RESUMEN
BACKGROUND: Cardiovascular disease is the major cause of death in the end-stage renal disease population. Novel risk factors such as homocysteine (Hcy) are of considerable interest in this group as hyperhomocysteinaemia is highly prevalent in the setting of renal impairment. Folic acid-vitamin B group therapies are only partially effective treatments. Hcy is highly protein-bound and thus poorly dialysed. Dialyzers with albumin-leaking properties have been shown to result in lowering of plasma Hcy. As the FX-class (Advanced Fresenius Polysulfone dialyzer) has greater clearance of larger molecular weight substances but is non-albumin-leaking, we explored the capacity of this new technology membrane to reduce plasma Hcy levels. METHODS: A prospective randomized cross-over trial in 35 prevalent haemodialysis patients, one group receiving 12 weeks dialysis using FX dialyzer then 12 weeks with standard high flux dialysis (SHF) and the other group SHF followed by FX dialyzer. All patients received vitamin B(6) 25 mg and folic acid 5 mg daily throughout the study. RESULTS: The primary outcome was plasma Hcy pre-dialysis at week 12. FX vs SHF showed no significant difference, 25+/-6.6 vs 25.9+/-5.8 microg/l, Delta95% CI = -2.77 to 4.59, P = 0.31. There was a non-significant trend toward a decrease in Hcy in both groups (27.43+/-7.68 to 25.91+/-5.78 micromol/l for SHF, P = 0.23 and 26.0+/-4.58 to 25.0+/-6.61 micromol/l for FX, P = 0.28). Analysis by repeated measures method demonstrated a statistically significantly lower Hcy with FX vs SHF dialyzer (adjusted beta = -1.30, 95% CI = -2.41 to -0.19, P = 0.022). K(t)/V(urea) was higher in FX vs SHF (1.35+/-0.18 vs 1.22+/-0.2; P = 0.013). Folate and B(6) levels did not change. CONCLUSIONS: The primary outcome analysis did not show any significant difference in pre-Hcy comparing FX and SHF membranes. Although our secondary analysis demonstrated a statistically significant difference between membranes, the magnitude of the difference (1.3 mumol/l) is not clinically significant. Thus the use of the FX dialyzer did not result in a clinically significant benefit in relation to improving pre-dialysis Hcy compared with standard high-flux dialysis.
Asunto(s)
Homocisteína/sangre , Riñones Artificiales , Diálisis Renal/métodos , Adulto , Anciano , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Estudios Cruzados , Femenino , Humanos , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de TiempoRESUMEN
BACKGROUND: Poor phosphate control is common among patients with end-stage renal disease. Sevelamer hydrochloride has been demonstrated to be a safe and effective phosphate binder when used as a monotherapy. However, cost limits its usefulness in many countries. Data assessing its effectiveness and safety in combination with conventional phosphate binders are lacking. METHODS: Dialysis patients meeting the following inclusion criteria participated in this study: (i) hyperphosphataemia >1.8 mmol/L (5.6 mg/dL); and (ii) an inability to tolerate currently available binders. The trial was conducted in three phases each lasting 3 months: (i) an observation phase (patients continued on their regular phosphate binders); (ii) a titration phase (sevelamer was added at a dose of 403 mg three times daily with meals, titrated to a maximum of 1209 mg three times daily); and (iii) a maintenance phase. RESULTS: Twenty-five patients were recruited into the study. Eighteen patients completed all three trial phases. Mean serum phosphate dropped from 2.11 +/- 0.06 mmol/L (6.6 +/- 0.2 mg/dL) during the observation period to 1.91 +/- 0.01 mmol/L (5.9 +/- 0.003 mg/dL) during the maintenance phase (P=0.02). Calcium x phosphate product fell from 5.49 +/- 0.17 mmol2/L2 (68.64 +/- 2.11 mg2 dL2) to 4.89 +/- 0.27 mmol2/L2 (61.36 +/- 3.35 mg2 dL2) (P=0.02). There was no significant change in serum calcium or parathyroid hormone. Total serum cholesterol fell from 3.8 mmol/L (3.4-4.37) 147 mg/dL (131-169) to 3.55 mmol/L (2.97-4.2) 137 mg/dL (115-162) (P=0.02). Serum low-density lipoprotein cholesterol also fell significantly from 1.67 +/- 0.10 mmol/L (65 +/- 4 mg/dL) to 1.52 +/- 0.11 mmol/L (59 +/- 4 mg/dL) (P=0.04). The average prescribed dose of sevelamer was 2.4 g/day. Elemental calcium dropped from 3.4 g/day (1.4 to 4.6) to 1.2 g/day (0.6-2.4) (P=0.04). Seventy-two per cent of patients reported mild flatulence, nausea and indigestion. Three patients discontinued treatment because of adverse effects. CONCLUSIONS: Sevelamer in combination with conventional phosphate binders is effective in lowering serum phosphate and calcium-phosphate product in patients with refractory hyperphosphataemia. Beneficial effects on lipid profile were also observed. Mild gastrointestinal upset is common.