New scenarios in secondary hyperparathyroidism: etelcalcetide. Position paper of working group on CKD-MBD of the Italian Society of Nephrology.

Bone mineral abnormalities (defined as Chronic Kidney Disease Mineral Bone Disorder; CKD-MBD) are prevalent and associated with a substantial risk burden and poor prognosis in CKD population. Several lines of evidence support the notion that a large proportion of patients receiving maintenance dialysis experience a suboptimal biochemical control of CKD-MBD. Although no study has ever demonstrated conclusively that CKD-MBD control is associated with improved survival, an expanding therapeutic armamentarium is available to correct bone mineral abnormalities. In this position paper of Lombardy Nephrologists, a summary of the state of art of CKD-MBD as well as a summary of the unmet clinical needs will be provided. Furthermore, this position paper will focus on the potential and drawbacks of a new injectable calcimimetic, etelcalcetide, a drug available in Italy since few months ago.

Sodium removal and plasma tonicity balance are not different in hemodialysis and hemodiafiltration using high-flux membranes.

BACKGROUND: The clinical benefits of on-line hemodiafiltration (HDF) versus high-flux membranes hemodialysis (hf-HD) are still debated. In fact, although a superiority of one treatment over the other, especially in terms of mortality, did not emerge from the analysis of clinical trials, improved intradialytic vascular stability and cardiovascular mortality have been observed in patients undergoing HDF rather than hf-HD; the lower removal of sodium (Na+) during HDF seems to play a major role. The plasma concentration of Na+ is the major determinant of plasma tonicity, which, by determining the flow of water between the intracellular and the extracellular compartment, contributes to the vascular refilling process and the maintenance of blood pressure during the hemodialysis treatment. Plasma tonicity also depends on plasma glucose concentration, especially in patients with diabetes mellitus with hyperglycaemia at the start of hemodialysis treatment. MATERIALS AND METHODS: We evaluated the removal of Na+ and plasma tonicity balance during a 2-week period by performing 2-3 consecutive sessions of hf-HD followed by 2-3 consecutive sessions of HDF, or vice versa, in 47 patients (40% diabetics) on chronic hemodialysis. Identical parameters were used in all dialytic sessions. RESULTS: Na+ removal per session was - 224 ± 144 mmol and - 219 ± 152 mmol, respectively, in hf-HD and in HDF (p = 0.79). The plasma tonicity balance per session was - 575 ± 310 mOsm and - 563 ± 328 mOsm, respectively, in hf-HD and in HDF (p = 0.75). CONCLUSIONS: The removal of Na+ and plasma tonicity balance did not differ between hf-HD and HDF. This observation suggests that factors other than those assessed in our study might explain the improved cardiovascular stability reported in HDF.

Current and potential treatment options for hyperphosphatemia.

INTRODUCTION: Hyperphosphatemia is common in late stages of chronic kidney disease and is often associated with elevated parathormone levels, abnormal bone mineralization, extra-osseous calcification, and increased risk of cardiovascular events and death. Several classes of oral phosphate binders are available to help control plasma phosphorus levels. Although effective at lowering serum phosphorus, they all have safety, tolerability, and compliance issues that need to be considered when selecting which one to use. AREAS COVERED: This paper reviews the most established treatment options for hyperphosphatemia, in patients with chronic kidney disease, focusing on the new inhibitors of active phosphate absorption. EXPERT OPINION: The prevention and the treatment of hyperphosphatemia is today far to be satisfactory. Nonetheless, an extending range of phosphate binders are now available. Aluminum has potentially serious toxic risks. Calcium-based binders are very effective but can lead to hypercalcemia and/or positive calcium balance and progression of cardiovascular calcification. No long-term data are available for the new calcium acetate/magnesium combination product. Lanthanum is an effective phosphate binder, and long-term effects of tissue deposition seem clinically irrelevant. Sevelamer, appear to have profiles that would lead to pleiotropic effects and reduced progression of vascular calcification, and the main adverse events seen with these agents are gastrointestinal. Iron has a powerful capability of binding phosphate, thus numerous preparations are available, both with and without significant systemic absorption of the iron component. The inhibitors of active intestinal phosphate transport, with their very selective mechanism of action and low pill burden seem the most interesting approach; however, do not seem at present to be effective alone, in reducing serum phosphorus levels.

[New scenarios in secondary hyperparathyroidism: etelcalcetide. Position paper of Nephrologists form Lombardy].

Bone mineral abnormalities (defined as Chronic Kidney Disease Mineral Bone Disorder; CKD-MBD) are prevalent and associated with a substantial risk burden and poor prognosis in CKD population. Several lines of evidence support the notion that a large proportion of patients receiving maintenance dialysis experience a suboptimal biochemical control of CKD-MBD. Although no study has ever demonstrated conclusively that CKD-MBD control is associated with improved survival, an expanding therapeutic armamentarium is available to correct bone mineral abnormalities. In this position paper of Lombardy Nephrologists, a summary of the state of art of CKD-MBD as well as a summary of the unmet clinical needs will be provided. Furthermore, this position paper will focus on the potential and drawbacks of a new injectable calcimimetic, etelcalcetide, a drug available in Italy since few months ago.

Predictors of first ischemic lower limb ulcer in dialysis patients: an observational cohort study.

BACKGROUND: Lower limb ischemia affects the quality of life, physical activity and life expectancy of dialysis patients. The aim of this study was to investigate the risk factors associated with ischemic foot ulcers considering clinical, laboratory and therapeutic domains. METHODS: This observational cohort study was based on data from the Nephrology and Dialysis Department database of Alessandro Manzoni Hospital, Lecco (Italy). All of the incident patients who started dialysis between 1 January 1999 and 29 February 2012 were enrolled, excluding temporary guests, patients with acute renal failure and patients with previous limb ischemia or amputation. Multivariate Cox regression analysis identified the predictors in each domain, which were matched in the final model. A time-dependent approach was used to take into account the evolution of some of the prognostic covariates. RESULTS: Of the 526 incident dialysis patients, 120 developed a lower limb ischemic lesion after a median of 13 months. The incidence of new ulcers was constant during the study period (6 per 100 person-years), but higher in the diabetics with a relative rate of 4.5. The variables significantly related to an increased risk of lower limb ulcers were age, male gender, diabetes, ischemic heart disease, treatment with proton pump inhibitors, iron, anticoagulants and calcium-based binders, and blood levels of phosphorus, triglycerides and C-reactive protein. CONCLUSION: The incidence of lower limb ulcers was highest during the early dialysis follow-up and was associated with, in addition to diabetes, modifiable laboratory and therapeutic predictors such as anticoagulants, proton pump inhibitors, calcium-containing binders, calcimimetics and iron.

Assessment of intradialysis calcium mass balance by a single pool variable-volume calcium kinetic model.

INTRODUCTION: A reliable method of intradialysis calcium mass balance quantification is far from been established. We herein investigated the use of a single-pool variable-volume Calcium kinetic model to assess calcium mass balance in chronic and stable dialysis patients. METHODS: Thirty-four patients on thrice-weekly HD were studied during 240 dialysis sessions. All patients were dialyzed with a nominal total calcium concentration of 1.50 mmol/L. The main assumption of the model is that the calcium distribution volume is equal to the extracellular volume during dialysis. This hypothesis is assumed valid if measured and predicted end dialysis plasma water ionized calcium concentrations are equal. A difference between predicted and measured end-dialysis ionized plasma water calcium concentration is a deviation on our main hypothesis, meaning that a substantial amount of calcium is exchanged between the extracellular volume and a nonmodeled compartment. FINDINGS: The difference between predicted and measured values was 0.02 mmol/L (range -0.08:0.16 mmol/L). With a mean ionized dialysate calcium concentration of 1.25 mmol/L, calcium mass balance was on average negative (mean ± SD -0.84 ± 1.33 mmol, range -5.42:2.75). Predialysis ionized plasma water concentration and total ultrafiltrate were the most important predictors of calcium mass balance. A significant mobilization of calcium from the extracellular pool to a nonmodeled pool was calculated in a group of patients. DISCUSSION: The proposed single pool variable-volume Calcium kinetic model is adequate for prediction and quantification of intradialysis calcium mass balance, it can evaluate the eventual calcium transfer outside the extracellular pool in clinical practice.

The peritoneal sieving of sodium: a simple and powerful test to rule out the onset of encapsulating peritoneal sclerosis in patients undergoing peritoneal dialysis.

BACKGROUND AND AIMS: Encapsulating peritoneal sclerosis (EPS) is an uncommon but severe complication of peritoneal dialysis (PD). A reliable screening tool to identify patients at risk of developing or not EPS is currently not available. We aimed to evaluate whether the reduction in dialysate sodium concentration (sodium sieving) at 60 min (ΔDNa60), during a peritoneal equilibration test with 3.86% glucose concentration (3.86%-PET) was able to early rule out patients who will not develop EPS. METHODS: Prospective controlled longitudinal (20-year) cohort study. All eligible incident PD patients attending the hospital underwent a 3.86%-PET during the first 3 months following start of PD and then once a year. The dip in ΔDNa60 and other factors were correlated with eventual EPS onset. RESULTS: Of 161 incident PD patients, with a median PD duration of 37.8 (24.7-58.3) months and 64.1 (34.5-108.3) months of follow-up, 13 patients (8%) developed EPS at a median PD duration of 72.7 (56.6-109.4) months and 105.0 (76.4-143.2) months of follow-up. ΔDNa60 demonstrated the best sensitivity and specificity values, estimated by conventional receiver operating characteristic (ROC) curve analysis with an area under the curve (AUC) of 0.90, 0.83 and 0.85 at 1, 2 and 3 years before the onset of EPS, respectively. Multifactorial analysis showed that the most useful factors for predicting EPS were age at start of PD, duration of PD, small solutes transport (D/PCreat) and ΔDNa60; the AUC at 1, 2 and 3 years before the onset of EPS was, respectively, 0.97, 0.96 and 0.94, the positive predictive value being 0.48, 0.57 and 0.42, and the negative predictive value 1.0, 1.0 and 1.0. CONCLUSIONS: It is possible to predict the occurrence and, better, the non-occurrence of EPS using simple parameters such as age at PD start, duration of PD, and parameters obtained by 3.86%-PET such as D/PCreat and ΔDNa60.

Sudden Death in End Stage Renal Disease: Comparing Hemodialysis versus Peritoneal Dialysis.

BACKGROUND/AIMS: This study aimed to evaluate total and sudden death (SD) in a cohort of dialysis patients, comparing hemodialysis (HD) vs. peritoneal dialysis (PD). METHODS: This is a multicenter retrospective cohort study. RESULTS: Deaths were 626 out of 1,823 in HD and 62 of 249 in PD patients. HD patients had a greater number of comorbidities (p < 0.05). PD patients had a lower risk of death than HD patients (p < 0.001); however, the advantage decreased with time (p < 0.001). Mortality predictors were left ventricular ejection fraction (LVEF) ≤35%, older age, ischemic heart disease, diabetes mellitus, previous stroke, and atrial fibrillation (p < 0.03). SDs were 84:71 in HD and 13 in PD population (12.1 and 22.8% of all causes of death, respectively). A non-significant risk of SD among PD compared to HD patients was detected. SD predictors were older age, ischemic heart disease, and LVEF ≤35% (p < 0.05). CONCLUSIONS: HD patients showed a greater presence of comorbidities and reduced survival compared to PD patients; however, the incidence of SD does not differ in the 2 populations. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=464347.

Efficacy of a remote web-based lung ultrasound training for nephrologists and cardiologists: a LUST trial sub-project.

Within the framework of the LUST trial (LUng water by Ultra-Sound guided Treatment to prevent death and cardiovascular events in high-risk end-stage renal disease patients), the European Renal and Cardiovascular Medicine (EURECA-m) working group of the European Renal Association-European Dialysis Transplant Association established a central core lab aimed at training and certifying nephrologists and cardiologists participating in this trial. All participants were trained by an expert trainer with an entirely web-based programme. Thirty nephrologists and 14 cardiologists successfully completed the training. At the end of training, a set of 47 lung ultrasound (US) videos was provided to trainees who were asked to estimate the number of B-lines in each video. The intraclass correlation coefficient (ICC) for the whole series of 47 videos between each trainee and the expert trainer was high (average 0.81 ± 0.21) and >0.70 in all but five cases. After further training, the five underperforming trainees achieved satisfactory agreement with the expert trainer (average post-retraining ICC 0.74 ± 0.14). The Bland-Altman plot showed virtually no bias (difference between the mean 0.03) and strict 95% limits of agreement lines (-1.52 and 1.45 US B-lines). Only four cases overlapped but did not exceed the same limits. Likewise, the Spearman correlation coefficient applied to the same data series was very high (r = 0.979, P < 0.0001). Nephrologists and cardiologists can be effectively trained to measure lung congestion by an entirely web-based programme. This web-based training programme ensures high-quality standardization of US B-line measurements and represents a simple, costless and effective preparatory step for clinical trials targeting lung congestion.

The Agreement between Auscultation and Lung Ultrasound in Hemodialysis Patients: The LUST Study.

BACKGROUND AND OBJECTIVES: Accumulation of fluid in the lung is the most concerning sequela of volume expansion in patients with ESRD. Lung auscultation is recommended to detect and monitor pulmonary congestion, but its reliability in ESRD is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a subproject of the ongoing Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, we compared a lung ultrasound-guided ultrafiltration prescription policy versus standard care in high-risk patients on hemodialysis. The reliability of peripheral edema was tested as well. This study was on the basis of 1106 pre- and postdialysis lung ultrasound studies (in 79 patients) simultaneous with standardized lung auscultation (crackles at the lung bases) and quantification of peripheral edema. RESULTS: Lung congestion by crackles, edema, or a combination thereof poorly reflected the severity of congestion as detected by ultrasound B lines in various analyses, including standard regression analysis weighting for repeated measures in individual patients (shared variance of 12% and 4% for crackles and edema, respectively) and κ-statistics (κ ranging from 0.00 to 0.16). In general, auscultation had very low discriminatory power for the diagnosis of mild (area under the receiver operating curve =0.61), moderate (area under the receiver operating curve =0.65), and severe (area under the receiver operating curve =0.68) lung congestion, and the same was true for peripheral edema (receiver operating curve =0.56 or lower) and the combination of the two physical signs. CONCLUSIONS: Lung crackles, either alone or combined with peripheral edema, very poorly reflect interstitial lung edema in patients with ESRD. These findings reinforce the rationale underlying the Lung Water by Ultra-Sound Guided Treatment to Prevent Death and Cardiovascular Complications in High Risk ESRD Patients with Cardiomyopathy Trial, a trial adopting ultrasound B lines as an instrument to guide interventions aimed at mitigating lung congestion in high-risk patients on hemodialysis.

Patient-specific modeling of multicompartmental fluid and mass exchange during dialysis.

BACKGROUND: Dialysis is associated with a non-negligible rate of morbidity, requiring treatment customization. Many mathematical models have been developed describing solute kinetics during hemodialysis (HD) for an average uremic patient. The clinical need can be more adequately addressed by developing a patient-specific, multicompartmental model. MATERIALS AND METHODS: The data from 148 sessions (20 patients), recorded at the Regional Hospital of Lugano, Switzerland, were used to develop and validate the mathematical model. Diffusive and convective interactions among patient, dialysate and substitution fluid were considered. Three parameters, related to mass transfer efficiency at the cell membrane, at the dialyzer and at the capillary wall, were used to tune the model. The ability of the model to describe the clinical evolution of a specific HD session was evaluated by comparing model outputs with clinically acquired data on solutes and catabolite concentrations. RESULTS: The model developed in this study allows electrolyte and catabolite concentration trends during each HD session to be described. The errors obtained before the estimation of the patient-specific parameters drastically decrease after their identification. With the optimized model, plasmatic concentration trends can be described with an average percent error lower than 2.1% for Na+, Cl-, Ca2+ and HCO3-, lower than 5% for K+ and lower than 8% for urea. CONCLUSIONS: The peculiarity of the proposed model is the possibility it offers to perform a real-time simulation enabling quantitative appraisal of hematochemical quantities whose direct measurement is prohibitive. These will be beneficial to dialysis therapy planning, reducing intradialysis complications and improving patients' quality of life.

Impact of European medicines agency recommendations for hypersensitivity reactions on intravenous iron prescription in haemodialysis centres of the Lombardy region.

BACKGROUND: The European Medicines Agency (EMA) has recommended measures to minimize the risk of hypersensitivity reactions (HSRs) to intravenous iron (IVFe). We analysed the effects of these recommendations on IVFe clinical management among haemodialysis centres (HDCs) in Lombardy, Italy. MATERIALS AND METHODS: A questionnaire was sent to all 117 HDCs to collect information on centre characteristics, e.g. HDC type [hospital centre (HC) vs. centre with limited assistance (CAL)], presence/absence of intensive care unit (ICU) and/or emergency trained staff, IVFe therapy regarding molecules, administration modalities, side effects, and percentage variations in iron prescription between 2014 and 2013 (outcome, Δ-IVFe%). A linear regression model was applied to evaluate the focus effect (ß) of HDC type on the outcome, controlling for possible confounding effects of the other characteristics. RESULTS: Response rate was 73.5 %. IVFe therapy was used in 69.1 % (HDC range 11-100) of patients. Following EMA recommendations, prescription was reduced by 12.6 %, with the largest reduction observed in CALs. No severe HSRs were reported. HCs had more frequently an ICU [97.2 vs. 20 %, odds ratio (OR) = 63.6 (95 % confidence interval 15.56; 537.47), p < 0.001], emergency trained staff [97.2 vs. 61.2 %, OR = 10.7 (2.68; 85.33), p < 0.001] and instrumental facilities (91.7 vs. 58 %, OR = 5.8 (2.03; 23.55), p < 0.001] than CALs. Linear regression demonstrated a significant raw effect of HDC type on Δ- IVFe% [ß =  19.6 (9.82; 30.63), p < 0.001]. No association was found when HDC type was adjusted for ICU-presence [ß = 6.7 (-2.32; 18.30), p = 0.199] or for all-confounding factors [ß = 5.6 (-5.50; 17.08), p = 0.337]. CONCLUSIONS: This survey shows a disparity in IVFe therapy prescription following EMA recommendations, which is largely influenced by the presence/absence of ICUs in HD centres.

Ionic conductivity of peritoneal dialysate: a new, easy and fast method of assessing peritoneal membrane function in patients undergoing peritoneal dialysis.

BACKGROUND: Peritoneal membrane function can be assessed using the peritoneal equilibration test (PET) and similar tests, but these are almost always complicated to use, require a considerable amount of working time and their results cannot always be easily interpreted. Ionic conductivity is a measure of the ability of an electrolyte solution to conduct electricity. We tested the hypothesis that the ionic conductivity of peritoneal dialysate can be used to evaluate peritoneal membrane function in peritoneal dialysis patients. METHODS: We measured the ionic conductivity and classic biochemical parameters of peritoneal dialysate in 69 patients during a modified PET and compared their ability to evaluate peritoneal membrane function and to diagnose ultrafiltration failure (UFF). RESULTS: Ionic conductivity was correlated well with classical parameters of peritoneal transport as glucose reabsorption of glucose (D/D0: r(2) = 0.62, P < 0.0001) and creatinine transport (D/PCreat: r(2) = 0.72, P < 0.0001). Twelve patients (17%) experienced UFF and, in them, the ionic conductivity area under the receiver-operating characteristic curve was 0.91 (95% confidence interval: 0.81-0.96) with sensitivity of 1.00 and specificity of 0.84 at a cut-off value of 12.75 mS/cm. CONCLUSIONS: These findings indicate that the ionic conductivity of peritoneal dialysate can be used as a new screening tool to evaluate peritoneal membrane function.

Mortality, sudden death and indication for cardioverter defibrillator implantation in a dialysis population.

BACKGROUND: The incidence of sudden death among dialysis patients is high, but end stage renal disease was an exclusion criterion in the trials that demonstrated the benefit of implantable cardioverter defibrillator (ICD) for sudden death prevention. METHODS: Dialysis patients alive on January 2010 or starting dialysis between January 2010 and January 2013 were enrolled and retrospectively evaluated. Patients were divided into three groups: No-Indication, Indication-With ICD and Indication-Without ICD. Cox and Fine and Gray regression models were used to estimate the total and cause-specific (sudden or non-sudden) mortality hazard ratio (HR, HR(cpRisk)), respectively. Survival was defined as the time from start of dialysis to the time of death. RESULTS: 154/2072 patients (7.4%) had indication for ICD implantation and 52 (33.8%) of them received the device; 688 (33.2%) deaths were recorded. Mortality was different among groups [Indication-With ICD vs No-Indication: HR 1.59 (95% CI 1.06-2.38) and Indication-Without ICD vs No-Indication: HR 2.67 (95% CI 2.09-3.39, p < 0.001)]. 84/688 (12.2%) were sudden deaths. The cumulative incidence of sudden death was higher in patients with ICD indication [Indication-With ICD vs No-Indication HR(cpRisk) 3.21 (95% CI 1.38-7.40) and Indication-Without ICD vs No-Indication: HR(cpRisk) 4.19 (95% CI 2.38-7.39), p < 0.001], but also No-Indication patients showed a high rate of sudden death [8.5% (95% CI.6.5-10.9) at 8 years of follow-up]. CONCLUSIONS: Dialysis patients with ICD indication had a worse survival than No-Indication subjects and the prognosis was particularly poor for the Indication-Without ICD group. Sudden death incidence was much higher than in the general population, even among No-Indication subjects.

Phosphate binders for the treatment of hyperphosphatemia in chronic kidney disease patients on dialysis: a comparison of safety profiles.

INTRODUCTION: Hyperphosphatemia is common in the late stages of chronic kidney disease (CKD) and is associated with elevated parathormone levels, abnormal bone mineralization, extraosseous calcification and increased risk of cardiovascular events and death. Several classes of oral phosphate binders are available to help control phosphorus levels. Although effective at lowering serum phosphorus, they all have safety issues that need to be considered when selecting which one to use. AREAS COVERED: This paper reviews the use of phosphate binders in patients with CKD on dialysis, with a focus on safety and tolerability. In addition to the more established agents, a new resin-based phosphate binder, colestilan, is discussed. EXPERT OPINION: Optimal phosphate control is still an unmet need in CKD. Nonetheless, we now have an extending range of phosphate binders available. Aluminium has potentially serious toxic risks. Calcium-based binders are still very useful but can lead to hypercalcemia and/or positive calcium balance and cardiovascular calcification. No long-term data are available for the new calcium acetate/magnesium combination product. Lanthanum is an effective phosphate binder, but there is insufficient evidence about possible long-term effects of tissue deposition. The resin-based binders, colestilan and sevelamer, appear to have profiles that would lead to less vascular calcification, and the main adverse events seen with these agents are gastrointestinal effects.

Phosphate levels in patients treated with low-flux haemodialysis, pre-dilution haemofiltration and haemodiafiltration: post hoc analysis of a multicentre, randomized and controlled trial.

BACKGROUND: Whether convective therapies allow better control of serum phosphate (P) is still undefined, and no data are available concerning on-line haemofiltration (HF). The objectives of the study are to evaluate the effect of convective treatments (CTs) on P levels in comparison with low-flux haemodialysis (HD) and to evaluate the correlates of serum phosphate in a post hoc analysis of a randomized clinical trial. METHODS: This analysis was performed in the database of a multicentre, open label and randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD (70 patients) or CTs: on-line pre-dilution HF (36 patients) or on-line pre-dilution haemodiafiltration (40 patients). RESULTS: CTs did not affect P (P = 0.526), calcium (Ca) (P = 0.849) and parathyroid hormone levels (P = 0.622). P levels were associated with the use of phosphate binders including aluminium-based phosphate binders (P < 0.001) and sevelamer (P < 0.001), pre-dialysis bicarbonate levels (P < 0.001) and pre-dialysis blood K levels (P < 0.001). On multivariate analysis (generalized linear model), serum P was again largely unassociated with CTs (P = 0.631). Notably, participating centres were by far the strongest independent correlate of serum P, explaining 45.3% of the variance of serum P over the trial and this association was confirmed at multivariate analysis. Bicarbonate (P < 0.001) and, to a weaker extent, serum K (P = 0.032) were independently related to serum P. CONCLUSIONS: In comparison with low-flux HD, CTs did not significantly affect serum P levels. Participating centres were the main source of P variability during the trial followed by treatment with phosphate binders, serum bicarbonate and, to a weak extent, serum potassium levels (ClinicalTrials.gov Identifier: NCT011583309).

The effects of colestilan versus placebo and sevelamer in patients with CKD 5D and hyperphosphataemia: a 1-year prospective randomized study.

BACKGROUND: This study compared the effects of short-term titrated colestilan (a novel non-absorbable, non-calcium, phosphate binder) with placebo, and evaluated the safety and efficacy of colestilan over 1 year compared with sevelamer, in patients with chronic kidney disease (CKD) 5D. METHODS: This prospective multicentre study comprised a 4-week phosphate binder washout period, a 16-week short-term, flexible-dose, treatment period (including a 4-week placebo-controlled withdrawal period) and a 40-week extension treatment phase. RESULTS: At Week 16 (the end of the 4-week placebo-controlled withdrawal period), serum phosphorus level was 0.43 mmol/L (1.32 mg/dL) lower with colestilan than placebo (P < 0.001; primary end point). Serum LDL-C level was also lower with colestilan than with placebo (P < 0.001). Both colestilan and sevelamer produced significant reductions from baseline in serum phosphorus levels (P < 0.001), maintained for 1 year, and the proportion of patients achieving target levels of ≤1.78 mmol/L (5.5 mg/dL) or ≤1.95 mmol/L (6.0 mg/dL) at study end were similar (65.3 and 73.3%, respectively, for colestilan, and 66.9 and 77.4%, respectively, for sevelamer). Serum calcium level remained stable in the colestilan group but tended to increase slightly in the sevelamer group (end-of-study increase of 0.035 mmol/L over baseline). Both binders produced similar reductions from baseline in LDL-C level (P < 0.001), and responder rates after 1 year, using a target of <1.83 mmol/L (70 mg/dL) or <2.59 mmol/L (100 mg/dL) were similar in both groups (50.7 and 85.3% for colestilan and 54.0 and 80.6% for sevelamer). Colestilan was generally well tolerated. CONCLUSIONS: Colestilan is effective and safe for the treatment of hyperphosphataemia in patients with CKD 5D, and affords similar long-term phosphorus and cholesterol reductions/responder rates to sevelamer.

Prospective randomized pilot study on the effects of two synthetic high-flux dialyzers on dialysis patient anemia.

PURPOSE: Anemia in chronic kidney disease dialysis patients is a complex syndrome involving many causes. Adequate dialysis can contribute to its correction through many mechanisms, including the removal of molecules that may inhibit erythropoiesis. The aim of this pilot study was to evaluate the effect on renal anemia of two synthetic, high-flux dialyzers (polynephron vs. high-flux polysulphone). METHODS: 20 dialysis patients (11 male; mean age: 72 years) were randomly assigned and studied for 6 months. There were 2 dropouts in each group. Each patient underwent 3 hemodialysis treatments per week without any difference in dialysis prescription. At T = 0 and T = 6 (after 6 months), instantaneous plasma clearances and reduction rates of small solutes, ß2-microglobulin protein (ß2-µ); hemoglobin (Hb), and iron pattern were measured. The effect on anemia was evaluated by calculating the Erythropoesis Stimulating Agent (ESA) doses and the Erythropoietin Resistance Index (ERI). RESULTS: Kt/V increased between T0 and T6 in both groups. ß2-µ pre-dialysis levels significantly decreased between T0 and T6 in both dialyzer groups (p<0.001 in both groups). The Hb levels increased between T0 and T6, but significantly only for the polynephron patient group (p = 0.006 and 0.142). ESA dose did not change significantly. The ERI decreased by 22.7% between T0 and T6 in the polynephron-group and increased by 14% in the others; these changes were not significant. CONCLUSIONS: High-flux filters improved Hb levels, although only significantly in the polynephron group, suggesting a possible different effect. The results should be interpreted with caution and tested in an appropriately powered, large, prospective, randomized control trial.