Effect of talactoferrin alfa on the immune system in adults with non-small cell lung cancer.

BACKGROUND: Talactoferrin alfa (talactoferrin), an agent with immune-stimulating properties, has demonstrated safety and preliminary efficacy in clinical trials. METHODS: Ten patients (five males and five females) with stage IV non-small cell lung cancer (NSCLC) in a single-arm pilot study received orally administered talactoferrin (1.5 g, b.i.d.) for up to 24 weeks. Radiographic and immunologic studies were performed at baseline and at weeks 6 and 12. Circulating immune cells (natural killer cells [NKCs], CD4+, CD8+, and regulatory T cells) and systemic cytokine levels were measured to assess immune response. RESULTS: Patients enrolled in the study had received a median of four prior chemotherapy regimens, and all patients were symptomatic. Talactoferrin was well tolerated, with no grade 3 or 4 toxicities. Median time to progression (TTP) and overall survival were 6 weeks and 14.5 weeks, respectively. The four patients with ≥9 weeks TTP had evidence of immunologic activity (three with increased NKC activity). CONCLUSIONS: The median of four previous chemotherapy regimens, with elevated levels of interleukin (IL) 6 and tumor necrosis factor-alfa in most patients, suggests these patients were poor candidates for immunotherapy.

Ipilimumab and a poxviral vaccine targeting prostate-specific antigen in metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial.

BACKGROUND: Therapeutic cancer vaccines have shown activity in metastatic castration-resistant prostate cancer (mCRPC), and methods are being assessed to enhance their efficacy. Ipilimumab is an antagonistic monoclonal antibody that binds cytotoxic T-lymphocyte-associated protein 4, an immunomodulatory molecule expressed by activated T cells, and to CD80 on antigen-presenting cells. We aimed to assess the safety and tolerability of ipilimumab in combination with a poxviral-based vaccine targeting prostate-specific antigen (PSA) and containing transgenes for T-cell co-stimulatory molecule expression, including CD80. METHODS: We did a phase 1 dose-escalation trial, with a subsequent expansion phase, to assess the safety and tolerability of escalating doses of ipilimumab in combination with a fixed dose of the PSA-Tricom vaccine. Patients with mCRPC received 2×10(8) plaque-forming units of recombinant vaccinia PSA-Tricom subcutaneously on day 1 of cycle 1, with subsequent monthly boosts of 1×10(9) plaque-forming units, starting on day 15. Intravenous ipilimumab was given monthly starting at day 15, in doses of 1, 3, 5, and 10 mg/kg. Our primary goal was to assess the safety of the combination. This study is registered with ClinicalTrials.gov, number NCT00113984. FINDINGS: We completed enrolment with 30 patients (24 of whom had not been previously treated with chemotherapy) and we did not identify any dose-limiting toxic effects. Grade 1 and 2 vaccination-site reactions were the most common toxic effects: three of 30 patients had grade 1 reactions and 26 had grade 2 reactions. 21 patients had grade 2 or greater immune-related adverse events. Grade 3 or 4 immune-related adverse events included diarrhoea or colitis in four patients and grade 3 rash (two patients), grade 3 raised aminotransferases (two patients), grade 3 endocrine immune-related adverse events (two patients), and grade 4 neutropenia (one patient). Only one of the six patients previously treated with chemotherapy had a PSA decline from baseline. Of the 24 patients who were chemotherapy-naive, 14 (58%) had PSA declines from baseline, of which six were greater than 50%. INTERPRETATION: The use of a vaccine targeting PSA that also enhances co-stimulation of the immune system did not seem to exacerbate the immune-related adverse events associated with ipilimumab. Randomised trials are needed to further assess clinical outcomes of the combination of ipilimumab and vaccine in mCRPC. FUNDING: US National Institutes of Health.

A pilot study of MUC-1/CEA/TRICOM poxviral-based vaccine in patients with metastatic breast and ovarian cancer.

PURPOSE: PANVAC is a recombinant poxviral vaccine that contains transgenes for MUC-1, CEA, and 3 T-cell costimulatory molecules. This study was conducted to obtain preliminary evidence of clinical response in metastatic breast and ovarian cancer patients. EXPERIMENTAL DESIGN: Twenty-six patients were enrolled and given monthly vaccinations. Clinical and immune outcomes were evaluated. RESULTS: These patients were heavily pretreated, with 21 of 26 patients having 3 or more prior chemotherapy regimens. Side effects were largely limited to mild injection-site reactions. For the 12 breast cancer patients enrolled, median time to progression was 2.5 months (1-37+) and median overall survival was 13.7 months. Four patients had stable disease. One patient had a complete response by RECIST and remained on study for 37 months or more, with a significant drop in serum interleukin (IL)-6 and IL-8 by day 71. Another patient with metastatic disease confined to the mediastinum had a 17% reduction in mediastinal mass and was on study for 10 months. Patients with stable or responding disease had fewer prior therapies and lower tumor marker levels than patients with no evidence of response. For the ovarian cancer patients (n = 14), the median time to progression was 2 months (1-6) and median overall survival was 15.0 months. Updated data are presented here for one patient treated with this vaccine in a previous trial, with a time to progression of 38 months. CONCLUSIONS: Some patients who had limited tumor burden with minimal prior chemotherapy seemed to benefit from the vaccine. Further studies to confirm these results are warranted.

New gene expressed in prostate: a potential target for T cell-mediated prostate cancer immunotherapy.

New gene expressed in prostate (NGEP) is a prostate-specific gene encoding either a small cytoplasmic protein (NGEP-S) or a larger polytopic membrane protein (NGEP-L). NGEP-L expression is detectable only in prostate cancer, benign prostatic hyperplasia and normal prostate. We have identified an HLA-A2 binding NGEP epitope (designated P703) which was used to generate T cell lines from several patients with localized and metastatic prostate cancer. These T cell lines were able to specifically lyse HLA-A2 and NGEP-expressing human tumor cells. NGEP-P703 tetramer binding assays demonstrated that metastatic prostate cancer patients had a higher frequency of NGEP-specific T cells when compared with healthy donors. Moreover, an increased frequency of NGEP-specific T cells was detected in the peripheral blood mononuclear cells of prostate cancer patients post-vaccination with a PSA-based vaccine, further indicating the immunogenicity of NGEP. These studies thus identify NGEP as a potential target for T cell-mediated immunotherapy of prostate cancer.

Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer.

A concurrent multicenter, randomized Phase II trial employing a recombinant poxviral vaccine provided evidence of enhanced median overall survival (OS) (p = 0.0061) in patients with metastatic castrate-resistant prostate cancer (mCRPC). The study reported here employed the identical vaccine in mCRPC to investigate the influence of GM-CSF with vaccine, and the influence of immunologic and prognostic factors on median OS. Thirty-two patients were vaccinated once with recombinant vaccinia containing the transgenes for prostate-specific antigen (PSA) and three costimulatory molecules. Patients received boosters with recombinant fowlpox containing the same four transgenes. Twelve of 32 patients showed declines in serum PSA post-vaccination and 2/12 showed decreases in index lesions. Median OS was 26.6 months (predicted median OS by the Halabi nomogram was 17.4 months). Patients with greater PSA-specific T-cell responses showed a trend (p = 0.055) toward enhanced survival. There was no difference in T-cell responses or survival in cohorts of patients receiving GM-CSF versus no GM-CSF. Patients with a Halabi predicted survival of <18 months (median predicted 12.3 months) had an actual median OS of 14.6 months, while those with a Halabi predicted survival of > or =18 months (median predicted survival 20.9 months) will meet or exceed 37.3 months, with 12/15 patients living longer than predicted (p = 0.035). Treg suppressive function was shown to decrease following vaccine in patients surviving longer than predicted, and increase in patients surviving less than predicted. This hypothesis-generating study provides evidence that patients with more indolent mCRPC (Halabi predicted survival > or =18 months) may best benefit from vaccine therapy.

Pilot study of vaccination with recombinant CEA-MUC-1-TRICOM poxviral-based vaccines in patients with metastatic carcinoma.

PURPOSE: Poxviral vectors have a proven safety record and can be used to incorporate multiple transgenes. Prior clinical trials with poxviral vaccines have shown that immunologic tolerance to self-antigens can be broken. Carcinoembryonic antigen (CEA) and MUC-1 are overexpressed in a substantial proportion of common solid carcinomas. The primary end point of this study was vaccine safety, with immunologic and clinical responses as secondary end points. EXPERIMENTAL DESIGN: We report here a pilot study of 25 patients treated with a poxviral vaccine regimen consisting of the genes for CEA and MUC-1, along with a triad of costimulatory molecules (TRICOM; composed of B7.1, intercellular adhesion molecule 1, and lymphocyte function-associated antigen 3) engineered into vaccinia (PANVAC-V) as a prime vaccination and into fowlpox (PANVAC-F) as a booster vaccination. RESULTS: The vaccine was well tolerated. Apart from injection-site reaction, no grade > or =2 toxicity was seen in more than 2% of the cycles. Immune responses to MUC-1 and/or CEA were seen following vaccination in 9 of 16 patients tested. A patient with clear cell ovarian cancer and symptomatic ascites had a durable (18-month) clinical response radiographically and biochemically, and one breast cancer patient had a confirmed decrease of >20% in the size of large liver metastasis. CONCLUSIONS: This vaccine strategy seems to be safe, is associated with both CD8 and CD4 immune responses, and has shown evidence of clinical activity. Further trials with this agent, either alone or in combination with immunopotentiating and other therapeutic agents, are warranted.

Clinical safety of a viral vector based prostate cancer vaccine strategy.

PURPOSE: The primary objective of this phase I study was to evaluate the clinical safety of a vaccine using recombinant vaccinia virus (prime) and recombinant fowlpox virus (boost) in combination with granulocyte-macrophage colony-stimulating factor in patients with prostate cancer. The vaccines contained transgenes for prostate specific antigen, a triad of co-stimulatory molecules and a tumor antigen whose amino acid sequence had been modified to enhance its immunogenicity. Secondary end points were immunological and clinical responses, changes in prostate specific antigen velocity, and the kinetics of vaccinia virus clearance from the vaccination site, serum, peripheral blood mononuclear cells, urine and saliva. MATERIALS AND METHODS: The 15 patients enrolled in this study had metastatic prostate cancer. Patients were given recombinant fowlpox-prostate specific antigen/triad of co-stimulatory molecules alone or recombinant vaccinia-prostate specific antigen/triad of co-stimulatory molecules followed by recombinant fowlpox-prostate specific antigen/triad of co-stimulatory molecules on a prime and boost schedule with or without recombinant-granulocyte-macrophage colony-stimulating factor protein or recombinant fowlpox-granulocyte-macrophage colony-stimulating factor vector. Prostate specific antigen specific immune responses were measured using an enzyme-linked immunosorbent spot assay for interferon-gamma production. Polymerase chain reaction for vaccinia DNA and a plaque assay for live virus were also used. RESULTS: Some grade 2 toxicity was seen in patients who received a higher dose of recombinant fowlpox-granulocyte-macrophage colony-stimulating factor but no toxicity exceeded grade 2. Viable vaccinia was detected after vaccination at the site swab of 1 of 4 patients analyzed. Prostate specific antigen specific immune responses were seen in 4 of 6 patients who were HLA-A2+ and decreases in serum prostate specific antigen velocity were observed in 9 of 15. CONCLUSIONS: Based on the safety and preliminary immunogenicity results of this trial we recommend initiating a randomized, phase II study of prostate specific antigen/triad of co-stimulatory molecules vaccines in patients with less advanced prostate cancer.

The effect of dialysis dose and membrane flux on nutritional parameters in hemodialysis patients: results of the HEMO Study.

BACKGROUND: The effect of standard or high dialysis dose and low or high dialysis flux on nutritional status was ascertained in 1846 maintenance hemodialysis patients enrolled in the HEMO Study. METHODS: Serum albumin levels, equilibrated protein catabolic rate, and postdialysis weight were obtained monthly, while adjusted protein and energy intake, self-reported appetite assessment, upper arm circumference, and calf circumference were obtained yearly. To account for patient attrition due to death or transfer, three statistical models were used to test the effects of the study interventions on longitudinal changes in nutritional parameters. RESULTS: During the first 3 years of follow-up, neither mean serum albumin levels, which declined by 0.21 g/dL, nor mean postdialysis weight, which declined by 2.7 kg, were significantly affected by either study intervention. Mean levels of all anthropometric measures declined during follow-up. For years 1, 2, and 3, the mean +/- SE declines in upper arm and calf circumferences were 0.35 +/- 0.16 cm (P= 0.031) and 0.31 +/- 0.13 (P= 0.015) cm less, respectively, in the high flux compared to the low flux group. Appetite scores and mean equilibrated protein catabolic rate also declined in all randomized groups; however, the average decline in equilibrated protein catabolic rate during years 1, 2, and 3 was 0.019 +/- 0.007 g/kg/day less in the high dose than the standard dose group (P= 0.007). There was no significant change in either mean energy or protein intake from diet records over time, and neither parameter was affected by the study interventions. CONCLUSION: Although the dose and flux interventions may subtly influence certain nutritional parameters, neither intervention prevented deterioration in nutritional status over time.

Modified vaccinia virus ankara recombinants are as potent as vaccinia recombinants in diversified prime and boost vaccine regimens to elicit therapeutic antitumor responses.

Cancer vaccine regimens use various strategies to enhance immune responses to specific tumor-associated antigens (TAAs), including the increasing use of recombinant poxviruses [vaccinia (rV) and fowlpox (rF)] for delivery of the TAA to the immune system. However, the use of replication competent vectors with the potential of adverse reactions have made attenuation a priority for next-generation vaccine strategies. Modified vaccinia Ankara (MVA) is a replication defective form of vaccinia virus. Here, we investigated the use of MVA encoding a tumor antigen gene, carcinoembryonic antigen (CEA), in addition to multiple costimulatory molecules (B7-1, intercellular adhesion molecule-1, and lymphocyte function-associated antigen-3 designated TRICOM). Vaccination of mice with MVA-CEA/TRICOM induced potent CD4+ and CD8+ T-cell responses specific for CEA. MVA-CEA/TRICOM could be administered twice in vaccinia naïve mice and only a single time in vaccinia-immune mice before being inhibited by antivector-immune responses. The use of MVA-CEA/TRICOM in a diversified prime and boost vaccine regimen with rF-CEA/TRICOM, however, induced significantly greater levels of both CD4+ and CD8+ T-cell responses specific for CEA than that seen with rV-CEA/TRICOM prime and rF-CEA/TRICOM boost. In a self-antigen tumor model, the diversified MVA-CEA/TRICOM/rF-CEA/ TRICOM vaccination regimen resulted in a significant therapeutic antitumor response as measured by increased survival, when compared with the diversified prime and boost regimen, rV-CEA/TRICOM/rF-CEA/TRICOM. The studies reported here demonstrate that MVA, when used as a prime in a diversified vaccination, is clearly comparable with the regimen using the recombinant vaccinia in both the induction of cellular immune responses specific for the "self"-TAA transgene and in antitumor activity.

Effects of dietary intake, appetite, and eating habits on dialysis and non-dialysis treatment days in hemodialysis patients: cross-sectional results from the HEMO study.

OBJECTIVE: To evaluate differences between dietary energy intake (DEI), dietary protein intake (DPI), appetite, dietary patterns, and eating habits during dialysis treatment days (DD) and non-dialysis treatment days (NDD) in 1,901 adults receiving maintenance hemodialysis who were enrolled in the baseline phase of the National Institutes of Health-sponsored Hemodialysis (HEMO) study. DESIGN: A cross-sectional analysis of participants at baseline (before randomization). SETTING: Fifteen clinical centers across the United States. MEASUREMENTS: DEI, DPI, and self-reported assessment of appetite, dietary patterns, and eating habits. RESULTS: For the entire study cohort, total mean (+/- SD) DEI (1,566 +/- 636 kcal/day) and weight-adjusted DEI (23.2 +/- 9.5 kcal/kg/day) were significantly higher (P <.0001) on NDD than on DD (1,488 +/- 620 kcal/day and 22.2 +/- 9.6 kcal/kg/day), respectively. Similarly, DPI was significantly higher (P <.0001) on NDD (65.0 +/- 29.0 g/day and 0.96 +/- 0.43 g/kg/day) than on DD (60.2 +/- 26.5 g/day and 0.90 +/- 0.41 g/kg/day). On DD and NDD, the mean weight-adjusted DEI for the entire cohort was less than the HEMO study standard of care (SOC) of > or =28 kcal/kg/day, whereas on NDD, several subgroups reported dietary protein intakes that were closer to the study's SOC. These included men, patients under 50 years of age, nonblack participants, those without diabetes, those with a normal or mild Index of Co-Existing Disease score, and those on dialysis for more than 5 years. Protein and energy intakes declined with worsening self-reported appetites in both DD and NDD after adjusting for other subgroup effects. CONCLUSION: Dietary energy and protein intakes of HEMO study participants were lower on DD than on NDD, and also lower than the SOC on both days, particularly with regard to energy intake. People receiving maintenance hemodialysis should be counseled to consume adequate amounts of energy and protein daily, especially on DD. Practitioners should monitor closely those patients who report poor appetite and should intervene appropriately.

Vaccine therapy of established tumors in the absence of autoimmunity.

PURPOSE: Many current clinical trials involve vaccination of patients with vaccines directed against tumor-associated antigens, which are, in actuality, "self-antigens" overexpressed in tumors as compared with normal tissues. As tumor vaccines become more potent through the addition of costimulatory molecules and cytokines and the use of diversified prime and boost regimes, the level of concern rises regarding the balance between antitumor immunity and pathological autoimmunity. Studies were conducted using mice bearing a transgenic self-antigen [human carcinoembryonic antigen (CEA)], which is expressed in some normal adult tissues, and tumor expressing the same self-antigen. These mice were vaccinated with recombinant poxviral vectors [recombinant vaccinia, recombinant fowlpox (rF)] encoding the CEA transgene as well as a triad of costimulatory molecules [B7-1, ICAM-1, and LFA-3 (TRICOM)]. Here we investigate the mechanism of tumor therapy and evaluate the safety of such a regimen in a self-antigen system. To our knowledge, the study reported here is the first description of a vaccine to a defined antigen where the regimen is potent enough to induce tumor therapy in the absence of autoimmunity. EXPERIMENTAL DESIGN: CEA transgenic mice were transplanted with CEA-expressing tumors. Fourteen days later, mice were vaccinated with recombinant vaccinia-CEA/TRICOM admixed with recombinant murine granulocyte macrophage colony-stimulating factor and then given low-dose interleukin 2. Mice were boosted on days 21, 28, and 35 with rF-CEA/TRICOM admixed with rF-granulocyte macrophage colony-stimulating factor and then given low-dose interleukin 2. Mice were monitored for survival and compared with groups of mice vaccinated in a similar manner with poxviral vectors containing CEA/B7-1 or CEA transgenes. To determine the mechanism of antitumor therapy, mice were depleted of T-cell subpopulations before vaccination with the CEA/TRICOM regimen. Mice successfully cured of tumor and age-matched control mice were monitored for 1 year. At 1 year, several clinical assays were carried out involving analysis of 9 serological parameters, 11 urinalysis parameters, and 14 immunological parameters. In addition, histopathology was performed on 42 tissues/mouse. RESULTS: The CEA/TRICOM vaccination regimen induced a therapeutic antitumor response as measured by increased survival, which was due largely to induced T-cell responses (both CD4(+) and CD8(+)) as determined by selective T-cell subset depletion. The CEA/TRICOM vaccination regimen induced a significant increase in proliferation of CD4(+) T cells to CEA protein and a significant increase in secretion of IFN-gamma from CD8(+) T cells in response to a defined CEA epitope. Despite CEA expression in normal adult gastrointestinal tissues, no toxicity was observed in the CEA/TRICOM-vaccinated group when an array of clinical serum and urine chemistry assays was conducted 1 year after vaccination. Moreover, a comprehensive histopathological evaluation of all tissues from these groups also showed no evidence of toxicity. CONCLUSIONS: Activation of T cells directed against a tumor-associated self-antigen, sufficient to mediate therapeutic antitumor immunity, was observed in vivo without the development of autoimmunity as analyzed by a comprehensive evaluation of biochemical, immunological, and histopathological criteria. These studies demonstrate that the use of vectors containing as many as three costimulatory molecules does not induce autoimmunity or other pathology. These studies thus demonstrate that a balance can indeed be achieved between the induction of an immune response to a self-antigen, which is capable of antitumor therapy, and the absence of autoimmunity.

Phase I study of a vaccine using recombinant vaccinia virus expressing PSA (rV-PSA) in patients with metastatic androgen-independent prostate cancer.

BACKGROUND: A Phase I trial of recombinant vaccinia prostate specific antigen (rV-PSA) in patients with advanced metastatic prostate cancer was conducted. This report describes 42 patients who were treated with up to three monthly vaccinations. METHODS: All patients were entered on a dose-escalation phase I study of recombinant vaccinia containing the gene for PSA (rV-PSA). The primary objective of this study was to determine the safety of this vaccine in metastatic androgen-independent prostate cancer patients. A secondary objective was to assess evidence of anti-tumor activity by PSA measurements, radiologic findings, and immunologic methods. RESULTS: There was no significant treatment-related toxicity apart from erythema, tenderness, and vesicle formation that lasted several days at the site of injection in some patients. There were immunologic responses, in selected patients, as evidenced by an increase in the proportion of PSA-specific T cells after vaccination. Furthermore, we show that these patients' T cells can lyse PSA-expressing tumor cells in vitro. CONCLUSION: Given the low toxicity profile and the evidence of immunologic activity, we believe future study is warranted with PSA-based vaccines in prostate cancer. New PSA-based vaccines and vaccine strategies are currently being evaluated.

Association of nutritional markers with physical and mental health status in prevalent hemodialysis patients from the HEMO study.

OBJECTIVE: To determine associations of potentially modifiable nutritional factors with physical and mental health status after adjusting for sociodemographic and comorbid conditions. DESIGN: Cross-sectional multivariable analysis. SETTING: Fifteen dialysis centers across the United States participating in the Reduction of Morbidity and Mortality Among Hemodialysis Patients (HEMO) study. PATIENTS: Enrollment of 1,545 prevalent hemodialysis subjects in the HEMO study. INDEPENDENT (PREDICTOR) VARIABLES: The following nutritional markers were assessed in this analysis: serum albumin, energy intake, protein catabolic rate, serum creatinine, midarm muscle circumference, calf circumference, and smoking status. Smoking status, although not a nutritional factor per se, was also included because it is a modifiable lifestyle factor. MAIN OUTCOME MEASURES: Physical and mental health status were assessed using the medical staff-assessed Karnofsky Index and the patient self-assessed Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). RESULTS: After adjusting for sociodemographic factors and comorbid conditions, serum albumin, serum creatinine, and calf circumference were independently associated with Karnofsky Index scores. Similarly, serum creatinine and calf circumference were also independently associated with the Physical Component Summary (PCS) score of the SF-36. Of the nutritional variables selected, no variables were significantly associated with the Mental Component Summary (MCS) score of the SF-36. CONCLUSIONS: Markers of poor nutrition were associated with decreased physical functioning scores, independent of case mix. Measures that improve nutrition may therefore have wide-reaching effects to improve not only morbidity and mortality but also health-related quality of life for patients with end-stage renal disease.

Cross-sectional relationship between dietary protein and energy intake, nutritional status, functional status, and comorbidity in older versus younger hemodialysis patients.

OBJECTIVE: To evaluate the dietary energy intakes (DEI) and dietary protein intakes (DPI) of older (> or = 65 years), middle-aged (50 to 64 years), and younger (< 50 years) maintenance hemodialysis patients enrolled in the Hemodialysis (HEMO) Study, and to describe the relationship between age, nutritional status, functional status, and comorbidity. DESIGN: A cross-sectional analysis of the first 1,397 participants in baseline (before randomization) was performed. MAIN OUTCOME MEASURES: DEI and DPI, serum albumin, creatinine, total cholesterol, normalized protein catabolic rate (nPCR), equilibrated nPCR (enPCR), functional status, and comorbidities. RESULTS: Mean DEI, DPI, serum albumin, creatinine, nPCR, and enPCR were significantly lower in the older compared with the younger patients, despite similar doses of dialysis as measured by equilibrated Kt/V. Mean DEI, DPI, nPCR, and enPCR were not significantly different between the middle-aged and older patients, whereas albumin and creatinine were significantly lower in the older patients. Mean dry weight and percent of standard body weight in the younger and older patients were similar. In all groups, mean DEI was lower than both the HEMO study's standard of care (SOC) and the Kidney Disease Outcomes Quality Initiative (K/DOQI) nutrition recommendations, whereas mean DPI was lower than the SOC and K/DOQI recommendations only in the middle-aged and older patients. Middle-aged and older patients had higher cholesterol, lower functional status, and more comorbidities than the younger patients. CONCLUSION: Middle-aged and older maintenance dialysis patients may be at greater risk for developing protein-energy malnutrition than their younger counterparts. Inadequate DEI and DPI reported in middle-aged and older patients were associated with lower levels of biomarkers of nutritional status, lower functional status, and higher comorbidities than in the younger patients.

Nutritional status in the HEMO Study cohort at baseline. Hemodialysis.

The nutritional status of the first 1,000 patients randomized into the Hemodialysis (HEMO) Study was analyzed at baseline when they received their typical dialysis dose (equilibrated Kt/V = 1.30 +/- 0.22) and dialysis membrane. This is the largest study to date of the nutritional status of chronic hemodialysis patients. The mean (+/- SD) values for these parameters included a serum albumin level of 3.65 +/- 0.38 g/dL, a dietary energy intake of 22.9 +/- 8.4 kcal/kg/day, a dietary protein intake of 0.93 +/- 0.36 g/kg/day, and a double pool normalized protein catabolic rate (enPCR) of 1.00 +/- 0.25 g/kg/day. The percentage of patients below HEMO Study nutritional standards of care included 29% of patients with a serum albumin level less than 3.5 g/dL, 76% of patients with a dietary energy intake less than 28 kcal/kg/day, 61% of patients with a dietary protein intake less than 1.0 g/kg/day, and 52% of patients with an enPCR of less than 1.0 g/kg/day. There was a strong correlation between dietary protein intake and dietary energy intake (r = 0.74, P < 0.0001). Significant correlations were also evident between serum albumin and double pool PCR and between dietary protein intake and double-pool PCR. Kt/V and membrane flux were not predictive of baseline dietary protein intake, dietary energy intake, or serum albumin level. Thus, a majority of patients in the HEMO Study had protein and energy intake levels and enPCR levels that were below National Kidney Foundation Kidney Dialysis Outcome Quality Improvement (NKF-K/DOQI) guidelines.