Reduction of free immunoglobulin light chains using adsorption properties of hemodiafiltration with endogenous reinfusion.

In this work we investigated the acute effects of hemodiafiltration with endogenous reinfusion (HFR therapy) on the removal of free immunoglobulin light chains (FIgLCs), which may be considered members of the family of uremic toxins. In two groups of patients - group 1 (polyclonal FIgLCs production) and group 2 (monoclonal plasma cell proliferative disorders), we analyzed the pre- and postdialysis levels of kappa- and lambda-chains. In group 1 we observed a significant reduction of FIgLCs (p < 0.01). A similar trend was found in patients of group 2 only for kappa-chains. The FIgLCs removal ratio was significantly higher for kappa- than lambda-chains in the two patient groups. In vitro data showed affinity of macroporous resin to binding FIgLCs. Our results show that the HFR therapy could be effective in removing FIgLCs, particularly kappa-chains in dialysis patients with polyclonal and monoclonal FIgLCs production.

Coronary calcifications in end-stage renal disease patients: a new link between osteoprotegerin, diabetes and body mass index?

The aim of the study was to assess the factors potentially involved in coronary artery calcifications (CAC) in end-stage renal disease patients. 253 hemodialysis (HD) patients (92 females, 161 males), aged 62.5 +/- 13.5, who had been on HD treatment for at least 6 months, were enrolled in a cross-sectional study. Calcium-phosphate product (Ca x P), body mass index (BMI), fetuin-A, osteoprotegerin (OPG), osteopontin, transforming growth factor-beta1 (TGF-beta1), fibroblast growth factor-23 (FGF-23) and matrix Gla protein (MGP) were considered. CAC was assessed using multislice spiral computed tomography and calcium score was quantified by means of the Agatston score. The median calcium score was 364 Agatston (range 0-7,336). CAC was detected in 228/253 patients (90.1%). Multivariate regression analysis, adjusted for age and for dialysis vintage, showed that TGF-beta1, OPG and days with Ca x P >55 mg/dl are independent predictors of CAC, while MGP was shown to be a protective factor. Surprisingly, results showed that BMI was a protective factor too: the interpolation with cubic spline function revealed a significant reduction in calcium score in patients with a high BMI (>28). However, when diabetes was considered in the regression analysis, only OPG emerged as a predictor of a high CAC score. The interpolation with spline function continued to show a significant reduction in CAC score in nondiabetic and in diabetic patients with the highest BMI quartile. The protective effect of a high BMI on CAC might represent another example of inverse biology in dialysis patients but it needs to be further addressed in larger longitudinal studies.

5-methyltetrahydrofolate administration is associated with prolonged survival and reduced inflammation in ESRD patients.

BACKGROUND: Hemodialysis (HD) patients have a greatly increased risk of cardiovascular morbidity and mortality. For this reason, attempts are often made to normalize hyperhomocysteinemia. This randomized prospective study sought to determine which risk factors are predictors of mortality and whether high doses of folates or 5-methyltetrahydrofolate (5-MTHF) could improve hyperhomocysteinemia and survival in HD patients. METHODS: 341 patients were divided into two groups: group A was treated with 50 mg i.v. 5-MTHF, and group B was treated with 5 mg/day oral folic acid. Both groups received i.v. vitamin B(6) and B(12). By dividing patients into C-reactive protein (CRP) quartiles, group A had the highest survival for CRP <12 mg/l, whereas no survival difference was found for group B. CRP was the only predictive risk factor for death (RR 1.17, range 1.04-1.30, p = 0.02). Dialysis age, hyperhomocysteinemia, methylenetetrahydrofolate reductase polymorphism, albumin, lipoprotein (a) and folate did not influence mortality risk. Survival in group A was higher than that in group B, namely 36.2 +/- 20.9 vs. 26.1 +/- 22.2 months (p = 0.003). RESULTS: Our results suggest that CRP, but not hyperhomocysteinemia, is the main risk factor for mortality in HD patients receiving vitamin supplements. Intravenous 5-MTHF seems to improve survival in HD patients independent from homocysteine lowering.

Reverse mid-dilution: new way to remove small and middle molecules as well as phosphate with high intrafilter convective clearance.

BACKGROUND: The removal of small and middle molecules has a relevant impact on haemodialysis (HD) patient survival. Mid-dilution (MD) is a technique combining ease of use with high diffusive-convective clearances. However, MD may increase the intrafilter blood pressure due to the high filtration fraction. We devised a new filter configuration, reverse MD, with an inverted blood inlet and outlet. We compared biochemical and technical performances of reverse MD vs standard MD. METHODS: Eight HD patients underwent one standard MD treatment and one reverse MD. Samples for instantaneous clearance and total mass removed from dialysate spilling (urea, phosphate, beta2-microglobulin, angiogenin) were obtained. Dialysate and blood pressures in the circuit were monitored every 15 min. The reinfusion rate was set at 6 l/h for both treatments. RESULTS: Absolute removals were very high and statistically comparable in both the configurations. Pressures were significantly lower with the reverse compared with the standard MD: inlet blood pressure was 731+/-222 and 595+/-119 mmHg in the standard and in the reverse MD, respectively. The transmembrane pressures were lower in the reverse compared with the standard MD (422+/-90 and 611+/-136 mmHg for 1st stage; 188+/-54 and 307+/-56 mmHg for 2nd stage). CONCLUSIONS: Reverse MD could be an ideal technique for high ultrafiltration routine treatments without any external fluid reinfusion. It allows a very high removal of small and middle molecules, with relatively lower intrafilter pressures.