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Background The original peritoneal equilibration test (PET) was used to classify peritoneal dialysis (PD) patients using a 2.27% glucose solution. It has since been suggested that a 3.86% glucose solution be used because this provides better information about ultrafiltration (UF) capacity and the sodium (Na) sieving of the peritoneal membrane. Objective The aim of this study was to determine reference values for a PET using a 3.86% glucose solution (PET-3.86%). Methods We evaluated the PET-3.86% in a large population of incident PD patients attending 27 Italian dialysis centers. Results We evaluated the results of 758 PET-3.86% in 758 incident PD patients (1 test per patient). The mean duration of PD was 5 ± 3 months. The ratio of the concentrations of creatinine in dialysate/plasma (D/PCreat) was 0.73 ± 0.1 (median 0.74). The ratio between the concentrations of glucose at the end/beginning of the test (D/D0) was 0.25 ± 0.08 (median 0.24). Ultrafiltration uncorrected and corrected for bag overfill was respectively 776 ± 295 mL (median 781 mL) and 675 ± 308 mL (median 689 mL). Sodium sieving was 8.4 ± 3.8 mmol/L (median 8.0 mmol/L). Conclusion The results of the study provide PET-3.86% reference values for the beginning of PD that can be used to classify PD patients into transport classes and monitor them over time.

Interference of conventional peritoneal dialysis fluids (cPDFs) with peritoneal membrane cell functions may be attributed to the dialysis fluid's low pH, high glucose concentration, and/or the presence of glucose degradation products (GDPs), the last of which leads to higher levels of advanced glycation end-products (AGEs). It has been suggested that the peritoneal membrane might be better preserved by using biocompatible solutions, including cancer antigetn 125 (CA125). This prospective, open-label, multicentre, randomized, controlled, cross-over phase IV study compared the in vivo biocompatibility of a neutral-pH, low-GDP peritoneal dialysis (PD) solution ( balance) with a cPDF in automated PD (APD) patients. Our study revealed a significantly increased appearance rate and concentration of CA125 in the peritoneal effluent of APD patients treated with the neutral-pH, low-GDP solution balance versus a conventional PD solution.

Background Predictors of haemoglobin (Hb) levels and resistance to erythropoiesis-stimulating agents (ESAs) in dialysis patients have not yet been clearly defined. Some mainly uncontrolled studies suggest that online haemodiafiltration (HDF) may have a beneficial effect on Hb, whereas no data are available concerning online haemofiltration (HF). The objectives of this study were to evaluate the effects of convective treatments (CTs) on Hb levels and ESA resistance in comparison with low-flux haemodialysis (HD) and to evaluate the predictors of these outcomes. Methods Primary multivariate analysis was made of a pre-specified secondary outcome of a multicentre, open-label, randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD (70 patients) or CTs: online pre-dilution HF (36 patients) or online pre-dilution HDF (40 patients). Results CTs did not affect Hb levels (P = 0.596) or ESA resistance (P = 0.984). Hb correlated with polycystic kidney disease (P = 0.001), C-reactive protein (P = 0.025), ferritin (P = 0.018), ESA dose (P < 0.001) and total cholesterol (P = 0.021). The participating centres were the main source of Hb variability (partial eta2 0.313, P < 0.001). ESA resistance directly correlated with serum ferritin (P = 0.030) and beta2 microglobulin (P = 0.065); participating centres were again a major source of variance (partial eta2 0.367, P < 0.001). Transferrin saturation did not predict either outcome variables (P = 0.277 and P = 0.170). Conclusions In comparison with low-flux HD, CTs did not significantly improve Hb levels or ESA resistance. The main sources of variability were participating centres, ESA dose and the underlying disease.

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.

A buffer is included in the peritoneal dialysis solution in order to offset the hydrogen ions normally produced during the metabolic processes. Nowadays, the buffer used is lactate, and its concentration in conventional peritoneal dialysis fluids is 35 or 40 mmol/L. Despite the general thought that peritoneal dialysis adequately corrects uremic acidosis, several studies have demonstrated that more than 50% of patients present mild to moderate acidosis with the solution containing 35 mmol/L of lactate, although with a 40 mmol/L solution this percentage decreases, a substantial number of patients still remain acidotic. This acid-base derangement is characterized by a normal pH and a below-normal plasma bicarbonate concentration, although the external body base balance is in equilibrium. There is evidence that this condition contributes to uremic osteodystrophy and has a detrimental effect on protein metabolism. Conventional solutions also affect mesothelial cell viability and local leukocyte function and have potential systemic effects such as the impairment of cellular redox state. New solutions containing pure bicarbonate or a mixture of bicarbonate and lactate have recently been investigated. A bicarbonate solution containing 34 mmol/L significantly increased plasma bicarbonate levels as compared with the lactate 35 mmol/L solution. It has been demonstrated that bicarbonate solutions have better biocompatibility than the lactate buffered solution and substantially reduce abdominal discomfort experienced by a certain percentage of patients during the solution infusion. These studies demonstrated that the bicarbonate-buffered CAPD solution is safe, well-tolerated, and does not present any, even potential, side effects. Thus, it seems reasonable to consider the bicarbonate buffered solution the standard instead of the alternative, and it might entirely replace lactate as buffer in peritoneal dialysis fluid.

Objective To evaluate bicarbonate fluxes across the peritoneal membrane and bicarbonate gain in patients treated with continuous ambulatory peritoneal dialysis (CAPD) using dialysis solutions with different bicarbonate concentrations. Patients and Design Ninety-seven exchanges, using different dwell times and glucose and bicarbonate concentrations were performed in 43 stable CAPD patients. Dialysate effluent bicarbonate concentration and volumes were measured at different dwell times. Net dialytic bicarbonate gain was calculated. Patients’ acid-base status was determined at the middle of the dwell. Results In prolonged dwells (6 –12 hours)thedialysate effluent bicarbonate concentration correlated with arterial plasma bicarbonate concentration (F = 129, p < 0.0001), but not with ultrafiltration rate or dialysis solution bicarbonate concentration. In 4-hour dwells, effluent bicarbonate concentration correlated with both plasma bicarbonate concentration and ultrafiltration rate (F = 32.52, p < 0.0001 and F = 4.4, p < 0.05, respectively). The effluent bicarbonate concentration may be predicted from the patient's plasma bicarbonate concentration and net ultrafiltration rate for either a 4-hour or prolonged (6 –12 hours) dwell time. Net bicarbonate gain by the patient correlated with ultrafiltration rate, plasma bicarbonate, and dialysis solution bicarbonate concentration (F = 100.56, p < 0.0001 at 4 hours and F = 108.08, p < 0.0001 at 6 12 hours), with the ultrafiltration rate being the predominant parameter. Conclusions The effluent bicarbonate concentration is related to plasma bicarbonate concentration, with ultrafiltration playing a marginal role only during short dwells. However, the ultrafiltration rate has a profound effect on net patient bicarbonate gain. Multiple linear regression analysis allows the prediction of the effect of acid-base status, ultrafiltration, dwell time, and dialysis solution bicarbonate content on net patient bicarbonate gain. It seems that bicarbonate content in the CAPD dialysis solution should be progressively increased with increasing solution osmolality.

The incidence of peritoneal dialysis-related infections has decreased markedly over the past 20 years. This is commonly believed to be the result of improvements in connection technology and eradication of nasal and exit-site Staphylococcus aureus. However, peritonitis is still the most important cause of technique failure. The good results of single centers with a long experience of peritoneal dialysis and the excellent randomized trial results have proved to be incomparable with those of nonselected populations. The analysis of organism-specific infections joined to the identification of the entry pathway into the peritoneum could allow individual centers to focus on the weaknesses of the used protocols and procedures.

For many years, lactate has been used successfully as a buffer in peritoneal dialysis solutions although its effectiveness in the correction of uremic acidosis and its biocompatibility on peritoneal resident cells have been questioned. In addition, some investigators have suggested other potential adverse metabolic effects resulting from the unphysiologically high lactate flux into the body during CAPD. These potential problems associated with lactate-containing CAPD solution prompted the search for alternative buffer-containing solutions. Bicarbonate, the physiological buffer, was considered when the problem of calcium and magnesium carbonate solubility was solved by the use of a two-compartment bag system allowing the mixing of bicarbonate and divalent cations immediately before infusion. The long-term tolerance, safety, efficacy and therapeutic value of a bicarbonate-buffered peritoneal dialysis solution have been evaluated for about 15 years. RCT studies demonstrated a benefit for acid base improvement, while observational reports showed other clinical effects such as a preservation of residual renal function, less inflammatory effect and peritonitis prevention. In addition, there is a consensus that local biocompatibility is improved. Therefore, as bicarbonate is the physiological buffer of the body, it should become the solution of choice in PD patients.

For many years, lactate has been used successfully as a buffer in peritoneal dialysis solutions although its effectiveness in the correction of uremic acidosis and its biocompatibility on peritoneal resident cells have been questioned. In addition, some investigators have suggested other potential adverse metabolic effects resulting from the unphysiologically high lactate flux into the body during CAPD. These potential problems associated with lactate-containing CAPD solution prompted the search for alternative buffer-containing solutions. Bicarbonate, the physiological buffer, was considered when the problem of calcium and magnesium carbonate solubility was solved by the use of a two-compartment bag system allowing the mixing of bicarbonate and divalent cations immediately before infusion. The long-term tolerance, safety, efficacy and therapeutic value of a bicarbonate-buffered peritoneal dialysis solution have been evaluated for about 15 years. RCT studies demonstrated a benefit for acid base improvement, while observational reports showed other clinical effects such as a preservation of residual renal function, less inflammatory effect and peritonitis prevention. In addition, there is a consensus that local biocompatibility is improved. Therefore, as bicarbonate is the physiological buffer of the body, it should become the solution of choice in PD patients.

Background Anemia is common among peritoneal dialysis (PD) patients, and most patients require erythropoiesis-stimulating agents (ESA) to maintain their hemoglobin concentrations within current guideline recommendations. Darbepoetin alfa is an ESA with a 3-fold longer half-life and greater in vivo biological activity than recombinant human erythropoietin, allowing less frequent dosing that may simplify anemia management in these patients, providing benefits to patients, care givers and health care providers. Clinical studies have confirmed the efficacy and safety of darbepoetin alfa administered at extended dosing intervals. However, there are limited data on the management of anemia with ESAs in PD patients in routine clinical practice. The aim of this multicenter observational study in European and Australian dialysis patients was to evaluate darbepoetin alfa administered once every 2 weeks (Q2W) in routine clinical practice for 12 months. Methods PD patients ≥18 years old and converting to treatment with darbepoetin alfa Q2W were eligible for enrollment regardless of previous or current ESA use. Patients enrolled in the study were treated according to local usual clinical practice. Data were collected up to 6 months prior to and 12 months after conversion to darbepoetin alfa Q2W. The primary endpoint was hemoglobin concentration 12 months after conversion to darbepoetin alfa Q2W. Results Of the 741 eligible PD patients (mean age, 61 years; male, 57%), 640 (86%) completed the study. Mean hemoglobin concentration (g/dL) was 11.69 (95% CI, 11.53-11.86) 6 months before the conversion, 12.25 (95% CI, 12.13-12.38) at conversion, and 11.88 (95% CI, 11.74-12.02) 12 months after conversion to darbepoetin alfa Q2W. The weekly equivalent ESA dose (μg/wk) was a geometric mean of 25.24 (95% CI, 23.46-27.15) 6 months before conversion, 20.90 (95% CI, 19.13-22.83) immediately before conversion, 18.89 (95% CI, 18.13-19.68) at conversion and 19.04 (95% CI, 17.69-20.49) 12 months after conversion. Twelve months after conversion, 70% of patients were receiving darbepoetin alfa Q2W and 73% had hemoglobin concentrations >11.0 g/dL. Conclusion In this large observational study, PD patients were able to maintain mean hemoglobin concentrations >11.0 g/dL after conversion to extended dosing of darbepoetin alfa Q2W, with no mean dose increase.

Cardiovascular disease represents the most common cause for the excess of morbidity and mortality found in end-stage renal disease (ESRD) and has prompted the exploration of multiple approaches to improve outcomes in these patients. Cardiovascular risk factors such as increased oxidative stress (OxSt) and inflammation are found in ESRD patients. A vitamin E-coated dialyzer using polysulfone membranes has been suggested to have positive effects on these factors. This 1-year study evaluated in 25 ESRD patients under chronic dialysis, the effects of a vitamin E-coated membrane (VitabranE ViE) "ex vivo" on mononuclear cells, OxSt, and inflammation-related biochemical and molecular biology markers using a molecular biology approach. p22(phox), heme oxygenase (HO)-1, plasminogen activator inhibitor (PAI)-1 protein level, and phosphorylated extracellular signal-regulated kinase (pERK)1/2 status were evaluated at the beginning of the study, after 6 months and after 12 months by Western blot analysis and oxidized low-density lipoprotein (OxLDL) plasma level by enzyme-linked immunosorbent assay, alongside vascular remodeling assessment as measured by carotid intima-media thickness (IMT) in a subgroup of nine randomly selected patients. p22(phox), PAI-1, OxLDL, and pERK all decreased with VitabranE use, while HO-1 increased. Carotid IMT did not increase. Treatment with VitabranE significantly decreases the expression of proteins and markers relevant to OxSt and inflammation tightly associated with cardiovascular disease, and it appears highly likely that VitabranE use will provide a benefit in terms of cardiovascular protection.

Cardiovascular disease represents the most common cause for the excess of morbidity and mortality found in end-stage renal disease (ESRD) and has prompted the exploration of multiple approaches to improve outcomes in these patients. Cardiovascular risk factors such as increased oxidative stress (OxSt) and inflammation are found in ESRD patients. A vitamin E-coated dialyzer using polysulfone membranes has been suggested to have positive effects on these factors. This 1-year study evaluated in 25 ESRD patients under chronic dialysis, the effects of a vitamin E-coated membrane (VitabranE ViE) "ex vivo" on mononuclear cells, OxSt, and inflammation-related biochemical and molecular biology markers using a molecular biology approach. p22(phox), heme oxygenase (HO)-1, plasminogen activator inhibitor (PAI)-1 protein level, and phosphorylated extracellular signal-regulated kinase (pERK)1/2 status were evaluated at the beginning of the study, after 6 months and after 12 months by Western blot analysis and oxidized low-density lipoprotein (OxLDL) plasma level by enzyme-linked immunosorbent assay, alongside vascular remodeling assessment as measured by carotid intima-media thickness (IMT) in a subgroup of nine randomly selected patients. p22(phox), PAI-1, OxLDL, and pERK all decreased with VitabranE use, while HO-1 increased. Carotid IMT did not increase. Treatment with VitabranE significantly decreases the expression of proteins and markers relevant to OxSt and inflammation tightly associated with cardiovascular disease, and it appears highly likely that VitabranE use will provide a benefit in terms of cardiovascular protection.

Objective The evaluation of the efficacy, adequacy, clinical tolerance, and safety of a new bicarbonate continuous ambulatory peritoneal dialysis (CAPD) solution. Design and Patients A 6–week cross-over clinical study in 6 stable CAPD patients was performed. After a control period (2 weeks) with a standard CAPD solution (lactate, 35 mmol/L), a two-chamber bag containing 34 mmol/L of bicarbonate was used for 4 weeks. A breakable valve divided the two chambers, one containing bicarbonate and the other calcium. The two solutions were mixed just before use, thus avoiding the calcium and magnesium carbonate precipitation. Results No differences between control and study periods were found for blood urea nitrogen, creatinine, total proteins, albumin, total and ionized calcium, phosphate, sodium, potassium, chlorine, and hemoglobin. Blood bicarbonate significantly increased from 21.25±2.02 to 23.36±1.15 (pConclusion A CAPD bicarbonate solution is effective in uremic acidosis correction, does not affect dialysis adequacy, is safe, and well tolerated.

Symptomatic intradialytic hypotension is a common complication of hemodialysis (HD). The application of convective therapies to the outpatient setting may improve outcomes, including intradialytic hypotension. In this multicenter, open-label, randomized controlled study, we randomly assigned 146 long-term dialysis patients to HD (n = 70), online predilution hemofiltration (HF; n = 36), or online predilution hemodiafiltration (HDF; n = 40). The primary end point was the frequency of intradialytic symptomatic hypotension (ISH). Compared with the run-in period, the frequency of sessions with ISH during the evaluation period increased for HD (7.1 to 7.9%) and decreased for both HF (9.8 to 8.0%) and HDF (10.6 to 5.2%) (P < 0.001). Mean pre-dialysis systolic BP increased by 4.2 mmHg among those who were assigned to HDF compared with decreases of 0.6 and 1.8 mmHg among those who were assigned to HD and HF, respectively (P = 0.038). Multivariate logistic regression demonstrated significant risk reductions in ISH for both HF (odds ratio 0.69; 95% confidence interval 0.51 to 0.92) and HDF (odds ratio 0.46, 95% confidence interval 0.33 to 0.63). There was a trend toward higher dropout for those who were assigned to HF (P = 0.107). In conclusion, compared with conventional HD, convective therapies (HDF and HF) reduce ISH in long-term dialysis patients.

Secondary hyperoxalemia is a common feature in patients with chronic renal failure, but oxalate removal is not adequately accomplished by regular dialysis treatment. Oxalate removal in two groups of patients, 11 on continuous ambulatory peritoneal dialysis (CAPD) and 12 on hemodialysis (HD), was investigated. HD patients were studied during a regular bicarbonate dialysis and during hemodiafiltration (HDF) with a high convective component (UF = 66 mL/min) and AN69 filter (Hospal Filtral 12, 1.2 m2, Hospal Industrie, Meyzieu, France). All HD and HDF spent dialysate and all 24 hr CAPD effluents were collected; oxalate concentration was measured by high performance liquid chromatography (HPLC) using an ion exchange column. Both oxalate flux and total extraction were statistically higher during HDF treatments (HDF = 1.87 +/- 0.77 mg/min and 335.9 +/- 131.5 mg/session, respectively; HD = 0.99 +/- 0.74 mg/min, 226 +/- 153 mg/session, respectively; p < 0.02). The positive interaction of convective and diffusive fluxes probably played a major role in oxalate removal during treatment with a high convective component; solute-membrane interactions can occur by using either cellulosic or synthetic fibers. In CAPD patients, oxalate removal (76.42 +/- 50.85 mg/day) was lower than in patients on either HD or HDF, although weekly oxalate extraction was statistically no different between CAPD (535.46 +/- 356 mg/week) and HD (677.72 +/- 460.82 mg/week). It was concluded that HDF is more effective than HD or CAPD in oxalate removal. Long-term studies are needed to demonstrate whether these kinetic findings have clinical relevance.

Mild derangements of acid-base status are common features in peritoneal dialysis patients, metabolic acidosis being the most frequent alteration. One of the main tasks of dialysis is to correct these derangements and the target is the normalization of the acid-base parameters since they affect several organs and functions. Since factors affecting acid-base homeostasis are intrinsic characteristics of the individual patient (metabolic acid production, distribution space for bicarbonate, dialytic prescription, etc.), it is not surprising that only relatively few patients achieve the normal range. Only a certain modulation of buffer infusion by using different buffer concentrations in the dialysis fluid may ensure a good correction in a large percentage of patients.

Mild derangements of acid-base status are common features in peritoneal dialysis patients, metabolic acidosis being the most frequent alteration. One of the main tasks of dialysis is to correct these

Several strategies have been proposed to increase dialysis efficiency in order to reduce dialysis treatment time. Paired filtration dialysis (two-chamber technique) is a new technique combining the advantages of highly permeable membranes and convective transport with the high depurative efficacy of diffusion. The system operates with two units in series (hemofilter + dialyzer) with membranes of polysulfone and hemophan, respectively. A detailed analysis of the hydraulic properties of the system and its possible optimization in terms of depurative efficiency is reported in this paper. In vitro and in vivo tests provided data sufficient to draw some hypotheses on a new utilization of the system. The system appears to be adequate for operating under conditions of high blood flows, however, some limitations were evidenced during our evaluation: the convective component may be insufficient and further increases are impossible because of the limiting effect of the low surface area of the hemofilter; the configuration in which the weight loss is achieved in the hemofilter exposes to the risk of backfiltration in the dialyzer, reducing the benefits of a highly biocompatible system, and the use of acetate in the dialysate and/or lactate in the substitution fluid may interfere with a satisfactory correction of metabolic acidosis. On the basis of our evaluations, some changes can be proposed such as: (1) increased surface area of the hemofilter; (2) use of blood flows higher than 300 ml/min; (3) use of bicarbonate in the dialysate and in the replacement solution; (4) increased convective component with ultrafiltration rates of 50-60 ml/min and full replacement with substitution fluid in between the two filters, and (5) weight loss achieved in the dialyzer with a constantly positive transmembrane pressure. With such a modification of the operative conditions, paired filtration dialysis can be probably applied as a highly efficient dialysis technique in a large number of patients with a significant reduction of dialysis treatment time.

Alpha 1-Antichymotrypsin (alpha 1-AK) and alpha-1-antitrypsin (alpha 1-AT) represent a defense mechanism to protect the tissues from proteolytic enzyme activity. We studied the implication of alpha 1-AK and alpha 1-AT in glomeruli of patients with different nephropathies based on the analysis of 52 paraffin-embedded renal biopsies with alpha 1-AK and alpha 1-AT antisera. The results demonstrate an intense alpha 1-AK glomerular staining in renal biopsies from patients with minimal-change disease, while a minor staining of this protein was found in the other nephropathies. No significant evidence of alpha 1-AT deposits was observed in our cases. Our findings suggest that when alpha 1-AK is lacking in glomeruli the defense mechanisms against proteolytic enzymes may not be efficient enough to protect the glomerular structures and limit the damage. Since alpha 1-AK is a reactant of the acute phase of inflammation, it may be considered as a marker of activity for monocyte-macrophages in glomerular damage.