Adherence to ketoacids/essential amino acids-supplemented low protein diets and new indications for patients with chronic kidney disease.

BACKGROUND: Low protein diets (LPD) have long been prescribed to chronic kidney disease patients with the goals of improving metabolic abnormalities and postpone the start of maintenance dialysis. METHODS: We reviewed the recent literature addressing low protein diets supplemented with ketoacids/essential aminoacids prescribed during chronic kidney disease and their effects on metabolic, nutritional and renal parameters since 2013. RESULTS: We show new information on how to improve adherence to these diets, on metabolic improvement and delay of the dialysis needs, and preliminary data in chronic kidney disease associated pregnancy. In addition, data on incremental dialysis have been reviewed, as well as potential strategies to reverse protein energy wasting in patients undergoing maintenance dialysis. CONCLUSION: These recent data help to better identify the use of low protein diets supplemented with ketoacids/essential aminoacids during chronic kidney disease.

Diets for patients with chronic kidney disease, should we reconsider?

Here we revisit how dietary factors could affect the treatment of patients with complications of chronic kidney disease (CKD), bringing to the attention of the reader the most recent developments in the field. We will briefly discuss five CKD-induced complications that are substantially improved by dietary manipulation: 1) metabolic acidosis and the progression of CKD; 2) improving the diet to take advantage of the benefits of angiotensin converting enzyme inhibitors (ACEi) on slowing the progression of CKD; 3) the diet and mineral bone disorders in CKD; 4) the safety of nutritional methods utilizing dietary protein restriction; and 5) evidence that new strategies can treat the loss of lean body mass that is commonly present in patients with CKD.

Protein-restricted diets plus keto/amino acids--a valid therapeutic approach for chronic kidney disease patients.

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.

Decreased miR-29 suppresses myogenesis in CKD.

The mechanisms underlying the muscle wasting that accompanies CKD are not well understood. Animal models suggest that impaired differentiation of muscle progenitor cells may contribute. Expression of the myogenesis-suppressing transcription factor Ying Yang-1 increases in muscle of animals with CKD, but the mechanism underlying this increased expression is unknown. Here, we examined a profile of microRNAs in muscles from mice with CKD and observed downregulation of both microRNA-29a (miR-29a) and miR-29b. Because miR-29 has a complementary sequence to the 3'-untranslated region of Ying Yang-1 mRNA, a decrease in miR-29 could increase Ying Yang-1. We used adenovirus-mediated gene transfer to express miR-29 in C2C12 myoblasts and measured its effect on both Ying Yang-1 and myoblast differentiation. An increase in miR-29 decreased the abundance of Ying Yang-1 and improved the differentiation of myoblasts into myotubes. Similarly, using myoblasts isolated from muscles of mice with CKD, an increase in miR-29 improved differentiation of muscle progenitor cells into myotubes. In conclusion, CKD suppresses miR-29 in muscle, which leads to higher expression of the transcription factor Ying Yang-1, thereby suppressing myogenesis. These data suggest a potential mechanism for the impaired muscle cell differentiation associated with CKD.

Effect of bicarbonate on muscle protein in patients receiving hemodialysis.

BACKGROUND: Metabolic acidosis stimulates whole-body net protein breakdown in healthy adults and patients with kidney failure, but few studies investigated how acidosis affects protein metabolism in individual tissues, such as skeletal muscle. METHODS: We evaluated the effect of metabolic acidosis on protein turnover in skeletal muscle, assessed by means of phenylalanine kinetics and free amino acid concentrations in plasma and muscle. Long-term hemodialysis patients (n = 16) were divided into 2 groups in an open crossover study design. In group A, we administered bicarbonate supplements and increased blood standard bicarbonate levels from 17.8 +/- 0.03 to 27.1 +/- 1.2 mEq/L (17.8 +/- 0.03 to 27.1 +/- 1.2 mmol/L). In group B, we decreased bicarbonate supplements, which caused a decrease in standard bicarbonate levels from 26.6 +/- 0.7 to 18.6 +/- 0.3 mEq/L (26.6 +/- 0.7 to 18.6 +/- 0.3 mmol/L). RESULTS: Net phenylalanine efflux from leg tissues (muscle) was significantly less when acid-base balance was corrected compared with acidosis (10.8 +/- 1.5 versus 18.6 +/- 3.8 nmol/min/100 g tissue; P = 0.014), as was the rate of phenylalanine appearance (28.3 +/- 3.0 versus 38.4 +/- 5.9 nmol/min/100 g tissue; P = 0.016); the rate of phenylalanine disposal was unchanged. Cortisol and C-reactive protein levels in blood were unchanged after correction of acidosis, as were levels of messenger RNAs encoding components of the ubiquitin-proteasome pathway in muscle biopsy specimens. CONCLUSION: Our findings indicate that acidosis increases protein breakdown in skeletal muscle, but additional studies are needed to identify the pathways stimulated to degrade muscle protein in response to acidosis.

Cachexia in chronic kidney disease: a link to defective central nervous system control of appetite.

Anorexia is one of several abnormalities characterizing chronic kidney disease (CKD) that cause cachexia, the loss of muscle and adipose stores. It has been attributed to mechanisms ranging from accumulation of toxic "middle molecules" to psychological problems. In this issue of the JCI, Cheung and coworkers used elegant techniques to demonstrate that CKD-associated anorexia is caused by defective hypothalamic regulation of appetite. They attributed the defect to an alteration in the hypothalamus's response to leptin and inflammation. Since similar hypothalamic defects suppress appetite in inflammatory states and in cancer, it is possible that anorexia in several cachexia-inducing conditions results from a common set of hypothalamic abnormalities. The development of small molecules capable of preventing these regulatory abnormalities holds the promise of eliminating the contribution of anorexia to the development of cachexia.