Supplemented low-protein diets protect the rat kidney without causing undernutrition

Low-protein diets supplemented with keto-analogues and essential amino acid (KA-EAA) mixtures or with EAA have been widely used to retard renal deterioration without affecting nutrition. These assumptions have recently been challenged in clinical studies and rest on little or no experimental data. The effects of EAA and KA-EAA supplementations have not been compared. We compared three groups of rats with subtotal nephrectomy that were fed (1) a 16% casein reference (R) diet, (2) a 6% casein plus EAA (A) diet, or (3) a 6% casein plus KA-EAA (K) diet with KA as amino acid salts. The three diets had the same energy and mineral contents, and they induced comparable growth. The two supplements had the same nitrogen content. The only difference found until month 3 was higher proteinuria and plasma urea levels in group R rats. Renal biopsies performed at month 3 showed more severe glomerular sclerosis and tubular changes in R rats than in A and K rats. From months 3 through 7, R rats developed higher plasma creatinine levels than did A and K rats (final median values: 167, 106, and 83 mumol/L; p < 0.04), had more proteinuria (232, 56, and 84 mg/day), and showed greater mortality rates. At the time the rats were killed, 2 R, 6 A, and 5 K rats had survived while receiving the diets. Examination of the remnant kidneys, regardless of time of death, showed that renal lesions were significantly worse in R than in A and K rats, with sclerosis affecting more than 50% of the glomeruli in 7 of 13 R, 4 of 14 A, and 4 of 15 K rats, and less than 25% glomeruli in 2 of 13 R, 10 of 14 A, and 10 of 15 K rats (A and K vs R: p < 0.03). In conclusion, restriction of nonessential amino acids compensated by EAA or by KA-EAA mixtures retards renal damage without affecting growth, but no real benefit of KA or EAA has been observed.