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 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.