title: 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.
abstract: 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.
authors.affiliation: Department of Nephrology, Institute for Clinical and Experimental Medicine, Postgraduate Medical School, Prague, Czech Republic. vladimir.teplan@medicon.cz
authors.forename: V
authors.initials: V
authors.lastname: Teplan
authors.forename: O
authors.initials: O
authors.lastname: Schück
authors.forename: M
authors.initials: M
authors.lastname: Votruba
authors.forename: R
authors.initials: R
authors.lastname: Poledne
authors.forename: L
authors.initials: L
authors.lastname: Kazdová
authors.forename: J
authors.initials: J
authors.lastname: Skibová
authors.forename: J
authors.initials: J
authors.lastname: Malý
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000627:therapeutic use; D000597:Amino Acids, Branched-Chain / Q000097:blood; D000601:Amino Acids, Essential / Q000627:therapeutic use; D018753:Diet, Protein-Restricted / Q000379:methods*; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D005526:Food, Formulated; D005609:Free Radicals / Q000097:blood; D006801:Humans; D007651:Keto Acids / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism / Q000652:urine; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011506:Proteins / Q000378:metabolism; D011507:Proteinuria / Q000209:etiology; D011994:Recombinant Proteins; D016896:Treatment Outcome
chemical_list: D000596:Amino Acids; D000597:Amino Acids, Branched-Chain; D000601:Amino Acids, Essential; D005609:Free Radicals; D007651:Keto Acids; D008074:Lipoproteins; D011506:Proteins; D011994:Recombinant Proteins; D004921:Erythropoietin; C048995:ketosteril