Physiological and morphological responses of the rat kidney to reduced dietary protein

Abstract

Renal physiological and morphological adjustments to a reduced protein diet were studied in young Munich-Wistar rats. Two groups of animals were used for the correlative physiological-morphological studies: normal protein (NP, 24% dietary protein) rats and reduced protein (LP, 8% dietary protein) rats. Both groups were fed their respective diets for 4-5 wk and had free access to drinking water. Physiological measurements of GFR and urea clearance were made on five animals from each group. These data showed that the changes in renal function specifically and almost exclusively affected the handling of urea. There was no difference in GFR between the NP and LP rats. Urea clearance was substantially reduced in LP rats. Morphological analyses were made on perfusion-fixed kidneys of five animals from each group. Selected slices were examined and photographed by light and electron microscopy. These data showed no difference in size and number of elements within the vascular bundles but showed significantly smaller lumina of the thin limbs of the short-looped nephrons and a significant thinning of the wall of the thin descending limbs of the long-looped nephrons. These morphological changes may in part be responsible for the observed physiological adjustments to a reduced protein diet. An additional group of rats (6 NP and 5 LP, all dehydrated) were analyzed for distribution of solutes within the inner medulla. The data showed that the concentration of urea, but not that of Na+, was reduced at the papillary tip in LP rats.

Low protein diet alters urea transport and cell structure in rat initial inner medullary collecting duct.

“…In rats fed a low protein diet, fractional excretion of urea is significantly reduced compared to rats fed normal or high protein diets, consistent with stimulation ofurea reabsorption by protein restriction (1,5,8,10,12). Moreover, the normal inner medullary urea concentration profile is reversed by restricting dietary protein (1)(2)(3). In rats fed a low protein diet, the maximum inner medullary urea concentration is not found near the papillary tip, but instead, is near the base of the inner medulla (1-3), corresponding to the location of the initial inner medullary collecting duct (IMCD)l (20,21).…”

“…In rats fed a low protein diet, the maximum inner medullary urea concentration is not found near the papillary tip, but instead, is near the base of the inner medulla (1-3), corresponding to the location of the initial inner medullary collecting duct (IMCD)l (20,21). Taken together, these data suggest that a low protein diet might induce active urea transport in the IMCD (1)(2)(3)22).…”

“…In rats fed an 18-24% protein diet, the inner medullary urea concentration increases with depth, reaching a maximum at the papillary tip (1)(2)(3). The urinary urea concentration exceeds the maximal urea concentration in the papilla, consistent with passive urea reabsorption (1)(2)(3).…”

“…Low protein diets change inner medullary urea handling in the rat (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), sheep (13)(14)(15)(16)(17), camel (18), and man (19). In rats fed a low protein diet, fractional excretion of urea is significantly reduced compared to rats fed normal or high protein diets, consistent with stimulation ofurea reabsorption by protein restriction (1,5,8,10,12). Moreover, the normal inner medullary urea concentration profile is reversed by restricting dietary protein (1)(2)(3).…”

Sodium-dependent net urea transport in rat initial inner medullary collecting ducts.

“…It is well known that a low protein diet reduces maximum urinary concentrating ability, reduces the fractional excretion of urea, and reverses the normal inner medullary urea concentration gradient so that the maximum inner medullary urea concentration is at the base of the inner medulla, corresponding to the location of the initial IMCD, rather than at the papillary tip (13)(14)(15)(16). Micropuncture studies had suggested the possibility of active urea reabsorption in the collecting duct from rats fed a low protein diet (17,18), but could not prove or characterize active urea transport because -T1 (PC.er AR) Control 0mM Na* Recovery of the inability to measure the urea gradient across the collecting duct in vivo.…”