• Chiedozie Waturuocha OSU-CHS
  • Liming Fan OSU-CHS
  • Alexander Rouch Oklahoma State University Center for Health Sciences College of Osteopathic Medicine (OSU-COM)
Keywords: High protein diet, Urinary Protein Excretion, Casein, Soy, Sex differences


Introduction: High protein intake can accelerate kidney disease. Soy protein diet has been reported to reduce the progression of chronic kidney disease (CKD) compared to a milk (casein) protein diet. Sex differences play a key role in kidney function and disease with premenopausal women having fewer kidney diseases compared to age-matched men. The purpose of this study was to compare the effects of high soy protein consumption with that of high casein consumption on renal protein excretion in male and female mice. We hypothesized that sex differences exist in the renal handling of these two protein sources. Methods: Two separate studies, one with male mice and one with female mice, were conducted. Mice at 25 days of age were placed in metabolic cages. After a baseline period of three days on standard diet, one group consumed 40% casein and the other an isocaloric 40% soy diet for 25 days (n=6 per group). Daily measurements included body weight, food and water intake, urinary flow rate (UFR), and urinary protein excretion (UPE) via dipstick analysis. UPE (mg/day) was also determined on the final day of each study by measuring total urine protein concentration (TPC) and calculating UPE (UPE = TPC x UFR). Results: Independent of the diet, females excreted significantly less protein compared to males despite equal protein consumption. Regardless of sex, the casein groups excreted more protein than the soy groups via dipstick measurement. UPE (mg/day) measured on the 25th day was higher in the casein groups compared to the soy groups (males: 31.9 ± 2.5 vs. 17.8 ± 0.9, p<0.009; females: 10.2 ± 1.7 vs. 5.4 ± 0.8, NS). Conclusion: We conclude that high soy intake induces less proteinuria compared to that with high casein intake. Female mice on high casein and high soy diets excreted less protein when compared to male mice on the same diet. These results support the benefits of soy protein in patients with kidney disease and indicate sex differences in the renal handling of high protein diets.



Song S, Hooiveld GJ, Li M, et al. Dietary soy and meat proteins induce distinct physiological and gene expression changes in rats. Sci Reports. 2016;6.

Astrup A, Raben A, Geiker N. The role of higher protein diets in weight control and obesity-related comorbidities. Int J Obes (Lond). 2015;39(5):721-726.

Eisenstein J, Roberts SB, Dallal G, Saltzman E. High-protein weight-loss diets: Are they safe and do they work? A review of the experimental and epidemiologic data. Nutrition Reviews. 2002;60(7):189-200.

Lacroix M, Gaudichon C, Martin A, et al. A long-term high-protein diet markedly reduces adipose tissue without major side effects in Wistar male rats. Am J Physiol Regul Integr Comp Physiol. 2004;287:R934-R942.

Hall WL, Millward DJ, Long SJ, Morgan LM. Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite. Br J Nutr. 2003;89:239-248.

Mattson DL, Meister CJ, Marcelle ML. Dietary protein source determines the degree of hypertension and renal disease in the Dahl salt-sensitive rat. Hypertension. 2005;45(2):736-741.

Crouse JR, 3rd, Morgan T, Terry JG, Ellis J, Vitolins M, Burke GL. A randomized trial comparing the effect of casein with that of soy protein containing varying amounts of isoflavones on plasma concentrations of lipids and lipoproteins. Arch Intern Med. 1999;159(17):2070-2076.

Nevala R, Vaskonen T, Vehniainen J, Korpela R, Vapaatalo H. Soy based diet attenuates the development of hypertension when compared to casein based diet in spontaneously hypertensive rat. Life Sci. 2000;66(2):115-124.

Sacks FM, Lichtenstein A, Van Horn L, Harris W, Kris-Etherton P, Winston M. Soy protein, isoflavones, and cardiovascular health: a summary of a statement for professionals from the american heart association nutrition committee. Arterioscler Thromb Vasc Biol. 2006;26(8):1689-1692.

Park E, Shin JI, Park OJ, Kang MH. Soy isoflavone supplementation alleviates oxidative stress and improves systolic blood pressure in male spontaneously hypertensive rats. J Nutr Sci Vitaminol (Tokyo). 2005;51(4):254-259.

Xu YY, Yang C, Li SN. Effects of genistein on angiotensin-converting enzyme in rats. Life Sci. 2006;79(9):828-837.

Bouby N, Trinh-Trang-Tan M-M, Laouari D, et al. Role of the urinary concentrating process in the renal effects of high protein intake. Kidney International. 1988;34:4-12.

Brenner BM, Meyer TW, Hostetter TH. Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease. N Engl J Med. 1982;307(11):652-659.

Reckelhoff JF. Sex and sex steroids in cardiovascular-renal physiology and pathophysiology. Gender Medicine. 2008;5(Suppl. A):S1-S2.

Carneiro SS, Carminati RZ, Freitas FP, et al. Endogenous female sex hormones delay the development of renal dysfunction in apolipoprotein E-deficient mice. Lipids Health Dis. 2014;13:176.

Cheetham S, Smith A, Armstrong S, Beynon R, Hurst J. Limited variation in the major urinary proteins of laboratory mice. Physiol Behav. 2009;96:253-261.

Jean-Faucher C, Berger M, Gallon C, de Turckheim M, Veyssiere G, Jean C. Sex-related differences in renal size in mice: ontogeny and influence of neonatal androgens. J Endocrinol. 1987;115(2):241-246.

Ogborn MR, Bankovic-Calic N, Shoesmith C, Buist R, Peeling J. Soy protein modification of rat polycystic kidney disease. Am J Physiol Renal Physiol. 1998;274:F541-F549.

Pareira PM, Vincente AF. Meat nutritional composition and nutritive role in the human diet. Meat Sci. 2013;93(3):586-592.

Pechère-Bertschi A, Burnier M. Gonadal steroids, salt-sensitivity and renal function. Curr Opin Nephrol Hyper. 2007;16(1):16-21.

Doublier S, Lupia E, Catanuto P, et al. Testosterone and 17b-estradiol have opposite effects on podocyte apoptosis that precedes glomerulosclerosis in female estrogen receptor knockout mice. Kidney International. 2010;doi:10.1038:1-10.

Baylis C. Age-dependent glomerular damage in the rat. J Clin Invest. 1994;94:1823-1829.

Neugarten J. Gender and the progression of renal disease. J Am Soc Nephrol. 2002;13(11):2807-2809.

Verzola D, Gandolfo MT, Salvatore F, et al. Testosterone promotes apoptotic damage in human renal tubular cells. Kidney International. 2004;65:1252-1261.

Blush J, Lei J, Ju W, Silbiger SR, Pullman J, Neugarten J. Estradiol reverses renal injury in AIb/TGF-b1 transgenic mice. Kidney International. 2004;66:2148-2154.

Maric C, Sandberg K, Hinojosa-Laborde C. Glomerulosclerosis and tubulointerstitial fibrosis are attenuated with 17b-estradiol in the aging Dahl salt-sensitive rat. J Am Soc Nephrol. 2004;15:1546-1556.

Biomedical Sciences