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Malnutrition inflammation complex syndrome (MICS) occurs commonly in maintenance hemodialysis (MHD) patients and may correlate with increased morbidity and mortality. An optimal, comprehensive, quantitative system that assesses MICS could be a useful measure of clinical status and may be a predictor of outcome in MHD patients. We therefore attempted to develop and validate such an instrument, comparing it with conventional measures of nutrition and inflammation, as well as prospective hospitalization and mortality. Using components of the conventional Subjective Global Assessment (SGA), a semiquantitative scale with three severity levels, the Dialysis Malnutrition Score (DMS), a fully quantitative scoring system consisting of 7 SGA components, with total score ranging between 7 (normal) and 35 (severely malnourished), was recently developed. To improve the DMS, we added three new elements to the 7 DMS components: body mass index, serum albumin level, and total iron-binding capacity to represent serum transferrin level. This new comprehensive Malnutrition-Inflammation Score (MIS) has 10 components, each with four levels of severity, from 0 (normal) to 3 (very severe). The sum of all 10 MIS components ranges from 0 to 30, denoting increasing degree of severity. These scores were compared with anthropometric measurements, near-infrared-measured body fat percentage, laboratory measures that included serum C-reactive protein (CRP), and 12-month prospective hospitalization and mortality rates. Eighty-three outpatients (44 men, 39 women; age, 59 +/- 15 years) on MHD therapy for at least 3 months (43 +/- 33 months) were evaluated at the beginning of this study and followed up for 1 year. The SGA, DMS, and MIS were assessed simultaneously on all patients by a trained physician. Case-mix-adjusted correlation coefficients for the MIS were significant for hospitalization days (r = 0.45; P < 0.001) and frequency of hospitalization (r = 0.46; P < 0.001). Compared with the SGA and DMS, most pertinent correlation coefficients were stronger with the MIS. The MIS, but not the SGA or DMS, correlated significantly with creatinine level, hematocrit, and CRP level. During the 12-month follow-up, 9 patients died and 6 patients left the cohort. The Cox proportional hazard-calculated relative risk for death for each 10-unit increase in the MIS was 10.43 (95% confidence interval, 2.28 to 47.64; P = 0.002). The MIS was superior to its components or different subversions for predicting mortality. The MIS appears to be a comprehensive scoring system with significant associations with prospective hospitalization and mortality, as well as measures of nutrition, inflammation, and anemia in MHD patients. The MIS may be superior to the conventional SGA and the DMS, as well as to individual laboratory values, as a predictor of dialysis outcome and an indicator of MICS.

Protein-energy malnutrition (PEM) is a common phenomenon in maintenance dialysis (MD) patients and a risk factor for poor quality of life and increased morbidity and mortality, including cardiovascular death, in these individuals. The association between undernutrition and adverse outcome in MD patients, which stands in contrast to that seen in the general population, has been referred to as reverse epidemiology. Measures of food intake, body composition tools, nutritional scoring systems, and laboratory values are used to assess the degree of severity of PEM, but no uniform approach is available for rating the overall severity of PEM. Epidemiologic studies suggest that inflammation is a missing link between PEM and poor clinical outcome in MD patients, and the existence of a malnutrition inflammation complex syndrome is suggested in these patients. Inflammation may be due to subclinical and clinically apparent illnesses. Some investigators suggest that PEM may predispose to illness and inflammation. There is a paucity of information concerning the effect of nutritional therapy on morbidity and mortality in MD patients. Interventional studies of the effect of nutritional support on outcome often are difficult to interpret because of small sample sizes, short duration of study, and other limitations. Large-scale, randomized, clinical trials of the effects of nutritional intake, nutritional status, and inflammation on clinical outcome are needed to define better the relationships between these factors in MD patients.

This paper discusses two of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines for nutrition in chronic renal failure. These are the guidelines that recommend a dietary protein intake of 1.2 g protein/kg body weight/day for clinically stable maintenance hemodialysis (MHD) patients (Guideline 15) and 1.2 to 1.3 g protein/kg/day for clinically stable chronic peritoneal dialysis (CPD) patients (Guideline 16). These recommended protein intakes are greater than the usually ingested protein intakes of MHD and CPD patients and are also greater than the recommended protein intakes for healthy, nonpregnant, nonlactating adults. The possible mechanisms that engender these increased protein needs include (1) the substantial quantity of amino acids, peptides, and proteins removed by the dialysis procedure and (2) the protein catabolic or antianabolic state caused by the uremic milieu, the inflammatory state, the oxidative and carbonyl stress, and the bioincompatible dialysis materials to which MHD and CPD patients are exposed. There are a number of nitrogen balance studies that have been performed to identify the dietary protein needs of MHD and CPD patents. The results of this research as well as some of the methodological limitations of these studies are reviewed. The concepts of the average dietary protein intake required to maintain protein balance in MHD or CPD patients and the safe protein intake that will maintain protein balance in virtually all MHD and CPD patients are discussed.

The National Kidney Foundation Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Nutrition in Chronic Renal Failure was recently published in the American Journal of Kidney Diseases. This publication provides 27 clinical practice guidelines for adults and 10 clinical practice guidelines for children. The adult guidelines focus primarily on patients undergoing maintenance dialysis therapy, although there are several clinical practice guidelines on nutritional issues for patients with advanced chronic renal failure (CRF) not undergoing dialysis therapy. The pediatric guidelines focus entirely on children undergoing maintenance dialysis treatment. The present article discusses a number of the more prominent clinical practice guidelines for the adults. Among these is the recommendation that the protein-energy nutritional status in these patients should be assessed by a panel of measures rather than by any single measure. Also, non-dialyzed patients with advanced CRF (ie, glomerular filtration rate <25 mL/min) and those undergoing maintenance hemodialysis or chronic peritoneal dialysis should be prescribed a dietary energy intake of 35 kcal/kg/day for patients who are <60 years of age and 30 kcal/kg for patients >/=60 years of age. Maintenance hemodialysis patients should be prescribed 1.2 g protein/kg/d; chronic peritoneal dialysis patients should be prescribed 1.2 to 1.3 g protein/kg/d. For non-dialyzed patients with CRF (glomerular filtration rate <25 mL/min), 0.60 g protein/kg/d should be prescribed. For patients who will not accept such a diet or are unable to maintain an adequate energy intake on that diet, a protein intake of up to 0.75 g protein/kg/d may be prescribed. At least 50% of the protein intake for all of these patients should be of high biologic value. A guideline concerning indications for inaugurating maintenance dialysis treatment or renal transplantation on the basis of deteriorating nutritional status is also given.

The coming century will witness many changes in the science and practice of nephrology and in cultural attitudes and behavior that should have profound effects on the National Kidney Foundation (NKF). There will be marked advances in our understanding and treatment of kidney disease. Concomitantly, there should be continued advances in the technology of communication and more widespread utilization of this technology by the NKF. There should be substantial growth in the numbers of individuals with end-stage renal disease and a growing recognition of and respect for the psychosocial and material needs of these individuals. Rising prosperity will lead to many improvements in the delivery of health care to patients with renal disease and renal failure. It is anticipated that the financial resources of the NKF will continue to increase and that this factor will enhance the ability of the NKF to carry out its many programs. These changes will present new opportunities and new challenges to the NKF. It is anticipated that these changes will be manifest in at least the following five areas of NKF activity: (1) There will be increased advocacy for funding for renal research from federal agencies, especially from the National Institutes of Health; the NKF research fellowship and grants program will also grow. (2) There will be a continued NKF commitment to facilitate the translation of new scientific and medical advances into routine health care delivered to the average renal patient. (3) There will be improved techniques for professional education. (4) There will be greater international cooperation among kidney-focused organizations, particularly among different kidney foundations. (5) There will be an increase in the scope of activities that promote patient empowerment and rehabilitation.

Protein-energy malnutrition (PEM) is a common complication in maintenance hemodialysis and chronic peritoneal dialysis patients and is a powerful predictor of morbidity and mortality. Although this association does not prove that malnutrition is a cause of this increased morbidity and mortality, it is consistent with this possibility. There are a number of modalities of nutritional support for the prevention or treatment of PEM in maintenance dialysis patients. Routine methods include preventing PEM before the onset of maintenance dialysis therapy, dietary counseling, maintenance of an adequate dose of dialysis, avoidance of acidemia, and aggressive treatment of superimposed catabolic illness. Specific treatments of chronic dialysis patients who have persistently inadequate nutritional intake include food supplements, enteral tube feeding, intradialytic parenteral nutrition, and total parenteral nutrition. More experimental forms of nutritional therapy include dialytic nutrition (eg, using peritoneal dialysate or hemodialysate that contains amino acids), appetite stimulants (eg, megestrol acetate), or growth factors (eg, anabolic steroids, recombinant human growth hormone, or insulin-like growth factor-I).

The published reports of dietary protein and energy intake and protein and energy requirements for maintenance hemodialysis (MHD) patients and chronic peritoneal dialysis (CPD) patients are reviewed. Evidence indicates that the dietary energy intake of patients undergoing MHD or continuous ambulatory peritoneal dialysis (CAPD) is less than normal. Dietary protein intake in various surveys averages approximately 1.0 g/kg/d. The energy expenditure of MHD patients appears to be normal or slightly increased during resting and normal during various other daily activities. Energy expenditure in CAPD patients appears normal. Nitrogen balance and anthropometric studies in MHD or CAPD patients ingesting controlled diets in a metabolic unit research ward also indicate that dietary energy requirements are normal and are approximately 35 to 38 kcal/kg/d in MHD patients. For CAPD patients, total energy requirements (from diet and dialysate) also appear to be 35 to 38 kcal/kg/d. These recommended energy intakes are for adult patients aged approximately 60 years or younger. Thus, the low dietary energy intakes of MHD and CPD patients are maladaptive. Nitrogen balance studies indicate that a safe dietary allowance for protein is approximately 1.2 g/kg/d for MHD patients and 1.2 to 1.3 g/kg/d for CAPD patients. Because the nutritional status of patients at the onset of chronic dialysis therapy is a strong predictor of both their nutritional status during the course of chronic dialysis treatment and their subsequent morbidity and mortality, it is important to maintain good nutritional status in patients with chronic renal failure before their development of end-stage renal disease (ESRD) and establishment on chronic dialysis. Evidence indicates that there is a reduction in dietary protein and energy intake and a gradual deterioration of nutritional status in patients with chronic renal insufficiency as the glomerular filtration rate (GFR) decreases progressively to less than 50 to 60 mL/min/1.73 m2. More studies are needed to assess dietary protein and energy requirements both for MHD and CPD patients who are clinically stable and for those who have sustained comorbid conditions that increase energy expenditure or protein nitrogen appearance.

The effects of insulin-like growth factor 1 (IGF-1) on renal handling of phosphorus, calcium, and sodium were evaluated in eight healthy men while they lived in a clinical research center for slightly more than 5 days. Subjects received a continuous intravenous infusion throughout the study of 0.45% saline and 2.5% d-glucose at 50 mL/hr (group 1, four subjects) or 150 mL/hr (group 2, four subjects). Recombinant human IGF-1 (rhIGF-1), 60 micrograms/kg body weight, was injected subcutaneously three times daily for 10 doses from day 2 until the beginning of day 5. After commencing the rhIGF-1 injections, there was a marked decrease in the fractional excretion of phosphorus in both groups that was sustained throughout the study. Urine phosphorus excretion also decreased significantly on days 2 to 5 in group 1 and on day 2 in group 2. In group 1, the fractional excretion of calcium decreased on day 2; urine calcium did not change. The fractional excretion of sodium decreased on days 2 and 4; urine sodium decreased significantly only on day 2. In group 2, the fractional and absolute urine excretion of calcium did not change. Fractional sodium excretion was not altered, and urine sodium increased only on day 5. The average serum phosphorus, calcium, and sodium did not change from baseline in groups 1 or 2. The pattern of the circadian rhythms for serum concentrations, urine excretion, and fractional excretion of phosphorus and calcium did not appear to be affected by the rhIGF-1 injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Although malnutrition is not uncommon in continuous ambulatory peritoneal dialysis (CAPD) and maintenance hemodialysis (MHD) patients, there has never been a large-scale comparison study of nutritional status with these two dialysis modalities. We therefore assessed protein-calorie nutrition in 224 CAPD patients and 263 MHD patients who were treated in eight centers in Italy. The CAPD patients were slightly older than the MHD patients (60.2 +/- 14.2 years v 56.3 +/- 15.1 years; P < 0.01), had undergone dialysis for less time (2.32 +/- 2.10 years v 3.66 +/- 2.66 years; P < 0.0001), and had higher residual renal function (1.83 +/- 2.29 mL/min v 0.27 +/- 0.91 mL/min; P < 0.0001). Protein nitrogen appearance was 60.5 +/- 16.6 g/d and 61.9 +/- 16.5 g/d in the CAPD and MHD patients, respectively. In CAPD versus MHD patients, serum total protein and albumin tended to be lower; serum transferrin and midarm muscle circumference were similar; and relative body weight, skinfold thickness, and estimated percent body fat tended to be greater. These greater values in CAPD patients were particularly evident in those who were 65 years of age or older. Serum glucose, total cholesterol, and triglycerides also were greater in CAPD patients. The subjective global nutritional assessment indicated a significantly greater proportion of malnourished CAPD patients than MHD patients (42.3% v 30.8%). The greater prevalence of malnutrition in CAPD patients diminished with age. Maintenance hemodialysis patients older than 76 years were more likely to be malnourished than CAPD patients. In patients less than 65 years of age, protein-calorie malnutrition was more likely to be present in CAPD patients than in MHD patients.

Chronic renal failure is associated with abnormalities of skeletal muscle that include reduction in size, fibrosis, protein depletion, and functional disorders. These disorders may be caused by several factors, including protein-calorie malnutrition, acidemia, and superimposed illnesses. However, animal research suggests that these abnormalities may occur with chronic renal failure per se in the absence of the above complications. Insulin-like growth factor 1 (IGF-1) is an anabolic hormone that, in skeletal muscle, stimulates intracellular amino acid and glucose transport and protein synthesis, suppresses protein degradation, and causes hypertrophy. In chronic renal failure, there is evidence for inhibition of the actions of IGF-1. Studies in humans with chronic renal failure given a subcutaneous injection of recombinant human IGF-1 (rhIGF-1) indicate that the rhIGF-1 induced acute suppression of plasma amino acids, insulin, and C peptide is impaired. In skeletal muscle of rats with chronic renal failure, we observed reduced IGF-1 and IGF-1 mRNA levels, resistance to the rhIGF-1-induced suppression of protein degradation, and stimulation of protein synthesis, increased IGF-1 receptor mRNA and IGF-1 receptor number and impaired receptor tyrosine kinase activity. These findings suggest that in skeletal muscle in chronic renal failure there are several abnormalities in the physiology of IGF-1 and the sensitivity to IGF-1. It is possible that these alterations contribute to the disorders of skeletal muscle structure and function in chronic renal failure. Notwithstanding these abnormalities, repeated subcutaneous injections of rhIGF-1 in malnourished patients undergoing continuous ambulatory peritoneal dialysis led to strongly positive nitrogen balance that was sustained for the 20 days of study.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein-calorie malnutrition is common in maintenance dialysis patients. Malnutrition is mild to moderate in approximately 33% of maintenance dialysis patients and severe in approximately 6% to 8%. There are many causes of protein-calorie malnutrition in maintenance dialysis patients; the three major causes are probably low nutrient intakes, intercurrent or underlying illnesses, and the dialysis procedure itself. Malnutrition is a major risk factor for mortality in maintenance dialysis patients. This has been shown most clearly for serum albumin, which is the nutritional parameter that has been most heavily studied. Low dietary of protein or other nutrients and protein-calorie malnutrition revealed by the results of different chemistry analyses are also directly correlated with mortality rates. These data do not prove that poor nutritional intake or malnutrition is a cause of the high morbidity and mortality in maintenance dialysis patients, and randomized, prospective controlled clinical trials are necessary to answer this question. However, the data are consistent with the thesis that malnutrition or inadequate nutrient intake do contribute to high morbidity and mortality in these patients. Although it is possible that increasing the dose of dialysis (eg, Kt/V) will lead to increased appetite and nutrient intake, experience suggests that raising the dose of dialysis, by itself, will not optimize nutritional intake in these individuals. To achieve satisfactory nutritional intake and healthy nutritional status, other interventions will need to be developed.

Fasting plasma amino acid levels were measured in 78 patients with chronic renal insufficiency (glomerular filtration rate [GFR], 8.0 to 56.0 mL/min), who had been enrolled in phase II of the Modification of Diet in Renal Disease study, prior to their beginning the experimental portion of the protocol. Alterations in many plasma amino acid levels were observed in the patients with the mildest degrees of renal insufficiency, and the number and severity of abnormalities tended to be greater in the patients with more severe renal failure. In patients with GFRs greater than 24.5 mL/min, 15 to 24.5 mL/min, and less than 15 mL/min, statistically significant abnormalities were observed in the concentrations or ratios of 9, 14, and 18 amino acids, respectively. The following correlations of amino acid levels or ratios with GFR were observed (all P < 0.001): citrulline, r = -0.41; citrulline to arginine ratio, r = -0.42; glycine to serine ratio, r = -0.37; N-tau methylhistidine, r = -0.65; and cystine, r = -0.37. Other weaker correlations observed were valine, r = 0.26 (P < 0.025); valine to glycine ratio, r = 0.32 (P = 0.004); and sum of isoleucine, leucine, and valine, r = 0.21 (P = 0.061). N-tau methylhistidine and the essential to nonessential amino acid ratio became altered with declining GFR in a nonlinear fashion. Thus, many of the characteristic alterations in the plasma amino acid profile that are observed in chronic end-stage renal disease are already present in mild renal insufficiency. Progressive loss of renal function generally results in increasing abnormalities; these changes in plasma amino acid concentrations with reduction in GFR were usually linear.

When a patient presents with renal failure, it is often difficult to ascertain whether the individual is suffering from acute or chronic renal failure. Fingernail creatinine might help to differentiate between the two. To test this possibility, the relationship between the fingernail creatinine and the serum creatinine obtained concurrently or 1 or more months previously was examined in 22 normal adults, nine patients with acute renal failure, seven patients with chronic renal failure not undergoing dialysis, 16 maintenance hemodialysis patients, and 33 patients with a functioning renal transplant who had been transplanted 0.2 to 3.9 months (n = 21) or 4.3 to 33 months previously (n = 12). Fingernail creatinine was significantly greater than normal in the patients with chronic renal failure, patients undergoing maintenance hemodialysis, and patients who had a functioning renal transplant implanted 0.2 to 3.9 months previously. In contrast, fingernail creatinine was not different from normal in the patients with acute renal failure and in patients who had a functioning renal transplant placed 4.3 to 33 months previously. In the maintenance hemodialysis patients, fingernail creatinine showed the strongest correlation with the serum creatinine obtained between 5 and 10 months previously, with the highest correlation at 9 months. In the renal transplant recipients, the fingernail creatinine decreased to normal or near normal values within approximately 90 to 120 days after transplantation. These findings indicate that fingernail creatinine may reflect the serum creatinine values several months previously. The fingernail creatinine may help to identify whether patients have recent onset as compared with longstanding renal failure.

We compared taurine levels in plasma, erythrocytes, platelets, lymphocytes, and granulocytes from 11 normal adults and 11 maintenance hemodialysis (MHD) patients immediately before and following a routine hemodialysis treatment. Taurine concentrations were elevated in plasma predialysis, as compared with normal subjects (90 +/- 16 [SEM] v 54 +/- 2 mumol/L [1.1 +/- 0.2 v 0.7 +/- 0.03, mg/dL]), but decreased with a dialysis treatment (to 34 +/- 3 mumol/L [0.4 +/- 0.04 mg/dL]). Erythrocyte taurine levels tended to be higher in MHD patients predialysis (1.2 +/- 0.2 v 0.7 +/- 0.1 nmol/10(9) cells, P less than 0.05 where P less than 0.025 is significant) as compared with controls; erythrocyte taurine was increased after dialysis (to 1.8 +/- 0.3 nmol/10(9) cells, P less than 0.006). In contrast, platelet taurine concentrations in MHD patients were lower than normal predialysis (18 +/- 2 v 27 +/- 2 nmol/10(9) cells) and declined further during the dialysis procedure (to 14 +/- 1). Granulocyte and lymphocyte taurine levels were not different in MHD patients, as compared with normal adults, either before or after dialysis. The observed differences in blood cell taurine content (expressed per 10(9) cells) could not be explained by variation in cell volumes among the groups examined. Thus, both chronic renal failure and a routine hemodialysis treatment produce changes in cell and plasma taurine levels that tend to be specific for the individual cell type.

We examined the nutritional status of 224 patients from six centers in Europe and North America to assess the incidence of protein-energy malnutrition. A "subjective nutritional assessment" was made, using 21 variables derived from history and clinical examination, or anthropometry and biochemistry. Eighteen patients (8%) were severely malnourished, 73 (32.6%) were mildly to moderately malnourished, and 133 (59.4%) did not show evidence for malnutrition. There was a higher incidence of mild to moderate malnutrition in diabetics than in nondiabetics. A statistical analysis identified 12 variables, seven objective and five subjective, that correlated with subjective nutritional assessment. Actual intercenter differences for the incidence of malnutrition were related to patient age, nutritional status at the commencement of continuous ambulatory peritoneal dialysis (CAPD), the length of time on CAPD, and residual renal function. Variables that were most frequently correlated with subjective nutritional assessment and with one another included plasma albumin, mid-arm muscle circumference (MAMC), weight loss, and the clinical judgement of muscle wasting and loss of subcutaneous fat. Loss of residual renal function correlated with muscle wasting and months on CAPD. Our data identified differences between the two sexes. In women there was a trend for more anorexia, greater weight loss from muscle wasting, and a larger decrease in albumin, whereas in men there was a more gradual decrease in nutritional status. Loss of residual renal function contributed to anorexia and symptoms of severe malnutrition.

Pseudohyperphosphatemia was noted in four patients with hyperglobulinemia when inorganic phosphate levels were measured on the Vickers M-300 discrete automated analyzer (Vickers, Raritan, NJ) used by our clinical laboratory. When the same samples were reanalyzed after protein removal by sulfosalicylic acid precipitation, ultrafiltration, or more extensive dilution, the measured serum inorganic phosphate levels were invariably normal. The addition of human globulin (but not albumin), to pooled normal sera, caused an increase in serum inorganic phosphate levels as measured by the discrete analyzer. The increase correlated with the amount of globulin added (r = 0.72, P less than 0.05), but measured levels did not reach those observed in the hyperphosphatemic, hyperglobulinemic patients. Identification of 13 additional hyperglobulinemia patients revealed that hyperglobulinemia was not invariably associated with hyperphosphatemia. These data suggest that (1) with discrete automated analyzer use, hyperglobulinemia but not hyperalbuminemia may falsely elevate serum inorganic phosphate levels; (2) increased measured serum inorganic phosphate levels appear to be determined by both the concentration and the physicochemical characteristics of the globulin; (3) physicians should avoid prescribing phosphate binders to hyperglobulinemia patients with "hyperphosphatemia" unless they have ascertained that the serum inorganic phosphate level has been measured in a specimen that is free of protein; and (4) the occurrence of "pseudohyperphosphatemia" should suggest the need for an evaluation to rule out the presence of a monoclonal gammopathy.