Internal hemodiafiltration versus low-flux bicarbonate dialysis: Results from a long-term prospective study.

INTRODUCTION: About ten years ago it was discovered that changes in filter design which increase passive filtration improved dialysis efficiency. Later, these modified membranes showed similar intra-dialytic efficiency when used in on-line hemodiafiltration or in bicarbonate dialysis, called internal hemodiafiltration. AIM AND METHODS: On the basis of these previous results, we studied the long-term effects of internal hemodiafiltration, in comparison with low-flux bicarbonate dialysis. The pre-dialysis beta2-microglobulin level was chosen as the primary outcome variable. A prospective multicenter study with a cross-over scheme, 2 treatments and 3 periods, was designed. Twenty-four patients, followed in two dialysis centers, were enrolled. Many other parameters were measured every month at the first dialysis session of the week. The intra-dialytic removal of urea, beta2-microglobulin and homocysteine was also calculated. RESULTS: The removal of uremic toxins was significantly higher in internal hemodiafiltration than in low-flux bicarbonate dialysis. The pre-dialysis value of urea, phosphorus, beta2-microglobulin and homocysteine was lower during internal hemodiafiltration as compared with low-flux bicarbonate dialysis. The mean pre-dialysis value of hemoglobin was significantly higher during internal hemodiafiltration than low-flux bicarbonate dialysis, with a trend towards a significantly lower consumption of erythropoiesis stimulating agents during internal hemodiafiltration as compared with low-flux bicarbonate dialysis. CONCLUSIONS: Long-term treatment with internal hemodiafiltration improves the removal of small molecules and stops the continuous increase of middle molecules as seen in low-flux bicarbonate dialysis. Internal hemodiafiltration may substitute low-flux bicarbonate dialysis, but we need new prospective studies about long-term hard end-points.

Some old drugs improve late primary patency rate of native arteriovenous fistulas in hemodialysis patients.

Vascular access failure causes 20% of all hospitalizations of dialysis patients. Native arteriovenous fistulas, the best type of dialysis vascular access, have a 1-year primary patency rate that is extremely variable, ranging 40-80%. Neointimal hyperplasia is the most important cause of arteriovenous fistula late primary dysfunction. In recent years the arteriovenous fistula late primary patency rate has not improved because of the increase of old uremic patients with a high number of comorbidities and the lack of new therapeutic interventions. Therefore, we performed a long-term case-control study to analyze which factors or drugs may affect native arteriovenous fistula late primary patency rate in 60 incident hemodialysis patients. The arteriovenous fistula late primary patency rate was 75.1% after 12 months, 58.5% after 24 months, and 50% after 987 days. Homocysteine levels during follow-up had a significant direct association with vascular access failure (event vs. event-free 28.5+/-1.9 vs. 22.3+/-1.2 micromol/L, p<0.01). Folate values had a trend toward an inverse relationship with arteriovenous fistula failure (event vs. event-free 11.5+/-1.2 vs. 14.6 vs. 1.1 ng/mL, p=0.06). Patients treated with folic acid and/or statin had an arteriovenous fistula late primary patency rate significantly higher than patients without folic acid and statin therapy, respectively, 81.7% vs. 66% after 1 year and 71.5% vs. 39.1% after 2 years (p=0.02). Many other factors were not associated with vascular access failure. Statin and homocysteine-lowering folic acid therapy is associated with prolonged arteriovenous fistula survival. It is important to perform randomized trials to verify our observation.

Homocysteine-lowering vitamin B treatment decreases cardiovascular events in hemodialysis patients.

BACKGROUND: Dialysis patients have higher cardiovascular events rate than patients with normal renal function. Hyperhomocysteinemia, a risk factor for cardiovascular disease, is frequently detected in dialysis patients. Vitamin B supplementation lowers hyperhomocysteinemia, but it is unknown whether it reduces cardiovascular events rate. We planned a long-term study to analyze the effects of homocysteine-lowering vitamin B therapy on cardiovascular disease in hemodialysis patients. METHODS: We performed a single center open prospective trial. Patients, just on folate therapy at enrolment, were left out from randomization and maintained folate therapy according to study's protocol (group A). Patients, untreated with folic acid at recruitment, were randomly assigned to other 2 groups: patients submitted to folate supplementation according to study's protocol (group B), and untreated ones (group C). We instructed patients to take 5 mg oral daily folic acid or 5 mg every other day whether serum folate levels were up the normal high limit. We measured homocysteine, folate and vitamin B12 plasma levels at baseline and every 4 months. We chose the appearance of fatal and nonfatal cardiovascular events as end-points. RESULTS: We analyzed data of 114 patients for a median follow-up time of 871 days. Stepwise regression analysis demonstrated that baseline homocysteine levels were related to folate (coefficient: -1.02; F: 64.5), creatinine (coefficient: 0.98; F: 11.3), and C reactive protein (coefficient: -0.64; F: 4.3). Patients ended the study for the following reasons: cardiovascular morbidity (n = 44), death (n = 25), renal transplant (n = 9), moved away (n = 4). Cardiovascular events occurred in 58 of 114 patients (51%), in 26 of 63 (41%) treated patients (both group A and group B) and in 32 of 51 (63%; chi2 = 6.0; p = 0.05) untreated patients (group C). Kaplan-Meier survival analysis showed that cardiovascular events were less frequent in treated patients with low homocysteine levels (chi2 24.1; p < 0.0001). Cox regression analysis showed that cardiovascular events were explained by homocysteine, dialysis vintage, past cardiovascular accidents, and age. We noticed not only lower homocysteine levels, but also higher protein catabolic rate values in events-free patients as compared with patients with nonfatal cardiovascular events. After having divided patients into 4 subgroups according to high and low, split at median, Hcy and protein catabolic rate values, we observed in Kaplan-Meier survival curves for cardiovascular events by these subgroups that patients with low Hcy and high protein catabolic rate values showed a significant lower hazard rate than patients with high Hcy and low protein catabolic rate levels (chi2 = 21.7; p < 0.0001). CONCLUSIONS: This trial shows for the first time that homocysteine-lowering folate therapy decreases cardiovascular events in dialysis patients. It is necessary to perform large prospective studies to confirm our results.

Effects of folic acid treatment on homocysteine levels and vascular disease in hemodialysis patients.

BACKGROUND: Cardiovascular disease is the most important cause of morbidity and mortality in hemodialysis patients. These patients frequently have hyperhomocysteinemia, a putative risk factor for cardiovascular disease. Treatment with folate, B6 and B12 partially reduces hyperhomocysteinemia. We conducted a long-term study to evaluate whether 15 mg is more effective than 5 mg oral folic acid as a daily dosage to decrease hyperhomocysteinemia, and to assess whether homocysteine-lowering treatment reduces the risk of cardiovascular disease in hemodialysis patients. MATERIAL/METHODS: In a 1-year prospective randomised trial, 81 chronic hemodialysis patients, matched for age, gender and dialytic age, were divided into three groups: 30 untreated patients, 26 patients receiving 5 mg per day, and 25 patients receiving 15 mg per day. RESULTS: There was a significant reduction in hyperhomocysteinemia over time in treated patients as compared to untreated, but there were no significant differences between the two treated groups. Only 12% of the treated patients reached normal total homocysteine plasma levels. We observed a trend towards a significant difference in survival rate in cardiovascular morbidity between treated and untreated patients. Furthermore, hemodialysis patients with new vascular events showed higher homocysteine levels than patients without events. CONCLUSIONS: High-dose folic acid treatment did not improve outcome in hyperhomocysteinemia, and 88% of treated patients maintained higher than normal homocysteine levels. There was a trend towards a decreased rate of cardiovascular events in treated participants as compared to untreated ones.