Observational pilot study: A comparison of amino acids and derangement of intestinal function between healthy ageing subjects and patients affected by chronic kidney disease stage CKD3b-4 in conservative management.

BACKGROUND AND AIMS: A comparison of the amino acid (AA) plasma profile and markers of intestinal absorption-inflammation between healthy subjects aged 65-70 years and age-matched patients affected by stage 3b-4 chronic kidney disease (CKD3b-4) was performed. METHODS: Eleven healthy volunteers were compared with 12 CKD3b-4 patients at their first outpatient control (T0) and after 12-months (T12). Adherence to a low protein diet (LPD, 0.6 ± 0.1 g/kg/day) was assessed by Urea Nitrogen Appearance. The following parameters were assessed: renal function, nutritional parameters, bioelectrical impedance analysis, plasma levels of 20 total amino acids (TAAs), both essential (EAAs) including branched-chain amino acids (BCAAs) and non-essential (NEAAs). Zonulin and faecal Calprotectin markers were used to evaluate intestinal permeability/inflammation. RESULTS: Four patients dropped out of the study; in the remaining 8 residual kidney function (RKF) remained stable, their LPD adherence had risen to 0.89  g/kg/day, anaemia had worsened and extracellular body fluid had increased. In comparison to healthy subjects, TAA levels of histidine, arginine, asparagine, threonine, glycine, and glutamine had all increased. No variation in BCAAs was observed. A significant increase was detected in faecal calprotectin and zonulin levels in CKD patients as the disease progressed. CONCLUSIONS: This study confirms the finding in aged patients of an alteration in plasmatic levels of several AAs secondary to uraemia. Intestinal markers provide confirmation of a relevant alteration to the intestinal function in CKD patients.

Effects of a Metabolic Mixture on Gut Inflammation and Permeability in Elderly Patients with Chronic Kidney Disease: A Proof-of-Concept Study.

Intestinal barrier dysfunction is a risk factor for the progression of Chronic Kidney Disease (CKD). In this proof-of-concept study, we tested the effects of a mixture of Essential Amino Acids (EAAs) and mitochondrial substrates on intestinal inflammation and permeability of CKD patients. Eight patients with stage 3b-4 CKD and 11 healthy controls after overnight fasting underwent fecal measures of calprotectin and zonulin levels (indicators of gut inflammation and permeability, respectively) and determinations of plasma amino acids. Only CKD patients were supplemented with the mixture (8 g/d diluted in water). Compared to controls, baseline fecal calprotectin, zonulin and plasma levels of some AA in CKD patients were significantly higher (p = 0.005; p = 0.001 and p = 0.02 to 0.003, respectively). After six months of supplementation, CKD baseline fecal levels of calprotectin and zonulin significantly (borderline for zonulin) decreased (p = 0.008 and p = 0.05, respectively). Plasma AA concentrations, including glutamine and alanine, were higher than at the baseline (p: 0.05 to 0.008). The supplementation of this mixture was associated with improved intestinal barrier dysfunction. Increased plasma AA levels might contribute to the improvement of gut barrier dysfunction.

Effects of a Novel Amino Acid Formula on Nutritional and Metabolic Status, Anemia and Myocardial Function in Thrice-Weekly Hemodialysis Patients: Results of a Six-Month Randomized Double-Blind Placebo-Controlled Pilot Study.

(1) Background: Chronic Kidney Disease (CKD) induces metabolic derangement of amino acid (AA) kinetics, eliciting severe damage to the protein anabolism. This damage is further intensified by a significant loss of AAs through hemodialysis (HD), affecting all tissues with a high metabolic turnover, such as the myocardium and body muscle mass. (2) Aim: to illustrate the effects of a novel AA mixture in boosting mitochondrial energy production. (3) Methods: A strict selection of 164 dialysis patients was carried out, allowing us to finally identify 22 compliant patients who had not used any form of supplements over the previous year. The study design envisaged a 6-month randomized, double-blind trial for the comparison of two groups of hemodialysis patients: eleven patients (67.2 ± 9.5 years) received the novel AA mix (TRG), whilst the other eleven (68.2 ± 10.5 years) were given a placebo mix that was indistinguishable from the treatment mix (PLG). (4) Results: Despite the 6-month observation period, the following were observed: maintenance of target hemoglobin values with a reduced need for erythropoiesis-stimulating agents in TRG > 36% compared to PLG (p < 0.02), improved phase angle (PhA) accompanied by an increase in muscle mass solely in the TRG group (p < 0.05), improved Left Ventricular Ejection Fraction (LVEF > 67%) in the TRG versus PLG group (p < 0.05) with early but marked signs of improved diastolic function. Increased sensitivity to insulin with greater control of glycemic levels in TRG versus PLG (p = 0.016). (5) Conclusions: the new AA mix seemed to be effective, showing a positive result on nutritional metabolism and cardiac performance, stable hemoglobin levels with the need for lower doses of erythropoietin (EPO), insulin increased cell sensitivity, better muscle metabolism with less loss of mass.

Evaluation of Residual Kidney Function during Once-Weekly Incremental Hemodialysis.

BACKGROUND: The initial once-weekly administration of incremental hemodialysis to patients with residual kidney function (RKF) has recently attracted considerable interest. METHODS: The aim of our study was to assess the performance of a series of different methods in measuring serum urea nitrogen and serum Cr (sCr) RKF in patients on once-weekly hemodialysis (1WHD). Evaluations were carried out by means of 24-h predialysis urine collection (Kr-24H) or 6-day inter-dialysis collection (Kr-IDI) and estimation of glomerular filtration rate based on (KrSUN + KrsCr)/2 for the purpose of identifying a simple reference calculation to be used in assessing RKF in patients on 1WHD dialysis. Ninety-five urine samples were collected from 12 1WHD patients. A solute solver urea and Cr kinetic modeling program was used to calculate residual urea and Cr clearances. Mann-Whitney U test, Pearson's correlation coefficient (R), and linear determination coefficient (R2) were used for statistical analysis. RESULTS: 1WHD patients displayed a mean KrSUN-IDI of 4.5 ± 1.2 mL/min, while KrSUN-24H corresponded to 4.1 ± 0.9 mL/min, mean KrsCr-IDI to 9.1 ± 4.0 mL/min, and KrsCr 24H to 8.9 ± 4.2 mL/min, with a high regression between IDI and 24-h clearances (for IDI had R2 = 0.9149 and for 24H had R2 = 0.9595). A good correlation was also observed between KrSUN-24H and (KrSUN + KrsCR/2) (R2 = 0.7466, p < 0.01. DISCUSSION: Urine collection over a 24-h predialysis period yielded similar results for both KrSUN and KrsCr compared to collection over a longer interdialytic interval (KrSUN + KrsCr)/2 could be applied to reliably assess RKF in patients on 1WHD. CONCLUSION: The parameters evaluated are suitable for use as a routine daily method indicating the commencement and continued use of the 1WHD Incremental Program.

Differences and Effects of Metabolic Fate of Individual Amino Acid Loss in High-Efficiency Hemodialysis and Hemodiafiltration.

OBJECTIVE: The objective of the study was to quantify the loss and arterial blood concentration of the three main classes of amino acids (AAs)-nonessential amino acids (NEAAs), essential amino acids (EAAs), and branched-chain amino acids-as resulting from high-efficiency hemodialysis (HED) and hemodiafiltration (HDF). We moreover aimed to identify the different fates and metabolic effects manifested in patients undergoing hemodialysis and the consequences on body composition and influence of nutritional decline into protein energy wasting. DESIGN AND METHODS: Identical dialysis monitors, membranes, and dialysate/infusate were used to ensure consistency. Ten patients were recruited and randomized to receive treatment with on-line modern HED and HDF. Arterial plasma concentrations of individual AAs were compared in healthy volunteers and patients undergoing hemodialysis, and AA levels outflowing from the dialyzer were evaluated. Baseline AA plasma levels of patients undergoing hemodialysis were compared with findings obtained 1 year later. RESULTS: A severe loss of AA with HED/HDF was confirmed: a marked loss of total AAs (5 g/session) was detected, corresponding to more than 65% of all AAs. With regard to individual AAs, glutamine displayed a consistent increase (+150%), whereas all other AAs decreased after 12 months of HD/HDF. Only a few AAs, such as proline, cysteine, and histidine maintained normal levels. The most severe metabolic consequences may result from losses of EAAs such as valine, leucine, and histidine and from NEAAs including proline, cysteine, and glutamic acid eliciting the onset of hypercatabolism threatening muscle mass loss. CONCLUSION: Dialysis losses, together with the effect of chronic uremia, resulted in a reduction of fundamental EAAs and NEAAs, which progressively led our patients after 12 months to a deterioration of lean mass toward sarcopenia. Therefore, the reintroduction of a correctly balanced AA supplementation in patients undergoing HD to prevent or halt decline of hypercatabolism into cachexia is recommended.

Could there be Haemodynamic Stress Effects on Pro-Inflammatory CD14+CD16+ Monocytes during Convective-Diffusive Treatments? A Prospective Randomized Controlled Trial.

BACKGROUND: The main aim is to compare the pro-inflammatory CD14+CD16+ monocytes blood levels in patient in end-stage renal disease (ESRD) undergoing Mixed online Haemodiafiltration (Mixed OL-HDF) vs. post-dilution OL-HDF and online high-efficiency haemodialysis. METHODS: The study is a prospective double-blind randomized controlled cross-over trial. Dialysis monitor, membrane, duration and dialytic adequacy, volume ultrapure dialysate/infusion were the same in all treatments. Monocyte CD14+CD16+, CD14-CD16+, IL-2R, TNFα, IL-1ß, IL-8, IL-6, IL-10, ß2-microglobulin outcome were measured. RESULTS: Mixed OL-HDF showed a less expression on the activated monocytes CD14+CD16+, CD14-CD16+ (-15.5%). There was no difference between cytokines and high sensitivity C-reactive protein and in other haemato-chemical inflammatory parameters except a significative decrease of TNF-α during Mixed OL-HDF. CONCLUSION: We found that Mixed OL-HDF could inhibit the CD14+CD16+ peripheral blood lymphocytes related to a less hemorheology stress inside capillary dialysis filter but in this study there is not still ascertainable its superiority compared to post OL-HDF and post OL-HEH.

Differences in Amino Acid Loss Between High-Efficiency Hemodialysis and Postdilution and Predilution Hemodiafiltration Using High Convection Volume Exchange-A New Metabolic Scenario? A Pilot Study.

OBJECTIVE: The objective of the study was to quantify the loss of total amino acids (TAAs), nonessential amino acids, essential amino acids, and branched chain amino acids (BCAAs) produced by high-efficiency hemodialysis (HEHD), postdilution hemodiafiltration (HDFpost), and predilution hemodiafiltration (HDFpre) using high ultrafiltration volumes; and to define the specific AA losses registered in HEHD, HDFpost, and HDFpre; to identify a potential metabolic and nutritional decline into protein energy wasting; to compare AA analysis of arterial blood samples taken from healthy controls and patients with end-stage renal disease undergoing hemodialysis. DESIGN AND METHODS: Identical dialysis monitors, membranes, and dialysate/infusate were used to homogenize extracorporeal body influence. Ten patients were recruited and randomized to receive treatment with HEHD, HDFpost, and HDFpre it was used on-line dialytic water methodologies (OL); patients' AA arterial concentrations were measured at the start and on completion of dialysis; TAA from the dialyzer filter was calculated, and baseline levels were subsequently compared with findings obtained 1 year later. Finally, the results obtained were compared with the data from a study of 8 healthy volunteers conducted using bioimpedance analysis and laboratory blood tests to assess nutritional status. RESULTS: A higher convective dose results in a higher weekly loss of TAA, nonessential AAs, essential AAs, and BCAAs (HEHD: 15.7 g; HDFpost-OL: 16.1 g; HDFpre-OL: 16.3 g, P < .01). After 12 months, the same hemodialys patients showed a reduced body and water intracellular mass and reduced phase angle. Arterial concentrations of TAAs and BCAAs were lower than those detected in healthy subjects (P < .01). CONCLUSION: The study shows that the AA losses in dialytic liquid are greater after high exchange volume HDF techniques, especially HDFpre. The AA losses are not metabolically compensated, so these increase the derangements of predialytic arterial plasma AA levels. Both AA losses and arterial AA perturbations further worsened body composition already after 12 months of additional dialysis.

[Accurate compiling of the hospital discharge records according to clinicians' perception: critical issues and perspectives]. / L'accurata compilazione delle schede di dimissione ospedaliera secondo la percezione dei medici: criticità e prospettive.

OBJECTIVES: to explore clinicians vision on hospital discharge records in order to identify useful elements to foster a more accurate compiling. DESIGN: qualitative research with phenomenological approach. SETTING AND PARTICIPANTS: participants were selected through purposive sampling among clinicians of two hospitals located in Sardinia; the sample included 76 people (32 medical directors and 44 doctors in training). MAIN OUTCOME MEASURES: identified codes for themes under investigation: vision of accurate compiling, difficulties, and proposals. RESULTS: collected data highlighted two prevailing visions, respectively focused on the importance of an accurate compiling and on the burden of such activity. The accurate compiling is hindered by the lack of motivation and training, by the limits of the registration system and the information technology, by the distortions induced by the prominent role of the hospital discharge records in the evaluation processes. Training, timely updating of the information system accompanied by a proper cross-cultural validation process, improvement of the computer system, and activation of support services could promote more accurate compiling. CONCLUSIONS: the implementation of services, unconnected with evaluation and control processes, dedicated to training and support in the compiling of the hospital discharge records and in the conduction of related epidemiological studies would facilitate the compliance to the compilation. Such services will make tangible the benefits obtainable from this registration system, increasing skills, motivation, ownership, and facilitating greater accuracy in compiling.

[Infrequent and incremental dialysis: differences and definitions].

The purpose of this review is to give dignity at the Incremental Dialysis, which cannot be confused with the term and the therapeutic choice defined as Infrequent Dialysis. The Infrequent Dialysis is defined by each and every hemodialytic therapeutic choice like rhythms below thrice-weekly-hemodialytic treatments. Nonetheless, Infrequent Dialysis is a choice of replacement hemodialysis therapy with pays more special clinical attentions and nutritional monitoring and should also be accompanied by a slightly hypoproteic controlled nutrition. When talking about the Incremental Dialysis (CDDP) it is defined as a well-defined therapeutic program that requires a significant clinical attention. The CDDP begins with the pre-dialysis outpatient clinic in the short period of time when the patient passes, after a severe nutrition compliance assessment with a VFG of 5-10 mL / min / 1.73mq, from the conservative treatment to an hypoproteic diet composed of 0.6g/ Kg / day with or without essential amino acids and hyposaline diet supplemented by One-Weekly Dialysis. The Incremental Dialysis program is strictly tailored on the trend of Residual Renal Function (FRR). CDDP is a time variable therapeutic "bridge" that must provide a good metabolic status and a good quality of life of the treated patients. Recent studies have shown a lower mortality compared with thrice-weekly-dialysis and a neutral input/output balance of phosphorus pool due to the phosphaturia contribution compared to the thrice-weekly-patients who lose early their FRR. Further studies are needed to confirm the safety and validity of this therapeutic choice.

[Practical procedures to launch a once-weekly-dialysis program integrated into a personalized hypoproteic nutrition (CDDP)].

This work is aimed for showing in detail to the nephrologists the methodology applied in the Combined Diet Dialysis Program (CDDP) in selected patients especially with the use of the Urea Nitrogen Appearance which allows to verify the sustainability and collaboration of patients on the 0.6 g/Kg/day hypoproteic diet by calculating the Protein Catabolic Rate in patients with metabolic steady state. It is also confirmed that the combined action of nutrition and the minimal contact with hemodialysis may allow a longer maintenance of the residual renal function with the further possibility of a greater excretion of Protein Bound Uremic Toxins and to obtain a phosphate balance thanks for a good maintenance of phosphaturia. In this paper are described in detail all the necessary steps and calculations. But it is mandatory a greater clinical commitment to achieve the achievement of a personalized therapeutic protocol like CDDP that is easily applicable in everyday clinical practice.

Fabry Disease in Southern Sardinia: epidemiological results from screening in an extensive area. / Risultati dello screening epidemiologico sulla malattia di Fabry nell'area sud-est della Sardegna.

INTRODUCTION: Epidemiological data relating to the prevalence and incidence of Fabry disease (FD) and other Lysosomal Storage diseases (LSDs) are largely underestimated and not yet well known. Distribution of the disease varies according to geographical area and to ethnic origin. Heterozygous females are also at risk of contracting severe and multi-symptomatic forms of FD. AIM: To demonstrate the results obtained in outpatient surgeries situated in an area comprising 319,340 inhabitants. METHODS: Out of a total of 2710 nephrologist visits, 150 patients with suspected FD (73 undergoing dialysis and 77 conservative management) were selected. The relatives of one female patient on dialysis who had tested positive were investigated and a further 11 patients thus identified (total: 4 males and 7 females) within a micro-area of 21,822 inhabitants, i.e. a prevalence rate of one positive case every 1,818 inhabitants. These data relate to the first 18 months of screening. CONCLUSIONS: In the field of nephrology, patients with high levels of proteinuria or microalbuminuria (150-200 mg/day) should be screened for FD, particularly in areas with a high incidence and/or prevalence of kidney disease. Once positive patients of both sexes have been identified, they should immediately be referred for cardiologic and neurological assessment.

[The Power of Phosphaturia in the Infrequent Hemodialysis]. / L'importanza della Fosfaturia nei pazienti in Emodialisi Infrequente.

INTRODUCTION: Residual renal function (RRF) and phosphaturia had not stimulated particular interest in studies regarding patients on hemodialysis. In the current year the Authors have selected a series of patients with RRF undergoing infrequent hemodialysis treatments. PURPOSE: The Authors have carried out a study of the phosphate balance in patients on infrequent hemodialysis with the hypothesis that the phosphaturia was always neglected in hemodialysis patients, but it could represent a positive impact element on the cardiovascular events and mortality in hemodialysis. METHODS: During 6 months, the Authors have conducted forty urine collections in 10 patients on twice a week hemodialysis (TWH) (age: 69,3 years, dialysis vintage: 42,7 months and 40.9 months on TWH) and eighty urine collections in 8 patients on once a week hemodialysis and low-protein diet (CDDP) (age: 69.6 years, dialysis vintage: 24.7 months and 24 months in CDDP) to determine RRF and phosphaturia. We compared the balance of phosphate compared with a thrice-weekly hemodialysis considering on phosphate removal: dialysis efficiency, phosphate-binders power on the protein- phosphates intake and the extent of phosphaturia. RESULTS: The patients on infrequent hemodialysis have demonstrated a significant share of urinary phosphate output leading to a weekly phosphoric balance equal to zero or even negative. CONCLUSIONS: The phosphoric balance in infrequent hemodialysis patients is a decisive way to remove the phosphates, confirming that this factor could be decisive on the improved survival and reduced cardiovascular mortality compared to patients receiving thrice-weekly hemodialysis. The Authors stress again the need to keep as long as possible the FRR.

Clinical benefits of phosphate control in progression of end stage renal disease.

It is largely agreed that preservation of residual kidney function (RKF) has a directly proportional affect on general, and in particular cardiovascular, mortality. During evaluation of patients on infrequent hemodialysis (ID) as both as once-weekly or twice-weekly hemodialysis it has been frequently underestimated the importance of phosphaturia, Indeed, the native kidney preserves the ability to eliminate not only toxic molecules but also a significative output of phosphate despite of a severe decrease of RKF. This task the modern membranes are as yet not very efficient of reproducing. The hemodialysis patients on ID who adhere accurately to a low protein diet of 0.6-0.8 g/kg/day could reach a draw in the balance of phosphates. In view of the significant impact produced by poor phosphate control on both RKF and the frequency of even severe cardiovascular effects, infrequent dialysis with its negative or neutral weekly phosphate balance, may constitute a valid "bridging" treatment even in the long-term, thus explaining the improved survival rates compared to patients receiving conventional triweekly hemodialysis.

The evolution of technological strategies in the prevention of dialysis water pollution: sixteen years' experience.

AIM: This report attempts to illustrate the positive impact on the quality of dialysis water produced over a 16-year period through the progressive optimization of technological procedures. METHODS: Fundamental steps included the following: elimination of polyvinyl chloride (PVC), periodical controls, introduction of stainless steel and/or polyethylene polymer and substitution of single-pass reverse osmosis (SRO) with double-pass reverse osmosis (DRO). Daily overnight automatic thermal disinfection of distribution piping rings represented the final step. RESULTS: A dramatic improvement was observed in 645 water samples obtained from distribution piping. The measures applied resulted in a significant improvement of water quality, featuring levels of colony-forming units per milliliter ranging from 247.4 ± 393.7 in the presence of PVC and SRO to 14.1 ± 28.0 with stainless steel and DRO and 2.8 ± 3.2 with cross-linked polyethylene thermoplastic polymer and DRO (p < 0.01). CONCLUSIONS: Dialysis water should be viewed by nephrologists as a medicinal product, and every effort should be made to ensure a high-quality liquid.