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INTRODUCTION: Chronic kidney disease is a major public health problem. In the last decade, it has been shown that the early stages of chronic kidney disease are associated with an inflammatory condition involving an increased risk of cardiovascular morbidity and long-term mortality. In patients with chronic kidney disease and more specifically those on hemodialysis, cardiovascular events are the most common cause of death. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase and may be an independent risk factor for endothelial dysfunction and cardiovascular disease. METHODS: We performed a cross-sectional analysis to identify factors that were associated with ADMA such as certain medications related to cardiovascular disease in dialysis patients. RESULTS: Patients who were treated with paricalcitol had significantly lower levels of ADMA (0.21 ± 0.19 µmol/l) compared with those not treated with paricalcitol (0.42 ± 0.35 µmol/l) (P = 0.00027). Dividing ADMA levels by quartiles, patients treated with paricalcitol were less likely to have very high level ADMA (P = 0.014), whereas there were no significant differences with other medications. Higher dose of paricalcitol was also related to lower levels of ADMA noting an inverse correlation (r = -0.36, P = 0.013). DISCUSSION: Hemodialysis patients treated with paricalcitol presented significantly decreased ADMA levels compared with those who did not receive this treatment. Possible beneficial effects in terms of cardiovascular morbidity and mortality by paricalcitol and its association with ADMA and nitric oxide synthesis are unknown. Studies to confirm this effect and determine the underlying pathophysiological mechanism are necessary.
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BACKGROUND: Primary analysis of the European Automated Peritoneal Dialysis Outcomes Study (EAPOS) found that patients with daily ultrafiltration (UF) below a predefined target of 750 mL at baseline experienced increased mortality and continuing low UF over 2 years. SETTING: Multicenter, prospective observational study of prevalent, functionally anuric patients on automated peritoneal dialysis (APD) treated to predefined standards. METHODS: Secondary data analysis to determine clinical covariates that might support a link between poor UF and outcome, including pattern of comorbidity, prescription, nutrition as determined by Subjective Global Assessment (SGA), membrane function, and blood pressure (BP). Ultrafiltration was treated as a categorical (comparing patients above and below target at baseline) and continuous dependent variable in univariate and multivariate regression. The relationship between BP and survival was also explored. RESULTS: Of 177 patients recruited from 28 centers across Europe, 43 were below the UF target at baseline. Compared to those above target, there were no differences in the spread of comorbidity, type of APD prescription, SGA, BP, hemoglobin, HCO3, or parathyroid hormone, at baseline or at any later time. At baseline, plasma calcium and, at 12 months, plasma phosphate were lower in the low UF group. There was a weak positive correlation between baseline systolic or diastolic BP and UF, which remained on multivariate analysis but accounted for just 9% of the variability in BP. There was no clear relationship between baseline BP and survival, although, if anything, low BP was associated with earlier death. Poor UF was associated with lower mean dialysate glucose concentration during the first 4 months and with consistently worse membrane function. CONCLUSIONS: The increased mortality associated with poor UF is likely multifactorial and not easily explained by clear differences in comorbidity, nutritional state, or other indices of treatment at baseline. The lower plasma phosphate suggests a subsequent fall in appetite. Poor BP control is unlikely to be the explanation, and a link between lower BP, reduced UF, and earlier death is suggested. Failure to achieve adequate UF due to worse membrane function remains an important and potentially reversible or preventable cause.