improvements in P300 amplitude when haematocrit was increased to 22.7 30.6%. Improvement in the electroencephalogram (EEG) and P300 latency has also been reported by others, including Sagales et al. (Kidney Int 1993; 44: 1109-1115). The effect of complete reversal of anaemia (haematocrits 31.6 42.9%) on cognitive function was recently revealed by Pickett et al. (Am J Kidney Dis 1999; 33: 1122 1130), who found improvement in several cognitive ERP manoeuvres and a significant decrease in EEG slowing (P< 0.02) at higher haematocrits. Taken together, these various studies suggest that graded increments in haematocrit following epoetin therapy have a progressive effect on improving cognitive function in haemodialysis patients.
Asunto(s)
Anemia/tratamiento farmacológico , Anemia/psicología , Cognición , Trastornos del Conocimiento/diagnóstico , Hematócrito , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/psicología , Pruebas Neuropsicológicas , Uremia/psicologíaRESUMEN
Anemia in hemodialysis patients is effectively treated by intravenous (IV) injections of recombinant human erythropoietin (rHuEPO) at each dialysis session. Because the hormone is effective by subcutaneous (SC) administration, it was decided that this study would evaluate low-dose weekly SC rHuEPO therapy. To determine the safety and efficacy of weekly SC rHuEPO administration to hemodialysis patients, only one third the weekly IV dose was given and the effects were compared with those from an age-, gender-, and nephrologic disease-matched control group treated in the standard fashion. Forty-four patients entered the trial and 27 completed the protocol along with 27 control subjects. During Phase 1, experimental and control subjects received standard IV rHuEPO at dialysis for 6 months. During Phase 2, experimental patients received weekly SC rHuEPO at one third the weekly IV dose for 10 months; control subjects continued to receive IV therapy. In Phase 3, both groups were treated for 6 more months with IV rHuEPO. In Phase 2, there was no significant reduction in hematocrit value, reticulocyte count, transferrin saturation, or ferritin level in the experimental group, even with only one third the weekly rHuEPO IV dose over the 10-month period. There were no significant differences between IV and SC rHuEPO administration or between experimental and control subjects in blood pressure, serum chemistries, or parameters of "dialysis adequacy." It was concluded that low-dose weekly SC rHuEPO administration is a safe and effective method for maintaining the hematocrit level of stable hemodialysis patients. This therapy could enhance the efficacy of rHuEPO and substantially reduce costs while preserving patient care outcomes.
Asunto(s)
Eritropoyetina/administración & dosificación , Diálisis Renal , Anemia/sangre , Anemia/tratamiento farmacológico , Anemia/etiología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Eritropoyetina/efectos adversos , Femenino , Ferritinas/sangre , Hematócrito , Humanos , Inyecciones Intravenosas , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Diálisis Renal/efectos adversos , Recuento de Reticulocitos , Seguridad , Factores de Tiempo , Transferrina/metabolismoRESUMEN
Increasing use of medications designed specifically for intravenous administration during hemodialysis has dramatically improved the treatment of many comorbid conditions accompanying end-stage renal disease. Recombinant human erythropoietin has resulted in definitive treatment of the hypoproliferative anemia of uremia, while sustained response to this hormone has been facilitated by treatment with intravenous iron dextran. Simple and effective therapies for many gram-positive infections in end-stage renal disease patients have been realized through the favorable pharmacokinetics and low toxicity of vancomycin when administered during hemodialysis. Major improvements in the therapy of high-turnover bone disease have resulted from the increasing use of intravenous calcitriol during dialysis as well. The contributions of these four medications in improving patient care and the benefits of their administration during the dialysis procedure are reviewed.
Asunto(s)
Anemia Ferropénica/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Hiperparatiroidismo/tratamiento farmacológico , Fallo Renal Crónico/terapia , Preparaciones Farmacéuticas/administración & dosificación , Diálisis Renal , Anemia Ferropénica/etiología , Infecciones por Bacterias Grampositivas/etiología , Humanos , Hiperparatiroidismo/etiología , Inyecciones Intravenosas , Fallo Renal Crónico/complicacionesRESUMEN
Impoverished patients may represent a high-risk population with poor survival. With 1993 U.S. Renal Data System survival tables (to adjust the risk of death for differences in age, race, and ESRD diagnosis), the mortality rates of patients over 3 yr in a large inner-city dialysis facility using high-flux technique were compared with national averages. At least 93.7% of patients were African-American, 50% had incomes below $7,000 per year, and employment was 5% or less. Observed and expected deaths (the latter derived from the U.S. Renal Data System tables) were used to calculate a standardized mortality ratio (observed deaths/expected deaths); the U.S. average is 1.0. The standardized mortality ratio at this facility for each year was < 0.600 and was significantly lower than the U.S. average in 1991, in 1992 (P < 0.05), and for all 3 yr (P < .001). Over all 3 yr, it was lower for females (0.540, P < 0.05), males (0.620, P < 0.05), patients with diabetes (0.593, P < 0.05), and glomerulonephritis (0.318, P < 0.05). For the 3 yr, a Cox regression analysis revealed independent associations between mortality and age (P = 0.004), serum albumin (P = 0.02), Kt/V (P = 0.02), and dialysis for more than 2 yr (P = 0.01). Patients with economic hardship can attain survival significantly better than the national average with the provision of adequate dialysis, nutrition, and support services.
Asunto(s)
Diálisis Renal/mortalidad , Salud Urbana , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Sistemas de Información , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Estado Nutricional , Factores de Riesgo , Factores Sexuales , Análisis de Supervivencia , Estados Unidos , Servicios Urbanos de SaludRESUMEN
We evaluated the kinetics and efficacy of deferoxamine (DFO) therapy in iron-overloaded hemodialysis patients. Concentrations of DFO and its chelated product, feroxamine (Fx), were assessed following single-dose DFO administration in twelve patients, and during chronic therapy over one year's time in eight, similarly iron-overloaded dialysis patients. A functional assay which relies on measurements of iron and iron binding capacity for the determination of Fx and DFO, respectively, was corroborated with liquid chromatographic techniques. Half-life measurements were also corroborated with tracer doses of 14C-DFO and 59Fe-feroxamine. Intradialytic DFO half-life (2.3 +/- 1.1 h) was considerably less than interdialytic half-life (26 +/- 1 hr). Unbound DFO was found to persist throughout the interdialytic period. Calculation of the percent saturation of the DFO dose indicated that only 30% of a given dose is chelated. The amount of iron removed dialytically was approximately 13.1 +/- 2.7 mg per dialysis session. Chronic DFO administration was also shown to enhance gastrointestinal iron excretion threefold. However, ferritin levels decreased by only 25% after one year of thrice-weekly DFO therapy. We conclude that DFO therapy for iron-overloaded hemodialysis patients is optimized by its administration interdialytically, and results in slow removal of iron, via both dialytic and gastrointestinal routes.
Asunto(s)
Deferoxamina/farmacocinética , Deferoxamina/uso terapéutico , Hierro/efectos adversos , Diálisis Renal , Adulto , Femenino , Compuestos Férricos/farmacocinética , Humanos , Hierro/metabolismo , Quelantes del Hierro/farmacocinética , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
Recombinant human erythropoietin (r-HuEPO; EPOGEN [epoetin alfa], AMGEN Inc, Thousand Oaks, CA) has proven to be an effective agent in treating the anemia of chronic renal failure. Of patients enrolled in recent phase III trials in the United States, 97% have responded with near normalization of hematocrit within 12 weeks of therapy. Small numbers of patients, however, may exhibit sluggish or minimal responsiveness to treatment. In these patients, loss of responsiveness due to red cell substrate depletion (in particular, iron deficiency) or underlying inflammatory disease may occur at any time during the treatment calendar, whether at induction of therapy or during maintenance treatment. Primary unresponsiveness at initiation of treatment may also result from such potentially reversible abnormalities as aluminum intoxication, poorly controlled hyperparathyroidism, and, possibly, severe azotemia. These abnormalities can be investigated in a systemic fashion and frequently corrected so that successful treatment can resume.
Asunto(s)
Anemia/tratamiento farmacológico , Eritropoyetina/uso terapéutico , Fallo Renal Crónico/complicaciones , Anemia/etiología , Ensayos Clínicos como Asunto , Resistencia a Medicamentos , Hematócrito , Humanos , Proteínas Recombinantes/uso terapéuticoRESUMEN
Adequate body iron stores are crucial to assuring rapid and complete response to recombinant human erythropoietin (rHuEPO). In the present study, markers of iron storage were examined in 27 patients with normochromic, normocytic anemia undergoing acute rHuEPO (150 to 300 U/kg t.i.w.) treatment for anemia. We calculated projected iron needed for new hemoglobin synthesis from the difference between initial and target hemoglobin concentrations, initial iron reserves available from initial serum ferritin levels, and net projected surplus or deficit from the difference between needs and reserves. Of 22 patients predicted to develop iron deficiency (mean projected deficit 268 +/- 70 mg), 20 developed evidence of exhausted iron stores (transferrin %sat less than 16 or ferritin less than 30 micrograms/liter) before reaching target hemoglobin; two predicted to become deficient (projected deficit less than 100 mg) did not; and all five predicted to avoid iron deficiency (mean projected surplus 177 +/- 20 mg) remained iron replete. During acute rHuEPO therapy net body iron balance remained neutral in patients receiving no iron supplements and increased 5 mg/kg in patients prescribed oral ferrous sulfate. However, in patients given iron dextran i.v. less than 60% of elemental iron administered became measurable as iron stores or usable for hemoglobin synthesis.
Asunto(s)
Anemia/tratamiento farmacológico , Eritropoyetina/uso terapéutico , Hierro/metabolismo , Fallo Renal Crónico/terapia , Diálisis Renal/efectos adversos , Anemia/etiología , Deferoxamina , Humanos , Proteínas Recombinantes/uso terapéuticoRESUMEN
We developed a rapid acid-digestion method for preparing tissue samples for iron determination. Specimens were digested in nitric acid and hydrogen peroxide under high temperature and pressure in closed Teflon vessels, with microwave energy. Analysis for iron in 25- to 250-mg portions of digested bovine liver powder (National Bureau of Standards Certified Reference Material no. 1577a) showed excellent linearity ([predicted] = 1.007[actual] - 0.166 micrograms per sample) and analytical recovery (98%). Precision (CV) was 5.4% when iron content was 10 micrograms per sample. Assaying split samples of mouse tissues, we found a close correlation between iron concentrations obtained with closed vs open vessels ([closed] = 0.878[open] + 68 micrograms/g, r = 0.994, range 400-4600 micrograms/g dry weight). In contrast to time-consuming conventional procedures for tissue dissolution, closed-vessel digestion with microwave energy dramatically shortens time for tissue preparation, minimizes use of caustic acid, reduces risk of sample loss or contamination, and yields accurate and reproducible results.
Asunto(s)
Hierro/análisis , Microondas , Animales , Bovinos , Peróxido de Hidrógeno , Riñón/análisis , Hígado/análisis , Ratones , Nitratos , Ácido Nítrico , Control de Calidad , Bazo/análisis , Estadística como Asunto , Factores de TiempoRESUMEN
Iron overload from repeated transfusions of RBCs in long-term hemodialysis patients is a problem of increasing clinical significance. We report on the prevalence of and diagnostic criteria for identification of hemodialysis patients with iron overload. In 150 unselected hemodialysis patients, 62 (41%) had ferritin levels greater than 2,000 ng/mL (normal = 10 to 360 ng/mL). In 16 of these patients, accurate transfusion histories were obtained and ferritin levels correlated with calculated transfusional iron burden (r = 0.553, P less than .05). These patients could be divided into two distinct groups on the basis of their response to a single dose (2 g, IV) of deferoxamine: "high" responders had twice the level of feroxamine (the chelated product of deferoxamine and iron) of the "low" responders (P less than .001). High responders also had significantly higher prevalence of the "hemochromatosis" alleles A3, B7, and B14 than a large group of dialysis patients awaiting transplantation (71% v 37%, P less than .001). In two patients with iron overload and clinically significant bone disease, bone histology revealed prominent iron staining at the calcification front. We conclude that transfusional iron overload is a significant clinical problem in long-term hemodialysis patients, that may also be associated with bone pathology.