Remino

Approved and Clinically Accepted Indications:

• Chronic Kidney Disease (CKD):
• Non-dialysis-dependent CKD stages 3 to 5 — used as part of a protein-restricted diet to reduce nitrogenous waste and delay progression to dialysis.
• Pre-dialysis stage in combination with low-protein or very-low-protein diets to support nutritional needs and mitigate uremic symptoms.
• Protein Metabolism Disorders:
• In conditions with disturbed protein metabolism where standard amino acid supplementation may increase nitrogen load.
• Malnutrition in CKD:
• To prevent and manage protein-energy wasting while minimizing nitrogen intake.

General Dosage:

• Adults (CKD stage 3–5, not on dialysis):
• Typical dose: 1 tablet per 5 kg body weight per day (e.g., 6–12 tablets daily), divided into 3 doses with meals.
• To be used in combination with a low-protein diet (e.g., ≤40g/day).

Pediatric Use:

• Not well established. Use under specialist supervision with dosage adjustments based on weight and renal function.

Elderly:

• Same adult dosing. Monitor renal function and nutritional status closely.

Renal/Hepatic Impairment:

• Specifically indicated for patients with impaired renal function (CKD stages 3–5).
• No dose adjustment for hepatic impairment, but caution advised in severe liver dysfunction.

Route & Duration:

• Oral administration, taken with meals.
• Duration: Long-term use with continuous dietary supervision.

Ketoanalogues are nitrogen-free analogues of essential amino acids. Once ingested, they undergo transamination in the body, forming corresponding essential amino acids using endogenous nitrogen sources (e.g., ammonia). This process allows maintenance of nitrogen balance without increasing the nitrogen load, which is critical in CKD patients with reduced ability to excrete urea. Consequently, they help preserve renal function, reduce uremic toxins, and support muscle protein synthesis when combined with a low-protein diet.

• Absorption:
  Absorbed in the small intestine, particularly when taken with meals. Peak plasma levels vary depending on the specific ketoanalogue.
• Distribution:
  Distributed throughout extracellular and intracellular fluids. Crosses into systemic circulation rapidly.
• Metabolism:
  Undergoes hepatic and tissue-based transamination to form essential amino acids. Does not require renal excretion for activation.
• Excretion:
  Minimal renal elimination in original form. Nitrogen load is low, reducing urea production.
• Half-life:
  Not clearly defined due to rapid conversion and utilization.

• Pregnancy:
  Not formally assigned by FDA. Use only if clearly needed and under medical supervision. Safety data in pregnant women are limited.
• Lactation:
  Unknown if ketoanalogues are excreted in human milk. Use with caution in breastfeeding women. Clinical judgment is advised.

• Class: Amino Acid Derivatives / Protein Supplements
• Subclass: Ketoanalogues of Essential Amino Acids
• Related Use: Renal nutrition adjunct in CKD management

• Known hypersensitivity to ketoanalogues or any excipients.
• Hypercalcemia (due to calcium salts in formulation).
• Disturbed amino acid metabolism due to inborn errors.
• Severe liver failure with compromised amino acid processing.
• Patients not compliant with low-protein diet (ineffective without dietary restriction).

• Hypercalcemia Risk: Monitor serum calcium regularly due to calcium salts in formulation.
• Nutritional Monitoring: Require ongoing assessment of nutritional and renal status.
• Compliance Requirement: Ineffective without adherence to prescribed low-protein diet.
• Liver Dysfunction: Use caution in patients with severe hepatic impairment.
• Electrolyte Monitoring: Monitor phosphate, urea, and potassium levels periodically.

Common Adverse Effects:

• Gastrointestinal: Nausea, vomiting, abdominal pain, bloating
• Metabolic: Hypercalcemia, elevated phosphate

Rare/Serious Adverse Effects:

• Hypersensitivity reactions (rash, pruritus, anaphylaxis – rare)
• Electrolyte imbalances (esp. calcium-phosphate)
• Hepatic strain in cases with co-existing liver disease

Timing & Severity:

• Generally mild, dose-dependent GI effects; hypercalcemia risk increases with prolonged use or excessive intake.

• With Calcium or Vitamin D Supplements:
  Increased risk of hypercalcemia.
• Phosphate Binders (e.g., calcium acetate):
  May increase calcium load; adjust monitoring accordingly.
• Nephrotoxic Agents:
  Concurrent use requires strict renal monitoring.
• Food Interactions:
  Must be taken with meals to ensure proper absorption and nitrogen utilization.
• CYP Enzyme Involvement:
  Not significantly metabolized by CYP450 enzymes; low risk of CYP-mediated interactions.

• KDOQI Guidelines:
  Support use of ketoanalogues as adjunct therapy with very-low-protein diets (VLPD) in pre-dialysis CKD patients.
• EMA and KDIGO:
  Recommend use in well-selected, compliant patients under dietitian supervision.
• Recent Research:
  Suggests potential role in delaying dialysis initiation and preserving residual kidney function.

• Temperature: Store below 25°C.
• Humidity: Protect from moisture; keep in original container.
• Light: Store away from direct light.
• Handling: Do not freeze; keep tightly closed.
• Formulation-Specific Instructions: Follow label directions. Tablets should be taken whole, not crushed or chewed.