At what glomerular filtration rate (GFR) should ketoanalogues, such as ketosteril (keto acid analogues), be considered in patients with advanced chronic kidney disease (CKD)?

When to Start Ketoanalogues in Advanced CKD

Ketoanalogues should be initiated in CKD stage 3b-4 (eGFR 15-45 ml/min/1.73 m²) when implementing a low-protein diet (0.6 g/kg/day) or very low-protein diet (0.3-0.4 g/kg/day) to delay dialysis initiation and slow CKD progression while maintaining nutritional status. 1

Optimal GFR Threshold for Initiation

• Start ketoanalogues when eGFR falls to 30-45 ml/min/1.73 m² (CKD stage 3b), as earlier initiation may provide additional benefit in slowing progression 1
• The therapy remains appropriate through CKD stage 4 (eGFR 15-29 ml/min/1.73 m²) and can be continued until dialysis initiation 1, 2
• Studies demonstrate efficacy in patients with eGFR <30 ml/min/1.73 m², with some showing benefit even at mean GFR as low as 4.8 ml/min 2, 3

Patient Selection Criteria

Best candidates include:

• Diabetic patients, who demonstrate higher response rates to ketoanalogue supplementation 1
• Patients with adequate baseline albumin ≥3.5 g/dL, which predicts better response 1
• Non-nephrotic patients with proteinuria <1 g/g urinary creatinine and good nutritional status at baseline 2
• Patients with anticipated good compliance, as the regimen requires 9-14 tablets daily and strict dietary adherence 1, 2

Integration with Dietary Protein Restriction

The ketoanalogue regimen must be paired with appropriate protein restriction:

• Very low-protein diet (0.3-0.4 g/kg/day) of vegetable proteins plus ketoanalogues at 1 tablet per 5 kg body weight 1, 2
• Alternative approach: Low-protein diet (0.6 g/kg/day) with ketoanalogue supplementation 1
• Caloric intake must be maintained at 30-35 kcal/kg/day to prevent malnutrition 1
• The protein restriction without ketoanalogue supplementation risks malnutrition and is not recommended 2, 4

Expected Clinical Benefits

Ketoanalogue therapy provides multiple metabolic advantages:

• Delays dialysis initiation by approximately 1 year compared to conventional low-protein diet alone 1
• 57% slower decline in renal function versus low-protein diet without supplementation 1
• Significantly reduces urea nitrogen levels (from 56 to 43.2 mmol/L) within 48 weeks 2
• Improves serum bicarbonate (from 18.1 to 23.4 mmol/L), correcting metabolic acidosis 2
• Normalizes calcium-phosphorus metabolism, with increased serum calcium and decreased phosphate levels 2, 5
• Reduces short-term dialysis risk (6.8% vs 10.4% at one year in stage 4 CKD) 1

Monitoring Protocol

Essential parameters require regular assessment:

• Nutritional status: BMI and serum albumin every 3 months 1
• Renal function: eGFR, creatinine, and urea at baseline, then at 3,6,9, and 12 months 1
• Metabolic parameters: Serum potassium, phosphorus, and calcium regularly 1
• Nitrogen balance should be assessed to ensure neutral or positive balance 3
• Monitor for preservation of serum albumin and transferrin levels, which should stabilize or improve 3

Common Pitfalls to Avoid

• Do not prescribe ketoanalogues with higher protein intakes (>0.6 g/kg/day), as efficacy has only been established with very low-protein diets 4
• Ensure adequate caloric intake to prevent catabolism; inadequate calories will negate the nitrogen-sparing benefits 1, 2
• Do not delay initiation until eGFR <15 ml/min/1.73 m², as earlier intervention provides better outcomes 1
• Verify patient compliance capability before prescribing, as poor adherence to the complex regimen eliminates benefits 2
• Monitor for hyperphosphatemia correction, which occurs within one month and is a marker of therapeutic response 3

Safety Considerations

• No significant adverse effects have been documented in long-term studies up to 63 patient-months 3
• Nutritional status remains stable with appropriate monitoring, showing no decline in BMI or albumin 1, 2
• Therapy is safe in kidney transplant recipients with advanced CKD stages, though they require longer follow-up 6
• Good compliance is achievable in appropriately selected patients with adequate counseling 2