Omega-3 polyunsaturated fatty acids and proxies of cardiovascular disease in hemodialysis: a prospective cohort study.

BACKGROUND: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have antithrombotic, lipid-lowering and antiinflammatory properties. The aim of this study was to verify if dietary supplementation with omega-3 PUFAs is able to induce changes of blood pressure, nutritional and coagulative profile, inflammation and blood cell counts in patients on hemodialysis (HD). METHODS: We designed a 12-month, prospective, single-blind, sequential intervention, cohort study. All of the HD patients undergoing HD in our unit were eligible for the study. Patients on HD for at least 6 months with an autologous vascular access were enrolled. No thresholds for blood pressure or lab parameters were considered. Patients taking nonsteroidal antiinflammatory drugs, steroids or statins or those with catheters, grafts, liver diseases, malignancies, malnutrition or sepsis were excluded. After the baseline evaluations the patients underwent 3 consecutive 4-month study periods taking the following supplements: A (olive oil: 2 g/day), B (omega-3 PUFA: 2 g/day), C (olive oil: 2 g/day). RESULTS: Twenty-four patients met the inclusion criteria. All patients completed the follow-up. Fibrinogen, hemoglobin, platelet, red and white blood cell counts, parathormone (PTH), partial thromboplastin time (PTT), serum total cholesterol, triglycerides, apolipoprotein A and B, C-reactive protein (CRP) and albumin levels did not change significantly during the study. On the contrary, systolic (mean +/- SD) (A: 131 +/- 17.8 mm Hg; B: 122 +/- 12.8 mm Hg; C: 129 +/- 13.2 mm Hg), diastolic (A: 83 +/- 16.3 mm Hg; B: 72 +/- 14.8 mm Hg; C: 79 +/- 6.5 mm Hg) and mean blood pressure (A: 99 +/- 16.8 mm Hg; B: 88 +/- 14.1 mm Hg; C: 96 +/- 8.7 mm Hg) were significantly lower at the end of study period B (repeated measures ANOVA and Tukey's post hoc test: p<0.05). CONCLUSIONS: In our experience, blood pressure was the only parameter influenced by omega-3 PUFA supplementation in patients on long-term HD.

Italian audit on therapy of hypertension in chronic kidney disease: the TABLE-CKD study.

A large body of evidence supports the validity of decreasing blood pressure to target levels in patients with essential hypertension to prevent cardiovascular disease. This issue becomes even more critical in chronic kidney disease because of the remarkably greater risk for cardiovascular fatal and nonfatal events. Indeed, renal patients should maintain blood pressure levels less than those suggested for the general population. Paradoxically, management of hypertension in this high-risk patient population is far from optimal and certainly worse with respect to essential hypertension. The Target Blood Pressure Levels in Chronic Kidney Disease (TABLE-CKD) study, performed in Italian patients with mild to advanced chronic kidney disease regularly followed-up by nephrologists, has shown that the prevalence of patients at target blood pressure is less than 20%. The assessment of antihypertensive strategy in these patients, however, suggests that there is room for improvement; in particular, a more aggressive treatment of volume expansion may ameliorate hypertension control in this population characterized by a high salt sensitivity of blood pressure.

Comorbid conditions and gender impact the primary survival of distal radio-cephalic arteriovenous fistula inpatients on long-term hemodialysis.

BACKGROUND: Vascular access failure complicates the clinical picture of patients on long-term hemodialysis, increasing the number of hospitalizations and the respective costs. In these patients we analyzed the possible meaningful relationship between comorbidities and primary survival of the autologous distal radio-cephalic arteriovenous fistula (dAVF), pointing out the influence of other variables on that relationship. METHODS: We evaluated the dAVF placed in our unit between January 1, 1995, and December 31, 2003, on 105 patients (55 males) 63.8 +/- 14.1 (average +/- SD) years old. The dAVF creation date was the starting point while the dAVF failures due to either thrombosis or malfunction (KT/V < 1.2) were the study end-point. Death, conversion to peritoneal dialysis, transfer to other units and renal transplantation were assumed as censure criteria. ICED score, single comorbidities, use of temporary catheter at the hemodialysis initiation, serum lipids and CRP levels, hematocrit, blood platelet count and coagulative parameters (at the time of the dAVF creation) were considered as covariates. The Kaplan-Meier method and Cox's proportional hazards regression were used in the dAVF survival analysis. RESULTS: During the study we recorded 38 dAVF failures (median primary survival of the dAVF 487.3 days, with a failure rate of 0.645 per patient-year). Age, lab variables, single comorbidities, and use of temporary catheters did not impact the dAVF primary survival. Conversely ICED score > 1 (P = 0.014; hazard ratio = 1.648; 95% CI = 1.106-2.454) as well as feminine gender (P = 0.018; hazard ratio = 1.640; 95% CI = 1.024-2.256) increased the risk of dAVF failure. CONCLUSIONS: In our cohort of patients on long-term hemodialysis neither the single comorbidities nor the temporary catheterization influence the lifespan of the vascular access. However our data demonstrated the meaningful inverse relationship between dAVF primary survival and a composite comorbidity index reflecting not only the type of the diseases but also their associations and severities. This relationship was not influenced by other covariates although the feminine gender was significantly associated with worse survival of the vascular access.

Does atorvastatin influence serum C-reactive protein levels in patients on long-term hemodialysis?

BACKGROUND: The increase in serum C-reactive protein (CRP) levels is an independent determinant of cardiovascular events in long-term hemodialysis (HD) patients. Recently, statins have shown anti-inflammatory properties in addition to their lipid-lowering effect. METHODS: We designed a 6-month, prospective, randomized, controlled study to assess the safety and efficacy of atorvastatin in reducing serum CRP levels in long-term HD patients. Patients on HD therapy for at least 6 months, with autologous vascular access, were included. Patients presenting with illnesses and/or use of drugs that may affect CRP levels were excluded. After randomization, group A included 16 patients treated with atorvastatin (10 mg/d orally), and group B included 17 patients treated with placebo. Body mass index, Kt/V, normalized protein catabolic rate, mean blood pressure, and levels of hemoglobin, serum CRP, albumin, creatinine, lipids, and enzymes were recorded at baseline and after 6 months. RESULTS: Qualitative/quantitative parameters were homogeneous between the groups at baseline. In group A, median serum CRP levels decreased from 9 mg/L (range, 5 to 22 mg/L) at baseline to 5 mg/L (range, 3 to 16 mg/L) after 6 months (P = 0.004). In group B, values were 8 mg/L (range, 4 to 14 mg/L) at baseline and 7 mg/L (range, 3 to 17 mg/L) after 6 months (P = 0.98). Serum CRP levels were lower in group A than group B at month-4 (5 mg/L; range, 3 to 11 mg/L versus 7 mg/L; range, 3 to 10 mg/L, respectively; P = 0.054) and month-6 evaluations (5 mg/L; range, 3 to 16 mg/L versus 7 mg/L; range, 3 to 17 mg/L, respectively; P = 0.060). After 6 months, only in group A was there a significant decrease in serum cholesterol levels (P = 0.041) and a significant increase in serum albumin levels (P = 0.004). Enzyme levels were stable during the study in both groups. CONCLUSION: Administration of atorvastatin is safe in patients on long-term HD therapy and, in addition to its beneficial effects on lipid levels, induces a significant decrease in serum CRP levels, with a consequential increase in serum albumin levels.

Predictors of serum creatinine in haemodialysis patients: a cross-sectional analysis.

BACKGROUND: C-reactive protein (CRP) levels, an acute phase response index, predict cardiovascular outcome and are inversely related to visceral proteins, including albuminaemia in haemodialysis patients. Less definite is the relationship between inflammation and markers of somatic proteins such as serum creatinine in such patients. To explore these questions, a cross-sectional analysis of potential predictors of serum creatinine was performed. METHODS: One hundred and seventy-nine prevalent haemodialysis patients as of June 2001 were included in the cohort. Midweek pre-dialysis blood samples were collected during the months of June, September through to December 2001 inclusive, and determinations of serum urea (urease method), creatinine (alkaline picrate method) and CRP levels by means of a high sensitivity immunonephelometric method were performed. Furthermore, pre- and post-dialysis body weights were recorded and 2 min post-dialysis serum urea levels were determined three times. They were utilized for the calculation of single pool Kt/V and of normalized protein catabolic rate (nPCR). Each of the data represents the mean of three determinations made every 3 months in the study period. RESULTS: The analysis of multivariate linear regression was able to validate our model characterized by a dependent variable, serum creatinine and four independent variables (age, CRP, Kt/V and nPCR) (R(2)=0.60; F=24.10; P<0.00001; SE=1.94). Age (-0.08 mg/dl decrease in serum creatinine per 1-year increase in age), Kt/V (-0.25 mg/dl decrease in serum creatinine per 0.1 increase in Kt/V) and nPCR (0.10 mg/dl increase in serum creatinine per 0.1 g protein/kg/day increase in nPCR) were independently predictive of serum creatinine (P<0.00001). CRP and dialysis vintage did not predict serum creatinine. Stratifying the patients for the effects of CRP, only CRP values 4 mg/l were not. A further insight was given by the stratification of the patients for the effects of the interquartile ranges of CRP: it showed a progressive and statistically significant reduction of beta-coefficient inversely related to the increasing CRP values (P=0.003). Thus, the nature of the correlation between CRP and serum creatinine changes with increasing CRP values: from being a direct one, it shows a trend towards a transformation into an indirect one with beta=0 at a CRP value of approximately 9 mg/l. However, this indirect relationship does not reach statistical significance. CONCLUSIONS: The present cross-sectional study suggests that the activation of acute phase response does not influence creatinine metabolism in haemodialysis patients; in contrast, age, Kt/V and nPCR predict serum creatinine levels. Larger prospective trials are needed to achieve a definitive answer about the relationship between somatic proteins, acute phase response activation and nutrition in dialysis patients.