Dietary Protein, Metabolism, and Aging.

Dietary restriction (DR), a moderate reduction in food intake, improves health during aging and extends life span across multiple species. Specific nutrients, rather than overall calories, mediate the effects of DR, with protein and specific amino acids (AAs) playing a key role. Modulations of single dietary AAs affect traits including growth, reproduction, physiology, health, and longevity in animals. Epidemiological data in humans also link the quality and quantity of dietary proteins to long-term health. Intricate nutrient-sensing pathways fine tune the metabolic responses to dietary AAs in a highly conserved manner. In turn, these metabolic responses can affect the onset of insulin resistance, obesity, neurodegenerative disease, and other age-related diseases. In this review we discuss how AA requirements are shaped and how ingested AAs regulate a spectrum of homeostatic processes. Finally, we highlight the resulting opportunity to develop nutritional strategies to improve human health during aging.

Lower energy intake associated with higher risk of cardiovascular mortality in chronic kidney disease patients on a low-protein diets.

OBJECTIVE: An increasing number of studies shown that inadequate energy intake causes an increase in adverse incidents in chronic kidney disease (CKD) patients on low-protein diets (LPD). The study aimed to investigate the relationship between energy intake and cardiovascular mortality in CKD patients on a LPD. METHODS: This was a cross-sectional study, a total of 4264 CKD patients were enrolled from the NHANES database between 2009 and 2018. Restricted cubic spline plots and Cox regression analysis were used to analyze the association between energy intake and cardiovascular mortality in CKD patients on a LPD. Additionally, a nomogram was constructed to estimate cardiovascular survival in CKD patients on a LPD. RESULTS: Among CKD patients on a LPD in the United States, 90.05% had an energy intake of less than 25 kcal/kg/day, compared to 36.94% in CKD patients on a non-LPD. Energy intake and cardiovascular mortality showed a linear relationship in CKD patients on a LPD, while a 'U-shaped' relationship was observed in CKD patients on a non-LPD. Multifactorial Cox regression models revealed that for Per-standard deviation (Per-SD) decrement in energy intake, the risk of cardiovascular mortality increased by 41% (HR: 1.41, 95% CI: 1.12, 1.77; P = 0.004) in CKD patients on a LPD. The concordance index of the nomogram was 0.79 (95% CI, 0.75, 0.83). CONCLUSION: CKD patients, especially those on a LPD, have significantly inadequate energy intake. Lower energy intake is associated with higher cardiovascular mortality in CKD patients on a LPD.

In Vivo Metabolic Responses to Different Formulations of Amino Acid Mixtures for the Treatment of Phenylketonuria (PKU).

Phenylketonuria (PKU) is a rare autosomal recessive inborn error of metabolism where the mainstay of treatment is a Phe restricted diet consisting of a combination of limited amounts of natural protein with supplementation of Phe-free or low-Phe protein substitutes and special low protein foods. Suboptimal outcomes may be related to the different absorption kinetics of free AAs, which have lower biological efficacy than natural proteins. Physiomimic TechnologyTM is a technology engineered to prolong AA (AA-PT) release allowing physiological absorption and masking the odor and taste of free AAs. The aim of these studies was to assess the impact of AA-PT formulation on selected functional and metabolic parameters both in acute and long-term experimental studies. Adult rats in fasting conditions were randomized in different groups and treated by oral gavage. Acute AA-PT administration resulted in significantly lower BUN at 90 min versus baseline. Both BUN and glycemia were modulated in the same direction as intact casein protein. Long-term treatment with AA-PT significantly reduces the protein expression of the muscle degradation marker Bnip3L (-46%) while significantly increasing the proliferation of market myostatin (+58%). Animals dosed for 15 days with AA-PT had significantly stronger grip strength (+30%) versus baseline. In conclusion, the results suggest that the AA-PT formulation may have beneficial effects on both AA oxidation and catabolism with a direct impact on muscle as well as on other metabolic pathways.

Protein intake and outcome in critically ill patients.

PURPOSE OF REVIEW: The objective of this review is to describe the impact of protein intake on the outcomes of critically ill patients in the literature published in the preceding 2 years. RECENT FINDINGS: Observational studies showed inconsistent results regarding the association of higher protein intake and outcomes of critically ill patients. Randomized controlled trials that directly compared higher versus lower protein intake in ICU patients are scarce, varied considerably in their designs and primary outcomes, and generally had relatively small differences in the amount of delivered protein between the study arms. Systematic reviews of existing studies showed no difference in mortality with higher protein intake. In addition, there is uncertainty regarding high protein provision in the early phase of critical illness. SUMMARY: The optimal amount of protein intake in critically ill patients remains largely unclear and is considered a high priority for research. Ongoing clinical trials are likely to provide additional evidence on several important questions including the dose, timing, type of protein and the interaction with caloric intake and exercise.

Veganism, aging and longevity: new insight into old concepts.

PURPOSE OF REVIEW: Plant-based diets are associated with better health and longevity. Veganism is a strict form of vegetarianism, which has gained increasing attention in recent years. This review will focus on studies addressing mortality and health-span in vegans and vegetarians and discuss possible longevity-enhancing mechanisms. RECENT FINDINGS: Studies in vegans are still limited. Epidemiologic studies consistently show lower disease rates, such as lower incidence of cancer and cardiovascular disease, but mortality rates are comparable with rates in vegetarians and occasional meat eaters. Reasons for following strict vegan diets differ, which may affect diet quality, and thus health and life-span. New insights into some characteristics of veganism, such as protein restriction or restriction in certain amino acids (leucine or methionine) show potentially life-span-enhancing potential. Veganism improves insulin resistance and dyslipidemia and associated abnormalities. Gut microbiota as mediator of dietary impact on host metabolism is more diverse in vegans and has been suggested to be a health-promoting factor. Vegan diets do not fulfill the requirements of children, pregnant women or old individuals who should receive adequate supplements. SUMMARY: There is substantial evidence that plant-based diets are associated with better health but not necessarily lower mortality rates. The exact mechanisms of health promotion by vegan diets are still not entirely clear but most likely multifactorial. Reasons for and quality of the vegan diet should be assessed in longevity studies.

Muscle protein turnover and low-protein diets in patients with chronic kidney disease.

Adaptation to a low-protein diet (LPD) involves a reduction in the rate of amino acid (AA) flux and oxidation, leading to more efficient use of dietary AA and reduced ureagenesis. Of note, the concept of 'adaptation' to low-protein intakes has been separated from the concept of 'accommodation', the latter term implying a decrease in protein synthesis, with development of wasting, when dietary protein intake becomes inadequate, i.e. beyond the limits of the adaptive mechanisms. Acidosis, insulin resistance and inflammation are recognized mechanisms that can increase protein degradation and can impair the ability to activate an adaptive response when an LPD is prescribed in a chronic kidney disease (CKD) patient. Current evidence shows that, in the short term, clinically stable patients with CKD Stages 3-5 can efficiently adapt their muscle protein turnover to an LPD containing 0.55-0.6 g protein/kg or a supplemented very-low-protein diet (VLPD) by decreasing muscle protein degradation and increasing the efficiency of muscle protein turnover. Recent long-term randomized clinical trials on supplemented VLPDs in patients with CKD have shown a very good safety profile, suggesting that observations shown by short-term studies on muscle protein turnover can be extrapolated to the long-term period.

Dietary satisfaction and quality of life in chronic kidney disease patients on low-protein diets: a multicentre study with long-term outcome data (TOrino-Pisa study).

BACKGROUND: Concerns about adherence and quality of life (QoL) limit the diffusion of low-protein diets (LPDs) as a way to slow chronic kidney disease (CKD) progression and postpone dialysis. The aim of this multicentre study is to assess dietary satisfaction in stable CKD patients. METHODS: This was a multicentre cross-sectional study with long-term follow-up data. Prevalent patients on LPD for at least 6 months were selected in four Italian centres. QoL was assessed using the World Health Organization Quality of Life questionnaire, and diet satisfaction with the Modification of Diet in Renal Disease satisfaction questionnaire. Comorbidity was assessed by Charlson Comorbidity Index, estimated glomerular filtration rate (eGFR) was calculated by the CKD Epidemiology Collaboration equation and protein intake by Maroni-Mitch formula. Survival was analysed with Kaplan-Meier curves and Cox Proportional Hazard Model. RESULTS: Four hundred and twenty-two CKD Stages 3-5 patients were enrolled. Over 95% were on moderately restricted diets (0.6 g/kg/day). Compliance was good (protein intake: 0.59 g/kg/day at baseline, 0.72 at the end of follow-up). Median dietary satisfaction was 4 on a 1-5 scale. QoL was not affected by the type of diet, but was influenced by age, comorbidity and setting of care. Two years later, at the end of follow-up, 66.6% of the patients were still on a diet; the main causes of discontinuation were dialysis and death. The dropout rate was low (5.5%); in Cox analysis, patient and renal survival were influenced by age and eGFR, but not by QoL, setting of care or type of diet. CONCLUSIONS: LPDs are compatible with high dietary satisfaction and minimal dropout, at least in patients who are able to follow such a diet for at least 6 months.

Apigenin alleviated acetaminophen-induced hepatotoxicity in low protein-fed rats: Targeting oxidative stress, STAT3, and apoptosis signals.

Apigenin (API) is a natural flavonoid abundant in fruits and vegetables. The present study was undertaken to evaluate the effect of protein malnutrition (PMN) on acetaminophen (APAP)-induced hepatotoxicity, together with the protective effects of API, in male Wistar albino rats. In total, 64 male rats were divided into eight groups. Silymarin (SIL) (100 mg/kg, PO) as a reference standard and API (50 mg/kg, PO) were given to normal and APAP-induced hepatic injury in low protein-fed rats. The present results revealed that PMN significantly potentiated APAP-induced hepatotoxicity. Interestingly, the administration of SIL and API alleviated the induced damage, as revealed by reduced serum alanine aminotransferase and aspartate aminotransferase activities along with a significant improvement of the histopathological damage. API suppressed inflammatory response by reducing the interleukin-1ß level and signal transducer and activator of transcription 3 expressions along with attenuating oxidative stress as shown by a significant reduction in liver contents of malondialdehyde and nitrite/nitrate as well as restoration of hepatic content of reduced glutathione and superoxide dismutase activity. API also counteracted apoptosis through downregulation of caspase-3 expression level. In conclusion, PMN greatly potentiated the hepatotoxic effects of APAP, and API produced a multimechanistic hepatoprotective activity that can be attributed to its antioxidant, anti-inflammatory, and antiapoptotic effects.

The 1975 type Japanese diet improves the gut microbial flora and inhibits visceral fat accumulation in mice.

In this study, the 1975 type Japanese diet was prepared and its effects and related mechanism were examined in mice. Mice were assigned to three experimental groups, the CD group fed a control diet, the MD group fed a modern Japanese diet (MD), and the JD group fed the 1975 type Japanese diet (JD) for 4 weeks. MD and JD were low protein, high fat, and high carbohydrate diets compared to the CD. Total white adipose tissue weights were significantly increased in the MD group compared to those in the CD group and were decreased in the JD group compared to those in the MD group. In the JD group, adipocyte hypertrophy was inhibited and Hsl mRNA expression was enhanced in epididymal adipose tissue and the number of bacteria associated with the production of short chain fatty acids was increased. Therefore, the JD inhibits lipid accumulation in white adipose tissue. ABBREVIATIONS: Actb: ß-actin; ALT: alanine aminotransferase; ANOVA: analyses of variance; AST: aspartate aminotransferase; Fas: fatty acid synthase; G6pdx: glucose 6-phosphate dehydrogenase; HE: hematoxylin and eosin; HOMA-IR: Homeostatic model assessment for insulin resistance; Hsl: hormone-sensitive lipase; JD: 1975 type Japanese diet; Leptin: leptin; MD: modern Japanese diet; Me: malic enzyme; NEFA: non-esterified fatty acids; PL: phospholipids; Pparδ: peroxisome proliferator-activated receptor delta; Pparγ: peroxisome proliferator-activated receptor gamma; qRT-PCR: quantitative reverse transcriptase polymerase chain reaction; SAMP8: senescence-accelerated prone 8; SEM: standard error of the mean; Srebp1c: Sterol regulatory element binding protein 1c; TBARS: thiobarbituric acid reactive substance; TC: total cholesterol; TG: Triacylglycerol; V3: variable regions 3.

Effects of Low Protein Diet on Nuclear Factor Erythroid 2-Related Factor 2 Gene Expression in Nondialysis Chronic Kidney Disease Patients.

OBJECTIVE(S): Low protein diets (LPD; 0.6 g/kg/day), prescribed for nondialysis chronic kidney disease (CKD) patients, have demonstrated numerous benefits. LPDs may modulate inflammation and oxidative stress through the nuclear factor erythroid 2-related factor 2 (Nrf2), which encodes antioxidant and phase II detoxifying enzymes. LPDs also inhibit or antagonize nuclear factor kB (NF-kB) activity, which orchestrates inflammatory and oxidative stress responses. The objective of this study was to evaluate the effects of LPD on Nfr2 and NF-κB messenger RNA (mRNA) expression in nondialysis CKD patients. METHODS: In this longitudinal study, a LPD was prescribed for 30 nondialysis CKD patients for 6 months. Peripheral blood mononuclear cells were isolated, and quantitative real-time polymerase chain reaction analysis was performed to evaluate Nrf2, NF-κB, and NADPH quinine oxidoreductase-1 mRNA expression. Thiobarbituric acid-reactive substance (TBARS) levels, a marker of lipid peroxidation, were also evaluated. RESULTS: (Age 55.5 ± 14.0 years; body mass index 29.1 ± 5.9 kg/m2; glomerular filtration rate 35.6 ± 12.2 mL/minute). After 6 months of nutritional intervention, Nrf2 mRNA expression increased from 0.85 (0.47-1.56) to 1.28 (0.63-2.63) nmol/mL (P = .03), and TBARS levels were significantly decreased from 1.78 (1.31-2.38) to 1.30 (1.07-2.22) nmol/mL (P = .04). NF-κB mRNA expression showed no significant difference after 6 months, but the Nrf2/NF-κB ratio was increased. CONCLUSION(S): In this study, a LPD appeared to modulate Nrf2 expression and decrease the levels of TBARS in nondialysis CKD patients. However, more studies are needed to confirm the effectiveness of LPD on the modulation of transcription factors involved with oxidative stress and inflammation in nondialysis CKD patients.

The effect of dietary protein intake on factors associated with male infertility: A systematic literature review and meta-analysis of animal clinical trials in rats.

BACKGROUND: Studies have shown that the amount of protein in the diet affects the hypothalamic-pituitary-testis axis and sub-optimal quantity reduces male fertility potential in both animals and humans. However, individual research reports on the factors associated with male infertility are collectively uncharacterized. AIM: We systematically reviewed, and meta-analysed animal (rats) studies on the effect of low protein diet on factors associated with male infertility. METHODS: PubMed Central, EMBASE and Scopus databases were searched from inception to 30 March 2019 for the study concepts and related keywords in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Data on the outcome measures were extracted and pooled across trials using random-effects model and expressed as mean differences (MD) at a 95% confidence interval (CI). RESULTS: Twelve trials identified from 3327 studies, met our inclusion criteria in the comparison of a low protein diet (2-10% protein) vs control protein diet (17-23% protein). The results showed that a low protein diet caused a significant reduction in the body weight (P = 0.0001) testis weight (P = 0.0001), seminal vesicle weight (P = 0.0003), epididymis weight P = 0.02), serum testosterone (P = 0.001) and follicle-stimulating hormone (FSH) concentrations (P = 0.04) compared with the control treatments. No effect on luteinizing hormone (LH) plasma concentration (P = 0.13) was observed. CONCLUSION: This study revealed that low protein diet caused significant reductions in body weight, testis, epididymis and seminal vesicle weights, serum testosterone and FSH concentration in rats. We infer that sub-optimal protein consumption reduces the gonadal and endocrine function, and consequently male infertility.

The Role for Protein Restriction in Addition to Renin-Angiotensin-Aldosterone System Inhibitors in the Management of CKD.

In experimental studies a low-protein diet (LPD) and renin-angiotensin-aldosterone system (RAAS) inhibitors are both reported to slow the progression of chronic kidney disease (CKD) and reduce proteinuria. RAAS activity contributes to increased blood pressure, fluid retention, and positive sodium balance, but also to kidney damage by enhancing glomerular capillary filtration pressure and synthesis of profibrotic molecules such as transforming growth factor ß. It has been well established that an LPD decreases glomerular hyperfiltration and the generation of uremic toxins, as well as the burden of acid load, phosphorus, and sodium. In different animal CKD models, a significant reduction in proteinuria and glomerulosclerosis has been achieved when an RAAS inhibitor and LPD were combined. To date, high-quality intervention trials investigating this combined strategy are lacking. We summarize the experimental and clinical studies that have examined a potential additive action of these therapies on CKD progression. We outline potential mechanisms of action and additive efficacy of an LPD and RAAS inhibitors in CKD, with a particular emphasis on phosphate levels, uremic toxin production, acid load, and salt intake. Finally, although the evidence is inadequate to recommend combining RAAS inhibitors and an LPD to slow the progression of CKD, we provide a perspective to support a large-scale randomized clinical trial to study this combination.

Circadian clock genes' overexpression in Drosophila alters diet impact on lifespan.

Diet restriction is one of the most accurately confirmed interventions which extend lifespan. Genes coding circadian core clock elements are known to be the key controllers of cell metabolism especially in aging aspect. The molecular mechanisms standing behind the phenomenon of diet-restriction-mediated life extension are connected to circadian clock either. Here we investigate the effects of protein-rich and low-protein diets on lifespan observed in fruit flies overexpressing core clock genes (cry, per, Clk, cyc and tim). The majority of core clock genes being upregulated in peripheral tissues (muscles and fat body) on protein-rich diet significantly decrease the lifespan of male fruit flies from 5 to 61%. Nevertheless, positive increments of median lifespan were observed in both sexes, males overexpressing cry in fat body lived 20% longer on poor diet. Overexpression of per also on poor medium resulted in life extension in female fruit flies. Diet restriction reduces mortality caused by overexpression of core clock genes. Cox-regression model revealed that diet restriction seriously decreases mortality risks of flies which overexpress core clock genes. The hazard ratios are lower for flies overexpressing clock genes in fat body relatively to muscle-specific overexpression. The present work suggests a phenomenological view of how two peripheral circadian oscillators modify effects of rich and poor diets on lifespan and hazard ratios.

Efficacy of low-protein diet in diabetic nephropathy: a meta-analysis of randomized controlled trials.

PURPOSE: We aimed to systematically assess the efficacy of low-protein diet preventing progression of diabetic nephropathy based on randomized controlled trials (RCTs). METHODS: A systematic and electronic search was conducted. Initial searches of literature updated to September 2018 were made using the following databases including CNKI, VIP, Wanfang, Cochrane, PubMed, and Embase using the index words for qualified RCTs. Additional searches were performed to identify linked literature sources. Data of RCTs on low-protein diet versus control diet, efficacy analysis of kidney function, nutritional status or proteinuria were extracted. Random effects model and fixed effects model were applied to combine the data which were further analyzed by Chi-squared test and I2tests. The main outcomes were then analyzed through the use of relative risks (RR), mean difference (MD) and its 95% confidence interval (95% CI). RESULTS: Twenty articles were included in the present meta-analysis with a total of 690 patients in the low-protein diet group (LPD) and a total of 682 patients in the control group. Moderate to strong evidence indicated that LPD was significantly effective for decreasing the urinary albumin excretion rate (SMD:0.62, 95%CI:0.06-1.19) and proteinuria (SMD:0.69, 95%CI:0.22-1.16) versus the control group. No statistical difference, however, was found in glycosylated hemoglobin (SMD:0.17, 95%CI:-0.18-0.51), serum creatinine (SMD:0.20, 95%CI:-0.26-0.66), as well as glomerular filtration rate (SMD:0.21, 95%CI:-0.29-0.71) between the two groups. CONCLUSION: The current meta-analysis reveals an effective role of low-protein diet in improving diabetic nephropathy. However, the small number of involved patients may limit the accuracy of results. High-quality RCTs with a larger sample size in the future are required to confirm the current findings.

High-Resistant Starch, Low-Protein Flour Intervention on Patients With Early Type 2 Diabetic Nephropathy: A Randomized Trial.

OBJECTIVE: The objective of this study is to explore the effect of high-resistant starch (RS), low-protein flour as a source of RS on patients with early type 2 diabetic nephropathy (DN) through the clinical intervention trial. DESIGN: This was a single center, randomized, comparative, open-label trial. Seventy-five patients with early DN, aged 18 to 80 y, were recruited and randomly assigned to two groups. During the 12-week intervention, the control group patients (38 cases) followed protein-restriction diet daily with a common staple. The intervention group (37 cases) received 50 g of high-RS, low-protein flour instead of a common staple of equal quality at lunch and dinner each day. The blood glucose, blood lipids, nutritional parameters, indicators of renal function, oxidative stress, and inflammatory markers were measured. RESULTS: Compared with the control group, high-RS, low-protein flour intake led to a significant reduction in fasting blood glucose, HbA1c, total cholesterol, and triglycerides levels (P < .05 for all). The changes in serum uric acid (UA) and ß2-microglobulin (ß2-MG) level were observed after high-RS, low-protein flour intervention (uric acid [mean ± standard deviation]: -24.7 ± 38.5 µmol/L, P = .001; ß2-MG: 0.5 ± 0.9 mg/L, P = 0.018). In addition, high-RS, low-protein flour intake increased serum superoxide dismutase level by 10.1 ± 27.7 U/mL (P < .05); however, it did not change the interleukin-6 and Tumor Necrosis Factor α (TNF-α) concentration. CONCLUSIONS: Twelve-week intervention with high-RS, low-protein flour improved the blood glucose and blood lipid levels, decreased the serum uric acid (UA) and urine ß2-MG, and enhanced the ability to prevent antioxidative stress in patients with early DN.

Con: The role of diet for people with advanced Stage 5 CKD.

Restriction of dietary protein intake has been used in the management of chronic kidney disease (CKD) for many decades, yet remains controversial, with marked variations in its application in clinical practice. There is extensive literature on the subject, with some expert opinion advocating the use of protein restriction based on the balance of the available evidence. The largest randomized trial of low-protein diets is the Modification of Diet in Renal Disease study. Despite multiple secondary analyses, the essential intention-to-treat analysis failed to demonstrate a benefit in the primary outcome of rate of decline of glomerular filtration rate. There are criticisms of many published studies and meta-analyses, including the likelihood of publication bias and unsuitable biochemical endpoints that may be affected by dietary restriction in the absence of effects on kidney function, leading to false positive findings. It is also uncertain whether any benefits observed in these often older studies would be derived in patients undergoing modern standards of CKD management, including blood pressure control and renin-angiotensin blockade. Thus it is unclear whether, even in the strictly controlled environment of a clinical study, low-protein diets significantly slow CKD progression. Important questions exist regarding the applicability of these diets in routine clinical practice. Even in carefully selected study populations with intensive dietetic input, adherence to low-protein diets is poor. It is likely that only a small minority of CKD patients in routine practice could adhere to these diets, and although risks of malnutrition arising from protein restriction are uncertain, they will be greater in less supervised care outside of studies.

Pro: The rationale for dietary therapy for patients with advanced chronic kidney disease.

Dietary treatment offers many benefits to patients with advanced chronic kidney disease (CKD) who are approaching the need for renal replacement therapy. A large number of these benefits are independent of whether diets slow the rate of progression of CKD. These diets are low in protein and many minerals, and provide adequate energy for the CKD patient. The diets can reduce accumulation of potentially toxic metabolic products derived from protein and amino acid degradation, maintain a healthier balance of body water, sodium, potassium, phosphorus, calcium and other minerals, and prevent or improve protein-energy wasting. Such diets may enable patients to safely delay the onset of chronic dialysis therapy or kidney transplantation. Dietary therapy may also augment the effectiveness of infrequent or incremental dialysis by maintaining healthier metabolic and clinical status and may enable some end-stage renal disease patients to avoid the need for temporary placement of hemodialysis catheters while their arterial venous fistulae or grafts mature. The anxiety that many advanced CKD patients commonly experience with regard to starting dialysis may incentivize them to accept and adhere to dietary therapy.

Moderator's view: Low-protein diet in chronic kidney disease: effectiveness, efficacy and precision nutritional treatments in nephrology.

Intention-to-treat and per-protocol analyses provide complementary information about the usefulness of therapies. While intention-to-treat analyses of trials that tested low-protein diets remain debated, per-protocol analyses of the same trials show that low protein intake actually reduces the risk of kidney failure. Per-protocol analyses are notoriously open to bias but intention-to-treat analyses are less immaculate than commonly realized because they critically depend on adherence to the treatment being tested and therefore may not be directly relevant for informing clinical decisions when different degrees of adherence to therapy occur. Over the last 20 years new statistical techniques censoring patients at the time when they become uncompliant and that adjust for confounding attributable to incomplete adherence, i.e. for prognostic factors that predict adherence to treatment, have been developed. These techniques can be usefully applied to reanalyse the Modification Diet in Renal Disease (MDRD) and other trials. Intensive surveillance of patients on a low-protein diet is fundamental for early detection of malnutrition. However, the resources demanded by such surveillance are likely superior to the actual dietitians workforce dedicated to follow-up of the chronic kidney disease (CKD) population. Surveillance efforts may perhaps be preferentially devoted to preselected patients, i.e. patients that maintain good compliance and an adequate metabolic and nutritional status, while patients who are resistant to educational efforts and show persisting uncompliance may be reallocated to a diet with a higher protein content, which poses a lower risk of malnutrition and other adverse health outcomes.

Nutritional therapy reduces protein carbamylation through urea lowering in chronic kidney disease.

Background: Protein carbamylation is one of the non-enzymatic reactions involved in protein molecular ageing. We sought to investigate the relationship between urea levels and protein carbamylation, and whether a Mediterranean diet (MD) and a very low protein diet (VLPD) reduce protein carbamylation through reduction in urea levels in patients with chronic kidney disease (CKD). Methods: This is a prospective, randomized, crossover controlled trial that investigated 60 patients with CKD grades 3B-4 (46 males, mean age of 67 years). The enrolled CKD patients were randomly assigned (1:1) to two different nutritional treatment arms: (i) 3 months of free diet (FD), 6 months of VLPD, 3 months of FD and 6 months of MD; and (ii) 3 months of FD, 6 months of MD, 3 months of FD and 6 months of VLPD. Blood levels of lysine (Lys) and homocitrulline (Hcit) and their ratio were used as markers of cyanate levels. Due to a lack of pre-existing data on the potential effects of different dietary regimens and in light of the exploratory nature of the study, no formal sample size estimation was carried out. Results: At study completion, lower diastolic blood pressure and decreased serum levels of urea, sodium, phosphorus and parathyroid hormone, but higher serum levels of bicarbonate and haemoglobin, were noted with MD and VLPD. When compared with FD, both MD and VLPD were also associated with a decrease in serum Hcit levels and Hcit/Lys ratios (P < 0.001). Notably, reductions in urea levels correlated with substantial reductions in Hcit levels (R2 = 0.16 and 0.17 for VLPD and MD, respectively). Conclusion: In conclusion, nutritional treatments that significantly decrease serum levels of urea are associated with reduced protein carbamylation.

Nutrition education in the care of patients with chronic kidney disease and end-stage renal disease.

Diet counseling and nutrition education are recommended in the prevention and management of chronic kidney disease (CKD) and end-stage renal disease (ESRD). The importance of effectively addressing nutrition with patients has grown given the increasing prevalence of obesity, hypertension, and diabetes; conditions which influence CKD/ESRD. Dietary advice for individuals with CKD/ESRD can be seen as complex; and successful dietary management requires careful planning, periodic assessment of nutritional status, as well as monitoring of dietary compliance. In spite of recommendations and pressing need, formal training in nutrition and adequate preparation for providers is limited; and for physicians the lack of nutrition education has been acknowledged, repeatedly, as an area for improvement in medical training curricula. It has also been suggested that dietitians have an essential role in management of CKD in the primary care setting; however, dietitians who do not practice renal education daily may need training on the specific challenges in CKD/ESRD. The objectives of this chapter were to: characterize select nutrition education resources for providers who care for patients with CKD/ESRD; summarize key dietary components emphasized in the care of patients with CKD/ESRD; and address practical considerations in educational efforts focused on nutrition and CKD/ESRD.