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Biomedical subjects

Umberto Buoncristiani

Publications and source records attributed to Umberto Buoncristiani.

At least 19 recordsLinked to original sources

Antisepsis.

All dialysis treatments include a certain risk of infection because of the decreased immune defenses of the patients and because of dialytic techniques that increase the potential of microbial contamination. Peritoneal dialysis, and in particular continuous ambulatory peritoneal dialysis (CAPD), has a higher risk of infections of the peritoneum, but even of the subcutaneous tunnel. These infections are caused by environmental microorganisms principally gram-positives (Staphylococcus epidermidis and Staphylococcus aureus). We tested three active ingredients, electrolytic chloroxidizer, iodine and chlorhexidine gluconate. It is evident that because of the large spectrum of activity, the good effectiveness even at the lowest concentration, coupled with good tolerability (and to the fact of not causing allergic reactions) the electrolytic chloroxidizer appears to be an ideal antiseptic in CAPD.

Anti-Infective Agents, Local↗

Use of sodium hypochlorite in peritoneal dialysis: the genesis of the 'Y' set and beyond.

The 'Y' set introduced in the clinical practice in the early 80s with the aim of reducing the peritonitis rate in patients on continuous ambulatory peritoneal dialysis, successfully revolutioned the philosophy of the connection system catheter-container of dialysate, which was the main way of bacterial contamination of the peritoneal cavity. In fact, while the previous connection systems had focused the attention on the reduction of the possible contaminating acts, the 'Y' system, taking into account the fact that soon or later a failure could occur even with the most skilled and compliant patient, introduced the possibility to kill the bacteria with a disinfectant and to remove it and the killed bacteria together with the bacteria eventually still surviving, by flushing the contaminated area. This goal was achieved thanks to a 'Y' shaped connector, having a third way connected to the discharge bag/container, besides the two connected to the new bag and to the catheter. From the 'Y' set have originated all the currently used continuous ambulatory peritoneal dialysis connection systems, where the 'Y' is mounted on the bag side (double-bag systems). However in these systems the disinfectant is no longer used, due to the fear of possible untoward effects on the peritoneal membrane. The groundlessness of this position and the possible further advantages of the use of a disinfectant in combination with the 'Y' are discussed and new 'Y' systems preventing every possibility of accidental entry of disinfectant into the peritoneal cavity are presented.

Bacterial Infections↗

Haemodialysis with on-line monitoring equipment: tools or toys?

BACKGROUND: On-line monitoring of chemical/physical signals during haemodialysis (HD) and bio-feedback represents the first step towards a 'physiological' HD system incorporating adaptive and logic controls in order to achieve pre-set treatment targets. METHODS: Discussions took place to achieve a consensus on key points relating to on-line monitoring and bio-feedback, focusing on the clinical applications. RESULTS: The relative blood volume (BV) reduction during HD can be monitored by optic devices detecting the variations in concentration of haemoglobin/haematocrit. BV changes result from an equilibrium between ultrafiltration and the refilling capacity. However, BV reduction has little power in predicting intra-HD hypotensive episodes, while the combination of the patient-dialysate sodium gradient, the relative BV reduction between the 20th and 40th minute of HD, the irregularity of the profile of BV reduction over time and the heart rate decrease from the start to the 20th minute of HD predict intra-HD hypotension with a sensitivity of 82%, a specificity of 73% and an accuracy of 80%. A bio-feedback system drives the relative BV reduction according to desired values by instantaneously changing the ultrafiltration rate and the dialysate conductivity. This system has proved to reduce the incidence of intra-HD hypotension episodes significantly. Ionic dialysance and the patient's plasma conductivity can be calculated easily from on-line inlet and outlet dialysate conductivity measurements at two different steps of dialysate conductivity. Ionic dialysance is equivalent to urea clearance corrected for recirculation and is a tool for continuously monitoring the dialysis efficiency and detecting early problems with the delivery of the prescribed dose of dialysis. Given the strict and linear relationship between conductivity and sodium content, the conductivity values replace the sodium concentration values and this permits the development of a conductivity kinetic model, by means of which sodium balance can be achieved at each dialysis session. The conductivity kinetic model has been demonstrated to improve intra-HD cardiovascular stability in hypotension-prone patients significantly. Ionic dialysance is also a useful tool to monitor vascular access function, as it can be used to obtain serial measurements of vascular access blood flow. On-line urea monitors provide detailed information on intra-HD urea kinetics and delivered dialysis dose, but they are not in widespread use because of the costs related to the disposable materials (e.g. urease cartridge). The body temperature monitor measures the blood temperature at the arterial and venous lines of the extra-corporeal circuit and, thanks to a bio-feedback system, is able to modulate the dialysate temperature in order to influence the patient's core body temperature, which can be kept at constant values. This is associated with improved intra-HD cardiovascular stability. The module can also be used to quantify total recirculation. CONCLUSIONS: On-line monitoring devices and bio-feedback systems have evolved from toys for research use to tools for routine clinical application, particularly in patients with clinical complications. Conductivity monitoring appears the most versatile tool, as it permits quantification of delivered dialysis dose, achievement of sodium balance and surveillance of vascular access function, potentially at each dialysis session and without extra cost.

Biofeedback, Psychology↗

Prognostic value of 24-hour ambulatory blood pressure monitoring and of night/day ratio in nondiabetic, cardiovascular events-free hemodialysis patients.

BACKGROUND: The use of 24-hour ambulatory blood pressure monitoring is increasing in end-stage renal disease (ESRD) patients but the prediction power for cardiovascular complications of time-averaged ambulatory blood pressure components has been little investigated in these patients. METHODS: We analyzed the prognostic power of 24-hour ambulatory blood pressure monitoring for all-cause and cardiovascular mortality in 168 nondiabetic, events-free hemodialysis patients selected from a total dialysis population of about 450 patients. RESULTS: During the follow-up period (38 +/- 22 months), 48 patients died, 29 of them of cardiovascular causes. On univariate Cox regression analyses, the night/day systolic ratio resulted to be the sole blood pressure indicator to be associated with all-cause and cardiovascular mortality while left ventricular hypertrophy (LVH) was a strong predictor of these outcomes. In multivariable Cox models not including LVH, the night/day systolic ratio maintained an independent prognostic value for incident outcomes. However, when both risk factors, LVH and night/day systolic ratio, were introduced into Cox models, LVH was no longer a significant predictor while the night/day systolic ratio became a predictor of marginal statistical significance. CONCLUSION: The night/day ratio emerges as the sole ambulatory blood pressure monitoring-derived indicator providing significant prognostic information in patients with ESRD. However, this indicator as well as LVH loses substantial prediction power in statistical models including both risk factors. The results suggest that the night/day systolic ratio and LVH provide overlapping prognostic information, a phenomenon in keeping with the hypothesis that they represent a common pathway leading to adverse outcomes in ESRD.

Adult↗

Glycoxidation and inflammatory markers in patients on treatment with PMMA-based protein-leaking dialyzers.

BACKGROUND: High-molecular-weight solutes such as glycation and oxidation protein products are putative proinflammatory mediators found in the uremic blood. The elimination of these and other large solutes by protein-leaking dialyzers (PLD) might help to correct the inflammatory status of maintenance hemodialysis (HD) patients. METHODS: Two matched groups of 13 standard 3 times/week HD patients were treated for 6 months with PMMA-based PLD and non-protein-leaking dialyzers (NPLD), respectively. At baseline, 1, 3, and 6 months, we measured the blood levels of the inflammatory cytokines IL-1beta, TNF-alpha, IL-6, the acute-phase protein C-reactive protein (CRP), the adhesion molecules ICAM-1, VCAM-1, and selectine-E, the chemotaxis factors MCP-1, and the glycation and oxidation protein end products pentosidine, protein carbonyls, and AOPP. RESULTS: In all the patients at baseline, pre-HD levels of glycation and oxidation protein markers, and inflammatory parameters were significantly higher than in healthy control subjects (P < 0.01 or greater). After 6 months, in the group on treatment with PLD, but not in that on NPLD, there was a significant decrease (P < 0.05 or greater) of pre-HD values of total pentosidine (mainly represented by pentosidine in serum albumin; -43%), protein carbonyls (-42%), AOPP (-38%), and the inflammatory cytokines IL-1beta (-49%), IL-6 (-39%), and TNF-alpha (-20%), while IL-10 and INF-gamma increased by 67% and 37%, respectively. Proinflammatory cytokines, and particularly IL-6, showed a positive correlation with the levels of circulating pentosidine. Protidemia was not significantly modified at the end of the study in both the groups. CONCLUSION: The results in this pilot study show that the removal of large solutes by PLD can improve some indices of chronic inflammation in HD patients. Further studies are required to determine the relevance of the individual solutes removed with PLD as proinflammatory mediators in the uremic environment.

Adult↗

Effect of daily hemodialysis on monocytes apoptosis.

Uremia is associated with a state of immune dysfunction with increased susceptibility to infection and malignancy possibly related to dysregulation of immune system cell apoptosis. Peritoneal dialysis can restore plasma apoptosis activity on monocytes compared to intermittent hemodialysis. Whether the continuous modality or diverse clearance mechanisms involved are responsible is unknown. Apoptosis rates correlate with phagocytic function highlighting the benefit of efficient toxin clearance. The plasma of 16 patients on daily hemodialysis (D-HD) was incubated with U937 monocytes and compared to 18 hemodialysis (HD) patients, 5 chronic renal failure (CRF) subjects and 5 healthy volunteers (controls). Apoptosis was evaluated by immunofluorescence microscopy dyes (Hoechst 33342, propidium iodide) and annexin V cytoflowmetry at 96 h. Plasma-induced U937 apoptosis (mean values) was significantly enhanced in D-HD (18.8 +/- 4.1), HD (19.67 +/- 5.5) and CRF patients (20.8 +/- 4.7) compared to controls (9.6 +/- 3.6; p < 0.05 for CRF vs. controls, HD vs. controls and D-HD vs. controls). No significant differences were observed between D-HD, HD and CRF sera on apoptosis rate, caspase-3 activity and phagocytic capacity of U937 monocytes. This study demonstrates that the plasma of various HD schedules was unable to reduce monocyte apoptosis induced by uremia.

Adult↗

Dialysis dose and frequency.

BACKGROUND: From the beginning of the dialysis era, the issue of optimal dialysis dose and frequency has been a central topic in the delivery of dialysis treatment. METHODS: We undertook a discussion to achieve a consensus on key points relating to dialysis dose and frequency, focusing on the relationships with clinical and patient outcomes. RESULTS: Traditionally, dialysis adequacy has been quantified referring to the kinetics of urea, taken as a paradigm of all uraemic toxins, and applying the principles of pharmacokinetics using either single- or double-pool variable volume models. An index of dialysis dose is the fractional clearance of urea, which is commonly expressed as Kt/V. It can be calculated from blood urea concentration and haemodialysis (HD) parameters, according to the respective urea kinetic model or by means of simplified formulas. Similar principles are applicable to peritoneal dialysis (PD), where weekly Kt/V and creatinine clearance are used. Recommended minimal targets for dialysis adequacy have been defined by both American and European guidelines (DOQI and European Best Practice Guidelines, respectively). The question of how to improve the severe outcome of dialysis patients has recently come back to the fore, since the results of two recent randomized controlled trials led to the conclusion that, in thrice weekly HD and in PD, increasing the dialysis dose well above the minimum requirements of current American guidelines did not improve patient outcome. Daily HD (defined as a minimum of six HD sessions per week), in the form of either short daytime HD or long slow nocturnal HD, is regarded as a possibility to improve dialysis patient outcome. The results of the studies published so far indicate excellent results with respect to all outcomes analysed: optimal blood pressure control, regression of left ventricular hypertrophy and amelioration of left ventricular performance, improvement of renal anaemia, optimal hyperphosphataemia control, improvement of nutritional status, reduction in oxidative stress indices and improvement in quality of life. The basis for these beneficial effects is thought to be a more physiological clearance of solutes and water, with reduced pre- and post-HD solute concentrations and interdialytic oscillation, compared with traditional HD. Apart from concerns regarding reimbursement and organizational issues, no serious adverse effects have been described with daily HD. However, the evidence accumulated is limited mainly to retrospective cohorts, with small patient numbers and no adequate controls in most instances. Therefore, large prospective studies with adequate controls are required to make daily HD accepted by reimbursing authorities and patients. CONCLUSIONS: Given the available observational and interventional body of evidence, there is no reason to reduce arbitrarily dialysis dose, particularly dialysis treatment time in HD patients treated three times weekly. Daily HD represents a very promising tool for improving dialysis outcomes and quality of life, although its impact on patient survival has not yet been proven definitively.

Biomarkers↗

Vitamin E in uremia and dialysis patients.

Vitamin E therapy (based either on oral supplements or new dialysis methods such as vitamin E-coated hemodialysers) has been suggested to yield a better clinical outcome in hemodialysis (HD) patients than in other populations of patients. Among other factors, the presence of a modified vitamin E status might help to explain this apparently paradoxical response to vitamin E. In this study we investigated 104 regular HD patients. The results indicate that, besides having a low dietary intake, these subjects show some abnormalities in the levels and metabolism of vitamin E, such as a disproportion between plasma tocopherols and lipids, low levels of gamma-T, and CEHC accumulation. Although further studies are needed to confirm the clinical relevance of vitamin E therapy in HD, these findings might lead to recommending a higher vitamin E intake in these patients.

Aged↗

Peroxynitrite-induced oxidation of plasma lipids is enhanced in stable hemodialysis patients.

BACKGROUND: The relationship between end-stage renal disease (ESRD), hemodialysis, and oxidative stress is controversial. To determine whether ESRD causes oxidative stress, we measured basal levels of plasma F2-isoprostanes as a marker of lipid peroxidation in vivo, and peroxynitrite-stimulated formation of F2-isoprostanes, as a marker of the oxidizibility of plasma lipids in vitro, before and after routine hemodialysis. METHODS: Total plasma F2-isoprostanes were measured by gas chromatography-mass spectrometry (GC-MS) before and after the oxidation of plasma lipids with the peroxynitrite-generating compound, 3-morpholino-sydnonimine (SIN-1), in 23 patients with ESRD patients undergoing regular hemodialysis, and 14 controls. Plasma vitamin E concentrations were measured by high-performance liquid chromatography (HPLC). RESULTS: There was no difference in basal plasma concentrations of F2-isoprostanes in the ESRD group prior to hemodialysis, 246 +/- 20 pg/mL, compared to controls, 252 +/- 28 pg/mL, or immediately on completion of hemodialysis, 236 +/- 14 pg/mL. Incubation of control plasma with SIN-1 caused the formation of F2-isoprostanes with plasma concentrations increasing to 987 +/- 54 pg/mL at 6 hours. The formation of F2-isoprostanes stimulated by SIN-1 was markedly enhanced in the plasma obtained from patients undergoing hemodialysis at 1861 +/- 174 pg/mL, P < 0.001, and SIN-1-induced formation of F2-isoprostanes was further increased in plasma obtained immediately after hemodialysis at 2437 +/- 168 pg/mL, P < 0.001. Incubation of plasma with SIN-1 resulted in the net consumption of vitamin E. CONCLUSION: Although basal plasma F2-isoprostanes were similar in patients with ESRD compared with controls, the presence of oxidative stress in patients with ESRD was unmasked when the plasma was stressed by peroxynitrite generated from SIN-1, and this was enhanced further by hemodialysis.

Adult↗

The effect of PMMA-based protein-leaking dialyzers on plasma homocysteine levels.

BACKGROUND: Hyperhomocysteinemia is a well-recognized independent risk factor for cardiovascular disease in end-stage renal disease (ESRD) patients. Since homocysteine (Hcy) largely binds to serum proteins (80 to 90%), in this study we investigated the possibility that polymethylmethacrylate (PMMA)-based protein-leaking dialyzers could reduce total plasma Hcy (tHcy) levels in ESRD patients. METHODS: Two matched groups of patients (N = 13) showing mild to intermediate hyperhomocysteinemia on standard hemodialysis (HD) with conventional non-protein-leaking dialyzers were included. In the control group membranes were maintained the same, while the study group was switched to protein-leaking dialyzers (BK-F series; Toray, Japan) and studied for 6 months. tHcy was measured by high performance liquid chromatography (HPLC) at baseline and after 1, 3, and 6 months. Proteins and Hcy were also measured in the spent dialysate. RESULTS: The pre-HD levels of tHcy in the control group remained close to baseline values (26.6 +/- 5.0 micromol/L), while in the study group at 1, 3, and 6 months they decreased from a baseline value (in micrormol/L) of 25.3 +/- 5.9 to 21.5 +/- 4.5, 16.9 +/- 4.0, and 17.2 +/- 4.2, respectively (P < 0.01 for values at 3 and 6 months vs. baseline). The intra-HD drop of tHcy (Delta HDHcy) slightly but progressively decreased during the 3 steps on protein-leaking dialyzers and a positive correlation was found between Delta HDHcy and pre-HD levels of tHcy. In spent dialysate samples from protein-leaking dialyzer-treated patients, the amount of protein-bound Hcy (bHcy) was approximately 10 times higher than in non-protein-leaking dialyzers, but the Delta HDHcy observed in non-protein-leaking dialyzers and protein-leaking dialyzers was comparable. Serum proteins and albumin were only slightly affected by protein-leaking dialyzers. CONCLUSION: This study demonstrates that protein-leaking dialyzers used with a pure diffusive technique significantly lower pre-HD tHcy (approximately 33% of starting levels after 3 months of treatment) in ESRD patients. A possible underlying mechanism for this effect could be the removal of large molecular weight solutes responsible for a defective metabolism of the Hcy, as the removal of bHcy with protein-leaking dialyzers seems not sufficient, per se, to explain this steady reduction of tHcy levels in pre-HD.

Aged↗

Mononuclear leukocyte apoptosis in haemodialysis patients: the role of cell thiols and vitamin E.

BACKGROUND: An increased apoptotic rate of peripheral blood mononuclear leukocytes (PBMLs) in haemodialysis (HD) patients has been reported in several studies, but its underlying mechanisms remain poorly understood. Oxidant stress is a well known cause of cell damage, and several lines of evidence suggest that it might influence the induction and signalling steps of mononuclear cell apoptosis through different mechanisms so as to provoke disturbances of the intracellular pool of thiols (SHi). In this study, we investigated the in vitro apoptotic rate and SHi of PBMLs in end-stage renal disease (ESRD) patients on HD or peritoneal dialysis (PD). METHODS: Apoptosis and SHi were evaluated in vitro in PBMLs obtained from 40 ESRD patients (HD, n = 30 and PD, n = 10) and 10 healthy controls. A subgroup of HD patients was also studied before and after 1 month of treatment with a vitamin E-coated dialyser (CL-E). Cell thiols and viability were also assessed in the monocyte-like cell line U937 and PBMLs after incubation in the presence of uraemic plasma with or without supplementation of the antioxidants vitamin E (70 micro M) or N-acetyl-cysteine (NAC) (0.5 mM). RESULTS: After 24 h in culture, the PBMLs of HD patients, but not those of CAPD patients, showed an apoptotic rate twice that of healthy controls and a 40% decrease of SHi levels (P < 0.01 in both). A negative correlation between the apoptotic rate and SHi was observed in both patients and controls (r = 0.648, P < 0.001). Plasma and ultrafiltrate samples from HD patients contained solutes (mainly in the low-middle molecular weight range) able to trigger apoptosis and oxidative stress in U937 cells. The treatment of HD patients with CL-E, as well as the in vitro supplementation of U937 cells with vitamin E or NAC during the exposure to uraemic plasma, decreased the rate of apoptosis and partially restored SHi. CONCLUSIONS: This study showed an association between an increased apoptotic rate and decreased SHi in PBML of HD patients, but not of CAPD patients. These changes are partially due to different pro-apoptogens that accumulate in the plasma and are at least partially prevented by exogenous antioxidants able to restore SHi, such as vitamin E or thiol suppliers.

Aged↗

Association between extracellular water, left ventricular mass and hypertension in haemodialysis patients.

BACKGROUND: Hypertension and left ventricular hypertrophy (LVH) are present in the majority of patients undergoing haemodialysis (HD). These two pathologies persist after dialysis onset, and pharmacological therapy is often required for adequate control of blood pressure (BP). Although fluid overload is a determinant of hypertension, clinical assessment of this parameter remains difficult and unsatisfactory. Bioimpedance analysis (BIA) spectroscopy and the relative determination of extracellular water (ECW%) may provide a simple and inexpensive tool for investigating fluid overload. We studied 110 patients on thrice-weekly HD to determine whether ECW body content correlates with hypertension and LVH in this patient population. METHODS: Hypertension was determined according to the WHO criteria (office BP >/= 140/90 and/or the use of antihypertensive therapy). Twenty-four hour BP monitoring and echocardiography were performed on midweek inter-HD days. Blood chemistries, dialysis dose (spKt/V) and bioimpedance were analysed on midweek HD days. RESULTS: Hypertension was present in 74.5% of patients. There were no differences for age, spKt/V, haemoglobin, serum creatinine and residual renal function between normotensive and hypertensive patients. Twenty-four hour systolic BP (SBP), 24 h diastolic BP and 24 h pulse pressure were higher in hypertensive patients, in spite of antihypertensive therapy. LVH was present in 61.8% of patients. BIA revealed that ECW% was increased in LVH+ patients (LVH+ = 47.5 +/- 7.9%, LVH- = 42.4 +/- 6.2%, P = 0.01) and in hypertensive patients compared with normotensives (46.5 +/- 7.7% vs 43 +/- 7.2%, P = 0.02). Dry body weights and inter-HD body weight increases did not differ between hypertensive and normotensive patients nor between patients with or without LVH. ECW was correlated with SBP (r = 0.35, P < 0.01) and with left ventricular mass index (LVMi(g/sqm)) (r = 0.49, P < 0.001). A stepwise multiple linear regression model revealed that LVMi(g/sqm) was significantly correlated with ECW%, SBP and male gender (r = 0.65, P < 0.001). CONCLUSIONS: LVH and hypertension are present in a majority of HD patients and they are closely correlated with one another. We found associations between fluid load, measured by BIA and expressed as ECW, and BP and LVM.

Adult↗

Behavior of non-protein-bound and protein-bound uremic solutes during daily hemodialysis.

BACKGROUND: In the last few years, renewed interest in daily short hemodialysis (DHD; six 2-hour sessions per week) has become apparent as a consequence of the better clinical outcome of patients treated by this schedule. Uremic syndrome is characterized by the retention of a large number of toxins with different molecular masses and chemical properties. Some toxins are water soluble and non-protein bound, whereas others are partially lipophilic and protein bound. There is increased evidence that protein-bound toxins are responsible for the biochemical and functional alterations present in uremic syndrome, and the kinetics of urea is not applicable to these substances for their removal. The aim of this study is to investigate whether DHD is accompanied by increased removal of non-protein-bound and protein-bound toxins and a decrease in their prehemodialysis (pre-HD) serum levels. PATIENTS AND METHODS: We studied 14 patients with end-stage renal disease treated by standard HD (SHD; three 4-hour sessions per week) for at least 6 months and randomly assigned them to a two-period crossover study (SHD to DHD and DHD to SHD). Patients maintained the same dialyzer, dialysate, and Kt/V during the entire study. At the end of 6 months of SHD and 6 months of DHD, we evaluated hemoglobin levels, hematocrits, recombinant human erythropoietin doses, and pre-HD and post-HD concentrations of serum urea, creatinine, uric acid, and the following protein-bound toxins: 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, p-cresol, indole-3-acetic acid, indoxyl sulfate, and hippuric acid. RESULTS: Values for hemoglobin, hematocrit, and recombinant human erythropoietin dose did not change during the two study periods. Pre-HD concentrations of creatinine, urea, and uric acid decreased on DHD (creatinine, from 8.7 +/- 1.9 to 7.8 +/- 1.6 mg/dL; P < 0.05; urea, from 149.4 +/- 28.8 to 132.7 +/- 40 mg/dL; P = 0.05; uric acid, from 9.14 +/- 1.49 to 8.16 +/- 1.98 mg/dL; P = 0.06). Concerning protein-bound toxins, lower pre-HD levels during DHD were reported for indole-3-acetic acid (SHD, 0.16 +/- 0.04 mg/dL; DHD, 0.13 +/- 0.03 mg/dL; P = 0.01), indoxyl sulfate (SHD, 3.35 +/- 1.68 mg/dL; DHD, 2.85 +/- 1.08 mg/dL; P = 0.02), and p-cresol at the borderline of significance (SHD, 0.96 +/- 0.59 mg/dL; DHD, 0.78 +/- 0.33 mg/dL; P = 0.07). CONCLUSION: Such non-protein-bound compounds as uric acid, creatinine, and urea were removed significantly better by DHD, and pre-HD serum levels were reduced. Furthermore, pre-HD concentrations of some protein-bound solutes, such as indole-3-acetic acid, indoxyl sulfate, and p-cresol, also were lower during DHD.

Creatinine↗

Daily haemodialysis improves indices of protein glycation.

BACKGROUND: Advanced glycation end-products (AGEs) accumulate in uraemia, regardless of hyperglycaemic conditions, and may contribute to the onset of some long-term complications, such as atherosclerosis, amyloidosis, and neurodegenerative processes. In this study, we compare a daily with a standard 3 times/week dialysis rhythm (DHD and SHD, respectively) in correcting some protein glycation indices in end-stage renal disease (ESRD) patients. METHODS: Twenty-one normoglycaemic and 11 diabetic patients on chronic haemodialysis (HD) with low-flux dialysers were studied in a prospective protocol to compare two different dialysis schedules, namely: 4 h, 3 times/week (SHD) and 2 h, 6 times/week (DHD). The patients were studied before and after 6 months of DHD. To further check the effect of DHD on glycation parameters, 4 normoglycaemic HD patients were studied in a third step in which they returned for 3 months to the SHD rhythm. Also, 11 chronic renal failure (CRF) patients not yet on HD and 11 age- and sex-matched healthy controls were studied. A new HPLC method was used to measure the following glycation indexes on plasma: the early product furosine and the advanced products protein-bound and free pentosidine, and two heterogeneous classes of low molecular mass (LMM) AGE peptides. RESULTS: All the parameters studied showed an accumulation that worsened with the progression of renal failure (controls <CRF <HD). Diabetic patients on SHD showed similar levels of glycation indexes as non-diabetic patients, except for the early product furosine that was notably higher. The shift from SHD to DHD was effective in lowering the concentration of all the glycation parameters measured, both in non-diabetic and diabetic patients. In the total HD population, LMM-AGEs (MM range of approx. 1.5-6.0 kDa) detected at 385 nm emission was lowered by 56% (P<0.001) and LMM-AGEs detected at 440 nm emission and furosine decreased by 23 and 19%, (P< or =0.001 and <0.01, respectively). All these three classes of compounds reached concentrations comparable with those observed in the CRF patients, even if remaining above the control range. The levels of both free and protein-bound pentosidine after DHD decreased by 34% (P<0.001) and 22% (P< or =0.05), respectively. The return for 3 months to SHD in four non-diabetic DHD patients led to a trend toward an increase in all five glycation parameters. CONCLUSIONS: This study demonstrates for the first time that a DHD regimen can effectively lower the mean levels of glycation-related substances observed in SHD. Therefore, DHD can provide a better control of AGE produced in ESRD. This could result in a lower incidence of long-term effects of AGE accumulation in HD.

Adult↗

Blunted nocturnal blood pressure decrease and left-ventricular mass in hypertensive hemodialysis patients.

Left-ventricular hypertrophy (LVH) represents a frequent complication in hemodialysis (HD) patients. Hypertension is a well-known risk factor of cardiac morbidity which is present in 2 of 3 patients: among them about 60% have a blunted nocturnal decrease of blood pressure (BP). Although some large studies on essential hypertensives have documented that non-dipper patients have a higher number of cardiac events and a higher left ventricle (LV) mass than dipper ones, conflicting results have been reported for dialysis patients. Therefore, the aim of our study was to assess differences in LV mass between dipper and non-dipper hypertensive HD patients. We studied 66 patients with 24-hour ambulatory BP monitoring performed on HD and on inter-HD day. They were classified as dipper when a decrease of at least 10% of nocturnal systolic blood pressure on the inter-HD day was present. Echocardiography and bioimpedance were performed. 29% of the patients were classified as dippers and 71% as non-dippers. The 48-hour systolic and diastolic BP were not significantly different between the two groups (SBP: dipper = 144 +/- 12.9 mm Hg, non-dipper = 149 +/- 17.8 mm Hg; DBP: dipper = 80 +/- 9.9 mm Hg, non-dipper = 81 +/- 10.6 mm Hg). LV mass index (LVMi) did not differ between the two groups (dipper = 143.1 +/- 40.7 g/m(2); non-dipper = 159.4 +/- 46.3 g/m(2)). No differences were reported between dipper and non-dipper patients regarding extracellular water distribution (ECW: 48.1 +/- 7.7 vs. 49.8 +/- 10.8%). SBP night/day ratio and 48-hour SBP were not correlated to LVMi. A strong correlation was reported between ECW% and LVMi (r = 0.53, p < 0.001). In conclusion, 2 of 3 hypertensive HD patients are non-dipper, and this condition does not seem to be associated with significant differences in 48-hour blood pressure and LV mass. Volume overload appears to be the main independent determinant of LVH in these patients.

Antihypertensive Agents↗

Lack of isoprene overproduction during peritoneal dialysis.

OBJECTIVE: Isoprene is the constitutive unit of isoprenoid lipids and sterols. However, it is also a potential toxic and carcinogenic agent. Recent findings of a marked and prolonged isoprene overproduction induced by hemodialysis sessions raises the question of isoprene behavior in patients on peritoneal dialysis. DESIGN: A study with repeated measures per patient and healthy control. SETTING: Nephrology and Dialysis Unit and Perugia University Medical School. PATIENTS: Sixteen consecutive patients on regular continuous ambulatory peritoneal dialysis (CAPD) were evaluated. Endogenous isoprene was analyzed using gas chromatographic assay of breath isoprene, collected at set times before and after dialysis fluid exchange. RESULTS: No significant variations were found in breath isoprene concentrations in the different samples from each patient, and levels were almost stable within the normal range of healthy controls. CONCLUSION: These results show that CAPD, unlike hemodialysis, has little or no effect on isoprene and isoprenoid-related lipid turnover. This lack of increased endogenous isoprene synthesis, in addition to being a distinctive metabolic feature of CAPD, could have important pathophysiological and clinical implications.

Adult↗