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

Supplement with keto acids/amino acids (KA) and erythropoietin can independ ently improve the metabolic sequels of chronic renal insufficiency. Our stu dy was designed to establish whether a supplementation with keto acids/amin o acids (KA) exerts additional beneficial metabolic effects in patients wit h chronic renal insufficiency (CRF) treated with a low-protein diet (LPD) a nd recombinant human erythropoietin (EPO). In a prospective randomized controlled trial over a period of 12 months, we evaluated a total of 38 patients (20M/18F) aged 32-68 years with a creatin ine clearance (C-Cr)of 20-36 ml/min. All patients were receiving EPO (40 U/ kg twice a week sc) 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 d osage of 100 mg/kg/day while 18 patients (Group II) received no supplementa tion. During the study period, the glomerular filtration rate slightly decreased (C-cr 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 C-in); this however was more m arked in Group II (Group I vs. Group II, p < 0.01). The serum levels of ure a 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 de crease in proteinuria (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<plus/ minus>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<plus/minus>0.1 to 1.2 +/-0.1 mmol/L, p < 0.01). A further remarkable finding was a reduction in the serum conce ntration of free radicals (p < 0.01). We conclude that a KA supplementation in patients with CRF receiving LPD an d EPO potentiates the beneficial effects on metabolism of proteins, amino a cids and surprisingly, also lipids. Long-term co-administration of KA, EPO and LPD was also associated with a delay in progression of renal insufficie ncy 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.