Paolo Rindi

Potassium Removal Increases the QTc Interval Dispersion during Hemodialysis

This study was planned to clarify the mechanism(s) by which hemodialysis increases the QTc dispersion, a marker of risk of ventricular arrhythmias. To this aim, 10 uremic patients, without any relevant heart diseases, underwent two different types of hemodialysis schedules. In the first, 1 h of isolated high rate ultrafiltration preceded the standard diffusive procedure. In the second, during the first hour of standard bicarbonate hemodialysis, the decrease of plasma potassium concentration was prevented by increasing K+ concentration in the dialysate, according to its pre dialysis plasma levels. During the high rate ultrafiltration period, together with ECG signs of increased sympathetic nervous system activity and catecholamines secretion, the QTc dispersion did not change significantly. Instead, an evident increment was observed 1 h after the start of the diffusive hemodialysis, then slowly progressing until the end of the dialysis and finally returning to the pre dialysis values within 2 h after the end of the session. To the contrary, the increase of the QTc dispersion was totally blunted during a standard hemodialysis procedure in absence of plasma K+ decrease, but appeared again when the K+ dialysate fluid concentration was restored to 2 mmol/l. This study provides evidence that the increase of QTc dispersion occurring on hemodialysis is mainly related to the diffusive process, more precisely to the K+ removal. This is one more reason to focus attention on K+ removal rate especially when hemodialysis treatment is given in uremics affected by cardiac diseases with high risk of arrhythmias.

Plasma C-reactive protein in hemodialysis patients: A cross-sectional, longitudinal clinical survey

In hemodialysis patients, C-reactive protein (CRP), an acute-phase reactant, is a sensitive and independent marker of malnutrition, anemia, and amyloidosis. The aim of the present studies was to evaluate CRP and interleukin 6 levels in plasma samples from long-term hemodialysis patients on different extracorporeal modalities associated with or without backfiltration. Two hundred and forty-seven patients were recruited in eight hospital-based centers. All patients had been on their dialytic modality for at least 6 months. At enrollment, 46 hemodialysis patients out of 247 (18.6%) had clinical evidence of pathologies known to be associated with high CRP values. The 201 remaining patients were defined as clinically stable and were on conventional hemodialysis (34%), hemodiafiltration with infusion volumes <10 liters/session (10%), hemodiafiltration with infusion volumes <20 liters/session (32%), and double-chamber hemodiafiltration with infusion volumes <10 liters/session (22%). Analysis of CRP values in the clinically stable patients showed that an unexpectedly high proportion (47%) of the patients had CRP values higher than 5 mg/l (taken as the upper limit in normal human subjects). The values of CRP and interleukin 6 were significantly higher in hemodiafiltration with infusion volumes <10 liters/session than in hemodiafiltration with infusion volumes >20 liters/session, in hemodialysis and in double-chamber hemodiafiltration. The same pattern occurred after 6 months of follow-up in 171 out of 201 clinically stable patients. Hemodialytic conditions that expose to the risk of backfiltration such as low exchange volume hemodiafiltration may induce a chronic inflammatory state as reflected by increased plasma values of both CRP and interleukin 6, thus suggesting the need for hemodialytic strategies that reduce (hemodialysis with low-permeability membranes or hemodiafiltration with infusion volumes >20 liters) or eliminate (double-chamber hemodiafiltration) backfiltration of bacteria-derived contaminants.

PLASMA C-REACTIVE PROTEIN IS LINKED TO BACKFILTRATION ASSOCIATED INTERLEUKIN-6 PRODUCTION

Bacterial contamination of dialysate may enhance cytokine production in hemodialysis. The authors tested the hypothesis that C-reactive protein and interleukin-6 (IL-6) may be linked in a large group of patients exposed to backfiltration of dialysate over a long period of observation. Plasmas stored in a recently published multicenter study were reevaluated. Plasma C-reactive protein and IL-6 concentrations in patients with chronic uremia undergoing hemodiafiltration, which is known to be associated with backfiltration (Group II, 12 patients), were compared with those found in patients treated with a modified hemodiafiltration modality without backfiltration (Group I, 16 patients), and in patients shifted from one modality to the other (Group III, 27 patients), and in 10 patients on hemodialysis (Group IV) in a 1 year multicenter study. Plasma C-reactive and IL-6 both increased significantly (p < 0.002), but slowly (after 8 months) in Group II compared with I, and during the 4 month period in hemodiafiltration with backfiltration in Group III. Backfiltration of dialysate with a moderate to low degree of contamination may enhance synthesis of cytokine and C-reactive protein in the long term. Thus, the relevance for dialytic strategies aiming at improving dialysate quality or at reducing backfiltration is highlighted.

Changes in Heart Rate Variability in Chronic Uremic Patients during Ultrafiltration and Hemodialysis

Background: The analysis of heart rate variability (HRV) is a useful tool to evaluate cardiac autonomic modulation, which is frequently impaired in chronic uremia. Aims: The aim of this study was to evaluate HRV in chronic uremics and to separately investigate the acute changes induced by volume depletion and solute removal during a hemodialysis session. Methods: Fourteen uremic patients (8 males and 6 females, aged 50 ± 15 years) on maintenance hemodialysis and 14 sex- and age-matched healthy controls were studied. Both groups underwent ambulatory electrocardiogram monitoring to evaluate the HRV time and frequency domain indices. The hemodialysis session was performed by 1 h of high-rate isolated ultrafiltration followed by 3 h of bicarbonate diffusive procedure. Results: In uremic patients, the overall variability in the frequency [low-frequency power (LF): 505 ± 473, vs. 1,446 ± 654; high-frequency power (HF): 133 ± 162 vs. 512 ± 417; p < 0.001] and time domain indices (standard deviation of normal R-R intervals: 101.9 ± 33.3 vs. 181.7 ± 44.1 ms; p < 0.001) was markedly reduced compared to controls, whereas mean heart rate (83 ± 12.4 vs. 60.9 ± 8.8 bpm; p < 0.001) and LF/HF ratio (5.8 ± 3.5 vs. 2.2 ± 0.8; p < 0.001) were increased. Isolated ultrafiltration produced a marked further decrease in HRV indices, but the subsequent diffusive hemodialysis procedure, with a low ultrafiltration rate, made HRV increase again. Conclusions: Chronic uremics showed abnormal autonomic modulation with sympathetic-vagal imbalance. The unbalanced hypersympathetic response to body fluid depletion is related to the ultrafiltration rate. Low interdialytic weight gain and a low ultrafiltration rate, associated with adequate hemodialysis, should be the preferable strategy for uremic patients with autonomic dysfunction.

Effects of hemodialysis and vitamin E supplementation on low-density lipoprotein oxidizability in end-stage renal failure.

BACKGROUND Cardiovascular diseases represent the major cause of mortality in hemodialysis (HD) patients. HD increases oxidative stress and oxidation of low-density lipoprotein (LDL) is a crucial step in the development of atherosclerosis. Vitamin E has been shown to reduce LDL oxidation. Our aim was to test the effect of a single HD session and chronic vitamin E supplementation on LDL oxidizability in HD patients. METHODS LDL susceptibility to copper-induced oxidation (lag-phase, LP) was measured in 19 HD patients, both immediately before and after hemodialysis; 18 age-matched healthy subjects served as controls. Both pre-HD and post-HD measurements were repeated after 12 weeks of vitamin E supplementation (800 IU/day) in a placebo-controlled, randomized design. RESULTS At baseline, HD patients showed hypertriglyceridemia, a significant triglyceride enrichment in LDL and HDL and an enhanced LDL resistance to oxidation (186 ± 6 vs. 163 ± 4 min, p<0.003). A single HD session decreased (to 172 ± 6 min, or -8%, p<0.002), and chronic vitamin E administration increased, LDL resistance to oxidation (+19%, p = 0.002 vs. placebo) without changing the serum lipid profile or lipoprotein lipid composition. CONCLUSIONS We conclude that in patients on chronic hemodialysis, hypertriglyceridemia and triglyceride enrichment of LDL and HDL particles are associated with increased resistance of LDL to in vitro oxidation despite the fact that each dialysis session acutely increases LDL oxidizability. Vitamin E supplementation improves LDL resistance to oxidation without modifying circulating lipid levels and partitioning.

Automatic continuous venovenous hemodiafiltration in cardiosurgical patients.

Intermittent substitutive treatments in severely ill patients with acute renal failure are difficult or not suitable because of technical problems and/or hemodynamic instability. Continuous venovenous hemodiafiltration allows an adequate, slow removal of fluid, electrolytes, and waste products by combining diffusive and convective solute transport. Eight patients with acute renal failure, after cardiovascular surgery and cardiogenic shock, were treated by continuous venovenous hemodiafiltration. An automatic system (Equaline System, Amicon Division, USA) was employed. Venous accesses (femoral or subclavian) were used with double lumen catheters. A polysulfone filter (0.4 m2) was used in the study. Blood flow was 30 ml/min and dialysate flow rate 16.6 ml/min. Sterile pyrogen-free hemofiltration substitution fluid was used as dialysate. Mean duration of treatment was 10.3 +/- 3.2 days. After 72 hours blood urea nitrogen levels dropped from 136 +/- 46.13 to 53.5 +/- 12.3 mg/dl and creatinine levels dropped from 6.9 +/- 1.7 to 2.6 +/- 0.9 mg/dl. A controlled steady-state was then maintained. Mean urea clearance was 21 +/- 5.3 ml/min; mean ultrafiltration rate was 20.3 +/- 4.1 L/day. Continuous venovenous hemodiafiltration, with the Equaline System, is effective for the clearance of waste products and is able to maintain perfect fluid balance in catabolic patients with acute renal failure and multiple organ failure.

High-Flux Hemodiafiltration: 5 Years Experience

The introduction of hemodiafiltration in the substitutive treatment of chronic renal failure has arisen from the need to find new techniques that could improve the efficiency of the traditional systems and, therefore, to treat adequately chronic uremia in the shortest possible time. 61 months of experience at our institution have shown that such a goal can be achieved, offering also practical advantages such as a better quality of life for the patients as well as the possibility to treat a greater number of them.

Omega-3 Fatty Acid Supplementation and Lipoprotein(a) Concentrations in Patients with Chronic Glomerular Diseases

Renal disease patients often exhibit alterations in the lipid profile which may become an important risk of accelerated atherosclerosis and contribute to disease progression. Among such alterations, increased levels of lipoprotein(a) [Lp(a)] are common and may be related, in part, to the degree of proteinuria. Omega-3 polyunsaturated fatty acids (omega-3 FA) have been reported to decrease Lp(a) concentrations in nonrenal subjects. In addition, they have recently been shown to reduce proteinuria in patients with chronic glomerular disease. We therefore tested the hypothesis that omega-3 FA treatment in patients with chronic glomerular disease may reduce Lp(a) concentrations. Eight patients (2 with membranous glomerulonephritis, 6 with focal glomerular sclerosis) were submitted to a total of 13 six-week courses of treatment with omega-3 FA, at a dose of 3 g/day with a triglyceride preparation (n = 4) and of 7.7 g/day with an ethyl-ester preparation (n = 9). Both treatments significantly increased the proportions of omega-3 to omega-6 FA in total serum lipids, documenting compliance to treatment. Both treatments were also effective in decreasing serum thromboxane (from mean 490 +/- (SEM) 70 to 325 +/- 49 ng/ml, p < 0.05, in the high-dose group) and prolonging the bleeding time (from 5.8 +/- 0.4 to 7.7 +/- 0.5 min, p < 0.05, in the high-dose group), thus documenting the biological efficacy of treatment. However, despite a significant reduction in serum triglyceride levels (from 137 +/- 20 to 104 +/- 19 mg/dl in the high-dose group), Lp(a) concentrations did not change (292 +/- 120 U/l before, 315 +/- 130 U/l after the high-dose therapy). Treatment-related changes in proteinuria (from 2.9 +/- 0.5 to 2.1 +/- 0.7 g/24 h) were not related at all to changes in Lp(a) levels. We conclude that omega-3 FA do not decrease Lp(a) concentrations in renal patients with chronic glomerular diseases and that Lp(a) levels are unlikely to be related to the degree of proteinuria within the short-term modifications induced by omega-3 FA.

Hemodiafiltration: better efficiency with respect to hemodialysis and hemofiltration

Hemofiltration (HF) allows a better hemodynamic tolerance than hemodialysis (HD); middle molecular weight solutes can be efficiently removed, while small solutes such as urea, creatinine and phosphate are removed to a lesser extent. By applying HD and HF simultaneously (hemodiafiltration; HDF), the benefits of both methods can be advantageously combined and the length of treatment can be reduced accordingly. This paper presents a 15-month comparative study between HF and HDF performed on 16 patients previously undergoing regular HD.

Proteinuria-lowering effect of anti-inflammatory drugs.

SummaryIndomethacin is known to reduce proteinuria in most cases of the nephrotic syndrome, regardless of the type of the glomerular lesion. This study shows the effect of ibuprofen and flufenamic acid in a total of 25 cases of protein-losing nephropathy. The response was good in 11 out of 14 cases treated with ibuprofen and 6 out of 11 cases treated with flufenamic acid. Ibuprofen appeared to increase the glomerular filtration rate and flufenamic acid to lower it in association with the decrease in protein loss. The authors suggest that this may be a possible parameter for investigating the anti-inflammatory activity of a new compound.