What are the roles of alpha-keto analogs in renal (kidney) failure?

From the Guidelines

Alpha-keto analogs are a crucial component in the management of chronic kidney disease (CKD), particularly in patients at risk of kidney failure, as they provide essential amino acids while minimizing nitrogen load on the kidneys, and should be considered as part of a very low-protein diet (0.3-0.4 g/kg body weight/d) supplemented with essential amino acids or ketoacid analogs (up to 0.6 g/kg body weight/d) under close supervision, as recommended by the KDIGO 2024 clinical practice guideline 1. The role of alpha-keto analogs in renal failure is multifaceted, including:

• Providing essential amino acids to maintain nutritional status
• Reducing nitrogen waste production, which can slow CKD progression and delay the need for dialysis
• Decreasing metabolic acidosis and improving calcium-phosphorus metabolism
• Potentially reducing proteinuria In practice, alpha-keto analogs are commonly prescribed as part of a low-protein diet, with a typical regimen involving the use of Ketosteril tablets, each containing a mixture of different keto analogs, taken at a dose of 1 tablet per 5 kg body weight daily, divided into three doses with meals 1. Key considerations for the use of alpha-keto analogs in CKD management include:
• Patient motivation and ability to adhere to dietary restrictions
• Close supervision to monitor nutritional status, kidney function, and electrolyte balance
• Avoidance of high protein intake (>1.3 g/kg body weight/d) in adults with CKD at risk of progression, as recommended by the KDIGO 2024 clinical practice guideline 1
• Contraindication in metabolically unstable people with CKD, as stated in the KDIGO 2024 clinical practice guideline 1

From the Research

Roles of Alpha-Keto Analogs in Renal Failure

• Alpha-keto analogs, also known as ketoacid analogues, play a crucial role in the management of chronic kidney disease (CKD) by providing several potential advantages, including reducing the generation of potentially toxic metabolic products and the burden of potassium, phosphorus, and sodium 2.
• These analogs can be converted to their respective amino acids without providing additional nitrogen, making them a valuable supplement for patients with CKD who require a restricted protein diet 2, 3.
• Ketoacid analogs, in combination with essential amino acids, have been shown to improve insulin sensitivity, hyperparathyroidism, and nutritional status in patients with CKD, while also reducing the risk of uremic toxicity and delaying the need for dialysis 3, 4.

Mechanisms and Effects

• The use of alpha-keto analogs in CKD patients has been associated with a reduction in acidosis, phosphorus, and possibly sodium intake, while still providing adequate calcium intake 2, 5.
• These analogs may also reduce the production of uremic toxins, although more research is needed to fully understand their impact on intestinal microbiota and muscle protein metabolism 5.
• The supplementation of ketoacid analogs has been shown to be nutritionally safe, even in very-low protein diets, and may help to reduce the loss of glomerular filtration rate in patients with CKD 5.

Clinical Applications and Future Directions

• The current evidence suggests that ketoacid analogs should be included as part of the clinical recommendations for the nutritional prevention and metabolic management of CKD 5.
• More research is needed to examine the effectiveness of ketoacid analogs, particularly in terms of their dose and composition, cost-effective features, and indication to reduce the frequency of dialysis 5.
• The use of alpha-keto analogs in pediatric patients with CKD is an area that requires further investigation, with some studies suggesting that they may be a valuable tool in the conservative management of chronic renal insufficiency or failure 6.