COMPLICATIONS OF DIALYSIS - PART 6 ppsx

430 Druml reduction of body temperature can reduce oxygen con- sumption and may also reduce the extent of protein catabolism. Moreover, it has been convincingly shown that a decrease in blood temperature during hemofiltra- tion is a major factor responsible for improvement of cardiovascular stability (28). Thus, CRRT can contribute to a reduction of oxygen consumption in clinical states associated with hyper- metabolism and may help to optimize the relationship between oxygen consumption (fall in VO 2 by reduction of body temperature) and oxygen delivery (DO 2 ). How- ever, if intravascular volume is depleted by vigorous dehydration (such as was advocated in the treatment of ARDS), continuous hemofiltration can result in a fall in DO 2 and actually may deteriorate the VO 2 /DO 2 relationship. Potentially, the therapy-associated heat loss may also generate untoward effects by blunting the meta- bolic response to injury and may also impair immu- nocompetence. Therefore, several modern hemofiltra- tion machines include a heating system that can warm the substitution fluid as required. B. Glucose Balance The substitution fluids used in CRRT should contain glucose in a concentration of 100–180 mg/dL in order to maintain a zero glucose balance. The use of glucose- free solutions does not contribute—as sometimes mis- takingly assumed—to an improvement in the meta- bolic control in patients with impaired glucose utilization (such as in most patients with acute disease states). This will simply result in a glucose loss ac- counting for 40–80 g/day (depending on the filtration volume), which must be compensated for by an acti- vation of endogenous gluconeogenesis, mainly from amino acids (thus promoting protein breakdown). In this case, the glucose loss during the use of glucose- free solutions has to be considered in evaluating the energy balance of the patient and must be replaced by nutritional therapy. On the other hand, substitution fluid with high glu- cose concentrations (such as CAPD solutions used for CRRT by some centers) will result in a massive glucose uptake and induce major metabolic disturbances by the high glucose load and should thus no longer be used (29). C. Lactate and/or Acetate Intake Most available substitution solutions for CRRT contain lactate as an organic anion. Unfortunately, DL-lactate is still in use in several countries, and this should be replaced by the physiological L-lactate because of po- tential toxic side effects. Acetate-containing solutions are restricted to special indications; the infusion of large amounts of acetate is associated with well-docu- mented side effects in intensive care patients (e.g., va- sodilation, reduction of myocardial contractility, aggra- vation of cardiovascular instability). Depending on the filtered volume and the amount of fluid replacement, respectively, the organism is con- fronted with a potentially relevant if not excessive amount of lactate. This may account for more than 2000 mmol/day and can equal the endogenous lactate formation rate during physiological conditions (ϳ100 mmol/h in healthy subjects). This lactate load can gain clinical relevance either in disease states in which lactate utilization is impaired (such as in acute or chronic liver failure) or in any clinical condition associated with increased lactate for- mation (e.g., circulatory instability, septic shock, or hy- poxic states). In these situations any CRRT using lac- tate-containing solutions will increase plasma lactate concentrations, and thus lactate and/or acetate should be replaced by bicarbonate. Bicarbonate-buffered sub- stitution fluids for CRRT have become available in sev- eral countries. Recent evidence suggests that hyperlactemia in- duced by exogenous lactate infusion may present more than just a changed laboratory value and can assume pathophysiological relevance. Several negative side ef- fects such as an impairment of myocardial contractility, inhibition of endogenous lactate metabolism, and ag- gravation of insulin resistance have been reported (30,31). Furthermore, it was suggested that lactate-con- taining substitution fluids may promote protein catab- olism (32). The clinically acceptable elevation of blood lactate level during therapy remains to be defined but might range from 3 to 4 mmol/L. Both lactate and acetate are energy-yielding sub- strates, which are metabolized in the tricarboxylic acid cycle and generate bicarbonate. Little is known about the impact of these compounds on energy metabolism in the critically ill. The lactate load may correspond to an caloric intake of up to 500 kcal, which should be considered in calculating the energy balance of patients. D. Electrolyte Disturbances Most available substitution fluids used in CRRT were originally designed for intermittent hemofiltration in chronic renal failure patients. The use of these solutions Nutritional Problems and CRRT 431 can induce pronounced electrolyte disturbances in pa- tients with ARF. Inadequate sodium concentration for replacement of large quantities of plasma water (usu- ally with a higher sodium concentration) will result in a negative sodium balance and hyponatremia in a con- siderable fraction of patients. Most solutions do not contain phosphate and can aggravate hypophospha- temia, which is frequently present in patients with ARF. Similarily, because these solutions are free of magne- sium, a negative balance is induced by CRRT. E. Loss of Substrates Water-soluble molecules with low molecular weight and low protein binding, such as amino acids or water- soluble vitamins, are readily filtered, resulting in a con- siderable loss of several nutritional substrates during CRRT. During postdilutional hemofiltration, this loss is proportional to the filtered volume and the plasma concentration of the substrate and can thus be easily estimated. In the case of amino acids, this loss accounts for the average amino acid plasma concentration multiplied by the filtered volume (AA loss/day (g) = 0.25 ϫ 1/day). During continuous hemodialysis diffusive clearance of amino acids is also high, and it is more difficult to estimate the actual loss. Depending on filtrate volume/ day and/or dialysate flow, amino acid elimination will account for 6–15 g AA per day during CRRT (33,34). Thus, during CRRT there is an obligatory loss of amino acids, however nutritional therapy including amino acids does not increase this elimination substan- tially. The endogenous clearance of amino acids is up to 100 times higher than the filtration clearance, and consequently, amino acid infusions using clinically rel- evant infusion rates (1.0–1.5 g AA/kg/day) have a min- imal effect on plasma concentrations and do not aug- ment loss of amino acids (35). However, any exaggerated intake of amino acids (some authors used up to 2.25 g AA/kg/day) will also considerably increase the therapy-induced amino acid elimination (36). The dependence of amino acid losses on plasma concentra- tions exerts a smoothing effect on the plasma amino acids profile, particularly if unbalanced amino acid so- lutions are used for nutritional support. When designing a nutritional program this obliga- tory loss of substrates must be considered in the esti- mation of nitrogen requirements. Amino acid supply should be increased by approximately 0.2 g AA/kg/day to compensate for these CRRT-associated losses. F. Elimination of Peptides Convective transport during hemofiltration is charac- terized by a near linear clearance of molecules up to a molecular weight defined by the pore size of the filtra- tion membrane. This ‘‘cut-off’’ of the commonly used filtration membranes ranges between 20 and 40 kDa. Obviously, the convective clearance extends not only to ‘‘bad molecules’’ (mediators), which are implicated in the evolution of several disease states, such as sepsis, ARDS, SIRS and MODS, but also to other short-chain peptides, such as many hormones (37). For discussion of the pathophysiological relevance of the elimination of a substance by hemofiltration, the endogenous turnover must be taken into account. Even if a compound is filtered with a sieving coefficient of 1.0, the eliminated amount is negligible when the en- dogenous turnover rate is high (as for most mediators and hormones). For example, extracorporeal extraction rate of catecholamines is high, but this does not affect plasma concentration or the need for exogenous cate- cholamine infusion, nor does it impair cardiovascular stability (38). Similarily, insulin has excellent filtration properties, but glucose intolerance is not aggravated and insulin requirements are not increased during CRRT. G. Adsorption of ‘‘Mediators’’ and/or Endotoxin on the Artificial Membrane The elimination of substances during CRRT is caused not only by filtration/diffusion but also by adsorption of proteins (hormones, interleukins, complements fac- tors, and other potential mediators) and, possibly, also of endotoxins at the membrane (39). A ‘‘protein coat- ing’’ contributes to an improvement of biocompatibility of the membrane. When assessing the clinical relevance of these mechanisms, it must be considered that any potential effect is of limited duration. After saturation of the membrane, adsorption decreases sharply so that certainly after 8 hours of treatment, no further effectiv- ity is to be expected. This indicates that if an adsorptive property of the membrane is a therapeutically desired effect, the filters must be regularly replaced (maximum filter time 12 h ?). H. Bioincompatibility: Activation of an Inflammatory Reaction Any extracorporeal circuit induces obligatory phenom- ena of bioincompatibility by blood membrane interac- tions (40). The contact of blood with artificial surfaces 432 Druml Table 3 Side Effects and Complications of Energy Intake Above Requirements Induction of nutritional stress reaction Fatty infiltration of the liver Increase in body temperature Increase in CO 2 production and respiratory work Activation of protein breakdown Decreased survival (animal experiments) Table 4 Disadvantages and Complications of Hyperglycemia Aggravation of tissue injury/tubular dysfunction Fatty infiltration of the liver Impairment of immunocompetence Activation of proteolysis Stimulation of CO 2 production Inhibition of gastrointestinal motility will induce an activation of several biological cascade systems (e.g., coagulation factors, complement, kinins) and stimulation of cellular factors (platelets, polymor- phonuclear cells, monocytes, basophils). For these rea- sons nonsynthetic, poorly biocompatible membrane materials such as cuprophane should not be used in intensive care patients with ARF (41). Membranes used in CRRT are composed of syn- thetic materials characterized by a high biocompatibil- ity. Nevertheless, prolonged and continuous interaction for many days, even weeks, between blood components and the membrane will result in low-grade activation of various biological systems. There are indications that CRRT may cause a chronic inflammatory reaction, but these phenomena have not been systematically inves- tigated during CRRT (42). IV. NUTRITIONAL PROBLEMS ARISING FROM THE PROVISION OF SUBSTRATES A. Energy Substrates: Untoward Effects of Hyperalimentation There is overwhelming evidence that patients with acute disease processes should not receive more calo- ries than can be utilized (i.e. oxidized). Any excess caloric intake must be stored in the body, which essen- tially means that the substrates provided must be con- verted to fat (43). This liponeogenesis takes place within hepatocytes, but lipid particles cannot be ex- ported from the liver, resulting in fatty infiltration of the liver. The side effects and complications associated with calorie overfeeding are manyfold (Table 3). Besides the fatty infiltration of the liver, which can impair hepatic function and can even progress to liver failure, surplus calories increase oxygen consumption as well as body temperature (substrate-induced thermogenesis) and stimulate catecholamine secretion (nutritional stress) (44). Moreover, liponeogenesis is associated with an exaggerated release of carbon dioxide, which may re- sult in respiratory failure in patients with compromised respiratory reserve (45). Calorie overfeeding beyond actual energy requirements impairs survival in animal experiments (46). It is generally accepted that a normocaloric energy supply should be followed in artificial nutrition, which should be oriented to the actual needs of the patient. Earlier recommendations for provision of as much as 50 kcal/day originate from a time where individual en- ergy requirements were grossly overestimated (47). As individual energy expenditure can only rarely be measured directly in the clinical setting (either by in- direct calorimetrie or by using a Swan-Ganz catheter), formulas have to be used to estimate individual needs. There is good evidence that energy requirements in an ARF patient with sepsis but also multiple organ dys- function syndrome rarely exceed 25–30% above basic requirements (4–6). Thus in 90% of the patients an energy supply of 130% of basic energy expenditure (BEE) as estimated by the Harris-Benedict equation will be sufficient. 1. Carbohydrates Glucose should be used as the main energy substrate because it can be utilized by all organs even under hypoxic conditions. Glucose infusions in patients with ARF, however, are associated with several potential problems. Since ARF impairs glucose tolerance, ex- ogenous insulin is frequently necessary to maintain normoglycemia. One should keep in mind that exoge- nous insulin does not improve oxidative glucose dis- posal. Moreover, when glucose intake is increased above 5 g/kg of body weight per day, it will not be used for energy but will promote lipogenesis with fatty infiltration of the liver and excessive carbon dioxide production and hypercapnia (48). It must be recognized that hyperglycemia is not to be neglected as it is associated with several serious side effects (Table 4), among which are fatty infiltration of the liver, glycation of plasma proteins such as immu- Nutritional Problems and CRRT 433 noglobulins, aggravation of tissue injury and tubular dysfunction (49,50). Moreover, hyperglycemia impairs enteral nutrition by inhibition of intestinal motility (51). The most suitable means of providing the energy requirements in critically ill patients is not glucose or lipids, but glucose and lipids. Thirty to 50% of non- protein calories should consist of lipids (52,53). Car- bohydrates, including fructose, sorbitol, or xylitol, which are available in some countries, should be avoided because of potential adverse metabolic effects such as an increase in renal oxygen consumption. 2. Lipid Emulsions Advantages of intravenous lipids include a high spe- cific energy content, a low osmolality, provision of es- sential fatty acids but also of phospholipids to prevent deficiency syndromes, a lower frequency of hepatic side effects, and reduced carbon dioxide production, especially relevant in patients with respiratory failure. Lipid emulsions provide an excellent nutritional sub- strate even in critically ill patients with various organ dysfunctions and sepsis. These disease states are as- sociated with both enhanced lipid oxidation and sec- ondary insulin resistance (54). At clinically relevant in- fusion rates, the elimination of emulsion particles, triglyceride hydrolysis, and oxidation of released free fatty acids is adequate, also in the presence of pulmo- nary insufficiency, septicemia, hepatic and/or renal fail- ure (54). The changes in lipid metabolism associated with ARF increase the risk of inducing side effects but nev- ertheless should not prevent the use of lipid emulsions in these patients. Because of impaired elimination of lipid particles from the blood stream, the amount in- fused should be adjusted to meet the patient’s capacity to utilize lipids. Usually1gfat/kgofbody weight per day will not substantially increase plasma triglycerides, so that about 20–25% of energy requirements can be met (55). Lipids should not be administered to patients with hyperlipidemia (plasma triglycerides > 400 mg/dL), ac- tivated intravascular coagulation, acidosis (pH < 7.20), impaired circulation, or hypoxemia. Potential side ef- fects occur mainly during excessive infusion rates (short-term infusions of 500 mL 20% lipid emulsions were common practice in the past) and/or impaired clearance from the blood stream. These problems in- clude induction of hyperlipidemia, a lipid overload syn- drome, which may be associated with deposits of lipid particles mainly in the pulmonary vasculature, which may aggravate intravascular coagulation activation and, most importantly, affect reticuloendothelial clearance function and thus immunocompetence of the organism. With modern low infusion rates over prolonged periods and if plasma triglycerides levels are maintained below 400 mg/dL, these complications are rarely seen. Parenteral lipid emulsions usually contain long- chain triglycerides, mostly derived from soybean oil. Recently fat emulsions containing a mixture of long- and medium-chain triglycerides have been introduced for intravenous use. Proposed advantages include faster elimination from the plasma due to a higher affinity for the lipoprotein lipase enzyme, complete, rapid, and car- nitine-independent metabolism, and a triglyceride-low- ering effect. The use of medium-chain triglycerides does not promote lipolysis, and the elimination of both types of fat emulsions is equally retarded in ARF (26). B. Amino Acid Solutions and Protein Intake 1. Optimal Nitrogen Intake The relationship between nitrogen intake and protein catabolism presents a U-shaped curve: an insufficient intake will augment endogenous protein catabolism; conversely, any excessive intake will simply convert surplus amino acids into urea. An optimal intake will combine minimal endogenous protein breakdown and urea production with maximal protein synthesis (24). The optimal intake of protein or amino acids is influ- enced more by the nature of the illness causing ARF and the extent of protein catabolism and the type and frequency of renal replacement therapy than by renal dysfunction per se. The few studies that attempted to define the optimal requirements for protein or amino acids in ARF suggest that in nonhypercatabolic patients and in the recovery phase of ARF, a protein intake of about 1.0–1.2 g/kg of body weight per day is required to achieve a positive nitrogen balance (2). There is agreement that in hyper- catabolic critically ill patients with ARF on CRRT, nitrogen requirements are higher. In these subjects pro- vision of 1.5 g of amino acids or protein per kg of body weight per day is more effective in reducing nitrogen losses than lower rates of nitrogen intake (56–58). Again, it must be emphasized that hypercatabolism cannot be overcome by increasing protein or amino acid intake to more than 1.3–1.5 g/kg of body weight per day. Any exaggerated protein intake as high as >2 g kg as recommended in some studies (36), will simply stimulate the formation of urea and other nitrogenous waste products and may aggravate uremic complica- 434 Druml Table 5 Side Effects and Complications Associated with Unbalanced/Incomplete Amino Acid Solutions Amino acid deficiencies: conditionally indispensable (e.g., histidine, arginine, tyrosine, serine, cysteine) Amino acid toxicities: excessive amino acid content (e.g., methionine) Amino acid requirements higher than suggested in the past: the required high infusion rates can unmask the unbalanced composition of amino acid solutions Alterations in amino acid metabolism caused by ARF (and/ or hypercatabolism) can result in serious imbalances of plasma amino acid concentrations during infusion Infusion of more than 0.8 g exclusively essential amino acids/kg/day induces an imbalance syndrome and will simply lead to conversion of infused amino acids to waste products Use of essential amino acids to synthesize nonessential amino acids has no obvious metabolic advantage and wastes energy Complete amino acid mixtures adapted to the metabolic alterations in the critically ill patient with ARF may improve plasma amino acid pattern and net nitrogen retention tions. Moreover, this practice will also augment amino acid losses during CRRT. 2. Type of Amino Acid Solutions Side effects and complications of amino acid/protein intake beyond the absolute amount of nitrogen may be associated with deficiencies or toxic effects of certain amino acids. It may also induce an amino acid imbal- ance syndrome, which may be associated with various adverse effects on protein metabolism. This spectrum of potentially life-threatening side effects can be dem- onstrated with solutions of essential amino acids (EAA) only (Table 5). These solutions are suboptimal and can cause serious complications and should not be used in patients with ARF. They are deficient in various amino acids which become conditionally indispensable in pa- tients (e.g., histidine, arginine, tyrosine, serine, cyste- ine) (1,2,18). Arginine-free amino acid solutions can cause hyperammonemia, acidosis, and coma (59). The content of other amino acids such as methionine and phenylalanine is excessive, with pronounced rises in plasma concentrations during infusion again entailing the potential of inducing toxic effects. Furthermore, the unbalanced composition together with metabolic alter- ations characteristic for patients with ARF and the re- quired high infusion rates can result in excessive im- balances of plasma amino acid concentrations (1). These data suggest that solutions containing exclu- sively EAA should no longer be used in critically ill patients with ARF. Mixtures including both EAA, non- essential amino acids (NEAA), and those amino acids that might become conditionally essential in ARF (‘‘ne- phro’’ solutions), either in standard or in special pro- portions, should be preferred for nutritional support in patients with ARF (1,2). Because of the low water solubility of tyrosine, di- peptides containing tyrosine (such as glycyl-tyrosine) are contained in modern ‘‘nephro’’ solutions as a ty- rosine source (19,20). One should be aware of the fact that the amino acid analog N-acetyl tyrosine, previ- ously frequently used as tyrosine source, cannot be converted into tyrosine in humans and might even stim- ulate protein catabolism (19). Despite considerable investigation, there is not per- suasive evidence that amino acid solutions enriched in branched-chain amino acids will exert any clinically significant anticatabolic effect. These solutions entail the risk of inducing an amino acid imbalance syn- drome. Studies conduced so far have not demonstrated any advantage for these mixtures regarding nitrogen balance or concentrations of plasma proteins as com- pared to standard solutions (60). Glutamine, an amino acid that traditionally was termed nonessential, has been suggested to exert im- portant metabolic functions in regulating nitrogen me- tabolism and to support immunological functions and preserve gastrointestinal barrier. It may thus become conditionally indispensable in catabolic illness (61). Glutamine supplementation to animals with postis- chemic ARF decreased survival rate (62). However, this may not reflect the clinical situation where obvi- ously any excess nitrogen will be removed during renal replacement therapy. A recent study suggested that fewer critically ill patients died with ARF when glu- tamine supplementation was administered (63). Since free glutamine is not stable in aequous solutions, glu- tamine-containing dipeptides are used as a glutamine source in parenteral nutrition (61). It must be recog- nized that the utilization of dipeptides is in part depen- dent on intact renal function and that renal failure may impair hydrolysis (64). Side effects beyond the in- creased nitrogen load (and rise of plasma ammonia in the presence of hepatic failure) have not been reported during infusions of glutamine-containing dipeptides. It has been suggested that amino acids infused be- fore or during ischemia or nephrotoxicity may enhance tubular damage and accelerate loss of renal function (65). In part, this ‘‘therapeutic paradox’’ from amino acid alimentation in ARF is related to the increase in Nutritional Problems and CRRT 435 Table 6 Causes of Electrolyte Disturbances in Patients with Acute Renal Failure Hyperkalemia Decreased renal elimination Increased release during catabolism: (2.38 mmol/g N) (0.36 mmol/g glycogen) Decreased cellular uptake/increased release: Uremic intoxication, septicemia Drugs (ß-blockers, digitalis glycosides, ACE inhibitors) Metabolic acidosis (0.6 mmol/L rise of K ϩ /0.1 decrease in pH) Hyperphosphatemia Decreased renal elimination Increased release from bone Increased release during catabolism (2 mmol/g N) Decreased cellular uptake/utilization and/or increased release from cells metabolic work for transport processes when the oxy- gen supply is limited, which may aggravate ischemic injury (66). Similar observations have been made with excess glucose infusion during renal ischemia (67). During the insult phase of ARF, the ‘‘ebb phase’’ im- mediately after trauma, shock, major surgery, etc., any excess nutritional intake should be avoided. Infusion of modern adapted amino acid solution raises plasma amino acids levels marginally, eliminates concentration peaks, and limits the likelihood of these side effects. Amino acids may also have protective potential. Glycine and, to a lesser degree, alanine limit tubular injury in ischemic and nephrotoxic models of ARF (68). Arginine (possibly by producing nitric oxide) re- portedly acts to preserve renal perfusion and tubular function in both nephrotoxic and ischemic models of ARF, whereas inhibitors of nitric oxide synthase exert an opposite effect (69). C. Electrolytes Because of the high interindividual differences in and the rapid intraindividual changes of electrolyte require- ments during the course of disease, no standardized recommendations can be made for electrolyte supple- mentation. Electrolyte requirements are highly variable in patients with ARF and must be given as required according to the monitoring of electrolyte balance and plasma concentrations. Certainly, patients with ARF are the group of subjects with the highest risk of devel- oping electrolyte derangements. 1. Potassium Hyperkalemia is frequently observed in patients with ARF. Elevation of plasma potassium is caused not only by impaired renal excretion of the electrolyte but also by increased cellular release during accelerated protein catabolism and altered distribution between intra- and extracellular spaces (Table 6). Several factors contrib- ute to a decrease of cellular uptake of potassium, e.g., the uremic state per se, acidosis, drugs such as digitalis glycosides or beta-blocking agents. Thus, the potas- sium tolerance of the organism is impaired and the rise in plasma potassium level is augmented during exog- enous infusion. However, with modern infusion therapy and nutritional support, excessive hyperkalemia rarely is seen and in less than 5% of the cases, hyperkalemia presents the major indication for initiation of extracor- poreal therapy (70). It must be noted, however, that many patients with ARF may have a decreased serum potassium concen- tration on presentation. Infusion of glucose and/or amino acids causes a shift of potassium and phosphate into the cells, and thus nutritional support with low electrolyte contents may induce hypokalemia in a con- siderable number of patients (70). Potassium depletion may aggravate tissue injury and the severity of meta- bolic disturbances in ARF (71). 2. Phosphate Serum phosphate may increase in uremic patients, not only because of impaired renal excretion, but also be- cause of increased release from cells during catabolism, enhanced gastrointestinal adsorption, decreased meta- bolic utilization, and augmented mobilization from bone (Table 6). Thus, the type of underlying disease and the degree of hypercatabolism will also determine the occurrence and extent of electrolyte abnormalities. Hyperphosphatemia per se may predispose to the de- velopment of ARF, and in some cases of tumor lysis syndrome excessive release of phosphate from cells is the leading cause of renal shutdown by intrarenal pre- cipitation of calcium phosphate (72). However, in ARF decreased plasma phosphate levels are common and, in fact, in 20% of patients may pres- ent with hypophosphatemia on admission (70). Fur- thermore, during the diuretic phase of ARF (especially after renal transplantation), during phosphate-free CRRT, during artificial nutritional support with low phosphate contents, hypophosphatemia may develop in a considerable number of patients during the further 436 Druml course of disease (73). Even if hyperphosphatemia was present on admission, hypophosphatemia developed during phosphate-free nutritional therapy within several days (74). Phosphate depletion increases the risk initi- ation and maintenance of ARF (75). If phosphate is added to ‘‘all-in-one’’ solutions, or- ganic phosphates (glycero-phosphate, glucose-1-phos- phate) must be used to avoid incompatibilities with other ions in the solution. Divalent ions (calcium, mag- nesium) can impair the stability of fat emulsions and should be used with caution in lipid-containing nutri- tion solutions (76). 3. Calcium The majority of patients with ARF are hypocalcemic usually with a diminution of both protein-bound and ionized fractions. The causes of hypocalcemia are only partially understood, but hypoalbuminemia, hyperphos- phatemia, citrate anticoagulation, a reduced formation of 1,25(OH) 2 vitamin D 3 with reduced calcium adsorp- tion from the gastrointestinal tract, and potentially skel- etal resistance to the calcemic effect of parathyroid hor- mone all may contribute (77). If calcium supplements are added to all-in-one solution—similar to phosphate supplementation— organic compounds such as calcium gluconate must be used to avoid precipitation of calcium salts (76). Hypercalcemia may develop with high dialysate cal- cium concentrations, immobilization, acidosis, and/or hyperparathyreoidism because parathyroid hormone is also elevated in ARF (78). In ARF caused by rhabdo- myolysis, persistent elevations of serum calcitriol may result in a rebound hypercalcemia during the diuretic phase (79). Acute hypercalcemia per se can cause ARF by inducing acute nephrocalcinosis, arterial calcifica- tions, and interstitial nephritis. 4. Magnesium Elevations of serum magnesium are rarely encountered in patients with ARF. Symptomatic hypermagnesemia may only develop during increased magnesium intake and/or infusion. Hypomagnesemia, on the other hand, may be seen more frequently, such as during use of magnesium-free substitution fluids for hemofiltration, during citrate anticoagulation, in the presence of asso- ciated gastrointestinal disorders, and during the diuretic phase of ARF, especially after renal transplantation (80). Moreover, several nephrotoxic drugs such as cis- platin, aminoglycosides, and amphotericin B may cause renal magnesium wasting. In transplant recipients treated with cyclosporine, hypomagnesemia was seen in up to 100% of patients in several case series (81). D. Micronutrients 1. Vitamins Serum levels of water-soluble vitamins are decreased in patients on CRRT mainly because of losses induced by renal replacement therapy, but systematic informa- tion on vitamin metabolism in ARF is limited (82,83). In addition, nutritional status before hospital admission and the type, severity, and duration of underlying dis- ease determine vitamin body stores. Depletion of thiamine (vitamin B 1 ) during CRRT and inadequate exogenous supplementation may result in perturbations in energy metabolism and lactic aci- dosis (84). A routine supplementation of additional thi- amine should be performed in intensive care patients and especially those with liver disease. On the other hand, the potential of inducing toxic effects during overdosage is low for water-soluble vi- tamins. An exception is vitamin C, an excess supply of which should be avoided. Ascorbic acid is metabolized via oxalic acid, and any exaggerated intake may induce a secondary oxalosis and initiate or retard resolution of ARF (85). Fat-soluble vitamins are obviously not eliminated by renal replacement therapy. Nevertheless, with the ex- ception of vitamin K, body stores of these vitamins are depleted in patients with ARF (78). On the other hand, the risk of inducing toxic effects have rarely been re- ported with the exception of vitamin K and vitamin A. Activation of vitamin D 3 is—as in chronic renal failure—decreased in patients with ARF. Plasma levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D plasma levels are profoundly depressed (77,78). Whether—as in patients with chronic renal failure— active vitamin D metabolites should be supplemented in patients with ARF remains to be shown. Vitamin K pools are mostly normal or even elevated in patients with ARF (78). With additional exogenous vitamin K supplementation, toxic effects may occur; high-dose vitamin K administration was implicated as the cause of a prolonged nonoliguric ARF in a renal transplant recipient (86). Vitamin K deficiency is much less frequent and has been mainly reported in patients receiving certain antibiotics that may reduce intestinal vitamin K production. The prolonged plasma half-life of the drug in the presence of the ARF might contribute to vitamin depletion (87). In experimental ARF (and patients with chronic re- nal failure), hepatic release of retinol and retinol-bind- Nutritional Problems and CRRT 437 ing protein is increased concomitant with the decreased renal breakdown of the transport protein, resulting in elevated vitamin A plasma levels. In contrast, in pa- tients with ARF, associated or not with multiple organ dysfunctions, a severe depression of plasma concentra- tions of both retinol and the vitamin A precursor ␤- carotene was seen (78,88). Similarly (and in contrast to findings in chronic renal failure), plasma and intraerythrocyte concentrations of vitamin E (␣-tocopherol) are decreased in patients with both isolated ARF and ARF and associated MODS (78,88). 2. Trace Elements With supplementation of trace elements, one should keep in mind the possibility of inducing toxic effects because during parenteral administration in ARF, both main regulatory functions in trace element homeostasis —intestinal absorption and renal excretion—are cir- cumvented (89). Moreover, it must be recognized that due to the high protein binding, trace elements losses are negligible during renal replacement therapy and thus CRRT does not increase trace element require- ments in critically ill patients (90). Nevertheless, available information on trace element metabolism in ARF is limited and somewhat contra- dictory. The cause and stage of underlying disease and type of tissue in which the concentration of an element is measured must be considered in the interpretation of specific findings and, in fact, may be more relevant than the acutely uremic state per se (91). Many of the reported findings such as decreases in plasma concentrations of iron, zinc, and selenium or increases in copper levels might present unspecific al- terations within the spectrum of ‘‘acute phase reaction’’ and do not necessarily reflect disturbances of external trace element balance (deficiency or toxicity states) but may be the consequence of alterations in tissue distri- bution (92). Geographic and therapeutic factors such as the content of tap water, type of therapy, and espe- cially the highly variable contamination of infusion/ dialysis/hemofiltration fluids with trace elements may profoundly affect tract element balance (93). Selenium concentrations in plasma and erythrocytes have been found to be decreased in patients with chronic as well as acute renal failure (88,90). Selenium deficiency has been implicated in accelerated lipid per- oxidation, impaired immune function, and cardiomy- opathy. In critically ill patients, selenium administra- tion not only replenished selenium stores and improved various aspects of antioxidative system, but also re- duced the development of renal dysfunction and im- proved prognosis (94). Similarly, it was suggested that zinc requirements may be increased in critically ill pa- tients, particularly in those with gastrointestinal disease (91,92). Several vitamins and trace elements are components of the nonenzymatic oxygen radical scavenger system. A profoundly reduced antioxidant status has been found in patients with MODS and associated ARF (88). In the rat model of ARF, antioxidant deficiency of the organism (decreased vitamin E and/or selenium status) exacerbates an ischemic renal injury, worsens the course of disease, and increases mortality (95). In turn, administration of antioxidants can attenuate tissue in- jury in experimental ARF (96). These data support the concept of a crucial role of reactive oxygen species and peroxidation of lipid membrane components in initiat- ing and/or mediating tissue injury. V. CONCLUSION Acute renal dysfunction is associated not only with the obvious disturbances of water and electrolyte metabo- lism and acid base balance but also with a complex pattern of specific alterations of amino acid, carbohy- drate, and lipid metabolism. In addition, in the critically ill patient with ARF, the metabolic environment will be determined by the acute disease state per se (‘‘systemic inflammatory response syndrome’’) and, most impor- tantly, by the underlying disease process and/or asso- ciated organ dysfunctions and/or complications, such as severe infections. Moreover, the type and intensity of renal replacement therapy and especially modern CRRT will exert a major impact on nutrient require- ments and metabolism. These complex metabolic al- terations render patients with ARF with/without CRRT extremely susceptible to development of side effects and complications of nutritional interventions. In any patient with ARF, this broad pattern of metabolic al- teration must be taken into account to define an optimal nutritional program, to increase the efficiency of nutri- tional therapy, to correct existing and avoid the devel- opment or aggravation of metabolic disturbances, and to avoid complications during nutrition and renal re- placement therapy. REFERENCES 1. Druml W. Nutritional support in acute renal failure. In: Mitch WE, Klahr S, eds. Nutrition and the Kidney. Bos- ton: Little Brown, 1998: 314–345. 438 Druml 2. Druml W, Mitch WE. Metabolic abnormalities in acute renal failure. Semin Dialysis 1996; 9:484–490. 3. Druml W. Metabolic aspects of continuous renal re- placement therapies. Kidney Int 1999; 56(suppl 72): S56–S61. 4. Schneeweiß B, Graninger W. Stockenhuber F, Druml W. Ferenci P, Eichinger S, Grimm G, Laggner AN, Grimm G. Energy metabolism in acute and chronic re- nal failure. Am J Clin Nutr 1990; 52:596–601. 5. Bouffard Y, Viale JP, Annat G, Delafosse B, Guillaume C, Motin J. Energy expenditure in the acute renal fail- ure patient mechanically ventilated. Intens Care Med 1987; 13:401–406. 6. Soop M, Forsberg E, Tho¨rne A, Alvestrand A. Energy expenditure in postoperative multiple organ failure with acute renal failure. Clin Nephrol 1989; 31:139–143. 7. Druml W. Protein metabolism in acute renal failure. Miner Electrolyte Metab 1998; 24:47–54. 8. Mitch WE. Amino acid release from the hindquarter and urea appearance in acute uremia. Am J Physiol 1981; 241:E415–E419. 9. Clark AS, Mitch WE. Muscle protein turnover and glu- cose uptake in acutely uremic rats. J Clin Invest 1983; 72:836–845. 10. Fro¨hlich J, Scho¨lmerich J, Hoppe-Seyler G, Maier KP, Talke H, Schollmeyer P, Gerok W. The effect of acute uremia on gluconeogenesis in isolated perfused rat liv- ers. Eur J Clin Invest 1974; 4:453–458. 11. Maroni BJ, Haesemeyer RW, Kutner MH, Mitch WE. Kinetics of system A amino acid uptake by muscle: ef- fects of insulin and acute uremia. Am J Physiol 1990; 258:F1304–F1310. 12. Druml W, Bu¨rger U, Kleinberger G, Lenz K, Laggner AN. Elimination of amino acids in acute renal failure. Nephron 1986; 42:62–67. 13. Druml W, Fischer M, Liebisch B, Lenz K, Roth E. Elimination of amino acids in renal failure. Am J Clin Nutr 1994; 60:418–423. 14. Wilmore DW. Catabolic illness; strategies for enhanc- ing recovery. N Engl J Med 1991; 325:695–702. 15. Mitch WE, May RC, Maroni BJ, Druml W. Protein and amino acid metabolism in uremia: influence of meta- bolic acidosis. Kidney Int 1989; 36(suppl 27):S205– S207. 16. Mault JR, Bartlett RH, Dechert RE, Clark SF, Schwartz RD. Starvation: a major contributor to mortality in acute renal failure. Trans Am Soc Artif Intern Organs 1983; 29:390–394. 17. Mitch ME, Chesney RW. Amino acid metabolism by the kidney. Miner Electrolyte Metab 1983; 9:190–202. 18. Laidlaw SA, Kopple JD. Newer concepts of indispen- sable amino acids. Am J Clin Nutr 1987; 46:593–605. 19. Druml W, Roth E, Lenz K, Lochs H, Kopsa H. Phen- ylalanine and tyrosine metabolism in renal failure. Kid- ney Int 1989; 36 (suppl 27):S282–S286. 20. Druml W, Lochs H, Roth E, Hu¨bl W, Balcke P, Lenz K. Utilisation of tyrosine dipeptides and acetyl-tyrosine in normal and uremic humans. Am J Physiol 1991; 260: E280–E285. 21. Naschitz JE, Barak C, Yeshurun D. Reversible dimin- ished insulin requirement in acute renal failure. Post- grad Med J 1983; 59:269–271. 22. May RC, Clark AS, Goheer MA, Mitch WE. Specific defects in insulin-mediated muscle metabolism in acute uremia. Kidney Int 1985; 28:490–497. 23. Cianciaruso B, Bellizzi V, Napoli R, Sacca L, Kopple JD. Hepatic uptake and release of glucose, lactate and amino acids in acutely uremic dogs. Metabolism 1991; 40:261–290. 24. Shaw JFH, Wildbore M, Wolfe RR. Whole body protein kinetics in severely septic patients: the response to glu- cose infusion and total parenteral nutrition. Ann Surg 1987; 205:288. 25. Druml W, Fischer M, Sertl S, Schneeweiss B, Lenz K, Widhalm K. Fat elimination in acute renal failure: Long chain versus medium chain triglycerides. Am J Clin Nutr 1992; 55:468–472. 26. Druml W, Zechner R, Magometschnigg D, Lenz K, Kleinberger G, Laggner AN, Kostner G. Post-heparin lipolytic activity in acute renal failure. Clin Nephrol 1985; 23:289–293. 27. Adolph M, Eckart J, Metges C, Neeser G, Wolfram G. Oxidative utilization of lipid emulsions in septic pa- tients with and without acute renal failure. Clin Nutr 1995; 14 (suppl 2):35A. 28. VanKuijk WHM, Hillion D, Saoiu C, Leunissen KML. Critical role of the extracorporeal blood temperature in the hemodynamic response during hemofiltration. JASN 1997; 8:949–955. 29. Monaghan R, Watters JM, Clancey SM, Moulton SB, Rabin EZ. Uptake of glucose during continuous arte- riovenous hemofiltration. Crit Care Med 1993; 21: 1159–1163. 30. Yatani A, Fujiono T, Kinoshita K, Goto M. Excess lac- tate modulates ionic currents and tension components in frog atrial muscle. J Mol Cell Cardiol 1981; 13:147– 161. 31. Lovejoy J, Newby FD, Gebhart SSP, DiGirolamo M. Insulin resistance in obesity is associated with elevated lactate levels and diminished lactate appearance follow- ing intravenous glucose and insulin. Metabolism 1992; 41:22–27. 32. Olbricht CJ, Huxman-Na¨geli D, Koch KM. Harnstoff- generation bei kontinuierlicher arterioveno¨ser Ha¨mofil- tration (CAVH) mit Laktat- und Bikarbonat-Lo¨sungen. Nieren Hochdruckkrankh 1992; 21:410A. 33. Davies SP, Reaveley DA, Brown EA, Kox WJ. Amino acid clearances and daily losses in patients with acute renal failure treated by continuous arteriovenous he- modialysis. Crit Care Med 1991; 19:1510–1515. 34. Davenport A, Robert NB. Amino acid losses during continuous high-flux hemofiltration in the critically ill patient. Crit Care Med 1989; 17:1010–1015. Nutritional Problems and CRRT 439 35. Druml W. Nutritional considerations in the treatment of acute renal failure in septic patients. Nephrol Dial Transplant 1994; 9 (suppl4):219–223. 36. Frankenfeld DC, Badellino MM, Reynolds N, Wiles CE, Siegel JH, Goodarzi S. Amino acid loss and plasma concentration during continuous hemofiltration. JPEN 1993; 17:551–561. 37. Druml W. Prophylactic use of CRRT in patients with normal renal function. Am J Kidney Dis 1996; 28 (suppl 3):S-114–120. 38. Bellomo R, McGrath B, Boyce N. In vivo catechol- amine extraction during continuous hemodiafiltration in inotrope-dependent patients Trans Am Soc Intern Or- gans 1991; 37:324–325. 39. Gasche Y, Pascual M, Suter PM, Favre H, Chevrolet JC, Schifferli JA. Complement depeletion during hae- mofiltration with polyacrylonitrile membranes. Nephrol Dial Transplant 1996; 11:117–119. 40. Gutierrez A, Alvestrand A, Bergstro¨m J. Membrane se- lection and muscle protein catabolism. Kidney Int 1992; 42 (suppl.38):S-86–S-90. 41. Himmelfarb J, Tolkoff R, Chandran P, Parker RA, Win- gard RL, Hakim R. A multicenter comparison of dial- ysis membranes in the treatment of acute renal failure requiring dialysis. J Am Soc Nephrol 1998; 9:257–266. 42. Riegel W. Ziegenfuss T, Rose, Bauer M, Marzi I. Influ- ence of venovenous hemofiltration on posttraumatic in- flammation and hemodynamics. Contrib Nephrol 1995; 116:56–61. 43. Burke JF, Wolfe RR, Mullany CJ, Mathews DE, Bier DM. Glucose requirements following burn injury. Ann Surg 1979; 190:274–285. 44. Nordenstro¨m J, Jeevanadam M, Elwyn DH, Carpentier YA, Askanazi J, Robin A, Kinney JM. Increasing glu- cose intake during parenteral nutrition increases nor- epinephrine excretion in trauma and sepsis. Clin Phy- siol 1981; 1:525–534. 45. Askenazi J, Elwyn DH, Silberberg PA, Rosenbaum SH, Kinney JM. Respiratory distress secondary to a high carbohydrate load. Surgery 1980; 87:596–598. 46. Alexander JW, Gonce SJ, Miskell PW. A new model for studying nutrition in peritonitis. The adverse effect of overfeeding. Ann Surg 1989; 209:334–340. 47. Spreiter SC, Myers BD, Swenson RS. Protein-energy requirements in subjects with acute renal failure receiv- ing intermittent hemodialysis. Am J Clin Nutr 1980; 33: 1433–1437. 48. Wolfe RR, Allsop JR, Burke JF. Glucose metabolism in man: response to intravenous glucose infusion. Metab- olism 1979; 28:210–220. 49. Flakoll PJ, Hill JO, Abumrad NN. Acute hyperglycemia enhances proteolysis in normal man. Am J Physiol 1993; 265:E715–E721. 50. Hennessey PJ, Black CT, Andrassy RJ. Nonenzymatic glycosylation of immunoglobulinG impairs comple- ment fixation. JPEN 1991; 15:60–64. 51. Bjo¨rnsson ES, Urbanavicius V, Eliasoson B, Attval S, Smith U. Effects of hyperglycemia on interdigestive gastrointestinal motility in humans. Scand J Gastroen- terol 1994; 29:1096–1104. 52. Bresson JL, Bader B, Rocchiccioli F, Mariotti A, Ricour C, Sachs C, Rey J. Protein-metabolism kinetics and en- ergy-substrate utilization in infants fed parenteral so- lutions with different glucose-fat ratios. Am J Clin Nutr 1991; 54:346–350. 53. Schneeweiß B, Graninger W, Ferenci P, Druml W, Ratheiser K, Steger G, Grimm G, Schurz B, Laggner AN, Siostrzonek P, Lenz K. Short term energy balance in patients with infections: Carbohydrate-based versus fat-based diets. Metabolism 1992; 41:125–130. 54. Druml W, Fischer, M, Ratheiser K. Utilization of intra- venous lipids in critically ill patients with sepsis with- out and with hepatic failure. JPEN 1998; 22: 55. Druml W, Laggner AN, Lenz K, Balcke P. Kleinberger G, Schmidt P. Lipid metabolism and lipid utilization in renal failure. Infusionstherapie 1983; 10:206–212. 56. Kierdorf H, Kindler J, Sieberth HG. Nitrogen balance in patients with acute renal failure treated by continuous arteriovenous hemofiltration. Nephrol Dial Transplant 1986; 1:72. 57. Chima CS, Meyer L, Hummell AC, Bosworth C, Heyka R, Paganini EP, Werynski A. Protein catabolic rate in patients with acute renal failure on continuous arterio- venous hemofiltration and total parenteral nutrition. JASN 1993; 3:1516–1521. 58. Macias WL, Alaka KJ, Murphy MH, Miller ME, Clark WR, Mueller BA. Impact of nutritional regimen on pro- tein catabolism and nitrogen balance in patients with acute renal failure. JPEN 1996; 20:56–62. 59. Grazer RE, Sutton JM, Friedstrom S, McMarron FD. Hyperammoniemic encephalopathy due to essential amino acid hyperalimentation. Arch Int Med 1984; 144: 2278–2279. 60. Kierdorf HP. The nutritional management of acute renal failure in the intensive care unit. New Horizons 1995; 3:699–707. 61. Fu¨rst P, Stehle P. The potential use of dipeptides in clinical nutrition. Nutr Clin Pract 1993; 8:106–114. 62. Imai E, Yamanoto S, Isaka Y, Fukuhara Y, Fujii Y, Kik- uchi T, Tanaka T, Kamada T, Ueda N. Delay of recov- ery from renal ischemic injury by administration of glu- tamine. JASN 1991; 2:648A. 63. Griffiths RD, Jones CJ, Palmer TEA. Six-month out- come of critically ill patients given glutamine-supple- mented parenteral nutrition. Nutrition 1997; 13:295– 302. 64. Hu¨bl W, Druml W, Roth E, Lochs H. Importance of liver and kidney for the utilization of glutamine-con- taining dipeptides in man. Metabolism 1994; 43:1104– 1107. 65. Zager RA, Venkatachalam MA, Potentiation of ische- mic renal injury by amino acid infusion. Kidney Int 1983; 24:620–625. [...]... Sexual experience of the chronic peritoneal dialysis patient J Am Soc Nephrol 19 96; 7:1 165 –1 168 Glass CA, Fielding DM, Evans C, Ashcroft JB Factors related to sexual functioning in male patients undergoing hemodialysis and with kidney transplants Arch Sex Behav 1987; 16: 189–207 Foulks CJ, Cushner HM Sexual dysfunction in the 452 63 63 64 65 66 67 68 69 70 71 72 73 74 75 Mahmoud et al male dialysis patient:... patients These T4-binding inhibitors may include increased concentrations of hippuric acid, indoxyl sulfate, and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CPMF) as well as increased levels of cytokines, such as interleukin-1b, tumor necrosis factor-␣ and interleukin -6 (21,28–31) Binding of T4 to the carrier proteins may be further inhibited by drugs such as heparin and nonsteroidal anti-inflammatory... Nephron 1987; 46: 225– 230 Ross RJM, Goodwin FJ, Houghton BJ, Boucher BJ Alteration of pituitary-thyroid function in patients with chronic renal failure treated by haemodialysis or continuous ambulatory peritoneal dialysis Ann Clin Biochem 1985; 22:1 56 160 47 48 49 50 51 52 53 54 55 56 57 59 60 61 62 451 Seyrek N, Paydas S, Sagliker Y Effect of erythropoietin administration on thyroid functions of the patients... has been described as ‘‘half- 466 Naeyaert and Beele Fig 5 Pseudo-Kaposi’s sarcoma: swelling of the fingers of the left hand with bluish-red discoloration and early multinodular appearance and-half nail’’ or ‘‘red and white nails’’ (Fig 6) These have been reported in 35% of patients with chronic renal failure and in only 2% of the general hospital population (88) Half-and-half nails have also been observed... Metab 19 76; 43 :63 0 63 7 Lim SL, Fang VS, Katz AI, Refetoff S Thyroid dysfunction in chronic renal failure: a study of the pituitary-thyroid axis and peripheral turnover kinetics of thyroxine and triiodothyronine J Clin Invest 1977; 60 : 522–534 Ramirez G, O’Neill W, Jubiz W, Bloomer HA Thyroid dysfunction in uremia: evidence for thyroid and hypophyseal abnormalities Ann Intern Med 19 76; 84: 67 2 67 6 Ramirez... rather the result of the sexual problems Hormonal Causes Studies indicate sexual dysfunction in CRF /dialysis patients to be associated with low serum concentrations of total and free testosterone (63 ,64 ), hyperprolactinemia (11,54 ,65 ,66 ), hyperoestrogenemia (67 ,11,54), and elevated serum LH levels (63 ,64 ) These hormonal changes are common findings among men with renal failure Patients on hemodialysis may... throughout the distal part of the nail plate The observation of melanin deposits could not be confirmed by Kint et al (14), who described an increased number of capillaries with thickened walls In some patients on chronic hemodialysis, the width and the intensity of the brown distal arch may decrease over a period of months (14) In renal transplant pa- Half-and-half nails: the proximal part of the nail plate... with renal failure (6) These alterations depend on the pre- or pubertal status of the patient, the degree of chronic renal insufficiency or end-stage renal disease, and the type of treatment (conservative, hemodialysis, peritoneal dialysis, transplantation) The kidney plays a role in the metabolism and clearance of thyroid hormones, thyroid-stimulating hormone (TSH), and thyrotropin-releasing hormone... Kolendorf K, Friis T Simultaneous turnover studies of thyroxine 3,5,3Ј-triiodothyronine, 3, 5-, 3,3 - and 3Ј,5Ј-diiothyronine, and 3Ј-monoiodothyronine in chronic renal failure J Clin Endocrinol Metab 1983; 56: 211–217 Kaptein EM Clinical application of free thyroxine determinations Clin Lab Med 1993; 13 :65 3 67 2 Kaptein EM Thyroid in vitro testing in non-thyroidc illness Exp Clin Endocrinol 1994; 102:92–101... their specific inhibitors in undialyzed chronic renal failure, CAPD and hemodialysis patients Kidney Int 1994; 45:890–8 96 Brodersen HP, Korsten FW, Esser PW, Korlings K, Holtkamp W, Larbig D Release of thyroid hormones from protein-binding sites by low-molecular-weight heparin in hemodialysis patients Nephron 1997; 75: 366 – 367 Munro SL, Lim CF, Hall JG, Barlow JW, Craik DJ, Topliss DJ, Stockigt JR Drug . 3-car- boxy-4-methyl-5-propyl-2-furanpropanoic acid (CPMF) as well as increased levels of cytokines, such as inter- leukin-1b, tumor necrosis factor- ␣ and interleukin -6 (21,28–31). Binding of. increases the risk initi- ation and maintenance of ARF (75). If phosphate is added to ‘‘all-in-one’’ solutions, or- ganic phosphates (glycero-phosphate, glucose-1-phos- phate) must be used to. (hemodialysis vs. peri- toneal dialysis) , dialysis adequacy, and the use of eryth- ropoietin (EPO) on the likelihood of sexual inadequacy among patients on dialysis has been evaluated in sev- eral