Alpha-Ketoanalogue Dosing in Chronic Kidney Disease
The standard dose of alpha-ketoanalogues (KA) is 1 tablet per 5 kg body weight per day (approximately 0.1-0.2 g/kg/day), typically administered as part of a very-low-protein diet (0.3-0.4 g protein/kg/day) in patients with advanced CKD. 1, 2
Standard Dosing Regimen
The typical prescription is 1 tablet of ketoanalogue preparation (such as Ketosteril) per 5 kg of body weight daily, which translates to approximately 12-18 tablets per day for a 60-90 kg patient. 2 This dosing has been validated in clinical practice over multiple years of experience with patients who have advanced chronic renal failure. 2
- Historical studies used 6-14 g of ketoacid salts daily (as sodium or calcium salts) in patients with severe chronic uremia, though this represents older formulations. 3
Dose-Response Considerations
Higher daily dosages appear more effective: Real-world evidence demonstrates that KA supplementation at more than 5.5 tablets per day is associated with significantly lower risk for long-term dialysis and mortality in patients with anemic advanced CKD. 4 This suggests that adequate dosing is critical for clinical benefit, and underdosing may fail to provide the intended nephroprotective effects.
- The appropriate dose of KA/EAA supplements has not been definitively established through formal dose-response studies, representing a gap in the evidence base. 1
Timing of Initiation
Ketoanalogues should be introduced before end-stage renal failure for optimal results. 2 Evidence suggests better outcomes when treatment begins in patients with plasma creatinine lower than 700 μmol/L (approximately 8 mg/dL), corresponding to CKD stage 4-5 with eGFR <30 mL/min/1.73 m². 2
- The indications for when to inaugurate KA/EAA-supplemented very-low-protein diet therapy remain unclear in current practice. 1
Dietary Protein Restriction
KA supplementation must be combined with a very-low-protein diet of 0.3-0.4 g protein/kg/day to achieve the intended metabolic benefits. 1, 2 This combination:
- Reduces generation of potentially toxic metabolic products 1
- Decreases the burden of potassium, phosphorus, and possibly sodium 1
- Maintains good nutritional status while providing calcium 1
Important caveat: Some clinicians prescribe KA/EAA supplements with much higher protein intakes than the VLPDs in which these supplements have been studied, but the effectiveness of this approach lacks adequate research support. 1
Clinical Monitoring
Monitor for nutritional adequacy and muscle mass preservation. Real-world evidence shows that KA supplementation at appropriate doses prevents skeletal muscle mass loss and fat mass gain, particularly in elderly patients (≥68 years) with stage 4-5 CKD. 5
- Skeletal muscle and body fat mass should be monitored at baseline, 6 months, and 12 months using bioelectrical impedance analysis or similar methods. 5
- KA users tend to maintain skeletal muscle and body fat mass, whereas inadequate supplementation results in significant muscle mass reduction and body fat gain. 5
Duration of Therapy
Treatment can be continued for extended periods (8-52 months documented) with good tolerability and no evidence of malnutrition. 2 Mean renal survival in treated patients was 15.6 ± 12 months, with longer survival in patients whose plasma creatinine was lower at treatment initiation. 2