RESUMEN
Dyslipidemia is common in chronic hemodialysis patients and its underlying mechanism is complex. Hemodialysis causes an imbalance between antioxidants and production of reactive oxygen species, which induces the oxidative stress and thereby may lead to accelerated atherosclerosis. Statins have been found to be little effective in end-stage kidney disease and other lipid-lowering therapies have been only scarcely studied. The study aimed to assess the effect of low-dose fenofibrate therapy on plasma lipids and redox status in long-term hemodialysis patients with mild hypertriglyceridemia.Twenty seven chronic hemodialysis patients without any lipid-lowering therapy were included in a double-blind crossover, placebo-controlled study. The patients were randomized into two groups and were given a sequence of either 100 mg of fenofibrate per each hemodialysis day for 4 weeks or placebo with a week-long wash-out period between treatment periods. Plasma lipids, high sensitive C-reactive protein (CRP), urea, creatinine, electrolytes, phosphocreatine kinase (CK), GOT, GPT and plasma thiols (total and free glutathione, homocysteine, cysteine and cysteinylglycine) were measured at baseline and after each of the study periods. Plasma aminothiols were measured by reversed phase HPLC with thiol derivatization with 2-chloro-1-methylquinolinium tetrafluoroborate.Fenofibrate therapy caused a significant decrease of total serum cholesterol, LDL cholesterol and triglycerides and an increase of HDL cholesterol. The treatment was well tolerated with no side-effects but there was a small but significant increase of CK not exceeding the upper limit of normal range. There were no changes of serum CRP, potassium, urea, and creatinine and liver enzymes during the treatment. Neither total nor total free cysteinylglycine and cysteine changed during the study but both total and free glutathione increased during the therapy with fenofibrate and the same was observed in case of plasma homocysteine.The study shows that a treatment with reduced fenofibrate dose is safe and effective in reducing serum triglycerides and cholesterol in chronic dialysis patients and may shift plasma aminothiol balance towards a more antioxidative pattern.
Asunto(s)
Fenofibrato/administración & dosificación , Fenofibrato/farmacología , Hipolipemiantes/administración & dosificación , Hipolipemiantes/farmacología , Lípidos/sangre , Plasma/efectos de los fármacos , Diálisis Renal , Presión Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxidación-Reducción/efectos de los fármacos , Placebos , Plasma/metabolismo , Compuestos de Sulfhidrilo/sangreRESUMEN
INTRODUCTION: The phosphate-binders presently used in the treatment of calcium-phosphorus disorders in dialysis patients remain a crucial element of cardio-vascular protection. The aim of the study was to assess short-time magnesium carbonate treatment efficacy in hemodialysis patients with hyperphosphatemia. MATERIAL AND METHODS: The study involved 64 participants (32 male and 32 female) aged 29-84 years, with end-stage renal disease, hyperphosphatemia (> 1.78 mmol/l), dialysis 3 times a week, mean session time 4 hours 15 minutes. All the patients were divided into three groups: I--30 patients treated with magnesium carbonate 3 x 1 g; group II--10 patients treated with sevelamer hydrochloride 0.8 g--3 x 2 tabl (3 x 1.6 g); group III--24 patients treated with calcium carbonate 3 x 2 g. Participants were categorized randomly to groups I and II and to group III only patients with decreased serum calcium concentration (< 2.1 mmol/1) were assigned. The doses stayed constant within 12 weeks of therapy. RESULTS: In group treated with magnesium carbonate after 3 months of the treatment the decrease of plasma parathormon (iPTH) from 526.1 +/- 463.3 to 443.2 +/- 223.1 (pg/ml), calcium (Ca) from 2.4 +/- 0.2 to 2.3 +/- 0.1 (mmol/1); the highest reduction of phosphate (P) 2.1 +/- 0.5 to 1.6 +/- 0.4 (mmol/1) and calcium phosphate product (Cax P) from 4.6 +/- 2.3 to 3.5 +/- 1.1 (mmol2/ l2) were observed. In group II, iPTH slightly increased from initial 425.26 +/- 192.5 to 445.6 +/- 222.3 (pg/ml); serum calcium decreased from 2.23 +/- 0.17 to 2.0 +/- 0.2 (mmol/l); phosphates dropped from 2.35 +/- 0.43 to 2.0 +/- 0.3 (mmol/l) and Ca x P index from 5.1 +/- 1.2 to 4.1 +/- 0.7 (mmol2/l2). In group treated with calcium carbonate iPTH decreased from 308.2 +/- 196.6 to 301.9 +/- 188.5 (pg/ml). Calcium, phosphate and Ca x P dropped during the treatment from 2.06 +/- 0.23 to 2.05 +/- 0.2 (mmol/l), 2.17 +/- 0.36 to 1.86 +/- 0.45 (mmol/l) and from 4.7 +/- 0.8 to 3.7 +/- 0.9 (mmol2/l2), respectively. Calcium-phosphorus disorders were normalized to actual guidelines only in participants treated with magnesium carbonate. CONCLUSIONS: Magnesium carbonate seems to be the effective treatment of calcium-phosphorus disorders in hemodialysis patients. However its administration, similarly to other non-calcium phosphate-binders, is limited and dedicated to patients with normal serum calcium concentration.
Asunto(s)
Calcio/metabolismo , Hiperfosfatemia/tratamiento farmacológico , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Magnesio/uso terapéutico , Fósforo/metabolismo , Diálisis Renal/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Quelantes/uso terapéutico , Femenino , Humanos , Hiperfosfatemia/etiología , Hiperfosfatemia/metabolismo , Masculino , Persona de Mediana Edad , Poliaminas/uso terapéutico , SevelamerRESUMEN
INTRODUCTION: Calcimimetics are highly efficient drugs in treatment of secondary hyperparathyroidism (sHPT) in patients on haemodialysis. The effect and the dose of cinacalcet may depend on severity of sHPT, and alfacalcidol supplementation helps in the treatment optimization. The study evaluated cinacalcet and alfacalcidol treatment efficacy in haemodialysis patients with different secondary hyperparathyroidism severity recognized by iPTH. MATERIAL AND METHODS: The study group comprised of 82 participants (male 67 and 34 female) in aged from 36 to 75 years, on haemodialysis. All patients were divided into two groups: the study group--40 participants treated with cinacalcet accompanied by alfacalcidol started after 8 months of the study (0.25 to 0.5 microg/day) and the control group--42 patients. The study group comprises of two subgroups: I--moderate sHPT with iPTH 500 to 800 pg/ml and II--severe sHPT with iPTH > 800 pg/ml. The basic phosphate binder treatment throughout the study period in all groups was calcium carbonate. RESULTS: In the subgroup I initial mean iPTH 700 +/- 129 pg/ml was reduced to 550 +/- 61 pg/ml (p < 0.05) in the third month with no need of the Mimpara dose change. No further iPTH decrease up to eighth month of the treatment was observed despite the cinacalcet dose increase to 53 mg (p < 0.05). The alfacalcidol supplementation decreased iPTH to 331 +/-55 pg/ml (p < 0.05) and the cynacalcet dose to 42 mg (p < 0.05). In the II subgroup iPTH was reduced from 1035 +/- 149 pg/ml to 885 +/- 101 pg/ml (p < 0.05) in the third month of the treatment and Mimpara dose changed to 90 mg. Up to eighth month iPTH did not change (790 +/- 92 pg/ml; p > 0.05) despite the cinacalcet dose increase to 122 mg (p < 0.05). The alfacalcidol supplementation induced iPTH reduction to 622 +/- 71 pg/ml (p < 0.05) and the cinacalcet dose to 100 mg (p < 0.05). CONCLUSIONS: Cinacalcet convinced its effectiveness in the iPTH serum concentration control in haemodialysis patients independently of secondary hyperparathyroidism severity and alfacalcidol supplementation enhanced its efficacy. Still in case of the late introduction of Mimpara this drug was recognized as potent however the efficient dose was mandatory multiply.
Asunto(s)
Hidroxicolecalciferoles/administración & dosificación , Hiperparatiroidismo Secundario/tratamiento farmacológico , Naftalenos/administración & dosificación , Diálisis Renal , Adulto , Cinacalcet , Quimioterapia Combinada , Femenino , Humanos , Hiperparatiroidismo Secundario/sangre , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangreRESUMEN
AIM: Uremic neuropathy (UN) is a typical complication of long-term dialysis therapy and may manifest as distal, symmetric, and both senso-motoric and autonomic nerve dysfunction. Its clinical picture is highly variable and it is not known how the symptoms of UN reported by chronic dialysis patients correspond to positive results of clinical tests for autonomic dysfunction. The objective of this study was to compare the prevalence of self-reported symptoms of autonomic neuropathy (AN) revealed in patient questionnaires with the prevalence of findings from objective clinical tests. METHODS: The study group included 45 patients (26 males, 19 females), mean age 60 +/- 15.5 years, on chronic hemodialysis for 7.8 +/- 2.6 years. In all subjects, blood pressure (BPci) and heart rate (HRci) variability indexes (calculated as BP and HR during Ewing and Clarke' tests divided by HR and BP at rest) were measured using the Finapres which records beat-to-beat blood pressure and heart rate. Additionally, patients completed seven-question questionnaires which assessed the presence of most typical AN symptoms. The control group comprised 12 healthy subjects (age 52 +/- 19.5 years). RESULTS: The results from the questionnaires showed that falls of BP occurred in 73% of patients, itching of skin in 42%, constipation or diarrhea in 33%, filling of stomach in 25%, and decreased sweating in 17%. Altogether 85.9% of patients reported one or more subjective symptoms of neuropathy. In contrast, modified Ewing and Clarke's test revealed that only 17.7% of participants demonstrated overt pathologies. Neither blood pressure nor heart rate changeability indexes in patients and healthy subjects showed significant differences with the exception of intense inhalation and static effort. CONCLUSIONS: Our results show much higher frequency of subjective symptoms of AN in chronic dialysis patients than objective symptoms detected with clinical tests.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/epidemiología , Fallo Renal Crónico/epidemiología , Diálisis Renal , Encuestas y Cuestionarios , Anciano , Presión Sanguínea , Femenino , Frecuencia Cardíaca , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Prevalencia , Uremia/epidemiología , Uremia/terapiaRESUMEN
UNLABELLED: There are several parameters of left ventricular (LV) systolic function assessment. The calculation of the ejection fraction (EF) strongly relates to the preload and afterload conditions. Wall motion score index (WMSI) seems to be to impractical as the semi-quantitative method. Measurement of the LV pressure rise by Doppler evaluation of mitral regurgitation is a reproducible and an accurate method for dP/dt evaluation. As a method for LV systolic function estimation it does not depend on loading conditions. We have compared the prognostic value of these three methods in patients with a broad spectrum of systolic dysfunction. The study group consisted of 75 patients evaluated by all these methods in years 1995-1999 in our echocardiographic laboratory (73%--men, mean 54 +/- 12 years). In 13 patients the coronary artery disease was diagnosed but LV function was apparently normal, in 35--regional dysfunction after myocardial infarction was described, and in 27--global dysfunction due to idiopathic dilated cardiomyopathy. The EF ranged from 11% to 70% (mean 34 +/- 14%), WMSI--from 1 to 3.6 points (mean 2.2 +/- 0.7), and dP/dt from 235 to 4000 mmHg/s (mean 1108 +/- 698 mmHg/s). The closest relationship was noted between EF and dP/dt (R2=0.50). During 38 +/- 19 months of follow-up, 40 patients died (53%). In the multivariate logistic analysis the only significant parameter related to prognosis was EF (p=0.001). WMSI (p=0.12) and dP/dt (p=0.16) were not statistically significant correlated to death. CONCLUSION: The left ventricular ejection fraction still remains the most important parameter for the evaluation of prognosis in patients with depressed systolic function. Left ventricular pressure rise describes the systolic function but does not have impact on the prognostic evaluation.