Influence of ketoanalogs supplementation on the progression in chronic kidney disease patients who had training on low‐protein diet

Chang, Jae Hyun; Kim, Yon Su; Park, Sun-Hee; Kang, Ea Wha; Yoo, Tae‐Hyun; Kim, Beom Seok; Choi, Kyu Hun; Lee, Ho Yung; Han, Dae Suk; Shin, Sug Kyun

doi:10.1111/j.1440-1797.2009.01115.x

Cited by 41 publications

(55 citation statements)

References 21 publications

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“…Recent clinical trials of SVLPDs (Table 4) have shown stable or improved serum albumin concentrations (70)(71)(72)(73)(74)(75) and only subtle decreases in lean body mass and fat mass, although one study indicated a significant decrease in bone mass over 2 y (76). These recent studies of SVLPDs appear to confirm a decrease in proteinuria (56,67,71,72) and, in some studies, a less rapid progression of CKD (56,(72)(73)(74)(75)77). In one particularly intriguing multicenter prospective randomized trial, 112 elderly nondiabetic patients with advanced NDD CKD (glomerular filtration rate: 5-7 mL/min) were randomly assigned to receive a diet providing 35 kcal $ kg 21 $ d 21 and 0.3 g protein $ kg 21 $ d 21 supplemented with keto acids/EAAs, amino acids, and vitamins compared with starting regular dialysis therapy with higher protein intakes.…”

mentioning

confidence: 58%

Management of protein-energy wasting in non-dialysis-dependent chronic kidney disease: reconciling low protein intake with nutritional therapy

Kövesdy

Kopple²,

Kalantar-Zadeh³

2013

The American Journal of Clinical Nutrition

221

194

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Protein-energy wasting (PEW), characterized by a decline in body protein mass and energy reserves, including muscle and fat wasting and visceral protein pool contraction, is an underappreciated condition in early to moderate stages of chronic kidney disease (CKD) and a strong predictor of adverse outcomes. The prevalence of PEW in early to moderate CKD is $20-25% and increases as CKD progresses, in part because of activation of proinflammatory cytokines combined with superimposed hypercatabolic states and declines in appetite. This anorexia leads to inadequate protein and energy intake, which may be reinforced by prescribed dietary restrictions and inadequate monitoring of the patient's nutritional status. Worsening uremia also renders CKD patients vulnerable to potentially deleterious effects of uncontrolled diets, including higher phosphorus and potassium burden. Uremic metabolites, some of which are anorexigenic and many of which are products of protein metabolism, can exert harmful effects, ranging from oxidative stress to endothelial dysfunction, nitric oxide disarrays, renal interstitial fibrosis, sarcopenia, and worsening proteinuria and kidney function. Given such complex pathways, nutritional interventions in CKD, when applied in concert with nonnutritional therapeutic approaches, encompass an array of strategies (such as dietary restrictions and supplementations) aimed at optimizing both patients' biochemical variables and their clinical outcomes. The applicability of many nutritional interventions and their effects on outcomes in patients with CKD with PEW has not been well studied. This article reviews the definitions and pathophysiology of PEW in patients with non-dialysis-dependent CKD, examines the current indications for various dietary modification strategies in patients with CKD (eg, manufactured protein-based supplements, amino acids and their keto acid or hydroxyacid analogues), discusses the rationale behind their potential use in patients with PEW, and highlights areas in need of further research.

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confidence: 58%

Management of protein-energy wasting in non-dialysis-dependent chronic kidney disease: reconciling low protein intake with nutritional therapy

Kövesdy

Kopple²,

Kalantar-Zadeh³

2013

The American Journal of Clinical Nutrition

221

194

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“…However, the targeted production of 2-ketoisovalerate with C. glutamicum has thus far not been reported. 2-Ketoisovalerate is the precursor of L-valine, L-leucine, and pantothenate synthesis and serves today as a substitute for L-valine or L-leucine in chronic kidney disease patients (1,9,19,55). To our knowledge, the 2-ketoisovalerate demand today is exclusively covered by chemical synthesis, which can be done by a variety of methods (10).…”

mentioning

confidence: 99%

Metabolic Engineering of Corynebacterium glutamicum for 2-Ketoisovalerate Production

Krause

Blombach

Eikmanns

2010

Appl Environ Microbiol

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2-Ketoisovalerate is used as a therapeutic agent, and a 2-ketoisovalerate-producing organism may serve as a platform for products deriving from this 2-keto acid. We engineered the wild type of Corynebacterium glutamicum for the growth-decoupled production of 2-ketoisovalerate from glucose by deletion of the aceE gene encoding the E1p subunit of the pyruvate dehydrogenase complex, deletion of the transaminase B gene ilvE, and additional overexpression of the ilvBNCD genes, encoding the L-valine biosynthetic enzymes acetohydroxyacid synthase (AHAS), acetohydroxyacid isomeroreductase, and dihydroxyacid dehydratase. 2-Ketoisovalerate production was further improved by deletion of the pyruvate:quinone oxidoreductase gene pqo. In fed-batch fermentations at high cell densities, the newly constructed strains produced up to 188 ؎ 28 mM (21.8 ؎ 3.2 g liter ؊1 ) 2-ketoisovalerate and showed a product yield of about 0.47 ؎ 0.05 mol per mol (0.3 ؎ 0.03 g per g) of glucose and a volumetric productivity of about 4.6 ؎ 0.6 mM (0.53 ؎ 0.07 g liter ؊1 ) 2-ketoisovalerate per h in the overall production phase. In studying the influence of the three branched-chain 2-keto acids 2-ketoisovalerate, 2-ketoisocaproate, and 2-keto-3-methylvalerate on the AHAS activity, we observed a competitive inhibition of the AHAS enzyme by 2-ketoisovalerate.

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“…Regarding urea and creatinine, the ingestion of ketoanalogues together with a low protein diet content showed improvement in glomerular filtration rate, which may have promoted the maintenance of energetic balance and reduction of clinical signs of uremia in human adults (ETESA 2002, Prakash et al 2004, Chang et al 2009, Garneata & Mircescu 2013). However, a study in children showed no significant difference in glomerular filtration, but was effective to increase body cell mass as well as decrease the fraction of urea/creatinine in all children studied (Jones et al 1983).…”

Section: Discussionmentioning

confidence: 99%

“…It is considered as an important marker of progression of kidney disease (Methven et al 2010, Grauer 2013 and is also an inexpensive predictor of the glomerular filtration rate (Ruggenenti et al 1998). A human study with 6 months of follow up showed that the administration of 12 tablets of keto-supplement a , per day, with a low protein diet was efficient in decreased glomerular filtration rate (Chang et al 2009). Another study with humans showed that a low-protein diet associated with supplementation ketoanalogues was effective in delaying progression of the disease (Tzekov et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Randomized controlled clinical trial of ketoanalogues supplementation in dogs with chronic kidney disease

et al. 2018

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RESUMO.-[Estudo clínico randomizado controlado da suplementação de cetoanálogos em cães com doença renal crônica.] O objetivo foi de verificar a eficácia da suplementação com cetoanálogos em cães com Doença Renal Crônica (DRC) grau 3. Um ensaio clínico controlado e randomizado foi realizado com 20 cães com DRC grau 3. Os animais foram divididos em 4 grupos: grupo 1 (controle): terapia convencional (TC) para DRC; grupo 2: TC e 60mg/kg, VO, q48h de cetoanálogoa; grupo 3: TC e 60mg/kg, VO, q24h de cetoanálogoa; e grupo 4, TC e 120mg/kg, VO, q12h de cetoanálogoa. Todos os cães receberam ração renal para cães. Os animais foram avaliados no início da terapia e após 15 e 30 dias. Hemograma completo, ureia, creatinina, fósforo, cálcio, potássio e sódio séricos e a razão proteína creatinina (RPC) urinária foram analisados. Foi verificado que o uso dos cetoanálogos em cães com DRC grau 3 durante 30 dias não mostrou eficácia, em nenhuma das dosagens utilizadas, em melhorar os sinais clínicos e sintomatologia da doença, os valores do hemograma e ureia e creatinina séricos, normalizar eletrólitos e reduzir RPC. Concluiu-se que o uso de cetoanálogos

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Influence of ketoanalogs supplementation on the progression in chronic kidney disease patients who had training on low‐protein diet

Abstract: KA supplementation on over LPD delayed the progression of CKD without deteriorating nutritional status, and initial serum albumin levels could be an independent factor.

Cited by 41 publications

References 21 publications

Management of protein-energy wasting in non-dialysis-dependent chronic kidney disease: reconciling low protein intake with nutritional therapy

Management of protein-energy wasting in non-dialysis-dependent chronic kidney disease: reconciling low protein intake with nutritional therapy

Metabolic Engineering of Corynebacterium glutamicum for 2-Ketoisovalerate Production

Randomized controlled clinical trial of ketoanalogues supplementation in dogs with chronic kidney disease

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