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Background: Patients with chronic kidney disease (CKD) have reduced expression of erythroid nuclear factor-related factor 2 (NRF2) and increased nuclear factor κB (NF-κB). "Food as medicine" has been proposed as an adjuvant therapeutic alternative in modulating these factors. No studies have investigated the effects of sulforaphane (SFN) in cruciferous vegetables on the expression of these genes in patients with CKD., Objective: The study aimed to evaluate the effects of SFN on the expression of NRF2 and NF-κB in patients on hemodialysis (HD)., Design and Methods: A randomized, double-blind, crossover study was performed on 30 patients on regular HD. Fourteen patients were randomly allocated to the intervention group (1 sachet/day of 2.5 g containing 1% SFN extract with 0.5% myrosinase) and 16 patients to the placebo group (1 sachet/day of 2.5 g containing corn starch colored with chlorophyll) for 2 months. After a washout period of 2 months, the groups were switched. NRF2 and NF-κB mRNA expression was evaluated by real-time quantitative polymerase chain reaction, and tumor necrosis factor alpha and interleukin-6 levels were quantified by enzyme-linked immunosorbent assay. Malondialdehyde was evaluated as a marker of lipid peroxidation., Results: Twenty-five patients (17 women, 55 [interquartile range = 19] years and 55 [interquartile range = 74] months on HD) completed the study. There was no significant difference concerning the expression of mRNA NRF2 (P = .915) and mRNA NF-κB (P = .806) after supplementation with SFN. There was no difference in pro-inflammatory and oxidative stress biomarkers., Conclusion: 150 μmol of SFN for 2 months had no antioxidant and anti-inflammatory effect in patients with CKD undergoing HD., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of the present study was to assess the dietary intake and nutritional status of patients with chronic kidney disease (CKD) stage 4-5 according to the presence of diabetes., Methods: This observational and cross-sectional study included adult patients with CKD stage 4-5 referred to a nephrology unit, between October 2018 and March 2019. Daily dietary intake was evaluated by 24-hour dietary inquiry and urine excretion. Nutritional status was assessed by measuring body composition using bioimpedance analysis and muscle function using handgrip strength. Undernutrition was considered using the protein energy wasting score., Results: A total of 75 CKD patients were included, 36 (48%) of whom had diabetes; median age (interquartile range) was 71 (60-80) years. The median weight-adjusted dietary energy intake (DEI) was 22.6 (19.1-28.2) kcal/kg/day and the mean weight-adjusted dietary protein intake (DPI) was 0.86 ± 0.19 g/kg/day. There was no significant difference in DEI and DPI between patients with diabetes and those without, except for weight-adjusted DPI which was significantly lower in diabetic patients (P = .022). In univariate analysis, diabetes was associated with weight-adjusted DPI (coefficient [95% confidence interval] -0.237 [-0.446; -0.004] kcal/kg/day; P = .040), but this association did not remain significant in multivariate analysis. Nutritional status did not differ significantly between diabetic and nondiabetic patients except for lean tissue mass, which was lower in diabetic patients (P = .046). The proportion of patients with protein energy wasting was not significantly different between diabetic and nondiabetic patients (13.9% vs. 10.2%, respectively)., Conclusions: In the present cohort, DPI and DEI were not significantly different between diabetic and nondiabetic CKD patients. Diabetes was not found to be associated with dietary intakes in CKD stage 4-5 patients., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

An expert advisory board discussed the prevention and treatment of chronic kidney disease (CKD), with a focus on dietary options. This is timely, given the uptake of value based models for kidney care in the United States. Timing of dialysis start is influenced by patients' clinical status and complex patient-clinician interactions. Patients value personal freedom and quality of life and may want to delay dialysis, whilst physicians are sometimes more concerned with clinical outcomes. Kidney-preserving therapy can prolong the dialysis-free period and preserve residual kidney function, thus patients are asked to adjust their lifestyle and diet, to follow a low- or very low-protein diet, with or without ketoacid analogues. Multi-modal approaches include pharmacotherapies, management of symptoms, and a gradual, individualized dialysis transition. Patient empowerment is vital, including CKD education and involvement in decision making. These ideas may help patients, their families, and clinical teams to improve the management of CKD., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Imbalance between anabolism and catabolism is linked to cachexia and protein-energy wasting (PEW), especially in frail populations such as patients with chronic kidney disease. PEW is responsible of poor outcomes with increased morbidity and mortality. Several causes are involved in PEW such as insulin resistance, acidosis, or hyperparathyroidism. Natriuretic peptides (NPs) have recently been described as activators of resting energy expenditure through the induction of browning of white adipose tissue in rodents with chronic kidney disease. The present study was therefore implemented to investigate whether NPs could be associated with PEW criteria and predict clinical outcomes., Methods: We quantified serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) in a prospective cohort of 231 patients undergoing maintenance hemodialysis and atrial natriuretic peptide in a subgroup of 35 patients. Body composition parameters were measured with bioimpedance spectroscopy., Results: NT-proBNP was inversely associated with serum albumin, prealbumin, and body mass index and, conversely, positively associated with age and C-reactive protein. NT-proBNP as well as atrial natriuretic peptide were significantly higher in patients with PEW criteria. NT-proBNP was negatively associated with body fat mass. In multiple linear regression, NT-proBNP remained associated with body mass index. Kaplan-Meier analysis revealed a significant correlation between serum NT-proBNP concentrations and all-cause mortality and cardiovascular events. This association remained significant after multivariable Cox regression models adjusted for demographic factors and cardiovascular risk factors., Conclusion: Accumulation of NPs seems to be associated with poor nutritional status and reduced survival among hemodialysis patients. Further studies are needed to confirm this association using resting energy expenditure measurement and adipose tissue biopsy., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Haemodialysis (HD) patients suffer from nutritional problems, which include muscle wasting, weakness, and cachexia, and are associated with poor clinical outcomes. The European Working Group for Sarcopenia in Older People (EWGSOP) and Foundations for the National Institute of Health (FNIH) have developed criteria for the assessment of sarcopenia, including the use of non-invasive techniques such as bioelectrical impedance assessment (BIA), anthropometry, and hand grip strength (HGS) dynamometry. This study investigated the prevalence of muscle wasting, weakness, and sarcopenia using the EWGSOP and FNIH criteria., Methods: BIA was performed in 24 females (f) and 63 males (m) in the post-dialysis period. Total skeletal muscle mass and appendicular skeletal muscle mass were estimated and index values (i.e., muscle mass divided by height 2 [kg/m 2 ]) were calculated (Total Skeletal Muscle Index (TSMI) and Appendicular Skeletal Muscle Index (ASMI)). Mid-arm circumference and triceps skin-fold thickness were measured and mid-upper arm muscle circumference (MUAMC) calculated. HGS was measured using a standard protocol and Jamar dynamometer. Suggested cut-points for low muscle mass and grip strength were utilized using the EWGSOP and FNIH criteria with prevalence estimated, including sarcopenia., Results: The prevalence varied depending on methodology: low TSMI (moderate and severe sarcopenia combined) was 55% for whole group: 21% (f) and 68% (m). Low ASMI was 32% for whole group: 25% (f) and 35% (m). Low MUAMC was 25% for whole group: 0% (f) and 30% (m). ASMI highly correlated with Body Mass Index (r = 0.78, P < .001) and MUAMC (r = 0.68, P < .001). Muscle weakness was high regardless of cut-points used (50-71% (f); 60-79% (m))., Conclusions: Internationally, this is the first study comparing measures of muscle mass (TSMM and ASMM by BIA and MUAMC) and muscle strength (HGS) using this specific methodology in a hemodialysis population. Future work is required to confirm findings., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: We tested the hypothesis that correcting acidosis may improve urinary Klotho excretion and serum α-Klotho., Design: This is a prospective, interventional, nonrandomized, open-label trial study. In this study setting, metabolic acidosis is commonly observed during chronic kidney disease (CKD). We reported a positive relationship between serum bicarbonate (Sbicar) and serum α-Klotho in these patients., Subjects: The study involved 20 patients with a known kidney disease referred for renal checkup. Inclusion criteria were age ≥ 18 years, CKD stage 3-5 non dialysis, Sbicar < 22 mmol/L, and not receiving bicarbonate supplementation., Intervention: Patients were then prescribed 1 g of oral sodium bicarbonate 3 times per day for 4 weeks., Main Outcome Measure: Patients were evaluated at two and 4 weeks by blood and urine measurements., Results: Mean serum Klotho was 615 ± 287 pg/mL, and mean serum Sbicar was 19.3 ± 1.7 mmol/L at baseline. Sbicar increased from baseline at two (23.9 ± 2.9 mmol/L, P < .001) and 4 weeks (23.4 ± 1.9 mmol/L, P < .001). There was no change in serum Klotho at two (630 ± 333 mmol/L) and 4 weeks (632 ± 285 mmol/L). By contrast, urine Klotho/creatinine ratio, which was very low at baseline (34.6 ± 31.6 pg/mmoL), increased by 320% at two weeks (P < .005) and by 280% at 4 weeks (P < .01)., Conclusions: Correcting acidosis by oral administration of sodium bicarbonate rapidly increases the urine excretion of soluble α-Klotho in CKD patients. However, a 4-week bicarbonate treatment was not able to increase serum α-Klotho. A longer study may confirm this pilot observation and increase serum Klotho, which has been shown to exert a protective cardiovascular effect during CKD., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Oxidative stress and inflammation are common findings in chronic kidney disease (CKD) patients, and they are directly linked to clinical outcomes such as protein energy wasting and cardiovascular disease. Nuclear factor-erythroid 2-related factor 2 (Nrf2) is the master regulator of antioxidant genes, regulating the expression of detoxifying enzymes of phase II and antioxidant responses. Furthermore, Nrf2 can also regulate anti-inflammatory cellular responses, by inhibiting nuclear factor kappa B activity (transcription factor that promotes inflammation). Therefore, modulating Nrf2 can be a new therapeutic approach to reduce inflammation and oxidative stress in CKD. Low-protein diet (LPD) prescribed for nondialysis CKD patients presents numerous benefits already well established, including reduction of inflammation and oxidative stress. However, there is no available data regarding the relationship between LPD and Nrf2 modulation in these patients. This review aims to discuss the impact, if any, of LPD on Nrf2 expression, in nondialysis CKD patients., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Poor nutritional status and protein-energy wasting are common among maintenance dialysis patients and associated with unfavorable outcomes. Providing foods, meal trays, snack boxes, and/or oral nutritional supplements during hemodialysis can improve nutritional status and might also reduce inflammation, enhance health-related quality of life, boost patient satisfaction, and improve survival. Potential challenges include postprandial hypotension and other hemodynamic instabilities, aspiration risk, gastrointestinal symptoms, hygiene issues, staff burden, reduced solute removal, and increased costs. Differing in-center nutrition policies exist within organizations and countries around the world. Recent studies have demonstrated clinical benefits and highlight the need to work toward clear guidelines. Meals or supplements during hemodialysis may be an effective strategy to improve nutritional status with limited reports of complications in real-world scenarios. Whereas larger multicenter randomized trials are needed, meals and supplements during hemodialysis should be considered as a part of the standard-of-care practice for patients without contraindications., (Copyright © 2017. Published by Elsevier Inc.)

Objective: The objective of the study was to evaluate the effects of probiotic supplementation on the gut microbiota profile and inflammatory markers in chronic kidney disease patients undergoing maintenance hemodialysis (HD)., Design and Methods: This was a randomized, double-blind, placebo-controlled study. Forty-six HD patients were assigned to receive 1 of 2 treatments: probiotic (n = 23; Streptococcus thermophilus, Lactobacillus acidophilus e Bifidobacterialongum, 90 billion colony-forming units per day) or placebo (n = 23) daily for 3 months. Blood and feces were collected at baseline and after intervention. The inflammatory markers (C-reactive protein and interleukin-6) were analyzed by immunoenzymatic assay (enzyme-linked immunosorbent assay). Uremic toxins plasma levels (indoxyl sulfate, p-cresyl sulfate, and indole-3-acetic acid) were obtained by Reversed-Phase High-Performance Liquid Chromatography. Routine laboratory parameters were measured by standard techniques. Fecal pH was measured by the colorimetric method, and the gut microbiota profile was assessed by Denaturing Gradient Gel Electrophoresis analysis., Results: Sixteen patients remained in the probiotic group (11 men, 53.6 ± 11.0 year old, 25.3 ± 4.6 kg/m 2 ) and 17 in the placebo group (10 men, 50.3 ± 8.5 year old, 25.2 ± 5.7 kg/m 2 ). After probiotic supplementation there was a significant increase in serum urea (from 149.6 ± 34.2 mg/dL to 172.6 ± 45.0 mg/dL, P = .02), potassium (from 4.4 ± 0.4 mmol/L to 4.8 ± 0.4 mmol/L, P = .02), and indoxyl sulfate (from 31.2 ± 15.9 to 36.5 ± 15.0 mg/dL, P = .02). The fecal pH was reduced from 7.2 ± 0.8 to 6.5 ± 0.5 (P = .01). These parameters did not change significantly in placebo group. Changes in the percentage delta (Δ) between groups were exhibited with no statistical differences observed. The inflammatory markers and gut profile were not altered by supplementation., Conclusions: Aprobiotic supplementation failed to reduce uremic toxins and inflammatory markers. Therefore, probiotic therapy should be chosen with caution in HD patients. Further studies addressing probiotic therapy in chronic kidney disease patients are needed., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Protein-bound uremic toxins from gut microbiota tend to accumulate in chronic kidney disease (CKD) patients and are poorly removed by current dialysis techniques. These toxins induce inflammation and are associated with cardiovascular disease (CVD). The aim of this study was to report the relationship between uremic toxins and inflammatory and cardiovascular markers in CKD patients., Design: This was a cross sectional study., Subjects: Twenty-one nondialysis patients were included (43% men, 63.0 ± 7.8 years, glomerular filtration rate: 34.4 ± 12.5 mL/min) as well as 29 hemodialysis (HD) patients [58% men, 52.7 ± 10.3 years, time on dialysis 54 (31-94.5 months)]., Main Outcome Measure: Total levels of uremic toxins (IS, p-CS, and IAA) were assessed by high-performance liquid chromatography with fluorescence detection. C-reactive protein, Interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and calprotectin plasma levels were determined by immunometric assays., Results: HD patients presented higher inflammatory markers and uremic toxins levels than nondialysis patients. IL-6 levels were positively correlated with IS (r = 0.49; P = .03), p-CS (r = 0.35; P = .04) and IAA (r = 0.36; P = .03). A positive correlation was also observed between MCP-1 levels with IS (r = 0.72; P = .001), p-CS (r = 0.48; P = .001) and IAA (r = 0.75; P = .0001). Linear regression showed that IS was an independent predictor for IL-6 and MCP-1 levels after adjustment., Conclusion: Plasma uremic toxins were associated with higher IL-6 and MCP-1 levels in CKD patients, potentially playing a role in the development of CVD., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Abnormalities in mineral and bone metabolism are frequent in chronic kidney disease patients. Physical exercise can improve many indicators of physical functioning, and recent studies showed beneficial effects on bone mineral density in the general population. The aim of this study was to evaluate the effects of resistance exercise training on bone markers and body composition in hemodialysis (HD) patients., Design: This was a randomized controlled trial., Subjects: The study included 13 HD patients (46.2% men)., Intervention: Patients were divided into a control group and an exercise group, which performed 8 weeks of intradialytic resistance exercise. Serum sclerostin, bone alkaline phosphatase (BAP), insulin, leptin, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and body composition were measured before and after the exercise period., Results: In the exercise group, BAP levels increased from 11.4 ± 6.5 to 14.6 ± 6.4 U/L (P < .05) and serum 1,25-dihydroxyvitamin D levels from 46.0 ± 23.5 to 87.2 ± 31.8 ng/mL (P < .05). After exercise, serum BAP levels were inversely correlated with serum sclerostin (r = -0.96, P < .05). There was no change in body composition in either group., Conclusion: Resistance exercise training appears to be an interesting approach for stimulating BAP production in HD patients and may prevent bone loss and stimulate bone formation., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: In elderly hemodialysis patients, protein-energy wasting is associated with poor outcome; however, the association between body mass index (BMI) changes over time, and survival has been seldom studied in this particularly frail population., Design and Methods: This prospective study recruited 502 hemodialysis patients aged ≥75 years from the French cohort ARNOS and followed them from 2005 to 2009. BMI changes over time were modeled by individual linear regression models. Survival analyses used frailty Cox models., Results: The population average age was 80.9 years. Forty-one percent of the patients died during follow-up. A 1 kg/m(2) lower baseline BMI was associated with a 4% increase in the risk of death over the study period (hazard ratio [HR] 1.04, 95% confidence interval [1.01-1.08], P = .02). A 5% BMI loss per year was associated with a 52% increase in the risk of death (HR 1.52, 95% confidence interval [1.32-1.75], P < .001). In patients who lost weight (>5% BMI loss per year), the lower was the baseline BMI, the higher was the HR for death. There was a similar trend in the patients with stable weight (5% BMI loss-5% BMI gain per year). In patients who gained weight, the HR was unexpectedly higher than in those with stable weight., Conclusions: In elderly hemodialysis patients, the impact of the BMI percent change on survival was stronger than that of the baseline BMI. Patients with stable weight had longer survivals than patients who lost or gained weight. Thus, in this population, BMI changes should be regularly assessed. Further studies should assess the safety of weight gain strategies., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Low-protein diet is the recommended nutritional intervention for nondialysis chronic kidney disease (CKD) patients because excess protein intake can damage kidney function and produce uremic toxins. Some of these toxins are generated from amino acids breakdown by gut microbiota as p-cresyl sulfate and indoxyl sulfate that have been clearly associated with cardiovascular mortality in CKD patients. Another uremic toxin, trimethylamine N-oxide (TMAO), a degradation product of choline and L-carnitine (which come mainly from animal protein such as red meat and eggs) is now considered as a proatherogenic metabolite. In the present review, we will highlight the relationship between TMAO, diet and cardiovascular aspects, and the potential concerns about TMAO in nondialysis CKD patients., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: The "Pas à Pas" initiative aimed at evaluating the weekly physical activity (PA) and its determinants in a large cohort of dialysis patients., Setting: Physical inactivity is a risk factor for mortality in maintenance dialysis patients and is still poorly documented in this population., Design: A prospective national epidemiological study was performed., Subjects: A total of 1,163 patients on maintenance dialysis (hemodialysis and peritoneal dialysis) were included., Intervention and Main Outcome Measure: PA was recorded during seven consecutive days using a pedometer to measure daily step numbers., Results: Median age was 63 years (Q1 51-Q3 75). Sixty-three percent were sedentary (<5000 steps/day) with a median of 3,688 steps/day (1,866-6,271)]. PA level was similar between hemodialysis patients and those on peritoneal dialysis (3,693 steps [1,896-6,307] vs. 3,320 [1,478-5,926], P = .33). In hemodialysis patients, PA was lower on dialysis days compared with nondialysis days (2,912 [1,439-5,232] vs. 4,054 [2,136-7,108], respectively, P < .01). PA gradually decreased with age, 57% being sedentary between 50 and 65 years and 83% of patients after 80 years. Beyond this age effect, we identified, for the first time, specific phenotypes of patients with lower PA, such as inflammation, cardiovascular disease, protein energy wasting, obesity, and diabetes. By contrast, previous kidney transplantation and a higher muscle mass were associated with higher PA., Conclusions: Dialysis patients present a very low level of PA with high sedentary. Acting on patient's modifiable phenotypes may help to increase PA to improve morbidity, mortality, and quality of life., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to test the ability of a newly developed nutrition algorithm on (1) clinical utility and (2) ability to capture patient outcomes., Research Design: This was a prospective observational study, using a practice based research network structure, involving renal dietitians and hemodialysis [HD] patients., Setting: This study took place in HD outpatient units in five different countries., Subjects: Hundred chronic HD patients were included in this study. To select subjects, dietitians screened and consented patients in their facilities until 4 patients "at nutrition risk" based on the algorithm screening tool were identified. Inclusion criteria were patients aged older than 19 years, not on hospice or equivalent, able to read the informed consent and ask questions, and receiving HD., Main Outcome Measure: The ability of the algorithm screening tool is to identify patients at nutrition risk, to guide clinicians in logical renal-modified nutrition care process chains including follow-up on relevant parameters, and capture change in outcomes over 3 months. Statistics were performed using SPSS version 20.0 and significance was set at P < .05., Results: One hundred patients on HD, enrolled by 29 dietitians, were included in this analysis. The average number of out-of-range screening parameters per patient was 3.7 (standard deviation 1.5, range 1-7), and the most prevalent risk factors were elevated parathyroid hormone (PTH; 62.8%) and low serum cholesterol (56.5%). At the initial screening step, 8 of the 14 factors led to chains with nonrandom selection patterns (by χ(2) test with P < .05). In the subsequent diagnosis step, patients diagnosed within the insufficient protein group (n = 38), increased protein intake by 0.11 g/kg/day (P = .022). In patients with a diagnosis in the high PTH group, PTH decreased by a mean of 176.85 pg/mL (n = 19, P = .011) and in those with a diagnosis in the high phosphorous group, serum phosphorous decreased by a mean of 0.91 mg/dL (n = 33, P = .006). Finally, the relative likelihood of each assessment being completed after making the related diagnosis at the previous visit compared with those for whom that diagnosis was not made was assessed, including the likelihood of a patient's protein intake assessed after a diagnosis in the insufficient protein group was made (odds ratio = 4.08, P < .05)., Conclusions: This study demonstrates the clinical utility of a web-based HD-specific nutrition algorithm, including the ability to track changes in outcomes over time. There is potential for future research to use this tool and investigate the comparative impact of nutrition interventions., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Klotho is an "aging-suppressor" gene and encodes a single-pass transmembrane protein predominantly expressed in renal tubules. Whether chronic kidney disease (CKD) affects serum Klotho is poorly documented. We aimed to measure the relationship of serum α-Klotho with renal function, acid-base status, bone biomarkers, and proteinuria in CKD patients., Design Setting, Participants, and Measurements: We measured serum α-Klotho, serum FGF23, and glomerular filtration rate by inulin clearance in 60 CKD patients between January and July 2011. We also measured serum creatinine, bicarbonate, calcium, phosphorus, parathyroid hormone, C-reactive protein, and 25-OH vitamin D. Proteinuria was obtained from a 24-h urine collection., Results: The median serum α-Klotho was 478 (348-658) pg/mL. We found an inverse relationship between serum α-Klotho and serum creatinine (r = -0.36, P = .007), proteinuria (r = -0.36, P = .013), and a positive relationship with serum bicarbonate (r = 0.33, P = .011). There was no further significant relation between serum α-Klotho and inulin clearance or serum FGF23. Multiple regression analysis including serum bicarbonate, serum creatinine, and proteinuria indicated that only serum bicarbonate was associated with serum α-Klotho (P = .003)., Conclusions: This study shows that in CKD, serum α-Klotho is related to serum bicarbonate and proteinuria and not to renal function. Further research is required to determine whether correcting these 2 amenable conditions would improve serum α-Klotho., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Nutritional status is a powerful predictor of survival in maintenance hemodialysis patients but remains challenging to assess. We defined a new Protein Energy Wasting (PEW) score based on the nomenclature proposed by the International Society of Renal Nutrition and Metabolism in 2008., Design and Methods: This score, graded from 0 (worse) to 4 (best) was derived from 4 body nutrition compartments: serum albumin, body mass index, a normalized serum creatinine value, and protein intake as assessed by nPNA., Subjects: We applied this score to 1443 patients from the ARNOS prospective dialysis cohort and provide survival data from 2005 until 2008., Main Outcome Measure: Patients survival at 3.5 year., Results: Survival ranged from 84%-69% according to the protein-energy wasting score. There was a clear-cut reduction in survival (5%-7%; P < 0.01) for each unit decrement in the score grade. There was a 99% survival at 1 year for patients with the score of 4. In addition, the 6-month variation of this PEW score also strongly predicted patients' survival (P < 0.01)., Conclusion: A new simple and easy-to-get PEW score predicts survival in maintenance hemodialysis patients. Furthermore, increase of this nutritional score over time also indicates survival improvement, and may help to better identify subgroups of patients with a high mortality rate, in which nutrition support should be enforced., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Hyperphosphatemia is strongly associated with cardiovascular morbidity and mortality in patients with chronic kidney disease. Phosphate in beverages is readily absorbed and could have a significant impact on serum phosphate levels. Patients are routinely warned about the phosphoric acid in colas, but information on the phosphate content of other beverages is difficult to find. We have shown that the phosphomolybdate method, which is used in the vast majority of hospital laboratories for measuring phosphate in urine, can give an accurate measurement of the phosphate content of beer, cider, wine, and soft drinks. No change to the standard assay protocol is required. There was considerable variation between different types of wine and beer, probably due to the methods of production. The information the assay provides could enable staff providing dietary advice to compare locally available beverages and help patients to avoid or limit their intake of those with high phosphate content., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Protein-bound uremic toxins (i.e., indoxyl sulfate or p-cresyl sulfate), produced by intestinal bacteria, are accumulated in the plasma of chronic kidney disease (CKD) patients. These toxins interact negatively with biological functions, having potent oxidative stress-inducing effects and a pathological effect on cardiovascular disease. Recent research in CKD has shown that oxidative stress and inflammation can be compounded by impaired activation of the nuclear factor (erythroid-2-related factor)-2 (Nrf2)-Kelch-like ECH associating protein-1 (Keap1) pathway, a major cellular defense mechanism. However, to date, many questions arise regarding the role of this system in CKD. For example, protein-bound uremic toxins promote oxidative stress in CKD patients, but their putative effect on the Nrf2-Keap1 system has yet to be examined in these patients. This review will focus on the putative relationship among protein-bound uremic toxins, oxidative stress, and a possible decreased expression of Nrf2 in CKD., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: The most recent literature has shown extensively that a low-protein diet in patients with chronic kidney disease (CKD) delays the natural progression of end-stage renal disease and the necessary treatment of chronic dialysis. The aim of this study was to estimate the cost-effectiveness of a very low-protein diet compared with a moderate low-protein diet., Design: Markov model., Setting: The study was conducted from the perspective of the Italian National Health Service., Subjects: Patients with CKD stages 4 and 5. Seven hundred and two patients were considered, and half were treated with a very low-protein diet and the other half with a moderate low-protein diet., Intervention: The Markov model estimates the costs and the quality-adjusted life years (QALYs) associated with a very low-protein diet versus a moderate low-protein diet for patients with CKD Stages 4 and 5. The transition probability was estimated on data from 7 studies, which determined the efficacy of very low-protein diets in delaying the need to start maintenance dialysis. Utilities and cost were estimated from literature review and projected for the lifespan considered in the model. The annual cost of dialysis per patient was approximately €34,072. The cost of a very low-protein diet was €1,440 per patient per year in the Lazio region (conservative assumptions). Probabilistic and deterministic sensitivity analyses were performed., Main Outcome Measure: QALY, cost of treatment, incremental cost-effectiveness ratio., Results: The model estimates that a very low-protein diet should be more effective. Dietary treatment improved 0.09 QALYs after 2 years, 0.16 after 3 years, 0.36 after 5 years, and up to 0.93 incremental QALYs after the first 10 years. After 2 years, the model estimated increment cost in favor of the most restrictive dietary treatment of €826, €2,146, €5,203, and €10,375 for 2, 3, 5, and 10 years of follow-up respectively., Conclusions: The results of these simulations indicate that the treatment of CKD patients with a very low-protein diet is cost-effective relative to a moderate low-protein diet in an Italian setting. Further studies should test this model in other countries with different dialysis costs and dietary support., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to review the opinions and experiences of renal care professionals to examine dietary trends among patients with chronic kidney disease (CKD) and problems associated with the clinical management of hyperphosphatemia., Design: This was an online survey comprising open and closed questions requesting information on patient dietary trends and the clinical management of hyperphosphatemia. The study was conducted in 4 European countries (the Netherlands, Spain, Sweden, and the United Kingdom)., Subjects: Participants were 84 renal care professionals., Intervention: This was an online survey., Main Outcome Measure: Responder-reported experiences and perceptions of patient dietary trends and hyperphosphatemia management were assessed., Results: Most survey responders (56%) observed an increase in the consumption of processed convenience food, 48% noticed an increase in the consumption of foods rich in phosphorus-containing additives, and 60% believed that there has been a trend of increasing patient awareness of the phosphorus content of food. Patients undergoing hemodialysis (HD) were most likely to experience difficulties in following advice on dietary phosphorus restriction (38% of responders estimated that 25-50% of their patients experienced difficulties, and 29% estimated that 51-75% experienced difficulties). Maintaining protein intake and restricting dietary phosphorus were perceived as being equally important by at least half of responders for predialysis patients (56%) and for those undergoing peritoneal dialysis and HD (54% and 50%, respectively). There were international variations in dietary trends and hyperphosphatemia management., Conclusion: Although most responders have observed a trend of increasing awareness of the phosphorus content of food among patients with CKD, the survey results indicate that many patients continue to experience difficulties when attempting to restrict dietary phosphorus. The survey responses reflect the global trend of increasing consumption of processed convenience foods and phosphorus-containing additives, which has implications for the management of hyperphosphatemia in patients with CKD., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: This study assessed acyl-ghrelin and obestatin plasma levels in nondialysis chronic kidney disease (CKD) and hemodialysis (HD) patients compared with healthy volunteers., Design: This was a cross-sectional study conducted at Renal Vida Clinic (Rio de Janeiro, Brazil) and Renal Nutrition Ambulatory (Niterói, Brazil)., Subjects: Sixty-four subjects were studied: 29 HD patients (55.4 ± 10.5 years, body mass index [BMI], 24.4 ± 3.9 kg/m(2), 17 men); 19 nondialysis patients (59.8 ± 7.5 years, BMI, 26.3 ± 4.8 kg/m(2), glomerular filtration rate, 28.8 ± 10.5 mL/minute/1.73 m(2), 5 men), and 16 healthy volunteers (53.8 ± 5.4 years, BMI, 24.6 ± 2.7 kg/m(2), 7 men)., Main Outcome Measure: Acyl-ghrelin and obestatin were assessed using enzyme immunometric assays. Body weight, height, waist circumference (WC), and skinfold were measurement, and body fat percentage, arm muscle area, BMI, and conicity index were calculated. The average daily intake of calories and protein were estimated using a 3-day, 24-hour dietary recall, and the appetite was assessed by the first question of the Hemodialysis Study Appetite Questionnaire., Results: The highest serum acyl-ghrelin (34.1 ± 13.0 pg/mL) and acyl-ghrelin/obestatin ratio (34.0 [6.7-90.2]) were found in nondialysis CKD patients who also presented with the lowest obestatin levels (0.8 [0.30-2.7] ng/mL) when compared with HD patients and healthy volunteers. HD patients presented the highest obestatin plasma levels (3.0 [2.7-3.4] ng/mL) and the lowest acyl-ghrelin/obestatin ratio (P < .05). Obestatin levels inversely correlated with WC (r = -0.6, P < .04) and BMI (r = -0.56, P < .04) in healthy volunteers., Conclusion: Although no correlation was found for appetite and food intake with acyl-ghrelin and obestatin in CKD patients, HD patients have the most important alteration of acyl-ghrelin and obestatin plasma levels and had a more impaired nutritional status than nondialysis CKD individuals., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The retention of p-cresyl sulfate (PCS), the prototype of protein-bound uremic toxins that is produced by the gut microbiota and normally excreted by the kidney, may contribute to the development of insulin resistance in patients with chronic kidney disease. In a recent study, we demonstrated in mice, as in cultured muscle cells, that PCS interferes with intracellular insulin signaling pathways and triggers insulin resistance. The treatment of CKD mice with a prebiotic that reduces the intestinal production and decreases blood levels of PCS prevented insulin resistance and lipid abnormalities, suggesting new opportunities to prevent metabolic disturbances in patients with CKD. This study highlights the uremic toxins as new actors in metabolic alterations associated with CKD and allows for the consideration of new therapeutic approaches (e.g., prebiotics, probiotics, adsorbents) to better prevent them., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Vegetarian diet is a very old practice that is liable to confer some health benefits. Recent studies have demonstrated that modification of the dietary pattern with a reduction of animal protein intake and increased consumption of plant-based foods could influence cardiovascular risk profile and mortality rate. Moreover, phosphate bioavailability from plant proteins is reduced. These statements could lead to some benefits for chronic kidney disease (CKD) patients. This review summarizes the characteristics and benefits of vegetarian diets in the general population and the potential beneficial effects of such a diet on phosphate balance, insulin sensitivity, and the control of metabolic acidosis in CKD patients. Potential drawbacks exist when a vegetarian diet is associated with protein intake that is too restrictive and/or insufficient energy intake, justifying an early and regular nutritional follow-up jointly assumed by a nephrologist and a renal dietitian., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To analyze the reported energy intake (EI(rep)) in hemodialysis (HD) patients by total energy expenditure (TEE) measured by a dedicated device., Design: Cross-sectional study., Setting: RenalCor and RenalVida Clinics (Rio de Janeiro, Brazil)., Patients and Others Participants: Forty-eight HD patients (51.4 ± 12.2 years, 62% men, body mass index [BMI], 23.8 ± 4.5 kg/m(2)) were studied., Main Outcome Measure: EI(rep) was evaluated using a 3-day food record. TEE was measured over a 2-day period by SWA (SenseWear Pro2 Armband, BodyMedia Inc., Pittsburgh, PA). Subjects were identified as underreporters (URs), acceptable reporters (ARs), or overreporters (ORs) from their EI(rep)/TEE ratio. ARs were defined as having the EI(rep)/TEE ratio in the range of 0.76 to 1.24, URs as EI(rep)/TEE <0.76, ORs as EI(rep)/TEE >1.24 according to Goldberg index., Results: The mean TEE and EI(rep) were 34.7 ± 9.4 kcal/kg/day and 22.8 ± 10.6 kcal/kg/day, respectively, and 37.5% of patients presented overweight or obesity. Thirty-one patients (65%) were identified as URs, and the mean of Goldberg index was 0.54 ± 0.12 (0.23 to 0.75), versus 0.95 ± 0.12 (0.79 to 1.2) for ARs. There were no ORs among the patients studied. There were negative correlations between Goldberg index and BMI (r = -0.35, P < .01) and % body fat (r = -0.4, P < .01) and between EI(rep) and BMI (r = -0.58, P < .001)., Conclusion: These results confirm a high prevalence of underreporting of EI in HD patients, particularly in patients with high BMI., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Chronic kidney disease (CKD) is increasingly common, and there is an increasing awareness that every strategy should be used to avoid complications of CKD. Restriction of dietary protein intake has been a relevant part of the management of CKD for more than 100 years, but even today, the principal goal of protein-restricted regimens is to decrease the accumulation of nitrogen waste products, hydrogen ions, phosphates, and inorganic ions while maintaining an adequate nutritional status to avoid secondary problems such as metabolic acidosis, bone disease, and insulin resistance, as well as proteinuria and deterioration of renal function. This supplement focuses on recent experimental and clinical findings related to an optimized dietary management of predialysis, dialysis, and transplanted patients as an important aspect of patient care. Nutritional treatment strategies are linked toward ameliorating metabolic and endocrine disturbances, improving/maintaining nutritional status, as well as delaying the renal replacement initiation and improving outcomes in CKD patients. A final consensus states that dietary manipulations should be considered as one of the main approaches in the management program of CKD patients and that a reasonable number of patients with moderate or severe CKD benefit from dietary protein/phosphorus restriction., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: This study sought to better characterize the relationships between body mass index (BMI) and lean body mass (LBM) as assessed by serum creatinine (SCr) and mortality., Design: The data were collected from a prospective prevalent cohort in maintenance hemodialysis patients., Setting: The study was carried out in 25 dialysis units in Rhônes Alpes area (France and Switzerland)., Patient: A total of 1,205 patients were followed up for 1-year, starting July 1, 2005., Outcome: Mortality as well as clinical and biological routine parameters were recorded. Kaplan-Meier, Cox model, Log rank test were used for the statistical analysis., Results: We found that SCr was a strong predictor of mortality (P < .001), whereas BMI was not. Additionally, higher BMI lost its protective effect when it was associated with low SCr. Survival was strongly reduced in patients having a predialysis SCr <717 μmol/L in patients with a BMI >23 (P < .001)., Conclusion: BMI should not be used by itself but in conjunction with SCr as a surrogate of LBM to improve its morbid-mortality predictive power. LBM should also be taken into account in further survival studies carried out in hemodialysis patients., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Studies show that inflammation can contribute to an increase in resting energy expenditure in patients with chronic kidney disease; however, findings about total energy expenditure (TEE) have not been reported. The aim of this study was to evaluate the effects of inflammation on TEE and physical activity energy expenditure in hemodialysis (HD) patients., Design: This was a cross-sectional study., Setting: This study was conducted from Hôpital Edouard Herriot, Lyon, France., Patients: This study included 24 HD patients and 18 healthy subjects., Main Outcome Measure: TEE and step counts were measured over a 7-day period by the SenseWear Pro2 Armband in 24 HD patients (15 patients with C-reactive protein <5 mg/L, aged 67.0 ± 14.7 years, and 9 with C-reactive protein >5 mg/L, aged 69.0 ± 18.0 years) and compared with 18 healthy subjects (62.3 ± 15.3 years)., Results: Mean estimated TEE measured with SenseWear Pro2 Armband was significantly lower (25.5 ± 4.1 kcal/kg/day) in patients with inflammation when compared with those without inflammation (32.0 ± 6.7 kcal/kg/day) and with healthy subjects (31.8 ± 7.0 kcal/kg/day) (P = .012). There was a difference in the physical activity (step counts) between patient groups (P < .05). Healthy subjects and patients without inflammation walked more (8,107 ± 5,419 and 6,016 ± 3,752 steps/day, respectively) as compared with patients with inflammation (2,801 ± 2,754 steps/day, P = .001)., Conclusion: Our findings suggest that patients with inflammation have a lower TEE when compared with healthy subjects and patients without inflammation. TEE is influenced by physical activity because patients with inflammation appear to be less active., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Chronic kidney disease (CKD) is frequently associated with malnutrition, anorexia, and hyperleptinemia. This study was designed to test the hypothesis that a component of the uremic milieu may trigger leptin release by adipocytes. To this end, mouse 3T3-L1 adipocytes were incubated for 16 hours in culture medium containing urea (80 mM) or plasma from either healthy volunteers or patients with CKD (20%, v/v). Uremic plasma and not urea induced a large release of leptin (+557%, P < .01). These results suggest that the hyperleptinemia reported in patients with CKD, could be, at least in part, because of an overproduction of leptin by the adipose tissue., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The protein requirements recommended by international guidelines are uncommonly met in many dialysis patients. Recent large scale epidemiological studies have shown that survival impairs only when protein intake decreases below 0.9 g/kg body weight/day, and patients survival is highest for a protein intake comprised between 1.0 and 1.4 g/kg body weight/day. In case of inflammation, protein intake is frequently decreased by anorexia, however artificial nutritional support (either orally or intravenously) is able to improve nutritional status. Concerning phosphate intake, whereas increasing protein intake will slightly augment serum phosphate, the strongly observed beneficial survival benefit largely overcomes the serum phosphate increase risk. Finally, new dialysis techniques and/or membranes should be adequately assessed for their consequences on patients' nutritional status since there is a theoretical risk of increased nutrient losses., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Malnutrition is known to be highly prevalent in patients with kidney disease. It is associated with poor clinical prognosis and can result from restricted dietary protein-energy intake. The issue is also compounded by protein wasting that occurs in dialysis patients. In countering malnutrition, an adequate protein intake is essential but limited by its phosphate content. Therefore, an accurate assessment of nutritional status and intake is an important part of the therapeutic strategy for patients on dialysis. Assessing dietary phosphate intake is not straight forward, with many confounding factors requiring consideration. Interview and diet diaries are the preferred means by which dietary intake can be estimated. However, it is evident that these estimates can vary considerably and are subject to underreporting. Moreover, the use of phosphates as additives and their omission from available nutrient databases are significant contributors to this variation and underestimation. This review highlights the main limitations in assessing dietary phosphate intake and introduces the concept of monitoring changes in dietary habit (appetite) as a proxy for dietary protein and energy intake. This review discusses the use of monitoring dietary habit in trials, with phosphate binders as a simple tool to address the possibility that changes to dietary habits may influence phosphate binder efficacy., (Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Both leptin and ghrelin (in the forms of acyl ghrelin and des-acyl ghrelin) are involved in food intake, and appear to be dysregulated in chronic kidney disease. This study describes plasma leptin, acyl, and des-acyl ghrelin concentrations in relation to protein intake and body mass index (BMI) in hemodialysis (HD) patients., Design: This was a cross-sectional study., Setting: This study was conducted during the baseline phase of the French multicenter Influence of a High-Flux Dialyzer on Long-Term Leptin Levels Study., Patients: We studied 125 HD patients (aged 72.5+/-11.7 years; 59% males)., Main Outcome Measure: Blood samples were collected during fasting, and before a regular HD session. Plasma ghrelin and leptin were evaluated. The protein equivalents of total nitrogen appearance and BMI were calculated., Results: Patients demonstrated elevated serum leptin (48.0+/-49.0 ng/mL) and des-acyl ghrelin (646.6+/-489.5 pg/mL) levels, and low acyl ghrelin levels (29.8+/-58.5 pg/mL), according to normal values. Acyl ghrelin was negatively correlated with C-reactive protein (r=-0.34, P < .001). The des-acyl to acyl ghrelin ratio was negatively correlated with protein intake, as estimated by normalized Protein Nitrogen Appearance (r=-0.22, P=.01). Serum leptin exhibited its well-described positive correlation with BMI and waist circumference, but the other hormones did not., Conclusions: This study reports high des-acyl ghrelin and leptin levels and low acyl ghrelin levels in HD patients, a finding potentially associated with inflammation and food intake.

The stomach may play an important role in central feeding regulation because it produces two peptides, ghrelin and the recently identified obestatin. These peptide hormones exert opposite actions on weight regulation. Whereas ghrelin is orexigenic, obestatin seems to be anorexigenic. Studies on feeding regulation are of particular importance for patients with chronic kidney disease (CKD), because anorexia and weight loss are associated with wasting and increased morbidity and mortality. This review discusses recent information about ghrelin and obestatin and their potential role in CKD. In addition, it seems important to consider not only single values but also their ratios, because both compounds could be affected disharmoniously by CKD., (Copyright (c) 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The accurate estimation of total daily energy expenditure (TEE) in chronic kidney patients is essential to allow the provision of nutritional requirements; however, it remains a challenge to collect actual physical activity and resting energy expenditure in maintenance dialysis patients. The direct measurement of TEE by direct calorimetry or doubly labeled water cannot be used easily so that, in clinical practice, TEE is usually estimated from resting energy expenditure and physical activity. Prediction equations may also be used to estimate resting energy expenditure; however, their use has been poorly documented in dialysis patients. Recently, a new system called SenseWear Armband (BodyMedia, Pittsburgh, PA) was developed to assess TEE, but so far no data have been published in chronic kidney disease patients. The aim of this review is to describe new measurements of energy expenditure and physical activity in chronic kidney disease patients.

Bone damage because of chronic kidney disease (CKD) represents a daily challenge for nephrologists. The impact of CKD on bone health may be immediate (serum phosphocalcic disturbances) or delayed (bone fractures and vascular calcifications). Histomorphometry remains the gold standard to evaluate bone, but it is rarely performed in clinical practice. Areal measurement of bone mineral density by dual x-ray absorptiometry is routinely performed to evaluate bone mass. However, this technique presents some limitations. In 2000, the United States National Institutes of Health defined new "quality" criteria for the diagnosis of osteoporosis in addition to decreased bone mass. Bone strength actually integrates two concepts: bone quantity and bone quality (i.e., microarchitectural organization, bone turnover, bone material properties such as mineralization, collagen traits, and microdamage) that cannot be evaluated by dual x-ray absorptiometry. New three-dimensional, noninvasive bone-imaging techniques have thus been developed, e.g., high-resolution peripheral quantitative computed tomography. High-resolution peripheral quantitative computed tomography allows evaluation of both volumetric density and microarchitecture in different compartments of bone, at the distal radius and tibia. High-resolution peripheral quantitative computed tomography may be useful in predicting fractures and assessing bone preventive or therapeutic strategies in CKD patients. It should be evaluated in long-term, longitudinal follow-ups.

Enhanced chronic inflammation and reduced insulin sensitivity are often present in chronic kidney disease (CKD). Cardiovascular disease remains a major cause of morbidity and mortality in end-stage renal patients. Adiponectin (ADP) is a hormone exclusively produced by adipocytes and possesses anti-inflammatory and cardioprotective properties. Despite the high prevalence of insulin resistance and cardiovascular disease, levels of ADP are increased among end-stage renal disease patients on hemo or peritoneal dialysis but also among patients with moderate renal failure or with the nephrotic syndrome. Furthermore, lower ADP levels are associated with poor cardiovascular outcome. In this review, we examine ADP modifications in CKD and discuss the different factors that may have an impact on this adipokine metabolism in renal failure.

Background: Serum free carnitine is decreased and serum acylcarnitines are increased in maintenance hemodialysis (MHD) patients, and the causes for these abnormalities are not known. This study examined the role of renal failure in the occurrence of low serum carnitine and increased acylcarnitines in patients with advanced chronic kidney disease (CKD) by assessing the relationship between these compounds and renal function in normal individuals and patients with CKD. If these compounds decrease as glomerular filtration rate (GFR) decreases, this suggests that decreased intake or impaired synthesis in kidneys explain the low serum values. If serum compounds increase as GFR decreases, this suggests that impaired excretion may predispose to these values., Methods: The study, conducted in Lyon, France (part A), and Los Angeles, California (part B), compared serum free carnitine and acylcarnitines to renal function in 20 normal patients, 65 CKD patients, and 29 MHD patients. GFR was measured using inulin (A) and iothalamate (B) clearances. Carnitine compounds were measured by tandem mass spectrometry (A) and electron spray mass spectrometry (B)., Results: There was no relationship between serum total carnitine or free carnitine and GFR in the normal subjects and CKD patients. In contrast, serum acylcarnitines were inversely correlated with GFR in these 2 groups. Serum free carnitine was significantly lower in MHD patients than in CKD patients and normal controls in study B, whereas acylcarnitines were significantly greater than controls in studies A and B and than in CKD patients in study A., Conclusions: Serum free carnitine is not reduced in CKD and decreases in MHD patients. Serum acylcarnitines increase in CKD and MHD patients primarily because of impaired excretory function in the failing kidney.

In the past 10 years, 3 new metabolic compounds, leptin, adiponectin, and ghrelin, involved in energy metabolism, body composition, and appetite regulation, have been discovered. We have assessed their characteristics in 46 patients with stage 3 to 4 chronic kidney disease to evaluate the role of decreased renal function in the abnormal handling reported in more severe end-stage renal disease patients. In addition to the usual correlations with body mass index and body fat mass, the results show unexpected positive correlations between leptin and insulin, leptin and adiponectin, a weak inverse relationship between adiponectin and glomerular filtration rate, and no influence of C-reactive protein on either leptin or adiponectin in these noninflamed patients. Serum ghrelin was inversely correlated with body mass index and with glomerular filtration rate as measured by inulin clearance. Thus, ghrelin and leptin, 2 antagonist signals for energy balance, both seem to increase when glomerular filtration rate is reduced, potentially neutralizing their respective biologic effects in severe renal insufficiency.

High morbidity and mortality of maintenance dialysis patients have led to an increase in interest in outcome research in an attempt to identify causes for this adverse outcome. It has been proposed that a substantial amount of this risk can be explained by protein energy malnutrition, chronic inflammation, or concurrent combination of both, known as malnutrition-inflammation complex syndrome (MICS). Elements of overnutrition, such as increased weight or high serum cholesterol levels, which are deleterious in the general population, paradoxically are protective in dialysis patients. Conversely, a low body mass index and low serum levels of cholesterol, creatinine, and possibly homocysteine are risk factors for poor outcome in dialysis-dependent populations. These reverse or paradoxical relationships between nutritional markers and outcome are referred to as reverse epidemiology. The MICS appears to be a main contributor to the reverse epidemiology and poor outcome. Mortality is the most definitive and objective clinical outcome, whereas hospitalization and quality of life (QoL) are additional relevant but somewhat less objective outcome measures in dialysis populations. A systematic classification of outcome measures and their related epidemiologic and statistical assessment tools in dialysis patients are reviewed. The effect of MICS on outcome can be examined by epidemiologic studies that are based on large samples of dialysis patients, use multivariate techniques, and, as long as they follow strict methodologic requirements, provide an invaluable economical alternative to expensive clinical trials.

Malnutrition is a frequent state during maintenance dialysis. Among a variety of reasons, chronic catabolic events as well as resistance to anabolic compounds do induce an imbalance in protein metabolism and favor a chronic loss in protein mass. Anabolic effects have been obtained in pilot studies with recombinant growth hormone and insulin-like growth factor-1 in adult dialysis patients. More recently, the come back of androgen therapy provided reports of a positive impact on body composition and physical activity during maintenance dialysis. Strong improvement in nutritional status has also been obtained by more frequent dialysis sessions, either during long nocturnal or short daily schedules. Thus, promising new therapies are emerging to fight the important incidence of malnutrition in dialysis patients., (Copyright 2003 by the National Kidney Foundation, Inc.)