Metabolic effects of keto acid--amino acid supplementation in patients with chronic renal insufficiency receiving a low-protein diet and recombinant human erythropoietin--a randomized controlled trial

Wien Klin Wochenschr. 2001 Sep 17;113(17-18):661-9.


Supplement with keto acids/amino acids (KA) and erythropoietin can independently improve the metabolic sequels of chronic renal insufficiency. Our study was designed to establish whether a supplementation with keto acids/amino acids (KA) exerts additional beneficial metabolic effects in patients with chronic renal insufficiency (CRF) treated with a low-protein diet (LPD) and recombinant human erythropoietin (EPO). In a prospective randomized controlled trial over a period of 12 months, we evaluated a total of 38 patients (20 M/18 F) aged 32-68 years with a creatinine clearance (CCr) of 20-36 ml/min. All patients were receiving EPO (40 U/kg twice a week s.c.) and a low-protein diet (0.6 g protein/kg/day and 145 kJ/kg/day). The diet of 20 patients (Group I) was supplemented with KA at a dosage of 100 mg/kg/day while 18 patients (Group II) received no supplementation. During the study period, the glomerular filtration rate slightly decreased (CCr from 28.2 +/- 3.4 to 26.4 +/- 4.1 ml/min and 29.6 +/- 4.8 to 23.4 +/- 4.4 ml/min in groups I and II, respectively and Cin); this however was more marked in Group II (Group I vs. Group II, p < 0.01). The serum levels of urea also declined (p < 0.01), more pronouncedly in Group I (p < 0.025). In Group I, there was a significant rise in the levels of leucine (p < 0.01), isoleucine (p < 0.01), valine (p < 0.02) and albumin (p < 0.01) and a decrease in protein-uria (p < 0.01). Analysis of the lipid spectrum revealed a mild yet significant decrease in total cholesterol and LDL-cholesterol (p < 0.02), more pronounced in Group I. In Group I, there was a decrease in plasma triglycerides (from 4.2 +/- 0.8 down to values a low as 2.2 +/- 0.6 mmol/L; p < 0.01) whereas HDL-cholesterol levels increased (from 0.9 +/- 0.1 to 1.2 +/- 0.1 mmol/L, p < 0.01). A further remarkable finding was a reduction in the serum concentration of free radicals (p < 0.01). We conclude that a KA supplementation in patients with CRF receiving LPD and EPO potentiates the beneficial effects on metabolism of proteins, amino acids and surprisingly, also lipids. Long-term co-administration of KA, EPO and LPD was also associated with a delay in progression of renal insufficiency and a reduction in proteinuria. Thus, concomitant administration of KA and EPO during a low-protein diet presents an effective treatment modality in the conservative management of CRF.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acids / therapeutic use
  • Amino Acids, Branched-Chain / blood
  • Amino Acids, Essential / therapeutic use
  • Diet, Protein-Restricted / methods*
  • Erythropoietin / therapeutic use*
  • Female
  • Food, Formulated
  • Free Radicals / blood
  • Humans
  • Keto Acids / therapeutic use*
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / diet therapy*
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / urine
  • Lipoproteins / blood
  • Male
  • Middle Aged
  • Prospective Studies
  • Proteins / metabolism
  • Proteinuria / etiology
  • Recombinant Proteins
  • Treatment Outcome


  • Amino Acids
  • Amino Acids, Branched-Chain
  • Amino Acids, Essential
  • Free Radicals
  • Keto Acids
  • Lipoproteins
  • Proteins
  • Recombinant Proteins
  • Erythropoietin
  • ketosteril