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.

[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.

Effects of acetate-free haemodiafiltration (HDF) with endogenous reinfusion (HFR) on cardiac troponin levels.

BACKGROUND: Haemofiltrate reinfusion (HFR) is a form of haemodiafiltration (HDF) in which replacement fluid is constituted by ultrafiltrate from the patient 'regenerated' through a cartridge containing hydrophobic styrene resin. Bicarbonate-based dialysis solutions (DS) used in routine haemodialysis and HDF contain small quantities of acetate (3-5 mMol/L) as stabilizing agent, one of the major causes of intradialytic hypotension. Acetate-free (AF) DS have recently been made available, substituting acetate with hydrochloric acid. Cardiac troponin (cTnT) constitutes an appreciable marker of myocardial damage and cardiac hypertrophy, and correlates with left ventricular mass. METHODS: The aim of this study was to assess the impact of the presence or lack of acetate in DS on cTnT levels in patients treated with HFR and to evaluate outcome of intra-session cardiovascular stability. Twenty-five patients devoid of major cardiovascular comorbidity were randomized and treated with AF HFR for 3 months. The same patients were subsequently treated by means of HFR with DS containing 3 mMol/L acetate for 3 months and finally with AF HFR for a further 3 months. Prior and subsequent to each treatment period, samples were collected for cTnT measurement. RESULTS: A significant decrease was observed in cTnT levels throughout the first session of AF HFR (1.32 ± 0.35-1.12 ± 0.31 ng/mL, P < 0.05) with a subsequent rise being registered during HFR with acetate-containing DS (1.12 ± 0.31-1.28 ± 0.37 ng/mL, P < 0.05) and a further drop from 1.28 ± 0.37 to 1.21 ± 0.35 ng/mL in the last AF HFR period. During HFR with acetate-containing DS, a significant drop in systolic and diastolic arterial pressure was observed in conjunction with a higher heart rate at the end of the session. CONCLUSION: We observed an increase in cTnT during HFR with acetate and drops manifested during HFR without acetate; it may therefore be concluded that the drop in cTnT level, significantly correlated with lack of acetate, is indicative of improvement of cardiac microvascular function.