Daily physical activity and physical function in adult maintenance hemodialysis patients.

BACKGROUND: Maintenance hemodialysis (MHD) patients reportedly display reduced daily physical activity (DPA) and physical performance. Low daily physical activity and decreased physical performance are each associated with worse outcomes in chronic kidney disease patients. Although daily physical activity and physical performance might be expected to be related, few studies have examined such relationships in MHD patients, and methods for examining daily physical activity often utilized questionnaires rather than activity monitors. We hypothesized that daily physical activity and physical performance are reduced and correlated with each other even in relatively healthier MHD patients. METHODS: Daily physical activity, 6-min walk distance (6-MWT), sit-to-stand, and stair-climbing tests were measured in 72 MHD patients (32 % diabetics) with limited comorbidities and 39 normal adults of similar age and gender mix. Daily physical activity was examined by a physical activity monitor. The human activity profile was also employed. RESULTS: Daily physical activity with the activity monitor, time-averaged over 7 days, and all three physical performance tests were impaired in MHD patients, to about 60-70 % of normal values (p < 0.0001 for each measurement). Human activity profile scores were also impaired (p < 0.0001). MHD patients spent more time sleeping or in marked physical inactivity (p < 0.0001) and less time in ≥ moderate activity (p < 0.0001). These findings persisted when comparisons to normals were restricted to men or women separately. After adjustment, daily physical activity correlated with 6-MWT but not the two other physical performance tests. Human activity profile scores correlated more closely with all three performance tests than did DPA. CONCLUSIONS: Even in relatively healthy MHD patients, daily physical activity and physical performance are substantially impaired and correlated. Whether training that increases daily physical activity or physical performance will improve clinical outcome in MHD patients needs to be examined.

Oxymetholone ameliorates insulin sensitivity in maintenance hemodialysis patients: a randomized controlled trial.

AIMS: To investigate the beneficial effects of oral oxymetholone on IR in hemodialysis (HD) patients by increasing skeletal muscle function and stimulating myocyte glucose uptake and metabolism. METHODS: In a randomized, controlled double-blind study, 44 patients were randomly assigned to one of two groups: a treatment group that received oxymetholone 50 mg orally twice daily and a control group that received placebo twice daily for 24 weeks. IR was calculated by using HOMA, and dual-energy X-ray absorptiometry was used to determine body composition. All patients were encouraged to walk at least one kilometer daily and were monitored by the Barthel index activity score. RESULTS: 25 men (57%) and 19 women (43%) were studied. 23 subjects were in the control group, and 21 subjects were in the treatment group. The mean age of patients and the duration of dialysis were 43.5 +/- 9.9 years and 92.8 +/- 37.8 months, respectively. After treatment, the HOMA index and body fat mass (FM) were significantly decreased in the treatment group compared to those in the control group (10.8 +/- 16.4 vs. 3.1 +/- 4.5; p < 0.05 and 1.73 +/- 2.77 vs. 0.40 +/- 1.12 kg; p < 0.05, respectively). Concurrently, the mean change of fat free mass (FFM) in the treatment group was higher than that in the control group (3.24 +/- 1.74 vs. 0.65 +/- 1.21 kg, p < 0.05). Two patients in the treatment group experienced an elevation in serum liver enzymes (9.52%). CONCLUSION: HD patients treated with short-term oral oxymetholone showed an increase in insulin sensitivity when compared to the placebo group, and this effect depended on changes in FFM and FM.

HDL-inflammatory index correlates with poor outcome in hemodialysis patients.

Oxidative stress and cardiovascular disease are risk factor of patients with chronic kidney disease (CKD) on maintenance hemodialysis. We used the fluorescence of low-density lipoprotein as an index of its proinflammatory potential to examine any role that high-density lipoprotein (HDL) might have in promoting this effect. The total body fat of the patients was measured by means of near-infrared interactance and their quality of life by means of SF36 questionnaires. In 189 randomly selected patients, followed for 30 months, HDL was found to be significantly anti-inflammatory but with a large standard deviation. Fully 17% of the patients had a decidedly proinflammatory index along with inferior SF36 scores. The patients were divided into 10% increments of total body fat percentages up to 40%. HDL was found to be progressively proinflammatory the higher the body fat content. Patients with a higher HDL proinflammatory index had a higher 30-month adjusted hazard ratio for death than those whose HDL were seen to be anti-inflammatory. Our findings suggest an important role of inflammatory HDL in patients with CKD leading to poor outcome.

Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients.

Although renal osteodystrophy and vitamin D analogs may be related to survival in maintenance hemodialysis (MHD) patients, most studies have examined associations between baseline values and survival without accounting for variations in clinical and laboratory measures over time. We examined associations between survival and quarterly laboratory values and administered paricalcitol in a 2-year (July 2001-June 2003) cohort of 58,058 MHD patients from all DaVita dialysis clinics in USA using both time-dependent Cox models with repeated measures and fixed-covariate Cox models with only baseline values. Whereas hypercalcemia and hyperphosphatemia were robust predictors of higher death risk in all models, the association between serum calcium and mortality was different in time-varying models. Changes in baseline calcium and phosphorus values beyond the Kidney Disease Outcome Quality Initiative recommended targets were associated with increased mortality. Associations between high serum parathyroid hormone and increased death risk were masked by case-mix characteristics of MHD patients. Time-varying serum alkaline phosphatase had an incremental association with mortality. Administration of any dose of paricalcitol was associated with improved survival in time-varying models. Controlling for nutritional markers may introduce overadjustment bias owing to their strong collinearity with osteodystrophy surrogates. Whereas both time-dependent and fixed-covariate Cox models result in similar associations between osteodystrophy indicators and survival, subtle but potentially clinically relevant differences between the two models exist, probably because fixed models do not account for variations of osteodystrophy indices and changes in medication dose over time.

A low lymphocyte percentage is a predictor of mortality and hospitalization in hemodialysis patients.

OBJECTIVES: Lymphocyte percentage (LYM%), an independently measured value to reflect peripheral lymphocyte count and a possible nutritional marker, may be related to clinical outcome in maintenance dialysis (MHD) patients. STUDY DESIGN AND SETTING: We examined the associations of the baseline white blood cell count (WBC) and LYM% with 12-month mortality and three measures of hospitalization in a cohort of 1,283 MHD patients from 10 outpatient DaVita dialysis clinics in Los Angeles County, as well as in a subcohort of 372 MHD patients with additional measures of inflammation, nutrition and comorbidity. Multi-variate Cox and Poisson models that included 13 co-variates including case-mix features, dialysis dose, blood hemoglobin and serum albumin were explored. RESULTS: Patients, aged 57.8 +/- 15.2 years, included 49% men and 49% diabetics. Baseline WBC was 7,353 +/- 2.427 per microl, and LYM% was 21.2 +/- 7.3%. LYM% had significant correlations with "malnutrition-inflammation score" and inverse correlations with serum interleukin-6. The WBC and LYM% had significant but opposite predicting values for mortality and hospitalization, indicating that a high WBC and a low LYM% were each independently associated with increased mortality. After dividing each variable into four quartiles, only the highest WBC quartile (> or = 8,500) but not the other middle two quartiles, predicted increased mortality. However, all three lower quartiles of LYM% vs. the highest quartile (based on quartile cutoffs of 16%, 20.3% and 25.5%) were significantly and progressively associated with greater risks of mortality and hospitalizations. The absolute lymphocyte count (LYM% times WBC/100) exhibited somewhat similar trends but its outcome predictability was not as strong as LYM%. CONCLUSIONS: A high WBC and a low LYM% are associated with significant increase in mortality and hospitalization in MHD patients. Lymphocyte percentage, compared to absolute lymphocyte count, appears to be a better nutritional and anti-inflammatory marker and a more sensitive predictor of mortality and hospitalization in MHD patients.

A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients.

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.

Relative contributions of nutrition and inflammation to clinical outcome in dialysis patients.

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.

The National Kidney Foundation K/DOQI clinical practice guidelines for dietary protein intake for chronic dialysis 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.

Nutritional management of maintenance dialysis patients: why aren't we doing better?

About 40% of patients undergoing maintenance dialysis suffer from varying degrees of protein-energy malnutrition. This is a problem of substantial importance because many measures of nutritional status correlate with the risk of morbidity and mortality. There are many causes of protein-energy malnutrition in maintenance dialysis patients. Evidence indicates that nutritional decline begins even when the reduction in glomerular filtration rate is modest, and it is likely that the observed decrease in dietary protein and energy intake plays an important role. The nutrient intake of patients receiving maintenance dialysis also is often inadequate, and several lines of evidence suggest that toxins that accumulate with renal failure suppress appetite and contribute to nutritional decline once patients are on maintenance dialysis. Recent epidemiologic studies have suggested that both increased serum levels of leptin and inflammation may reduce nutrient intake and contribute to the development of protein-energy malnutrition. It is likely that associated illnesses, which are highly prevalent, contribute to malnutrition in maintenance dialysis patients. Recent data from the United States Renal Data System registry suggest that in the United States, the mortality rate of dialysis patients is improving. However, it remains high. We offer suggestions for predialysis and dialysis care of these patients that can result in improvement in their nutritional status. Whether this improvement will result in a decrease in patient morbidity and mortality is unknown.

National kidney foundation K/DOQI clinical practice guidelines for nutrition in chronic renal failure.

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.

Rationale for an International Federation of Kidney Foundations.

Kidney foundations serve a unique role with their focus on the medical, psychosocial, and health needs of the individual with kidney disease and with their community-based structure. The types of activities in which kidney foundations may become involved include, but are not limited to, educational programs for health care workers and for patients and their families; educational, rehabilitative, and financial support programs for patients or their families; advocacy to the government and to other organizations on behalf of the needs of the patient and the patient's family; and fund raising for research or for other kidney-related programs. Most of the world's population is not represented by kidney foundations. Moreover, there are major variations in the programmatic activities of most kidney foundations. The fact that the psychosocial and educational needs of individuals with renal disease and renal failure are often great and the fact that access of individuals with end-stage renal disease to long-term dialysis therapy or renal transplantation varies greatly in different parts of the world provide a strong rationale for the establishment of community-based kidney foundations to advocate for the patient. The International Federation of Kidney Foundations (IFKF), which was formed during the past year, has as its goal fostering international collaboration and exchange of ideas to improve the health, well-being, and quality of life for individuals with kidney disease. The IFKF will promote the establishment of kidney foundations in regions where none currently exist and will encourage the growth in programmatic activities of kidney foundations everywhere. The increasing globalization of the world, growing affluence worldwide, and the willingness of people to engage in charitable giving suggest that this is a most opportune time to launch this international organization.

Protein metabolism in patients with chronic renal failure: role of uremia and dialysis.

Individuals with chronic renal failure (CRF) have a high prevalence of protein-energy malnutrition. There are many causes for this condition, chief among which is probably reduced nutrient intake from anorexia. In nondialyzed patients with CRF, energy intake is often below the recommended amounts; in maintenance dialysis patients, both dietary protein and energy intake are often below their needs. Although a number of studies indicate that rats with CRF have increased protein catabolism in comparison to control animals, more recent evidence suggests that increased catabolism in CRF rats is largely if not entirely due to acidemia, particularly if these animals are compared to pair-fed control rats. Studies in humans with advanced CRF also indicate that acidemia can cause protein catabolism. Indeed, nitrogen balance studies and amino acid uptake and release and isotopic kinetic studies indicate that in nondialyzed individuals with CRF, who are not acidemic, both their ability to conserve body protein when they ingest low protein diets and their dietary protein requirements appear to be normal. For patients undergoing maintenance hemodialysis or chronic peritoneal dialysis, dietary protein requirements appear to be increased. The increased need for protein is due, in part, to the losses into dialysate of such biologically valuable nitrogenous compounds as amino acids, peptides, and proteins. However, the sum of the dietary protein needs for CRF patients (of about 0.60 g/kg/day) and the dialysis losses of amino acids, peptides and proteins do not equal the apparent dietary protein requirements for most maintenance dialysis patients. This discrepancy may be due to a chronic state of catabolism in the clinically stable maintenance dialysis patient that is not present in the clinically stable nondialyzed individual who has advanced CRF. Possible causes for such a low grade catabolic state include resistance to anabolic hormones (for example, insulin, IGF-1) and a chronic inflammatory state associated with increased levels of pro-inflammatory cytokines.

The scientific and professional challenges for the National Kidney Foundation in the 21st century.

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.

Relationship between nutritional status and the glomerular filtration rate: results from the MDRD study.

BACKGROUND: The relationship between the protein-energy nutritional status and renal function was assessed in 1785 clinically stable patients with moderate to advanced chronic renal failure who were evaluated during the baseline phase of the Modification of Diet in Renal Disease Study. Their mean +/- SD glomerular filtration rate (GFR) was 39.8 +/- 21.1 mL/min/1.73 m2. METHODS: The GFR was determined by 121I-iothalamate clearance and was correlated with dietary and nutritional parameters estimated from diet records, biochemistry measurements, and anthropometry. RESULTS: The following parameters correlated directly with the GFR in both men and women: dietary protein intake estimated from the urea nitrogen appearance, dietary protein and energy intake estimated from dietary diaries, serum albumin, transferrin, percentage body fat, skinfold thickness, and urine creatinine excretion. Serum total cholesterol, actual and relative body weights, body mass index, and arm muscle area also correlated with the GFR in men. The relationships generally persisted after statistically controlling for reported efforts to restrict diets. Compared with patients with GFR > 37 mL/min/1.73 m2, the means of several nutritional parameters were significantly lower for GFR between 21 and 37 mL/min/1.73 m2, and lower still for GFRs under 21 mL/min/1.73 m2. In multivariable regression analyses, the association of GFR with several of the anthropometric and biochemical nutritional parameters was either attenuated or eliminated completely after controlling for protein and energy intakes, which were themselves strongly associated with many of the nutritional parameters. On the other hand, few patients showed evidence for actual protein-energy malnutrition. CONCLUSIONS: These cross-sectional findings suggest that in patients with chronic renal disease, dietary protein and energy intakes and serum and anthropometric measures of protein-energy nutritional status progressively decline as the GFR decreases. The reduced protein and energy intakes, as GFR falls, may contribute to the decline in many of the nutritional measures.

Recombinant human insulin-like growth factor-1 induces an anabolic response in malnourished CAPD patients.

BACKGROUND: Insulin-like growth factor-1 (IGF-1) is an anabolic hormone that mediates most of the growth effects of growth hormone. This study tested the hypothesis that recombinant human IGF-1 (rhIGF-1) will induce an anabolic response in malnourished patients undergoing continuous ambulatory peritoneal dialysis (CAPD). METHODS: Six CAPD patients with protein-energy malnutrition underwent nitrogen balance studies in a clinical research center for 35 days each. Throughout the study, patients were maintained on their same CAPD regimen prior to hospitalization, and were fed a constant protein and energy intake that was similar to their diet prior to hospitalization. The first 15 hospital days were a baseline period; during the subsequent 20-day period, patients were given subcutaneous injections of rhIGF-1 (100 microg/kg/12 h), except for one patient who received 50 microg/kg/12 h for the first five days, followed by 100 microg/kg/12 h for the following 15 days. RESULTS: During the treatment with rhIGF-1, serum IGF-1 increased by about 100% (P = 0.03), and nitrogen balance became strongly positive (+2.0 g/day, P = 0.015 vs. baseline). This anabolic effect was observed within hours after commencing the rhIGF-1 treatment and was largely caused by a 20% decrease in peritoneal dialysate effluent nitrogen. There was a proportionate reduction in urine nitrogen and serum urea nitrogen. This decrease in nitrogen output was sustained during the entire 20 day of treatment with rhIGF-1. Serum phosphorus decreased significantly during the first several days of rhIGF-1 treatment, whereas serum calcium increased significantly during the rhIGF-1 treatment. Serum potassium and albumin did not change during the rhIGF-1 injections. There was no change in body weight and body composition, as assessed by anthropometry during the baseline or treatment phases of the study. Some patients exhibited minor possible adverse events that included a reduction in blood pressure and transient tachycardia. CONCLUSION: Injections of rhIGF-1 induce a strong and sustained anabolic effect, as indicated by a positive nitrogen balance in CAPD patients with protein-energy malnutrition. rhIGF-1 administration may be an effective method for treating malnutrition in maintenance dialysis patients.

Body weight-for-height relationships predict mortality in maintenance hemodialysis patients.

BACKGROUND: Protein-energy malnutrition is a strong predictor of mortality in maintenance hemodialysis (MHD) patients. This association has generally been described for serum chemistry measures of protein-energy malnutrition. We hypothesized that body weight-for-height relationships also predict survival in MHD patients. METHODS: During the last three months of 1993, data were obtained on 12,965 men and women concerning clinical characteristics (height, postdialysis weight, age, gender, race, and presence or absence of diabetes mellitus) and laboratory measurements (predialysis serum albumin, creatinine and cholesterol, and the urea reduction ratio). Patient survival during the next 12 months was evaluated retrospectively. RESULTS: In comparison to values for normal Americans determined from the National Health and Nutrition Evaluation Survey II data, weight-for-height relationships tended to be slightly lower than normal in African American men and women and Caucasian men undergoing MHD and were normal or slightly greater in the taller Caucasian women. In both men and women, the mortality rate decreased progressively as the patients' weight-for-height increased. MHD patients who weighed more than normal had the lowest mortality rates. After adjustment for clinical characteristics and laboratory measurements, the inverse relationship between mortality rates and weight-for-height percentiles was still highly significant for patients within the lower 50th percentile of body weight-for-height. Serum albumin correlated directly with weight-for-height in patients in the lower 50th percentile of weight-for-height. Serum creatinine and cholesterol correlated directly with weight-for-height in the entire population of men and women. In contrast, the urea reduction ratio was inversely correlated with weight-for-height. CONCLUSIONS: These data indicate that weight-for-height is a strong predictor of 12-month mortality in male and female MHD patients. Multivariate analyses indicate that body weight-for-height is an independent predictor of higher mortality in those patients who are in the lower 50th percentile for this measurement.

Elevated myocardial cytosolic calcium impairs insulin-like growth factor-1-stimulated protein synthesis in chronic renal failure.

Rats and humans with chronic renal failure (CRF) are reported to have resistance to recombinant human insulin-like growth factor-1 (rhIGF-1). Because basal cytosolic calcium ([Ca2+]i), a second messenger, may be increased in CRF, this study was conducted to examine whether elevated basal [Ca2+]i may cause resistance to IGF-1. Cardiomyocytes from four groups of rats were studied: untreated CRF, CRF with parathyroidectomy (PTX), CRF with the calcium channel blocker felodipine (F), and sham operation of the kidney (SO). CRF was created by ligation of two-thirds of the left renal artery and contralateral nephrectomy. Rats from each group were pair-fed the same diet for 20 to 22 d. Basal [Ca2+]i in cardiomyocytes (nM) in the CRF rats (102.0 +/- 2.8; SEM), was significantly higher than in each of the CRF-PTX, CRF-F, and SO groups (65.2 +/- 1.9, 63.8 +/- 2.6, and 63.5 +/- 2.0, respectively; P < 0.01). rhIGF-1 increased cardiomyocyte [Ca2+]i in all four groups of rats. The rise in [Ca2+]i was significantly diminished in the CRF rats (P < 0.05) and did not differ among the CRF-PTX, CRF-F, and SO rats. Protein synthesis after incubation with 0, 50, 100, 200, or 400 ng/ml rhIGF-1 was lower in cardiomyocytes from CRF rats than in each of the other three groups (P < 0.05) and was significantly less in the CRF-F rats compared with SO animals. IGF-1 receptor mRNA and IGF-1 receptor number and affinity were not different among the four groups. These findings suggest that cardiomyocytes from CRF rats display elevated basal [Ca2+]i and attenuated rhIGF-1-induced increase in [Ca2+]i; basal protein synthesis is decreased, and IGF-1-stimulated protein synthesis is impaired; elevated basal [Ca2+]i seems to contribute to this diminished response to rhIGF-1.

Therapeutic approaches to malnutrition in chronic dialysis patients: the different modalities of nutritional support.

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).

Pathophysiology of protein-energy wasting in chronic renal failure.

There is a high prevalence of protein-energy malnutrition in both nondialyzed patients with advanced chronic renal failure and in those individuals with end-stage renal disease who are receiving maintenance hemodialysis or chronic peritoneal dialysis therapy. Approximately one-third of maintenance dialysis patients have mild to moderate protein-energy malnutrition, and about 6 to 8 percent of these individuals have severe malnutrition. These statistics are of major concern because markers of protein-energy malnutrition are strong predictors of morbidity and mortality. The causes of protein-energy malnutrition in patients with chronic renal failure include: (1) decreased energy or protein intake; (2) concurrent chronic illnesses, and superimposed acute illnesses and possibly increased inflammatory cytokines; (3) the catabolic stimulus of hemodialysis; (4) losses of nutrients into dialysate, particularly amino acids, peptides, protein (with peritoneal dialysis), glucose (when hemodialysis is performed with glucose-free dialysate) and water-soluble vitamins; and (5) diagnostic or therapeutic (e.g., prednisone therapy) procedures that reduce nutrient intake or engender net protein breakdown. Other theoretically possible causes for protein-energy malnutrition include (6) chronic blood loss; (7) endocrine disorders (especially resistance to insulin and insulin-like growth factor-I, hyperglucagonemia, hyperparathyroidism and deficiency of 1,25-dihydroxycholecalciferol); (8) products of metabolism that accumulate in renal failure and may induce wasting, such as organic and inorganic acids; (9) loss of the metabolic actions of the kidney; and (10) the accumulation of toxic compounds that are taken up from the environment (e.g., aluminum).