Prescribing the dialysis dose and treatment frequency in home haemodialysis.

BACKGROUND: There is growing interest in home haemodialysis (HHD) performed with low-flow dialysate devices and variable treatment schedules. The target standard Kt/V (stdKt/V) should be 2.3 volumes/week, according to KDOQI guidelines (2015). The current formula for stdKt/V does not help prescribe the dialysis dose (eKt/V) and treatment frequency (TF). The aim of this study was to obtain a formula for stdKt/V that is able to define the minimum required values of eKt/V and TF to achieve the targeted stdKtV. METHODS: Thirty-eight prevalent patients on HHD were enrolled. A total of 231 clinical datasets were available for urea modelling using the Solute-Solver software (SS), recommended by KDOQI guidelines. A new formula (stdKt/V = a + b × Kru + c × eKt/V) was obtained from multivariable regression analysis of stdKt/V vs eKt/V and residual kidney urea clearance (Kru). The values of coefficients a, b and c depend on the treatment schedules and the day of the week of blood sampling for the kinetic study (labdayofwk) and then vary for each of their foreseen 62 combinations. For practical purposes, we used only seven combinations, assuming Monday as a labdayofwk for each of the most common schedules of the 7 days of the week. RESULTS: The stdKt/V values obtained with SS were compared with the paired ones obtained with the formula. The mean ± standard deviation stdKt/V values obtained with SS and the formula were 3.043 ± 0.530 and 2.990 ± 0.553, respectively, with 95% confidence interval +0.15 to -0.26. A 'prescription graph' was built using the formula to draw lines expressing the relationship between Kru and required eKt/V for each TF. Using this graph, TF could have been reduced from the delivered 5.8 ± 0.8 to 4.8 ± 0.8 weekly sessions. CONCLUSIONS: The new formula for stdKtV is reliable and can support clinicians to prescribe the dialysis dose and TF in patients undergoing HHD.

Kidney dysfunction requiring dialysis is a heterogeneous syndrome: we should treat it like one.

PURPOSE OF REVIEW: Advanced kidney failure requiring dialysis, commonly labeled end-stage kidney disease or chronic kidney disease stage 5D, is a heterogeneous syndrome -a key reason that may explain why: treating advanced kidney dysfunction is challenging and many clinical trials involving patients on dialysis have failed, thus far. Treatment with dialytic techniques - of which maintenance thrice-weekly hemodialysis is most commonly used - is broadly named kidney 'replacement' therapy, a term that casts the perception of a priori abandonment of intrinsic kidney function and subsumes patients into a single, homogeneous group. RECENT FINDINGS: Patients with advanced kidney failure necessitating dialytic therapy may have ongoing endogenous kidney function, and differ in their clinical manifestations and needs. Different terminology, for example, kidney dysfunction requiring dialysis (KDRD) with stages of progressive severity could better capture the range of phenotypes of patients who require kidney 'assistance' therapy. SUMMARY: Classifying patients with KDRD based on objective, quantitative levels of endogenous kidney function, as well as patient-reported symptoms and quality of life, would facilitate hemodialysis prescriptions tailored to level of kidney dysfunction, clinical needs, and personal priorities. Such classification would encourage clinicians to move toward personalized, physiological, and adaptive approach to hemodialysis therapy.

The spectrum of kidney dysfunction requiring chronic dialysis therapy: Implications for clinical practice and future clinical trials.

Staging to capture kidney function and pathophysiologic processes according to severity is widely used in chronic kidney disease or acute kidney injury not requiring dialysis. Yet the diagnosis of "end-stage kidney disease" (ESKD) considers patients as a single homogeneous group, with negligible kidney function, in need of kidney replacement therapy. Herein, we review the evidence behind the heterogeneous nature of ESKD and discuss potential benefits of recasting the terminology used to describe advanced kidney dysfunction from a monolithic entity to a disease with stages of ascending severity. We consider kidney assistance therapy in lieu of kidney replacement therapy to better reconcile all available types of therapy for advanced kidney failure including dietary intervention, kidney transplantation, and dialysis therapy at varied schedules. The lexicon "kidney dysfunction requiring dialysis" (KDRD) with stages of ascending severity based on levels of residual kidney function (RKF)-that is, renal urea clearance-and manifestations related to uremia, fluid status, and other abnormalities is discussed. Subtyping KDRD by levels of RKF could advance dialysis therapy as a form of kidney assistance therapy adjusted based on RKF and clinical symptoms. We focus on intermittent hemodialysis and underscore the need to personalize dialysis treatments and improve characterization of patients included in clinical trials.

IHDIP: a controlled randomized trial to assess the security and effectiveness of the incremental hemodialysis in incident patients.

BACKGROUND: Most people who make the transition to renal replacement therapy (RRT) are treated with a fixed dose thrice-weekly hemodialysis réegimen, without considering their residual kidney function (RKF). Recent papers inform us that incremental hemodialysis is associated with preservation of RKF, whenever compared with conventional hemodialysis. The objective of the present controlled randomized trial (RCT) is to determine if start HD with one sessions per week (1-Wk/HD), it is associated with better patient survival and other safety parameters. METHODS/DESIGN: IHDIP is a multicenter RCT experimental open trial. It is randomized in a 1:1 ratio and controlled through usual clinical practice, with a low intervention level and non-commercial. It includes 152 incident patients older than 18 years, with a RRF of ≥4 ml/min/1.73 m2, measured by renal clearance of urea (KrU). The intervention group includes 76 patients who will start with incremental HD (1-Wk/HD). The control group includes 76 patients who will start with thrice-weekly hemodialysis régimen. The primary outcome is assessing the survival rate, while the secondary outcomes are the morbidity rate, the clinical parameters, the quality of life and the efficiency. DISCUSSION: This study will enable to know the number of sessions a patient should receive when starting HD, depending on his RRF. The potentially important clinical and financial implications of incremental hemodialysis warrant this RCT. TRIAL REGISTRATION: U.S. National Institutes of Health, ClinicalTrials.gov . Number: NCT03239808 , completed 13/04/2017. SPONSOR: Foundation for Training and Research of Health Professionals of Extremadura.

A user-friendly tool for incremental haemodialysis prescription.

Background: There is a recently heightened interest in incremental haemodialysis (IHD), the main advantage of which could likely be a better preservation of the residual kidney function of the patients. The implementation of IHD, however, is hindered by many factors, among them, the mathematical complexity of its prescription. The aim of our study was to design a user-friendly tool for IHD prescription, consisting of only a few rows of a common spreadsheet. Methods: The keystone of our spreadsheet was the following fundamental concept: the dialysis dose to be prescribed in IHD depends only on the normalized urea clearance provided by the native kidneys (KRUn) of the patient for each frequency of treatment, according to the variable target model recently proposed by Casino and Basile (The variable target model: a paradigm shift in the incremental haemodialysis prescription. Nephrol Dial Transplant 2017. 32: 182-190). The first step was to put in sequence a series of equations in order to calculate, firstly, KRUn and, then, the key parameters to be prescribed for an adequate IHD; the second step was to compare KRUn values obtained with our spreadsheet with KRUn values obtainable with the gold standard Solute-solver (Daugirdas JT et al., Solute-solver: a web-based tool for modeling urea kinetics for a broad range of hemodialysis schedules in multiple patients. Am J Kidney Dis 2009. 54: 798-809) in a sample of 40 incident haemodialysis patients. Results: Our spreadsheet provided excellent results. The differences with Solute-solver were clinically negligible. This was confirmed by the Bland-Altman plot built to analyse the agreement between KRUn values obtained with the two methods: the difference was 0.07 ± 0.05 mL/min/35 L. Conclusions: Our spreadsheet is a user-friendly tool able to provide clinically acceptable results in IHD prescription. Two immediate consequences could derive: (i) a larger dissemination of IHD might occur; and (ii) our spreadsheet could represent a useful tool for an ineludibly needed full-fledged clinical trial, comparing IHD with standard thrice-weekly HD.

How to set the stage for a full-fledged clinical trial testing 'incremental haemodialysis'.

Most people who make the transition to maintenance haemodialysis (HD) therapy are treated with a fixed dose of thrice-weekly HD (3HD/week) regimen without consideration of their residual kidney function (RKF). The RKF provides an effective and naturally continuous clearance of both small and middle molecules, plays a major role in metabolic homeostasis, nutritional status and cardiovascular health, and aids in fluid management. The RKF is associated with better patient survival and greater health-related quality of life. Its preservation is instrumental to the prescription of incremental (1HD/week to 2HD/week) HD. The recently heightened interest in incremental HD has been hindered by the current limitations of the urea kinetic model (UKM), which tend to overestimate the needed dialysis dose in the presence of a substantial RKF. A recent paper by Casino and Basile suggested a variable target model (VTM), which gives more clinical weight to the RKF and allows less frequent HD treatments at lower RKF as opposed to the fixed target model, based on the wrong concept of the clinical equivalence between renal and dialysis clearance. A randomized controlled trial (RCT) enrolling incident patients and comparing incremental HD (prescribed according to the VTM) with the standard 3HD/week schedule and focused on hard outcomes, such as survival and health-related quality of life of patients, is urgently needed. The first step in designing such a study is to compute the 'adequacy lines' and the associated fitting equations necessary for the most appropriate allocation of the patients in the two arms and their correct and safe follow-up. In conclusion, the potentially important clinical and financial implications of the incremental HD render it highly promising and warrant RCTs. The UKM is the keystone for conducting such studies.

The variable target model: a paradigm shift in the incremental haemodialysis prescription.

Background: The recent interest in incremental haemodialysis (HD) is hindered by the current prescription based on a fixed target model (FTM) for the total (dialytic + renal) equivalent continuous clearance (ECC). The latter is expressed either as standard Kt/V (stdKt/V), i.e. the pre-dialysis averaged concentration of urea-based ECC, or EKRc, i.e. the time averaged concentration-based ECC, corrected for volume (V) = 40 L. Accordingly, there are two different targets: stdKt/V = 2.3 volumes per week (v/wk) and EKRc = 13 mL/min/40 L. However, fixing the total ECC necessarily implies perfect equivalence of its components-the residual renal urea clearance (Kru) and dialysis clearance (Kd). This assumption is wrong because Kru has much greater clinical weight than Kd. Here we propose that the ECC target varies as an inverse function of Kru, from a maximum value in anuria to a minimum value at Kru levels not yet requiring dialysis. The aim of the present study was to compare the current FTM with the proposed variable target model (VTM). Methods: The double pool urea kinetic model was used to model dialysis sessions for 360 virtual patients and establish equations predicting the ECC as a function of Kd, Kru and the number of sessions per week. An end-dialysis urea distribution V of 35 L (corresponding to a body surface area of 1.73 m 2 ) was used, so that the current EKRc target of 13 mL/min/40 L could be recalculated at an EKRc 35 value of 12 mL/min/35 L equal to 12 mL/min/1.73 m 2 . The latter also coincides with the maximum value of the EKRc 35 variable target in anuria. The minimum target value of EKRc 35 was assumed to coincide with Kru corrected for V = 35 L (i.e. Krc 35 = 6 mL/min/1.73 m 2 ). The corresponding target for stdKt/V was assumed to vary from 2.3 v/wk at Krc 35 = 0 to 1.7 v/wk at Krc 35 = 6 mL/min/1.73 m 2 . On this basis, the variable target values can be obtained from the following linear equations: target EKRc 35 = 12 - Krc 35 ; target stdKt/V = 2.3 - 0.1 × Krc 35 . Two versions of stdKt/V were considered: the classic version (stdKt/V Gotch ) with Kru at 70%, and the current version (stdKt/V Daug ) with Kru at 100%. Results: The VTM with stdKt/V Gotch produces results very close to those using the FTM with stdKt/V Daug . Once-weekly HD is virtually not allowed by the FTM. In contrast, the VTM allows dialysis to start at Krc 35 ∼5 mL/min/1.73 m 2 on a once-weekly HD schedule, at least in relatively healthy patients; this schedule can be maintained until Krc 35 falls below 4 mL/min/1.73 m 2 , at which point the schedule should be changed to a twice-weekly HD schedule, that, in turn, could be maintained until Krc 35 falls below 2 mL/min/1.73 m 2 . Conclusions: A paradigm shift from the FTM to the VTM in the prescription of incremental HD is proposed, whereby the VTM would allow less frequent treatments at lower Kru, with important clinical and economic implications. This approach is likely to be safe but needs to be confirmed by randomized controlled trials.

Parathyroidectomy and survival in a cohort of Italian dialysis patients: results of a multicenter, observational, prospective study.

BACKGROUND: Severe secondary hyperparathyroidism (SHPT) is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery. METHODS: We aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical therapy followed-up for 36 months. Inclusion criteria were age older than 18 years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of 418 patients treated in the same centers, who did not undergo parathyroidectomy was selected after matching for age, sex, and dialysis vintage. RESULTS: From 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients who underwent parathyroidectomy (age 58.2 ± 12.8 years; M/F: 44%/56%, dialysis vintage: 15.5 ± 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age 60.3 ± 14.4 years; M/F 44%/56%; dialysis vintage 11.2 ± 7.6 y). The survival rate was higher in the group that underwent parathyroidectomy (Kaplan-Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387-0.800, p = 0.002) and multivariable analysis (HR 0.671, CI:0.465-0.970, p = 0.034), identified parathyroidectomy as a protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients who underwent parathyroidectomy compared to controls (PTX vs non-PTX: PTH < 150 pg/ml: 59% vs 21%, p = 0.001; PTH at target: 18% vs 37% p = 0.001; PTH > 300 pg/ml 23% vs 42% p = 0.001). The control group received more intensive medical treatment with higher prevalence of vitamin D (65% vs 41%, p = 0.0001), calcimimetics (34% vs 14%, p = 0.0001) and phosphate binders (77% vs 66%, p = 0.002). CONCLUSIONS: Our data suggest that parathyroidectomy is associated with survival rate at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term.

Validation of formulas calculating normalized protein catabolic rate in patients undergoing home hemodialysis.

Depner and Daugirdas developed a simplified formula to estimate the normalized protein catabolic rate in patients on twice- or thrice-weekly hemodialysis (JASN, 1996). The aim of our work was to establish formulas in more frequent schedules and validate them in home-based hemodialysis patients. We realized that the structure of Depner and Daugirdas' normalized protein catabolic rate formulas has a general meaning and can be expressed as PCRn = C0/[a + b*(Kt/V) + c/(Kt/V)] + d, where C0 is pre-dialysis blood urea nitrogen, Kt/V is dialysis dose, a, b, c, d are the specific coefficients for each combination of home-based hemodialysis schedules and the day of blood sampling. The same applies to the formula that adjusts C0 (C'0) for residual kidney clearance of blood water urea (Kru) and urea distribution volume (V): C'0 = C0*[1 + (a1 + b1/(Kt/V))*Kru/V]. On this basis, we computed the six coefficients (a, b, c, d, a1, b1) for each of the 50 possible combinations and simulated a total of 24,000 weekly dialysis cycles using the Daugirdas Solute Solver software recommended by the KDOQI 2015 guidelines. From the associated statistical analyses we obtained 50 sets of coefficient values, which were validated comparing the paired normalized protein catabolic rate values (i.e., those estimated with our formulas with those modeled with Solute Solver) in 210 datasets of 27 patients on home-based hemodialysis. The mean values ± SD were 1.06 ± 0.262 and 1.07 ± 0.283 g/kg/day, respectively, with a mean difference of 0.004 ± 0.034 g/kg/day (p = 0.11). The paired values were highly correlated (R2 = 0.99). In conclusion, even if the coefficient values were validated in a relatively small sample of patients, they allow an accurate estimation of normalized protein catabolic rate in home-based hemodialysis patients.

New primary renal diagnosis codes for the ERA-EDTA.

The European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry has produced a new set of primary renal diagnosis (PRD) codes that are intended for use by affiliated registries. It is designed specifically for use in renal centres and registries but is aligned with international coding standards supported by the WHO (International Classification of Diseases) and the International Health Terminology Standards Development Organization (SNOMED Clinical Terms). It is available as supplementary material to this paper and free on the internet for non-commercial, clinical, quality improvement and research use, and by agreement with the ERA-EDTA Registry for use by commercial organizations. Conversion between the old and the new PRD codes is possible. The new codes are very flexible and will be actively managed to keep them up-to-date and to ensure that renal medicine can remain at the forefront of the electronic revolution in medicine, epidemiology research and the use of decision support systems to improve the care of patients.

Does delivering more dialysis improve clinical outcomes? What randomized controlled trials have shown.

Some randomized controlled trials (RCTs) have sought to determine whether different dialysis techniques, dialysis doses and frequencies of treatment are able to improve clinical outcomes in end-stage kidney disease (ESKD). Virtually all of these RCTs were enacted on the premise that 'more' haemodialysis might improve clinical outcomes compared to 'conventional' haemodialysis. Aim of the present narrative review was to analyse these landmark RCTs by posing the following question: were their intervention strategies (i.e., earlier dialysis start, higher haemodialysis dose, intensive haemodialysis, increase in convective transport, starting haemodialysis with three sessions per week) able to improve clinical outcomes? The answer is no. There are at least two main reasons why many RCTs have failed to demonstrate the expected benefits thus far: (1) in general, RCTs included relatively small cohorts and short follow-ups, thus producing low event rates and limited statistical power; (2) the designs of these studies did not take into account that ESKD does not result from a single disease entity: it is a collection of different diseases and subtypes of kidney dysfunction. Patients with advanced kidney failure requiring dialysis treatment differ on a multitude of levels including residual kidney function, biochemical parameters (e.g., acid base balance, serum electrolytes, mineral and bone disorder), and volume overload. In conclusion, the different intervention strategies of the RCTs herein reviewed were not able to improve clinical outcomes of ESKD patients. Higher quality studies are needed to guide patients and clinicians in the decision-making process. Future RCTs should account for the heterogeneity of patients when considering inclusion/exclusion criteria and study design, and should a priori consider subgroup analyses to highlight specific subgroups that can benefit most from a particular intervention.

Could incremental haemodialysis be a new standard of care? A suggestion from a long-term observational study.

Introduction: The term incremental haemodialysis (HD) means that both dialysis dose and frequency can be low at dialysis inception but should be progressively increased, to compensate for any subsequent reduction in residual kidney function. Policy of the Matera Dialysis Center is to attempt an incremental start of HD without a strict low-protein diet in all patients choosing HD and with urine output (UO) >500 ml/day. The present study aimed at analyzing the results of this policy over the last 20 years. Subjects and methods: The dataset of all patients starting HD between January 1st, 2000 and December 31st, 2019 was retrieved from the local electronic database. Exclusion criteria were: urine output <500 ml/day or follow-up <3 months after the start of the dialysis treatment. Results: A total of 266 patients were retrieved; 64 of them were excluded from the study. The remaining 202 patients were enrolled into the study and subdivided into 3 groups (G1, G2 and G3) according to the frequency of treatment at the start of dialysis: 117 patients (57.9%) started with once-a-week (1HD/wk) (G1); 46 (22.8%) with twice-a-week (2HD/wk) (G2); 39 (19.3%) with thrice-a-week (3HD/wk) dialysis regimen (G3). Patients of G1 remained on 1HD/wk for 11.9 ±14.8 months and then transferred to 2HD/wk for further 13.0 ±20.3 months. Patients of G2 remained on 2HD/wk for 16.7 ±23.2 months. Altogether, 25943 sessions were administered during the less frequent treatment periods instead of 47988, that would have been delivered if the patients had been on 3HD/wk, thus saving 22045 sessions (45.9%). Gross mortality of the entire group was 12.6%, comparable to the mean mortality of the Italian dialysis population (16.2%). Survival at 1 and 5 years was not significantly different among the 3 groups: 94% and 61% (G1); 83% and 39% (G2); 84% and 46% (G3). Conclusions: Our long-term observational study suggests that incremental HD is a valuable option for incident patients. For most of them (80.7%) it is viable for about 1-2 years, with obvious socio-economic benefits and survival rates comparable to that of the Italian dialysis population. However, randomized controlled trials are lacking and therefore urgently needed. If they will confirm observational data, incremental HD will be a new standard of care.

Removal of uraemic retention solutes in standard bicarbonate haemodialysis and long-hour slow-flow bicarbonate haemodialysis.

BACKGROUND: Several studies already stressed the importance of haemodialysis (HD) time in the removal of uraemic toxins. In those studies, however, also the amount of dialysate and/or processed blood was altered. The present study aimed to investigate the isolated effect of the factor time t (by processing the same total blood and dialysate volume in two different time schedules) on the removal and kinetic behaviour of some small, middle and protein-bound molecules. METHODS: The present study had a crossover design: 11 stable anuric HD patients underwent two bicarbonate HD sessions (~ 4 and ~ 8 h) in a random sequence, at least 1 week apart. The GENIUS single-pass batch dialysis system and the high-flux FX80 dialysers (Fresenius Medical Care, Bad Homburg, Germany) were used. The volume of blood and dialysate processed, volume of ultrafiltration, and dialysate composition were prescribed to be the same. For each patient, blood was sampled from the arterial line at 0, 60, 120, 180 and 240 min (all sessions), and at 360 and 480 min (8-h sessions). Dialysate was sampled at the end of HD from the dialysate tank. The following solutes were investigated: (i) small molecules: urea, creatinine, phosphorus and uric acid; (ii) middle molecule: ß(2)M; and (iii) protein-bound molecules: homocysteine, hippuric acid, indole-3-acetic acid and indoxyl sulphate. Total solute removals (solute concentration in the spent dialysate of each analyte × 90 L - the volume of dialysate) (TSR), clearances (TSR of a solute/area under the plasma water concentration time curve of the solute) (K), total cleared volumes (K × dialysis time) (TCV), and dialyser extraction ratios (K/blood flow rate) (ER) were determined. The percent differences of TSR, K, TCV and ER between 4- and 8-h dialyses were calculated. Single-pool Kt/Vurea, and post-dialysis percent rebounds of urea, creatinine and ß(2)M were computed. RESULTS: TSR, TCV and ER were statistically significantly larger during prolonged HD for all small and middle molecules (at least, P < 0.01). Specifically, the percent increases of TSR (8 h vs 4 h) were: for urea 22.6.0% (P < 0.003), for creatinine 24.8% (P < 0.002), for phosphorus 26.6% (P < 0.001), and for ß(2)M 39.2% (P < 0.005). No statistically significant difference was observed for protein-bound solutes in any of the parameters being studied. Single-pool Kt/Vurea was 1.41 ± 0.19 for the 4-h dialysis sessions and 1.80 ± 0.29 for the 8-h ones. The difference was statistically significant (P < 0.0001). Post-dialysis percent rebounds of urea, creatinine and ß(2)M were statistically significantly greater in the 4-h dialysis sessions (at least, P < 0.0002). CONCLUSIONS: The present controlled study using a crossover design indicates that small and middle molecules are removed more adequately from the deeper compartments when performing a prolonged HD, even if blood and dialysate volumes are kept constant. Hence, factor time t is very important for these retention solutes. The kinetic behaviour of protein-bound solutes is completely different from that of small and middle molecules, mainly because of the strength of their protein binding.

Long-term effects of high-efficiency on-line haemodiafiltration on uraemic toxicity. A multicentre prospective randomized study.

BACKGROUND: Haemodiafiltration (HDF) may improve survival of chronic dialysis patients. This prospective, multicentre randomized cross-over study evaluated the effects of long-term on-line HDF on the levels of solutes of different molecular weight markers or causative agents of the most common metabolic derangements in uraemia. METHODS: Sixty-nine patients from eight Italian centres were randomly assigned to two 6-month treatment sequences: A-B and B-A [A, low-flux haemodialysis (HD) and B, on-line HDF]. Comparative evaluation of basal levels of small, medium-sized and protein-bound solutes at the end of the two treatment periods and analysis of parameters dependence during the interventions were performed. RESULTS: On-line HDF showed greater efficiency than low-flux HD in removing small solutes (eKt/Vurea 1.60 ± 0.31 versus 1.44 ± 0.26, P < 0.0001) and in reducing basal levels of beta2-microglobulin (22.2 ± 7.8 versus 33.5 ± 11.8 mg/L, P < 0.0001), total homocysteine (15.4 ± 5.0 versus 18.7 ± 8.2 µmol/L, P = 0 .003), phosphate (4.6 ± 1.3 versus 5.0 ± 1.4 mg/dL, P = 0.008) and, remarkably, of intact parathyroid hormone (202 ± 154 versus 228 ± 176 pg/mL, P = 0.03). Moreover, in on-line HDF, lower levels of C-reactive protein (5.5 ± 5.5 versus 6.7 ± 6.1 mg/L, P = 0.03) and triglycerides (148 ± 77 versus 167 ± 87 mg/dL, P = 0.008) and increased HDL cholesterol (49.2 ± 12.7 versus 44.7 ± 12.4 mg/dL, P = <0.0001) were observed. The asymmetric dimethylarginine level was not significantly affected (0.97 ± 0.4 versus 0.84 ± 0.37 µmol/L). Erythropoietin and phosphate binders' doses could be reduced. CONCLUSIONS: On-line high-efficiency HDF resulted in enhanced removal and lower basal levels of small, medium-sized and protein-bound solutes, which are markers or causative agents of uraemic pathologies, mainly inflammation, secondary hyperparathyroidism and dyslipidaemia. This may contribute to reducing uraemic complications and possibly to improving patient survival.