The aim of this thesis was to explore some of the factors involved in the progression of chronic renal failure in experimental animals and in man. Dietary manipulations were used to indirectly explore some of the mechanisms of such progression to chronic renal failure. In rats, using a new experimental approach, I found that the progression to chronic renal failure (CRF) of the immune mediated nephrotoxic nephritis (NTN) depended on the degree of renal damage or compensatory changes during the sub-acute stage of the disease. The role of the host humoral immunity had little effect on such progression, In this model as well as in the sub-total nephrectomy model a low protein diet (LPD) prevented severe renal failure and protected against glomerulosclerosis. In NTN, a high protein diet (HPD) similarly provided some protection although through the prevention of renal tubulo—interstitial calcification and destruction. Such a beneficial effect was not reproduced by a urea induced osmotic diuresis or a DOCA and salt plasma volume expansion. In man, a low protein diet slowed the rate of decline of patients with CRF, However the LPD beneficial effect was selective with a preferential action in patients with chronic tubulo-interstitial diseases.