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Salvatore Di Filippo

Publications and source records attributed to Salvatore Di Filippo.

12 recordsLinked to original sources

A critical assessment of uremia research.

There are considerably fewer randomized controlled trials investigating hemodialysis (HD) than other fields of internal medicine, and no significant improvements have been observed over time. Only the National Cooperative Dialysis Study and the HEMO trial were based on hard endpoints such as morbidity and mortality, but neither considered on-line hemodiafiltration or super-flux membranes, which are thought to provide a number of advantages in terms of the cardiovascular condition of uremic patients. However, results of well-designed clinical trials showing that increasing convection may improve the clinical outcome of HD patients are still lacking. The need for maximizing removal of uremic toxins calls for more frequent HD sessions, but this may be affected by many organizational problems. Therefore, well-designed, long-term clinical trials are urgently needed to investigate which currently available therapeutic instruments can improve the clinical outcome of uremic patients.

Hemodiafiltration↗

Mini-peritoneal equilibration test: A simple and fast method to assess free water and small solute transport across the peritoneal membrane.

BACKGROUND: Loss of ultrafiltration (UF) of peritoneal membrane is one of the most important causes of peritoneal dialysis failure. UF is determined by osmotic forces acting mainly across small pores (UFSP) and ultrasmall pores or free water transport. At present, only semiquantitative estimates or complicated computer simulations are available to assess free water transport. The aim of this study was to assess free water transport during a 3.86% peritoneal equilibration test lasting 1 hour. In this condition, sodium transport is mainly due to convection, allowing the estimate of ultrafiltration of small pores and then of free water transport (total UF - UFSP). METHODS: In 52 peritoneal dialysis patients we performed a 3.86% peritoneal equilibration test (4 hours) and a 3.86% mini-peritoneal equilibration test (1 hour) and compared UF and small solute transports obtained with the two methods. RESULTS: During the 3.86% mini-peritoneal equilibration test, UFSP and free water transport were 279 +/- 142 mL and 215 +/- 86 mL, respectively; free water transport well correlated to total UF during the 3.86% peritoneal equilibration test (r= 0.67). The groups of peritoneal transporters, categorized according to glucose dialysate ratio (D/D(0)) and to creatinine/plasma ratio (D/P(Creat)), were in good agreement for the two peritoneal equilibration tests (weighted kappa 0.62 and 0.61, respectively). CONCLUSION: The 3.86% mini-peritoneal equilibration test is a simple and fast method to assess free water transport. It also gives information about total UF and small solute transports and it is in good agreement with the 3.86% peritoneal equilibration test.

Adult↗

Relationship between urea clearance and ionic dialysance determined using a single-step conductivity profile.

BACKGROUND: On-line determination of ionic dialysance (ID) has been used to measure the clearance of small solutes like urea. However, attempts to determine the in vivo relationship between ID and urea clearance have led to discordant findings. The aim of this study was to determine the relationship between the mean values of repeated instantaneous determinations of ID throughout a dialysis session ((m)ID), obtained using a single-step inlet dialysate conductivity profile, and the mean values of urea clearance corrected for access recirculation (K(eu1)), total recirculation (access plus cardiopulmonary recirculation, K(eu2)), and the entire postdialysis urea rebound (K(wb)). METHODS: Eighty-two anuric patients on chronic thrice-weekly hemodialysis were studied using an Integra machine equipped with the Diascan module for the automatic determination of ID. The mean values of repeated ID measurements made at 30-minute intervals were compared with K(eu1) (available for only 31 patients), K(eu2), and K(wb). RESULTS: The results in all 82 patients were: (m)ID = 176 +/- 23 mL/min; K(eu2) = 181 +/- 25 mL/min; K(wb) = 159 +/- 22 mL/min. The mean (m)ID/K(wb) and (m)ID/K(eu2) ratios were, respectively, 1.11 +/- 0.06 and 0.98 +/- 0.06. The results in the 31 patients for whom K(eu1) values were available were: (m)ID = 179 +/- 24 mL/min and K(eu1) = 200 +/- 27 mL/min; the mean (m)ID/K(eu1) ratio was 0.90 +/- 0.05. CONCLUSION: The mean value of repeated ID determinations obtained using a single-step conductivity profile underestimates urea clearance corrected for access recirculation, and may be considered an adequate estimate of urea clearance corrected for total recirculation.

Anuria↗

What are we expecting to learn from the MPO study?

High-flux membranes represented a major improvement in dialysis technique, but evidences supporting their clinical superiority over conventional low-flux dialysis are still inconclusive. Although several studies, most of which were observational, showed an association between high-flux dialysis and lower morbidity and mortality, the Hemodialysis (HEMO) study, the first large-scale randomized clinical trial specifically aimed at testing the effect of membrane permeability on patients' outcome, failed to demonstrate a statistical significant benefit of high-flux membranes on all-cause mortality. Although disappointing, these results should however be interpreted in light of some important limitations of the HEMO study, first of all the inclusion of both incident and prevalent hemodialysis patients, the exclusion of sicker patients and the allowance of dialyzer reuse. In this context, much is expected from the Membrane Permeability Outcome (MPO) study, a randomized clinical trial investigating the effect of high-flux membranes in a large population of incident hemodialysis patients across Europe. Inclusion of only incident patients, absence of severe exclusion criteria and no dialyzer reuse are all distinguishing features of this study. Analyses of the baseline data of the MPO study confirm the high burden of cardiovascular disease among incident dialysis patients, although comparison with the Dialysis Outcomes and Practice Patterns Study data provides further evidence of a positive selection of patients in clinical trials.

Equipment Design↗

Sodium removal and sodium concentration during peritoneal dialysis: effects of three methods of sodium measurement.

BACKGROUND: Sodium removal (NaR) may have a major impact on the survival of peritoneal dialysis patients. The dialysate/plasma sodium concentration ratio (D/P(Na)) is an indirect index of transcellular water transport by aquaporin channels, and thus of ultrafiltration. Sodium concentration can be assessed by means of flame photometry (F), and direct (D-ISE) or indirect ion-selective electrodes (I-ISE), but these methods have different properties. I-ISE is being used increasingly in clinical laboratories. The aim of this study was to evaluate NaR and D/P(Na) using the three different measurement methods. METHODS: We performed peritoneal equilibration tests (PETs) in 44 peritoneal dialysis patients and calculated the NaR. We also calculated D/P(Na) during the test; plasma and dialysate sodium concentrations were measured by F, D-ISE and I-ISE. RESULTS: NaR was lower (P<0.001) with D-ISE (69+/-29 mmol) than with F (81+/-29 mmol) or I-ISE (79+/-28 mmol). D/P(Na) was also lower at baseline (0.92+/-0.02 vs 0.95+/-0.02 and 0.95+/-0.02; P<0.001), after 60 min (0.87+/-0.03 vs 0.90+/-0.03 and 0.90+/-0.03; P<0.001) and at the end of PET (0.88+/-0.04 vs 0.92+/-0.04 and 0.92+/-0.04; P<0.001) when measured by D-ISE in comparison with F and I-ISE, respectively. CONCLUSIONS: NaR and D/P(Na) were lower when measured by the D-ISE method compared with the F and I-ISE methods. NaR and D/P(Na) were similar when measured by F or I-ISE. I-ISE can be used reliably in the evaluation of NaR and D/P(Na) in everyday clinical practice of peritoneal dialysis.

Clinical Chemistry Tests↗

Ionic dialysance allows an adequate estimate of urea distribution volume in hemodialysis patients.

BACKGROUND: An adequate estimation of urea distribution volume (V) in hemodialysis patients is useful to monitor protein nutrition. Direct dialysis quantification (DDQ) is the gold standard for determining V, but it is impractical for routine use because it requires equilibrated postdialysis plasma water urea concentration. The single pool variable volume urea kinetic model (SPVV-UKM), recommended as a standard by Kidney Disease Outcomes Quality Initiative (K/DOQI), does not need a delayed postdialysis blood sample but it requires a correct estimate of dialyser urea clearance. METHODS: Ionic dialysance (ID) may accurately estimate dialyzer urea clearance corrected for total recirculation. Using ID as input to SPVV-UKM, correct V values are expected when end-dialysis plasma water urea concentrations are determined in the end-of-session blood sample taken with the blood pump speed reduced to 50 mL/min for two minutes (U(pwt2')). The aim of this study was to determine whether the V values determined by means of SPVV-UKM, ID, and U(pwt2') (V(ID)) are similar to those determined by the "gold standard" DDQ method (V(DDQ)). Eighty-two anuric hemodialysis patients were studied. RESULTS: V(DDQ) was 26.3 +/- 5.2 L; V(ID) was 26.5 +/- 4.8 L. The (V(ID)-V(DDQ)) difference was 0.2 +/- 1.6 L, which is not statistically significant (P= 0.242). Anthropometric volume (V(A)) calculated using Watson equations was 33.6 +/- 6.0 L. The (V(A)-V(DDQ)) difference was 7.3 +/- 3.3 L, which is statistically significant (P < 0.001). CONCLUSION: Anthropometric-based V values overestimate urea distribution volume calculated by DDQ and SPVV-UKM. ID allows adequate V values to be determined, and circumvents the problem of delayed postdialysis blood samples.

Hemodialysis Solutions↗

Sodium removal during pre-dilution haemofiltration.

BACKGROUND: Cardiovascular instability still affects a large percentage of uraemic patients undergoing extracorporeal substitutive treatments. Post-dilution haemofiltration has been reported to be a method for improving cardiovascular stability; however, the limited removal of small molecular weight solutes together with the need for high blood flow from the fistula greatly restrict the use of this treatment. To increase the solute clearances and to partially resolve the necessity for high blood flow, the replacement solution, in a quantity about double that used in post-dilution mode, can be administered in pre-dilution mode. A high vascular stability has also been observed for pre-dilution haemofiltration. Since the lower morbidity may be due to less sodium removal when compared with haemodialysis, it would be important to characterize the sodium transport in this kind of treatment. METHODS: Nine patients underwent nine pre-dilution haemofiltration treatments (one for each patient) with on-line prepared substitution fluid. RESULTS: As mean values, total (NaF(pw)) and ionized (NaE(pw)) plasma water sodium concentrations increased from 149.4 +/- 2.8 mEq/l to 151.1 +/- 2.4 mEq/l, and from 143.1 +/- 2.8 to 144.5 +/- 1.2 mEq/l, respectively, during the treatment, suggesting a hypotonic concentration of net ultrafiltrate. Plotting the difference between final and initial ionized plasma water concentrations (fNaE(pw) - iNaE(pw)) against the difference between initial plasma water values and ionized sodium concentration in the reinfusate (iNaE(pw) - NaE(R)), a significant negative correlation was found, with the regression line that intercepts the abscissa at the (iNaE(pw) - NaE(R)) value of 8.8 mEq/l; this means that to avoid changes in NaE(pw) in our patients, the NaE(R) should be lower than the iNaE(pw) by this amount. This is quite different from the theoretical value of approximately 4 mEq/l necessary to avoid changes in NaE(pw) during haemodialysis. The ratio between the total sodium concentration in the ultrafiltrate (NaF(uf)) and NaF(pw) (alpha) at the post-reinfusion site was 0.96 and decreased to 0.94 when NaF(pw) values at the pre-reinfusion site were considered. This last value is quite close to the theoretical alpha value of post-dilution haemofiltration. CONCLUSION: As for post-dilution haemofiltration, less sodium removal, compared with haemodialysis, can partly explain the improved cardiovascular stability during pre-dilution haemofiltration.

Hemofiltration↗

Convection versus diffusion in dialysis: an Italian prospective multicentre study.

The concept of dialysis adequacy has to be widened to include medium size and large molecule removal in addition to urea kinetics. The HEMO study found a non-significant trend toward a beneficial effect on mortality of high-flux dialysis compared with low-flux dialysis. In that study, the beneficial effect of convection could have been attenuated by the fact that 'internal filtration' in high-flux haemodialysis (HD) is lower than that expected by convection in haemofiltration (HF) or haemodiafiltration (HDF). To explore the putative beneficial effect of convection, this Italian multicentre study was planned, comparing on-line convective treatments (HF and HDF) with standard, low-flux HD. The enrolled patients will be evaluated prospectively on their usual treatment for 2 months (baseline period) and subsequently randomized to continue either with low-flux HD (50%) or to start on-line convective treatment (50%), HF or HDF according to a 1:1 ratio. The primary end point of the study will be cardiovascular stability and blood pressure control. As secondary aims of the study, the impact on symptoms, morbidity and mortality will be assessed. Feasibility and patient compliance during HF and HDF treatments will also be evaluated. The experimental phase of the study, of at least 2 years, is divided into a 3-month adaptation period and a subsequent evaluation period. A recruitment period of 1 year is planned. The study design has adequate power to detect an absolute reduction of 3% hypotensive episodes with the experimental convective treatments compared with standard low-flux HD.

Convection↗

The importance of convective transport.

BACKGROUND: Despite technological advances in dialysis equipment and modalities, survival, morbidity, and quality of life of hemodialysis patients are still severely affected by acute intradialytic and long-term complications, possibly related to the treatment itself. Convective treatments, such as high-flux hemodialysis, hemodiafiltration, and hemofiltration are increasingly suggested as further improvements over standard diffusive hemodialysis. The membranes used for these techniques are high-flux semisynthetic and synthetic membranes. Characteristics of these membranes are high permeability, which allows convective removal of water and electrolytes and higher clearance of middle and large molecular weight solutes, and high biocompatibility, which minimizes the "inflammatory response" secondary to interactions between blood and the artificial material of the hemodialysis system. METHODS: With the specific aim of verifying the superiority of convective treatments in reducing morbidity and mortality, we performed a review of the published literature. RESULTS: Some epidemiological studies suggest that convective treatments reduce morbidity and mortality among dialysis patients. However, the results of the published prospective randomized controlled trials are conflicting. Moreover, since convective treatments are usually performed with synthetic biocompatible membranes, it is hard to separate the effect of convection from the effect of biocompatibility. CONCLUSIONS: To finally assess the effect of high-flux membranes on morbidity and mortality, the results of two randomized, controlled clinical trials (HEMO study and MPO study) specifically designed with this aim are needed.

Amyloidosis↗

Long-term outcome in hemodialysis: morbidity and mortality.

Despite technical and pharmacological improvements achieved over the past years, long-term prognosis of patients undergoing chronic hemodialysis is still rather poor. Cardiovascular disease is the leading cause of both morbidity and mortality in these patients, mostly because of their severely compromised cardiovascular conditions already at the time of starting hemodialysis. A proper management of factors involved in the development of cardiovascular abnormalities is therefore a basic pre-requisite for improving their clinical outcome. Hypertension and anemia should be adequately evaluated and corrected, in light of their primary involvement in the pathogenesis of left ventricular hypertrophy, whereas treatment of calcium and phosphate metabolism disorders, particularly of high serum phosphorus levels, is needed to prevent the development of severe secondary hyperparathyroidism and mainly vascular calcifications, whose detrimental pathophysiologic consequences on cardiovascular structures are huge. At the same time, the prescription of the hemodialytic treatment should be optimised, with a satisfactory removal of uremic toxins through the delivery of an adequate dialysis dose and with the use of biocompatible membranes, where possible, thus minimizing the inflammatory response secondary to the interaction between blood and the artificial material of the hemodialysis system. The clinical superiority of high-flux membranes, although suggested by all studies performed so far, has still to be demonstrated by well-conducted clinical studies; on-line convective treatments and daily hemodialysis, although promising, also need to be confirmed in randomized trials. In conclusion, long-term outcome of hemodialysis patients may only be improved by a complex, multi-factorial therapeutical approach.

Anemia↗