Possible role of the thick ascending limb and of the urine concentrating mechanism in the protein-induced increase in GFR and kidney mass.

The mechanisms by which high protein intake increases filtration rate and kidney hypertrophy in health and may be detrimental to the kidney in chronic renal failure are not well understood. We studied the kidneys of Sprague Dawley rats fed high (HP) and low (LP) isocaloric protein diets (32% and 10% casein, respectively) for 4 weeks. HP induced significant increases in kidney mass, GFR, and maximum urine concentrating ability (UMax). Kidney hypertrophy was characterized by (1) a selective increase in thickness of the inner stripe of the outer medulla (IS, +54%, P less than 0.001) while total kidney height (from cortex to papillary tip) increased only by 18%; (2) a considerable hypertrophy of the thick ascending limbs (TAL) in the IS (+43% epithelium volume/unit tubular length) but not in the outer stripe nor in the cortex; and (3), an increase in heterogeneity of glomerular volume between superficial and deep nephrons (P less than 0.05). these morphologic changes parallel those we previously reported in rats fed a normal protein diet (25% casein) but in which the operation of the urine concentrating mechanism was chronically stimulated by ADH infusion or by reduction in water intake. In contrast, normal kidney growth with age or kidney hypertrophy induced by uninephrectomy were not accompanied by preferential enlargement of IS structures.(ABSTRACT TRUNCATED AT 250 WORDS)