## 3 Nutritional and Therapeutic Interventions
### Replacing Amino Acid Losses by Hemodialysis  
An important issue has recently emerged with regard to the loss of amino acids (AAs) in dialysate. Indeed, due to their low molecular weight, AAs are lost in industrial quantities over one year of thrice weekly hemodialysis, particularly when using methods such as hemodiafiltration and hemofiltration, in which additional convective losses occur due to ultrafiltration. Recently, a study group on AAskinetics in extracorporeal methods showed annual losses \(>\) 800 g/year in thrice weekly hemodialysis patients with a consequent, significant loss of lean body and, in particular, muscle mass protein [20; 22]. Considering the more contained loss of Total AAs (TAAs) manifested using high-efficiency hemodialysis with a surface dialyzer area of 1.8 m\({}^{2}\) over a 240-min session, losses could be managed by varying dialytic strategy as shown in Table 2.  
The most severe metabolic consequences likely result from loss of essential amino acids (EAAs) such as threonine, tryptophan and lysine and from Non-Essential amino acids (NEAAs) such as tyrosine, aspartic acid, serine, glutamic acid and glycine, resulting in the onset of hypercatabolism and threatening muscle mass loss. Loss-replacement nutritional supplements have been proposed, with keto analogues being used to replace amino acids lost during hemodialysis. Keto analogues are made up of calcium salts, leucine, isoleucine, phenylalanine, valine and Ca-hydroxy-methionine, L-lysine, L-threonine, L-histidine, and L-tyrosine (alfa-kappa, Ketosteril (r), Fresenius Kabi, Bad Homburg, Germany), although taken alone are not sufficient to replace amino acid losses in HD patients. Moreover, supplementation may result in excessive doses of nitrogen, with each tablet containing 337 mg of this element; i.e., calculated on the dose recommended for 70 kg body weight, each patient would consume approx. 470 mg/day nitrogen, also implicating a potential interference with calcium-phosphorus metabolism (such as hypercalcemia) due to a higher calcium intake, with each tablet containing 45 mg calcium; i.e., for 70 kg body weight, an intake of approx. 570 mg/day calcium. This type of product should only be used in advanced stages of chronic kidney disease (CKD4-CKD5) in patients adhering to a very low protein diet regimen (VLPD) [85; 86]. In a paper by [PERSON] et al., nephrologists and nutritionists are warned to monitor for probable poor compliance, particularly if the low protein diet is associated with AA intake through keto-analogues. Indeed, in patients prescribed a higher number of tablets or sachets (8-12 per day), compliance with this schedule after six months was limited to 64.5% [87]. Moreover, keto-amino-acid analogues represent a considerably higher cost than other commercial products (over EUR 4000 per year), and treatment could be successfully replaced by a tailored, more efficient and less expensive amino acid supplement EUR 600-700 per year). Very few trials have been conducted to date to evaluate AA supplementation in hemodialysis patients; based on our previous experience [88], the daily administration of 5 grams of a combination of 6 EAA, 2 NEEA, 2 BCCAA, with no metabolic accelerators, plus vitamins B1 and B6 for three months, obtained highly promising results (Table 3). The results of this study led us to recommend the administration of a new amino acid combination of 20 main amino acids (EAAs, NEAAs and BCAAs), vitamins and micronutrients tailored to the quantities and qualities of amino acids lost through dialysis at the end of a hemodialysis day (Amino-HD, Professional Dietetics, Milano, Italy) [89], with administration during the interdialytic interval of an amino acid solution containing 10 EAAs with mitochondrial metabolic accelerators such as malic and succinic acids, group B vitamins and a minimum calorie intake ([PERSON], Professional Dietetics, Milano, Italy). Neither combination contains nitrogen or calcium.