Increased Protein Catabolism Research Articles

Anesthetic Management Of A Pediatric Patient With Arginase Deficiency

Arginase deficiency is an autosomal recessive disorder of the urea cycle in which a defect in conversion of arginine to urea and ornithine leads to hyperammonemia. Patients with urea cycle disorders may show increased protein catabolism due to inadequate intake of energy, protein and essential amino acids; infections, fever and surgery. A 12-year-old girl with arginase deficiency, ASA II who weighed 40 kg was scheduled for bilateral adductor, quadri-ceps and gastrocnemius tenotomies. She had mental retardation, spasticity and flexion posture of thelower limbs. Metabolic homeostasis was restored with appropriate diet. Successful anesthetic management allowed the patient to be discharged 48 hours after surgery. Increased levels of arginine and ammonia during or after surgery may lead to serious complications such as hypotension, cerebral edema, convulsions, hypothermia and spasticity. Thus special attention must be given to metabolic homeostasis and nutrition of the patients with arginase deficiency in the perioperative period. Primary goals should be to minimize stress levels by effective anxiolysis, provide an adequate amount of protein-free energy with proper fluid management and to obtain an effective preemptive and postoperative analgesia. In addition to a high level of knowledge, successful anesthesia requires professional communication among nursing staff, dietitians, pediatric metabolism specialist, surgeon and anesthesiologist.

Oxidative stress as a therapeutic target during muscle wasting: considering the complex interactions

The aim of this overview is to highlight the multiple ways in which oxidative stress could be exacerbating muscle wasting. Understanding these interactions in vivo will assist in identifying opportunities for more targeted therapies to reduce skeletal muscle wasting. There are many excellent reviews describing how oxidative stress can damage cellular macromolecules, as well as cause deleterious effects through the modulation of signalling pathways. In this overview, we highlight the potential for complex and possibly paradoxical interactions in vivo. Signalling pathways are discussed, using examples involving nuclear factor-kappa B, apoptosis signal-regulating kinase 1 and Akt. Oxidative stress may also be involved in complex interactions with other factors capable of stimulating the loss of muscle mass, possibly through amplifying feedback cycles. This is discussed using examples related to calcium and tumour necrosis factor. There is convincing evidence that oxidative stress can increase protein catabolism. The challenge is to demonstrate that oxidative stress is a significant player in the complex interplay that leads to the in-vivo muscle wasting that is caused by a range of conditions and diseases.

Malnutrition-inflammation-atherosclerosis syndrome in Chronic Kidney disease.

Chronic kidney disease is becoming a major health problem globally and in India an alarming number of about 8 million people are suffering from this disease. Patients undergoing hemodialysis have a high prevalence of protein-energy malnutrition and inflammation. As these two conditions often occur concomitantly in hemodialysis patients, they have been referred together as 'malnutrition-inflammation-atherosclerosis syndrome' to emphasize the important association with atherosclerotic cardiovascular disease. The three factors related to the pathophysiology in these patients are dialysis related nutrient loss, increased protein catabolism and hypoalbuminemia. Inflammation in Chronic Kidney disease is the most important factor in the genesis of several complications in renal disease. Pro-inflammatory cytokines like IL-1 and TNF-alpha play a major role in the onset of metabolic alterations in Chronic Kidney disease patients. Atherosclerosis is a very frequent complication in uremia due to the coexistence of hypertension, hyperhomocysteinemia, inflammation, malnutrition and increased oxidative stress, generation of advanced glycation end products, advanced oxidation protein products, hyperlipidemia and altered structural and functional ability of HDL. LDL-cholesterol, apolipoprotein (A), apolipoprotein (B), and Lp(a) are also associated with atherosclerosis. Studies have now provided enormous data to enable the evaluation of the severity of malnutrition-inflammation-atherosclerosis syndrome as well as effective monitoring of these patients.

Glucocorticoids and fatty acid metabolism in humans: fuelling fat redistribution in the metabolic syndrome

Glucocorticoid hormones constitute an integral component of the response to stress, and many of the manifestations of glucocorticoid excess (Cushing's syndrome) are predictable on the basis of their acute effects to raise blood pressure, induce insulin resistance, increase protein catabolism and elevate plasma glucose. However, it appears to be a paradox that the acute lipolytic effect of glucocorticoids is not manifest in long-term weight loss in humans. The effects of glucocorticoids on glucose metabolism are well characterised, involving impaired peripheral glucose uptake and hepatic insulin resistance, and there is mounting evidence that subtle abnormalities in glucocorticoid concentrations in the plasma and/or in tissue sensitivity to glucocorticoids are important in metabolic syndrome. The effects of glucocorticoids on fatty acid metabolism are less well understood than their influence on glucose metabolism. In this article, we review the literature describing the effects of glucocorticoids on fatty acid metabolism, with particular reference to in vivo human studies. We consider the implications for contrasting acute versus chronic effects of glucocorticoids on fat accumulation, effects in different adipose depots and the potential role of glucocorticoid signalling in the pathogenesis and therapy of metabolic syndrome.

Quelles méthodes d’évaluation de la composition corporelle doivent être utilisées en néphrologie ?

Onset of chronic kidney disease is rapidly followed by the occurrence of body composition alterations due to imbalance in sodium homeostasis and increased protein catabolism. These alterations lead to malnutrition and an increased cardiovascular risk and need to be accurately analysed. Numerous methods of body composition analysis are available but currently none is able to measure the five physiologic compartments -- extracellular fluid, intracellular fluid, body cell mass, bone mass and fat mass. Some are difficult to realize such the underwater weighing or neutron activation analysis, others are easier to do as skinfolds thickness or midarm muscle circumference measurements, dual energy X-ray absorptiometry (Dexa) or spectroscopic impedancemetry. These two techniques seem currently the most appropriate to measure fat mass, bone mass and lean mass for Dexa and body fluids for impedancemetry. The combination of Dexa and impedancemetry allows the calculation of body cell mass which is one of the most important parameter to evaluate nutritional status of patients with chronic kidney disease.

Acidose metabólica na doença renal crônica: abordagem nutricional

A acidose metabólica é uma das complicações da doença renal crônica e está associada ao aumento do catabolismo protéico, à diminuição da síntese de proteínas e ao balanço nitrogenado negativo. A dieta tem forte influência sobre a geração de ácidos, podendo contribuir, portanto, para determinar a gravidade da acidose no paciente com doença renal crônica. Alguns pesquisadores têm observado que é possível estimar a excreção ácida renal, e que o cálculo dessa carga ácida a partir de alguns componentes da dieta, permitiria uma predição apropriada dos efeitos da dieta na acidose metabólica. Este artigo é uma comunicação sobre as bases fisiológicas, bem como as implicações clínicas da acidose em pacientes com doença renal crônica e a influência da dieta no balanço ácido-básico desses pacientes.

The impact of specific oxidized amino acids on protein turnover in J774 cells

Oxidized protein deposition and accumulation have been implicated in the aetiology of a wide variety of age-related pathologies. Protein oxidation in vivo commonly results in the in situ modification of amino acid side chains, generating new oxidized amino acid residues in proteins. We have demonstrated previously that certain oxidized amino acids can be (mis)incorporated into cell proteins in vitro via protein synthesis. In the present study, we show that incorporation of o- and m-tyrosine resulted in increased protein catabolism, whereas dopa incorporation generated proteins that were inefficiently degraded by cells. Incorporation of higher levels of L-dopa into proteins resulted in an increase in the activity of lysosomal cathepsins, increased autofluorescence and the generation of high-molecular-mass SDS-stable complexes, indicative of protein aggregation. These effects were due to proteins containing incorporated L-dopa, since they were not seen with the stereoisomer D-dopa, which enters the cell and generates the same reactive species as L-dopa, but cannot be incorporated into proteins. The present study highlights how the nature of the oxidative modification to the protein can determine the efficiency of its removal from the cell by proteolysis. Protection against the generation of dopa and other species that promote resistance to proteolysis might prove to be critical in preventing toxicity from oxidative stress in pathologies associated with protein deposition, such as atherosclerosis, Alzheimer's disease and Parkinson's disease.

Assessment of Renal Function in Transfused b-Thalassemia Patients Based on Cystatin C Measurements and Equations.

Cystatin C is a non-glycosylated protein that belongs to the cystatin superfamily of cysteine protease inhibitors. Its low molecular weight (13.3kDa) and positive charge at physiological pH levels facilitates its glomerular filtration and subsequently it is reabsorbed and almost completely catabolized in the proximal renal tubules. Therefore and due to its constant rate of production, its serum concentration is determined by the rate of glomerular filtration (GFR). Cystatin C production in the body is a stable process that is not influenced by renal conditions, increased protein catabolism or dietary factors. Moreover, in contrary to creatinine, it does not change with age or muscle mass. For these reasons, serum cystatin C has been suggested to be an ideal endogenous marker of GFR. Studies on the renal function of patients with transfusion-dependent β-thalassemia are sparse. These studies suggested that the renal abnormalities observed in β-thalassemia are due to proximal tubular dysfunction and postulated that their severity is related with the degree of anemia. They were less severe in patients on hypertransfusion and appropriate desferrioxamine therapy suggesting that the damage might be caused by both anemia and increased oxidation induced by excess iron deposition. None of these studies have demonstrated renal insufficiency as reflected by decreased GFR. This was probably due to the fact that all estimations were based on creatinine measurements. In this study we estimated GFR in 195 transfused patients with β-thalassemia major by measuring cystatin C and calculating GFR according to the recently proposed cystatin C-based prediction equation using only concentration in mg/L and a prepubertal factor:1GFR [mL/min/1.73m2] = 84.7 × cystatin C (mg/L)−1.68 × 1.38* (*if a child <14 years). We found that 136 patients had normal cystatin C levels (0.66–1.03mg/L) and GFR values (80–170mL/min/1.73m2), 36 patients had mild renal insufficiency (cystatin C levels: 1.04–1.22mg/L and GFR values: 60–79mL/min/1.73m2), 21 patients had moderate renal insufficiency (cystatin C levels: 1.23–1.72mg/L and GFR values: 34–59mL/min/1.73m2), while 2 patients had severe renal insufficiency with cystatin C levels >2.5mg/L and GFR values <20mL/min/1.73m2. We further determined plasma levels of Neutrophil gelatinase-associated lipocalin (NGAL) in 30 randomly selected patients. NGAL is a protein expressed on tubular cells of which the production is markedly increased in response to harmful stimuli, such as ischemia or toxicity. We found increased NGAL levels in 19 β-thalassemia patients (mean: 95.0±45.0mg/L compared to normal values of 51.2±11.8mg/L, p<0.0003). NGAL levels correlated significantly with cystatin C levels (r=0.740, p<0.0001), indicating that the renal impairment in these patients seems to be originated from tubular injury. The findings of this study indicate that renal insufficiency is present in a significant proportion of transfusion-dependent β-thalassemia patients. Further studies are warranted in order to identify predisposing factors that contribute to the renal damage in thalassemia and to establish appropriate guidelines for the evaluation and follow up of renal function in these patients. 1. Clin Chem 2005; 51:1420–143.

Postburn trauma insulin resistance and fat metabolism

Hyperglycemia and insulin resistance have long been recognized in severe burn patients. More recently, it has been observed that controlling hyperglycemia, or alleviating insulin resistance, is associated with improved outcomes. This has led to a renewed interest in the etiology of insulin resistance in this population. The postinjury hyperglycemic response appears to be associated with multiple metabolic abnormalities, such as elevated basal energy expenditure, increased protein catabolism, and, notably, significant alterations in fat metabolism. The synergy of all of the responses is not understood, although many studies have been conducted. In this article we will review the present understanding of the relationship between fat metabolism and insulin resistance posttrauma, and discuss some of the recent discoveries and potential therapeutic measures. We propose that the insulin resistance is likely related to the development of "ectopic" fat stores, i.e., triglyceride (TG) storage in sites such as the liver and muscle cells. Deposition of TG in ectopic sites is due to an increase in free fatty acid delivery secondary to catecholamine-induced lipolysis, in conjunction with decreased beta-oxidation within muscle and decreased hepatic secretion of fats. The resultant increases in intracellular TG or related lipid products may in turn contribute to alterations in insulin signaling.

Poster Session PA4: Internal mdicine, basic science and alcohol--Part 1

Aims. Toxic liver damage induced by ethanol consumption is followed by decrease of functional capacity of liver tissue. Among the other functions, liver has an important contribution in the process of ammonia fixation and detoxication. Ethanol is shown primarily as neurotoxin and hepetotoxin. Hyperammonemia is one of the mechanisms of neurotoxicity. Increased level of ammonia in alcoholic intoxication occurs as a consequence of increased protein catabolism and effects of ethanol on the enzymes involved in ammonia fixations and detoxication. Synthesis of urea occurs primarily in the liver of ureothelic animals and is the main process in ammonia detoxication. We have studied the effect of L-arginine supplementation on urea production in rats treated with ethanol.

Morphological changes of the rat intestinal lining in relation to body stores depletion during fasting and after refeeding

Intestinal villus atrophy through prolonged fasting was studied according to two different metabolic phases reached by fasting animals and characterized by (a) the mobilization of fat stores as body fuel and (b) an increase in protein catabolism for energy expenditure. The mechanisms involved in the rapid jejunal restoration after refeeding were also determined. Mucosal structural atrophy during fasting proved to worsen over the two phases due mainly to the retraction of the lacteals in the lamina propria, as observed through the immunolocalization of aquaporin 1 in the endothelial cells of the lymphatic vessels and the detachment of the basal membrane of the epithelial lining at the tip of the villi. Microvilli surface area is preserved through fasting, and apical PepT1 expression increases during both metabolic fasting phases. Refeeding after both fasting phases induces an increase in FATP4 accompanied by a rapid lipid uptake by the enterocytes at the tip of the villi and a rapid extension of the lamina propria due to inflated lymphatic vessels. These mechanisms were more prevalent in animals refed after the phase III fast and could be considered as the major processes allowing complete morphological restoration of the jejunum within only 3 days after refeeding.

Inflammation and wasting in chronic kidney disease: Partners in crime

Protein energy malnutrition (PEM) is often present in patients with chronic kidney disease with or without ongoing renal replacement therapy. Muscle wasting (sarcopenia) is one of the hallmarks of PEM in these patients and recent studies have reported a link between sarcopenia and inflammation. The low-grade inflammation often observed in end-stage renal disease (ESRD) can lead to sarcopenia through an increase in protein catabolism, a decrease in protein syntheses or both. The activation of the ATP-ubiquitin-proteasome pathway, insulin resistance, hypermetabolism, and decreased appetite are all plausible pathophysiological pathyways whereby inflammation can contribute to sarcopenia and PEM. In the present review we discuss these interactions between inflammation and wasting in ESRD patients and explore putative pathways involved in this condition.

Effects of long-term hypoxia on enzymes of carbohydrate metabolism in the Gulf killifish,Fundulus grandis

The goal of the current study was to generate a comprehensive, multi-tissue perspective of the effects of chronic hypoxic exposure on carbohydrate metabolism in the Gulf killifish Fundulus grandis. Fish were held at approximately 1.3 mg l(-1) dissolved oxygen (approximately 3.6 kPa) for 4 weeks, after which maximal activities were measured for all glycolytic enzymes in four tissues (white skeletal muscle, liver, heart and brain), as well as for enzymes of glycogen metabolism (in muscle and liver) and gluconeogenesis (in liver). The specific activities of enzymes of glycolysis and glycogen metabolism were strongly suppressed by hypoxia in white skeletal muscle, which may reflect decreased energy demand in this tissue during chronic hypoxia. In contrast, several enzyme specific activities were higher in liver tissue after hypoxic exposure, suggesting increased capacity for carbohydrate metabolism. Hypoxic exposure affected fewer enzymes in heart and brain than in skeletal muscle and liver, and the changes were smaller in magnitude, perhaps due to preferential perfusion of heart and brain during hypoxia. The specific activities of some gluconeogenic enzymes increased in liver during long-term hypoxic exposure, which may be coupled to increased protein catabolism in skeletal muscle. These results demonstrate that when intact fish are subjected to prolonged hypoxia, enzyme activities respond in a tissue-specific fashion reflecting the balance of energetic demands, metabolic role and oxygen supply of particular tissues. Furthermore, within glycolysis, the effects of hypoxia varied among enzymes, rather than being uniformly distributed among pathway enzymes.

Evolving Practices in Critical Care and Potential Implications for Management of Acute Kidney Injury

Acute kidney injury (AKI) is a common complication in hospitalized patients, with an incidence of 3 to 10% (1–4). In-hospital mortality rates that are associated with AKI remain high, in the range of 30 to 70% (5–8), despite significant improvements in dialytic technology as well as important advances in critical care, which have resulted in improved survival for other critical illnesses, including acute lung injury and sepsis (9). These improvements include continuous renal replacement therapies, which allow for continuous removal of solutes and fluid and may be tolerated better from a hemodynamic standpoint, and biocompatible dialysis membranes, which are associated with reduced complement and granulocyte activation. In general, indications for dialysis in the acute care setting have been extrapolated from those that are applied in chronic kidney disease, including volume overload that is refractory to diuretic therapy; electrolyte abnormalities (in particular hyperkalemia); uremic complications (pericarditis or pleuritis); severe acidosis (pH < 7.20); and selected toxic ingestions, such as methanol, ethylene glycol, and other water-soluble agents (10,11). However, the evidence base supporting specific dialysis practices in the acute care setting is limited. For example, several studies that were completed in the 1960s and 1970s compared “early” and “late” initiation of dialysis, using blood urea nitrogen (BUN) to define early and late (Table 1). These studies primarily were cohort studies that used historical controls, not randomized, clinical trials. The results of these investigations, along with extrapolation from the ESRD population, promoted recent practice patterns. Currently, many nephrologists often delay dialysis in the acute care setting until the patient has an impending complication of AKI, such as hyperkalemia leading to cardiac arrhythmias, acidosis resulting in hypotension, or oliguria leading to volume overload or hypoxemia, or until the BUN exceeds 100 mg/dl (18). Given differences in protein catabolism, …

The effects of intravenous and intraduodenal feeding on nitrogen balance after surgery.

Abstract To assess the value of nutrition in the first week after surgery, total nitrogen balance was determined in three groups of patients (two experimental, one control) undergoing vagotomy and pyloroplasty from 1 day before to 8 days after operation. In the experimental groups nutrition was maintained postoperatively by the intravenous route in one and intraduodenally in the other at a level adequate for normal non-postoperative subjects. Water and electrolyte intakes were similar in the three groups, but patients in the control group received no calories or nitrogen in the immediate postoperative period. With respect to nitrogen economy, the group fed largely by the intraduodenal route fared best. Nevertheless, nitrogen balance did not reach equilibrium until day 5 in any group, probably indicating a relative increase in protein catabolism in the early postoperative period.

Risks of chronic metabolic acidosis in patients with chronic kidney disease

Risks of chronic metabolic acidosis in patients with chronic kidney disease. Metabolic acidosis is associated with chronic renal failure (CRF). Often, maintenance dialysis therapies are not able to reverse this condition. The major systemic consequences of chronic metabolic acidosis are increased protein catabolism, decreased protein synthesis, and a negative protein balance that improves after bicarbonate supplementation. Metabolic acidosis also induces insulin resistance and a decrease in the elevated serum leptin levels associated with CRF. These three factors may promote protein catabolism in maintenance dialysis patients. Available data suggest that metabolic acidosis is both catabolic and anti-anabolic. Several clinical studies have shown that correction of metabolic acidosis in maintenance dialysis patients is associated with modest improvements in nutritional status. Preliminary evidence indicates that metabolic acidosis may play a role in beta2-microglobulin accumulation, as well as the hypertriglyceridemia seen in renal failure. Interventional studies for metabolic acidosis have yielded inconsistent results in CRF and maintenance hemodialysis patients. In chronic peritoneal dialysis patients, the mitigation of acidemia appears more consistently to improve nutritional status and reduce hospitalizations. Large-scale, prospective, randomized interventional studies are needed to ascertain the potential benefits of correcting acidemia in maintenance hemodialysis patients. To avoid adverse events, an aggressive management approach is necessary to correct metabolic acidosis. Clinicians should attempt to adhere to the National Kidney Foundation Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines for maintenance dialysis patients. The guidelines recommend maintenance of serum bicarbonate levels at 22 mEq/L or greater.

Diagnosis of MSUD by newborn screening allows early intervention without extraneous detoxification

Maple syrup urine disease (MSUD) is a genetic metabolic disorder resulting from the defective activity of branched-chain 2-ketoacid dehydrogenase complex. Due to the metabolic block, high concentrations of the branched-chain amino acids (BCAA) leucine, valine, isoleucine, and allo-isoleucine as well as their corresponding branched-chain 2-keto acids accumulate in patients on a BCAA-unrestricted diet or during episodes with increased protein catabolism. Early diagnosis and management are essential to prevent permanent brain damage. Newborn screening by tandem MS allows for detection of elevated BCAA concentrations in blood in patients with classical MSUD before they show severe encephalopathic symptoms. Here, we report that newborn screening by expanded tandem MS enables for reversing the intoxication in newborns with MSUD within 24–48 h without any need for extraneous detoxification and thus decreasing the risk of brain damage during a particularly vulnerable period.

Role of carnitine in modulating acute-phase protein synthesis in hemodialysis patients

Increased serum levels of C-reactive protein (CRP) in uremic and dialysis patients are associated with low serum prealbumin and albumin concentrations and increased mortality and greater risk of cardiovascular disease. Proinflammatory cytokines may cause malnutrition by increasing protein catabolism. Many studies have shown that L-carnitine supplementation leads to improvements in several conditions seen in uremic patients, including cardiac complications, impaired exercise and functional capacities, muscle symptoms, increased symptomatic intradialytic hypotension, and erythropoietin-resistant anemia. L-carnitine therapy may either suppress the inflammatory response or act independently on both inflammation and appetite and/or anabolic processes. Moreover, L-carnitine may suppress proinflammatory cytokines in sick individuals without renal disease and may improve protein synthesis or nitrogen balance in patients without renal disease and in hemodialysis and peritoneal dialysis patients. In a pilot study, we provided preliminary evidence that treatment with L-carnitine, 20 mg/kg 3 times weekly at the end of each hemodialysis treatment, was associated with a reduction in serum CRP levels and improvement in anabolic status. The improvement or normalization of serum concentrations of serum CRP also was correlated with increased serum concentrations of albumin, transferrin, and blood hemoglobin. The possibility that some or all of these changes may have been caused by improved nutritional intake cannot be ruled out. Further randomized clinical trials will be necessary to confirm the role of L-carnitine as a modulator of inflammatory protein synthesis in hemodialysis patients.

Plasma amino acids in critically ill patients

Stress states, sepsis and trauma markedly increase protein catabolism in skeletal muscle, gut, and connective tissue. Catabolism is potentiated by a sepsis-induced decrease in amino acid uptake in skeletal muscle. One-third of the total amino acid output from skeletal muscle is glutamine and one-third is alanine.

POOR NUTRITIONAL STATUS AND INFLAMMATION: Metabolic Acidosis and Malnutrition‐Inflammation Complex Syndrome in Chronic Renal Failure

ABSTRACTMetabolic acidosis, a common condition in patients with renal failure, may be linked to protein‐energy malnutrition (PEM) and inflammation, together also known as malnutrition‐inflammation complex syndrome (MICS). Methods of serum bicarbonate measurement may misrepresent the true bicarbonate level, since the total serum carbon dioxide measurement usually overestimates the serum bicarbonate concentration. Moreover, the air transportation of blood samples to distant laboratories may lead to erroneous readings. In patients with chronic kidney disease (CKD) or end‐stage renal disease (ESRD), a significant number of endocrine, musculoskeletal, and metabolic abnormalities are believed to result from acidemia. Metabolic acidosis may be related to PEM and MICS due to an increased protein catabolism, decreased protein synthesis, endocrine abnormalities including insulin resistance, decreased serum leptin level, and inflammation among individuals with renal failure. Evidence suggests that the catabolic effects of metabolic acidosis may result from an increased activity of the adenosine triphosphate (ATP)‐dependent ubiquitin‐proteasome and branched‐chain keto acid dehydrogenase. In contrast to the metabolic studies, many epidemiologic studies in maintenance dialysis patients have indicated a paradoxically inverse association between mildly decreased serum bicarbonate and improved markers of protein‐energy nutritional state. Hence metabolic acidosis may be considered as yet another element of the reverse epidemiology in ESRD patients. Interventional studies have yielded inconsistent results in CKD and ESRD patients, although in peritoneal dialysis patients, mitigating acidemia appears to more consistently improve nutritional status and reduce hospitalizations. Large‐scale, prospective randomized interventional studies are needed to ascertain the potential benefits of correcting acidemia in malnourished and/or inflamed CKD and maintenance hemodialysis patients. Until then, all attempts should be made to adhere to the National Kidney Foundation Kidney Disease and Dialysis Outcome Quality Initiative guidelines to maintain a serum bicarbonate level in ESRD patients of at least 22 mEq/L.