An investigation of the cause of renal hypertrophy in rats fed on a high protein diet

Abstract

THE problem of the enlargement of the kidneys of rats fed on diets rich in protein has, in recent years, been receiving considerable attention notably by Addis and the Mackays [1926, 1, 2] who have shown that the hypertrophy is proportional to the protein consumption and have elaborated a formula which expresses this relationship in terms of protein consumed and kidney weight per unit of surface area. The cause of this enlargement, however, stillremains obscure. The excretion of urea naturally suggests itself as a causal factor. The feeding of urea, however, in amounts equivalent to what would be excreted on a high protein diet has been shown to produce a much smaller effect on the kidneys [Osborne et al., 1926; Mackay, Mackay and Addis, 1931]. The effect of feeding proteins of different origin has however scarcely been investigated. Osborne et al. [1926] found that caseinogen, gliadin and beef residues all produced an enlargement of the kidneys but no actual numerical data on the basis worked out by the Mackays and Addis [1927; 1928] were elaborated. The object of the following experiments was an attempt to find out the cause of this hypertrophy. Two possibilities suggest themselves. Do the kidneys in the rat form a depot for reserve protein, or is the hypertrophy a response to an increase in physiological function? It is possible in this connection that the kidneys are associated in some way with the intermediary metabolism of protein quite apart from the mere excretion of nitrogenous end-products. EXPERiMENTAL. A series of experiments was carried out to compare the following proteins and protein derivatives, and in addition the effect of an acid and alkaline dietcaseinogen, liver, gelatin, wheat gluten, glycine, glutamic acid, urea, NaH2PO4 and NaHCO3. The experimental procedure adopted in these experiments was practically the same as that employed by the Mackays [1927]. Standard albino rats 30 days old and obtained from the same source as far as each particular series of experiments is concerned were employed throughout. They were kept in cages open to the front with not more than 6 rats to a cage. The sexes were kept apart. The room in which they were kept was well lit and open to the south and was maintained fairly constant in temperature day and night. Water and food were allowed ad lib., and the food consumption was measured each day. The rats were weighed about every third day. The duration of the experiments varied from 30 to 39 days in the different series. At the end of the experimental

Compensatory Growth and Other Growth Responses of the Kidney

“…Zein and a casein-like amino acid mixture gave weight increases similar to casein [200], The kidneys of rats on 24% casein averaged 15% larger than those on 24% soya protein, and their inulin and PAH clearances were higher by 48 and 74% [510] but the inter pretation is complicated by the lower utilization rate of the soya protein. Liver protein in the diet was apparently associated with less weight gain than casein but the data are not clear [499,515]. Gelatin as the protein source gave a 56% increase in weight in 6 days compared with 19-25% with casein.…”

“…This together with a 25% increase in DNA in this time suggests an injury response [200]. Combination of 37% gelatin with 20% casein as a source of essential amino acids resulted in a kidney weight 30% greater than with a 57% all-casein diet [515]. Glycine or glutamate supplements to a casein diet increased kidney size in proportion to their nitrogen contents [515].…”

The Effect of Feeding Protein and Urea on the Renal Concentrating Process 1

“…When the diet of rats is supplemented by nitrogen in the form of urea, renal hypertrophy, less marked than with protein feeding, has been reported (2,15,16) and denied (1,3). Other urinary solutes, with the possible exception of phosphate, do not enhance renal growth (1).…”

“…In the rat much evidence has accumulated that high-protein intakes lead to renal hypertrophy (1)(2)(3) and that low-protein diets may be associated with impairment of some renal functions (4 (6), creatinine (7), urea (8), sodium and potassium (9) were also determined. The "t" test of "Student" was used in analyzing the data.…”

Protein intake, calcium balance and health consequences

“…Indeed, as shown previously, HP diets cause elevation of glomerular filtration rate and hyperfiltration (Kim and Linkswiler, 1979;Schuette et al, 1980;Zemel et al, 1981;Brenner et al, 1982;Bilo et al, 1989;Metges and Barth, 2000;Tuttle et al, 2002;Frank et al, 2009;Burodom, 2010). In animal models, HP diets induce a renal hypertrophy (Addis, 1926;Wilson, 1933;Hammond and Janes, 1998) but not systematically (Robertson et al, 1986;Collins et al, 1990;Lacroix et al, 2004), and to our knowledge, the link between protein-induced renal hypertrophy or hyperfiltration and the initiation of renal disease in healthy individuals has not been clearly shown. Only one recent study showed in pigs that a long-term HP diet (4 or 8 months) resulted in enlarged kidneys and increased evidence of renal damages (Jia et al, 2010).…”