What is the recommended dose of ketoanalogue supplements?

Ketoanalogue Dosing in Chronic Kidney Disease

For adults with CKD stages 3-5 not on dialysis, the recommended dose of ketoanalogue supplements is 1 tablet per 5 kg body weight per day (approximately 0.1-0.12 g/kg/day), administered alongside a very low-protein diet of 0.28-0.43 g dietary protein/kg/day to achieve total protein equivalents of 0.55-0.60 g/kg/day. 1

Standard Dosing Protocol

Very Low-Protein Diet with Ketoanalogues (Preferred Approach)

• Ketoanalogue dose: 1 tablet per 5 kg body weight per day 2, 3, 4
• Dietary protein: 0.28-0.43 g/kg/day (vegetarian sources preferred) 1
• Total protein equivalents: 0.55-0.60 g/kg/day when combining dietary protein plus ketoanalogue supplementation 1

This regimen is specifically recommended by KDOQI 2020 guidelines to reduce risk of end-stage kidney disease (ESKD)/death (Level 1A evidence) and improve quality of life (Level 2C evidence). 1

Alternative Low-Protein Diet (Without Ketoanalogues)

• Dietary protein: 0.55-0.60 g/kg/day without ketoanalogue supplementation 1
• This approach is acceptable but may be less effective at delaying dialysis initiation compared to the ketoanalogue-supplemented very low-protein diet 4

Patient Selection and Timing

Optimal Candidates

• CKD stage 3-5 patients who are metabolically stable 1
• eGFR <30 ml/min per 1.73 m²: Most evidence supports use at this threshold 4
• eGFR <20 ml/min per 1.73 m²: Greatest benefit observed, with number needed to treat of 2.7 to avoid dialysis 4
• Patients without diabetes or with well-controlled diabetes 1

Important Exclusions

• Patients with proteinuria >1 g/g urinary creatinine were excluded from key trials 4
• Those with poor nutritional status or inability to comply with dietary restrictions 4
• Patients already on dialysis (CKD 5D) do not use ketoanalogues; they require higher protein intake of 1.0-1.2 g/kg/day 1

Clinical Implementation

Run-In Phase

• Initial assessment period: 3 months on conventional low-protein diet (0.6 g/kg/day) before initiating ketoanalogue-supplemented very low-protein diet 4
• This run-in phase identifies compliant patients who can safely follow the more restrictive regimen 4
• Only 14% of screened patients in clinical trials were ultimately randomized, highlighting the need for careful patient selection 4

Monitoring Requirements

Close clinical supervision is mandatory when prescribing protein restriction with ketoanalogues. 1

• Nutritional parameters: Monitor appetite, dietary intake, body weight changes, anthropometric measurements, and nutrition-focused physical findings 1
• Biochemical data: Regular assessment to ensure metabolic stability 1
• Registered dietitian involvement: Essential for successful implementation and monitoring 1

Evidence for Efficacy

Dialysis Delay

• Short-term benefit (1 year): Ketoanalogue continuation reduced new-onset ESKD requiring dialysis from 10.4% to 6.8% (HR 0.62,95% CI 0.41-0.94) 5
• Long-term benefit: Mean renal survival of 15.6 ± 12 months in advanced CKD patients with mean creatinine clearance of 8.4 ml/min 2
• Number needed to treat: 4.0 patients to avoid composite endpoint (dialysis or >50% eGFR reduction) in those with eGFR <30 ml/min per 1.73 m² 4

Metabolic Benefits

• Urea reduction: 28% decrease in plasma urea level and daily urinary urea output after 1 month 2
• Nitrogen balance: Improved by 1.73 g/day with ketoanalogue supplementation 6
• Correction of metabolic abnormalities occurs specifically with ketoanalogue-supplemented diet, not with conventional low-protein diet alone 4

Safety Considerations

Nutritional Safety

• No malnutrition observed in clinical trials when properly monitored 2, 4
• Good compliance achievable with appropriate patient selection and dietitian support 4
• No adverse reactions reported in well-designed trials 4

Common Pitfall to Avoid

Do not use ketoanalogue-supplemented very low-protein diets without close supervision by a registered dietitian nutritionist. 1 The rigid dietary controls and pill burden make this approach difficult to follow, and inadequate monitoring can lead to malnutrition. Only patients demonstrating good compliance during a run-in phase should proceed with this regimen. 4

Special Populations

Diabetic CKD Patients

• Recommended protein intake: 0.6-0.8 g/kg/day (opinion-based recommendation) 1
• The evidence for ketoanalogue supplementation is less robust in diabetic patients, and the primary goal shifts to maintaining stable nutritional status while optimizing glycemic control 1

Cost-Effectiveness

• Ketoanalogue-supplemented very low-protein diet reduces lifetime care costs compared to conventional low-protein diet in Taiwan and Thailand healthcare systems 3
• Increased quality-adjusted life years (QALYs) at lower total cost supports this as a cost-effective intervention 3