Protection of Renal Function and of Nutritional Status in Uremic Rats by Means of a Low-Protein, Low-Phosphorus Supplemented Diet

Barsotti, Giovanni; Moriconi, L; Cupisti, Adamasco; Dani, L; Ciardella, F; Lupetti, S.; Giovannetti, S

doi:10.1159/000185055

Cited by 14 publications

(7 citation statements)

References 9 publications

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“…Twelve to 24 weeks of ketoacid treatment enhanced renal function, exemplified by decreased proteinuria, glomerular sclerosis, and tubulointerstitial fibrosis ( Gao et al, 2010 ; Meisinger et al, 1987 ; Zhang et al, 2016 ; Liu et al, 2018 ). Previous studies have reported similar findings ( Maniar et al, 1992 ), in addition to enhanced globular filtration rate and survival in rats ( Barsotti et al, 1988 ). More recently, a study by Wang et al found that 24 weeks of ketoacid treatment in rats with CRF increased body weight, mitochondrial electron transport chain activity and decrease oxidative damage in muscle ( Wang D. et al, 2018 ).…”

Section: Effect Of Different Diseases On Bcaa Catabolism In Skeletal Musclesupporting

confidence: 77%

Branched-chain Amino Acids: Catabolism in Skeletal Muscle and Implications for Muscle and Whole-body Metabolism

et al. 2021

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Branched-chain amino acids (BCAAs) are critical for skeletal muscle and whole-body anabolism and energy homeostasis. They also serve as signaling molecules, for example, being able to activate mammalian/mechanistic target of rapamycin complex 1 (mTORC1). This has implication for macronutrient metabolism. However, elevated circulating levels of BCAAs and of their ketoacids as well as impaired catabolism of these amino acids (AAs) are implicated in the development of insulin resistance and its sequelae, including type 2 diabetes, cardiovascular disease, and of some cancers, although other studies indicate supplements of these AAs may help in the management of some chronic diseases. Here, we first reviewed the catabolism of these AAs especially in skeletal muscle as this tissue contributes the most to whole body disposal of the BCAA. We then reviewed emerging mechanisms of control of enzymes involved in regulating BCAA catabolism. Such mechanisms include regulation of their abundance by microRNA and by post translational modifications such as phosphorylation, acetylation, and ubiquitination. We also reviewed implications of impaired metabolism of BCAA for muscle and whole-body metabolism. We comment on outstanding questions in the regulation of catabolism of these AAs, including regulation of the abundance and post-transcriptional/post-translational modification of enzymes that regulate BCAA catabolism, as well the impact of circadian rhythm, age and mTORC1 on these enzymes. Answers to such questions may facilitate emergence of treatment/management options that can help patients suffering from chronic diseases linked to impaired metabolism of the BCAAs.

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Section: Effect Of Different Diseases On Bcaa Catabolism In Skeletal Musclesupporting

confidence: 77%

Branched-chain Amino Acids: Catabolism in Skeletal Muscle and Implications for Muscle and Whole-body Metabolism

et al. 2021

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“…The beneficial role of KAs supplementation on renal function is well established in experimental models, but the effects are different in human clinical trials. LPD/VLPD + KAs were able to decrease proteinuria, renal fibrosis, and severe glomerular sclerosis in different CKD rodent models, as disclosed in Table 2 [9,10,13,14,15,17,18,19]. However, the majority of these preclinical studies have compared a normal protein diet vs. VLPD/LPD + KAs.…”

Section: Do Ketoacid Analogues Have An Impact On Renal Function Anmentioning

confidence: 99%

“…However, the majority of these preclinical studies have compared a normal protein diet vs. VLPD/LPD + KAs. It is, therefore, difficult to decipher the specific effect of the KAs supplementation [9,10,15,17,18,19]. Gao et al highlighted that supplementation of KAs increased the Kruppel-like factor-15, which is a transcription factor shown to reduce fibrosis in 5/6 nephrectomized rats [14].…”

Section: Do Ketoacid Analogues Have An Impact On Renal Function Anmentioning

confidence: 99%

Ketoacid Analogues Supplementation in Chronic Kidney Disease and Future Perspectives

2019

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Diet is a key component of care during chronic kidney disease (CKD). Nutritional interventions, and, specifically, a restricted protein diet has been under debate for decades. In order to reduce the risk of nutritional disorders in very-low protein diets (VLDP), supplementation by nitrogen-free ketoacid analogues (KAs) have been proposed. The aim of this review is to summarize the potential effects of this dietary therapy on renal function, uremic toxins levels, and nutritional and metabolic parameters and propose future directions. The purpose of this paper is also to select all experimental and randomized clinical studies (RCTs) that have compared VLDP + KA to normal diet or/and low protein diet (LPD). We reviewed the SCOPUS, WEB of SCIENCES, CENTRAL, and PUBMED databases from their inception to 1 January, 2019. Following duplicate removal and application of exclusion criteria, 23 RCTs and 12 experimental studies were included. LPD/VLPD + KAs appear nutritionally safe even if how muscle protein metabolism adapts to an LPD/VLPD + KAs is still largely unknown. VLPD + KAs seem to reduce uremic toxins production but the impact on intestinal microbiota remains unexplored. All studies observed a reduction of acidosis, phosphorus, and possibly sodium intake, while still providing adequate calcium intake. The impact of this diet on carbohydrate and bone parameters are only preliminary and need to be confirmed with RCTs. The Modification of Diet in Renal Disease study, the largest RCTs, failed to demonstrate a benefit in the primary outcome of the decline rate for the glomerular filtration rate. However, the design of this study was challenged and data were subsequently reanalyzed. However, when adherent patients were selected, with a rapid rate of progression and a long-term follow up, more recent meta-analysis and RCTs suggest that these diets can reduce the loss of the glomerular filtration rate in addition to the beneficial effects of renin-angiotensin-aldosterone system (RAAS) inhibitors. The current evidence suggests that KAs supplemented LPD diets should be included as part of the clinical recommendations for both the nutritional prevention and metabolic management of CKD. More research is needed to examine the effectiveness of KAs especially on uremic toxins. A reflection about the dose and composition of the KAs supplement, the cost-effective features, and their indication to reduce the frequency of dialysis needs to be completed.

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“…Studies in CKD rodent models have suggested a strong positive correlation between dietary phosphate consumption and CKD progression (2,3,14,18,19,24,25,48). Moreover, serum concentrations of FGF23 in patients predict a higher risk for loss of kidney function in both native and transplanted kidneys (11,30,43).…”

Section: Introductionmentioning

confidence: 99%

Dietary phosphate restriction attenuates polycystic kidney disease in mice

Omede

Zhang

Johnson

et al. 2020

American Journal of Physiology-Renal Physiology

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Studies in rodents with reduced nephron mass have suggested a strong positive correlation between dietary phosphate consumption and CKD progression. Prior work by our group demonstrated that dietary phosphate restriction can prevent tubular injury and microcyst formation in rodents with glomerulonephritis. Tubular injury and cystic dilation of tubules are key contributors to kidney function decline in polycystic kidney disease (PKD). Here, we determined whether dietary phosphate restriction slows renal cyst growth and fibrosis in a mouse model of PKD. Pcy/pcy mice received a normal phosphate (0.54%) or a phosphate-restricted (0.02%) diet ( n = 10/group) from 7 to 20 wk of age. All of the other major dietary constituents, including protein source and content, were comparable between the two diets. At 20 wk, body weight, kidney weight-to-body weight ratio (KW/BW), cystic area, cyst number, and kidney fibrosis were quantified. Pcy/pcy mice fed a phosphate-restricted diet had lower serum phosphate, fibroblast growth factor 23, and parathyroid hormone levels, along with elevated serum calcium levels and increased kidney Klotho gene expression compared with mice that consumed the control diet. Dietary phosphate restriction resulted in a 25% lower KW/BW ratio and reduced the cyst number, cystic index, and gene expression for the tubular injury markers neutrophil gelatinase-associated lipocalin and interleukin-18. Mice fed the phosphate-restricted diet exhibited lower kidney expression for pathways involved in collagen deposition and myofibroblast activation (collagen type I-α1, phosphorylated SMAD3, and α-smooth muscle actin); however, histological differences in kidney fibrosis were not appreciated. Dietary phosphate restriction slows cystogenesis and inhibits the activation of key pathways in the generation of kidney fibrosis in PKD mice.

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Protection of Renal Function and of Nutritional Status in Uremic Rats by Means of a Low-Protein, Low-Phosphorus Supplemented Diet

Cited by 14 publications

References 9 publications

Branched-chain Amino Acids: Catabolism in Skeletal Muscle and Implications for Muscle and Whole-body Metabolism

Branched-chain Amino Acids: Catabolism in Skeletal Muscle and Implications for Muscle and Whole-body Metabolism

Ketoacid Analogues Supplementation in Chronic Kidney Disease and Future Perspectives

Dietary phosphate restriction attenuates polycystic kidney disease in mice

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