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The suppressive effects of dietary protein restriction on the progression of renal impairment in OLETF rats

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Abstract

Background

The suppressive effect of dietary protein restriction on the progression of diabetic nephropathy remains controversial. We investigated the effects of protein and energy restrictions on both albuminuria and morphology using diabetic-prone Otsuka Long-Evans Tokushima fatty (OLETF) rats.

Methods

In this study, male OLETF rats were divided into two groups according to their energy intake. They were then further divided into three subgroups based on their amount of dietary protein, which ranged between 10% and 30% of their total intake. Urinary albumin excretion (UAE) was used as a marker of renal impairment, and body weight fasting (F) and postchallenge (P), blood glucose (BG) levels, and systolic blood pressure (SBP) were all measured during various experimental periods up to 28 weeks of age.

Results

The OLETF rats fed with the high-calorie diet started to gain weight at 12 weeks, and their FBG and PBG were elevated at 22 weeks, while SBP did not differ between the two groups. In addition, UAE increased significantly in the rats fed with the high-calorie diet. However, the increasing rates of UAE with age were higher in the rats with a higher protein diet within the same energy groups. UAE correlated well with the amounts of dietary energy and protein at 16 and 28 weeks of age, while it correlated with both the FBG and PBG at only 28 weeks of age. A linear regression analysis, using the data obtained at 28 weeks, showed that the amount of protein intake and FBG explained 63.4% and 23.9% of the variation in UAE, respectively. Histological studies revealed that protein and energy restriction markedly reduced the sclerotic changes of the glomeruli.

Conclusion

Dietary protein restriction starting very early in the life of OLETF rats, in combination with energy restriction, clearly suppressed UAE and the typical morphological changes that otherwise occurred at around 16 weeks of age. This method also seemed to be more effective than energy restriction alone in slowing down any increase in UAE. The influence of BG levels on UAE was lower at an early age, while it became an increasingly important factor at later ages in the experimental rat model.

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References

  1. AR Andersen JS Christiansen JK Andersen S Kreiner T Deckert (1983) ArticleTitleDiabetic nephropathy in type 1 (insulin-dependent) diabetes: an epidemiological study Diabetologia 25 496–501 Occurrence Handle6363177 Occurrence Handle10.1007/BF00284458 Occurrence Handle1:STN:280:DyaL2c7gvFaqtA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  2. M Krolewski PW Eggers JH Warram (1996) ArticleTitleMagnitude of end-stage renal disease in IDDM: a 35-year follow-up study Kidney Int 50 2041–6 Occurrence Handle8943488 Occurrence Handle1:STN:280:DyaK2s%2FpvVyitQ%3D%3D

    PubMed  CAS  Google Scholar 

  3. HH Parving AR Andersen UM Smidt E Hommel ER Mathiesen PA Svendsen (1987) ArticleTitleEffect of antihypertensive treatment on kidney function in diabetic nephropathy BMJ 294 1443–7 Occurrence Handle3111583 Occurrence Handle1:STN:280:DyaL2s3nt1ersA%3D%3D Occurrence Handle10.1136/bmj.294.6585.1443

    Article  PubMed  CAS  Google Scholar 

  4. Hostetter TH, Meyer TW, Rennke HG, Brenner BM, with the technical assistance of Noddin JA, Sandstrom DJ. Chronic effects of dietary protein in the rat with intact and reduced renal mass. Kidney Int 1986;30:509–17

    Google Scholar 

  5. KA Nath SM Kren TH Hostetter (1986) ArticleTitleDietary protein restriction in established renal injury in the rat: selective role of glomerular capillary pressure in progressive glomerular dysfunction J Clin Invest 78 1199–205 Occurrence Handle3771792 Occurrence Handle1:CAS:528:DyaL2sXktFWj

    PubMed  CAS  Google Scholar 

  6. PF Dullaart JJ Doormaal BJ Beusekamp WJ Slutter S Meijer (1993) ArticleTitleLong-term effects of protein-restricted diet on albuminuria and renal function in IDDM patients without clinical nephropathy and hypertension Diabetes Care 16 483–92 Occurrence Handle8432221 Occurrence Handle1:STN:280:DyaK3s7mtFyqtg%3D%3D

    PubMed  CAS  Google Scholar 

  7. C Meloni M Morosetti C Suraci MG Pennafina C Tozzo MT Gallucci et al. (2002) ArticleTitleSevere dietary protein restriction in overt diabetic nephropathy: benefits or risks? J Ren Nutr 12 96–101 Occurrence Handle11953922

    PubMed  Google Scholar 

  8. A Ciavarella G Di Mizio S Stefoni LC Borgnino P Vannini (1987) ArticleTitleReduced albuminuria after dietary protein restriction in insulin-dependent diabetic patients with clinical nephropathy Diabetes Care 10 407–13 Occurrence Handle3622197 Occurrence Handle1:STN:280:DyaL2szgtlGksQ%3D%3D

    PubMed  CAS  Google Scholar 

  9. HP Hansen PK Christensen ET Lassen A Klaus BR Jensen HH Parving (1999) ArticleTitleLow-protein diet and kidney function in insulin-dependent diabetic patients with diabetic nephropathy Kidney Int 55 621–8 Occurrence Handle9987086 Occurrence Handle10.1046/j.1523-1755.1999.00274.x Occurrence Handle1:CAS:528:DyaK1MXht1Ghu7k%3D

    Article  PubMed  CAS  Google Scholar 

  10. RP Dullaart BJ Beusekamp S Meijer JJ van Doormaal WJ Sluiter (1993) ArticleTitleLong-term effects of protein-restricted diet on albuminuria and renal function in IDDM patients without clinical nephropathy and hypertension Diabetes Care 16 483–92 Occurrence Handle8432221 Occurrence Handle1:STN:280:DyaK3s7mtFyqtg%3D%3D

    PubMed  CAS  Google Scholar 

  11. HP Hansen TL Lassen BR Jensen HH Parving (2002) ArticleTitleEffect of dietary protein restriction on prognosis in patients with diabetic nephropathy Kidney Int 62 220–8 Occurrence Handle12081581 Occurrence Handle10.1046/j.1523-1755.2002.00421.x

    Article  PubMed  Google Scholar 

  12. LT Pijls H de Vries AJ Donker JT van Eijk (1999) ArticleTitleThe effect of protein restriction on albuminuria in patients with type 2 diabetes mellitus: a randomized trial Nephrol Dial Transplant 14 1445–53 Occurrence Handle10383006 Occurrence Handle10.1093/ndt/14.6.1445 Occurrence Handle1:STN:280:DyaK1MzhtVekuw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  13. LT Pijls H de Vries JT van Eijk AJ Donker (2002) ArticleTitleProtein restriction, glomerular filtration rate and albuminuria in patients with type 2 diabetes mellitus: a randomized trial Eur J Clin Nutr 56 1200–7 Occurrence Handle12494305 Occurrence Handle10.1038/sj.ejcn.1601474 Occurrence Handle1:CAS:528:DC%2BD38Xps1eltLk%3D

    Article  PubMed  CAS  Google Scholar 

  14. K Kawano T Hirashima S Mori Y Saitoh M Kurosumi T Natori (1992) ArticleTitleSpontaneous long-term hyperglycemic rat with diabetic complications: Otsuka Long-Evans Tokushima fatty (OLETF) strain Diabetes 41 1422–8 Occurrence Handle1397718 Occurrence Handle1:STN:280:DyaK3s%2Fht1GitA%3D%3D

    PubMed  CAS  Google Scholar 

  15. Y Fukuzawa Y Watanabe D Inaguma N Hotta (1996) ArticleTitleEvaluation of glomerular lesion and abnormal urinary findings in OLETF rats resulting from a long-term diabetic state J Lab Clin Med 128 568–78 Occurrence Handle8960640 Occurrence Handle10.1016/S0022-2143(96)90129-8 Occurrence Handle1:CAS:528:DyaK2sXhsFaltw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  16. N Okauchi A Mizuno S Yoshimoto M Zhu T Sano K Shima (1995) ArticleTitleIs caloric restriction effective in preventing diabetes mellitus in the Otsuka Long Evans Tokushima fatty rat: a model of spontaneous non-insulin-dependent diabetes mellitus? Diabetes Res Clin Pract 27 97–106 Occurrence Handle7607057 Occurrence Handle10.1016/0168-8227(95)01029-D Occurrence Handle1:CAS:528:DyaK2MXlvFGmtLc%3D

    Article  PubMed  CAS  Google Scholar 

  17. S Mori K Kawano T Hirashima T Natori (1996) ArticleTitleRelationships between diet control and the development of spontaneous type II diabetes and diabetic nephropathy in OLETF rats Diabetes Res Clin Pract 33 145–52 Occurrence Handle8922535 Occurrence Handle10.1016/0168-8227(96)01290-9 Occurrence Handle1:STN:280:DyaK2s%2FotFaqsg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  18. K Kawano S Mori T Hirashima ZW Man T Natori (1999) ArticleTitleExamination of the pathogenesis of diabetic nephropathy in OLETF rats J Vet Med Sci 61 1219–28 Occurrence Handle10593580 Occurrence Handle10.1292/jvms.61.1219 Occurrence Handle1:STN:280:DC%2BD3c%2FlvFWmsQ%3D%3D

    Article  PubMed  CAS  Google Scholar 

  19. E Ishikawa (1982) Sensitivity of the measurement T Kawai E Ishikawa K Miyai (Eds) Enzyme immunoassay EditionNumber2nd ed. Igakushoin Tokyo 50–66

    Google Scholar 

  20. K Kawakami A Ago T Gonda (1996) ArticleTitleEvaluation of an automated blood-pressure analyzer, UR-5000 J Exp Ani Tech 31 115–22

    Google Scholar 

  21. S Matsuda K Iwata K Takahashi H Homma Y Tamura Y Kanda et al. (2004) ArticleTitleA low-protein diet concomitant with high-calorie intake preserves renal function and structure in diabetic OLETF rats Clin Exp Nephrol 8 322–30 Occurrence Handle15619031 Occurrence Handle10.1007/s10157-004-0312-0 Occurrence Handle1:CAS:528:DC%2BD2MXnvFShtw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  22. TH Hostetter JL Olson HG Rennke MA Venkatachalam BM Brenner (1981) ArticleTitleHyperfiltration in remnant nephrons: a potentially adverse response to renal ablation Am J Physiol 241 F85–93 Occurrence Handle7246778 Occurrence Handle1:STN:280:DyaL3M3ivFyrsQ%3D%3D

    PubMed  CAS  Google Scholar 

  23. LL Woods (1993) ArticleTitleMechanisms of renal hemodynamic regulation in response to protein feeding Kidney Int 44 659–75 Occurrence Handle8258943 Occurrence Handle1:CAS:528:DyaK2cXhvFSht7s%3D

    PubMed  CAS  Google Scholar 

  24. S Okuda T Nakamura T Yamamoto E Ruoslahti WA Border (1991) ArticleTitleDietary protein restriction rapidly reduces transforming growth factorβ1 expression in experimental glomerulonephritis Proc Natl Acad Sci 88 9765–9 Occurrence Handle1946401 Occurrence Handle10.1073/pnas.88.21.9765 Occurrence Handle1:CAS:528:DyaK3MXmslyltbY%3D

    Article  PubMed  CAS  Google Scholar 

  25. S Okuda LR Languino E Ruoslahti WA Border (1990) ArticleTitleElevated expression of transforming growth factor-beta and proteoglycan production in experimental glomerulonephritis. Possible role in expansion of the mesangial extracellular matrix J Clin Invest 86 453–62 Occurrence Handle2200803 Occurrence Handle1:CAS:528:DyaK3cXltlSnsLs%3D Occurrence Handle10.1172/JCI114731

    Article  PubMed  CAS  Google Scholar 

  26. L Schaefer K Meier C Hafner M Teschner A Heidland RM Schaefer (1996) ArticleTitleProtein restriction influences glomerular matrix turnover and tubular hypertrophy by modulation of renal proteinase activities Miner Electrolyte Metab 22 162–7 Occurrence Handle8676812 Occurrence Handle1:CAS:528:DyaK2MXps1OqsL4%3D

    PubMed  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Department of Laboratory Medicine, School of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan

    Miyoko Sakamoto, Yuko Akehi & Junko Ono

  2. Morinoki Diabetes Clinic, Kumamoto, Japan

    Goro Mimura & Mayumi Yano

  3. School of Food and Nutrition, Shokei Junior College, Kumamoto, Japan

    Machiko Tanaka

  4. Department of Human Health and Nutrition, Faculty of Comprehensive Human Sciences, Shokei Gakuin College, Kumamoto, Japan

    Takeyuki Ohshita

  5. Kumamoto University School of Health Science, Kumamoto, Japan

    Yasuji Ishimaru

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  1. Miyoko Sakamoto
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  2. Yuko Akehi
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  3. Goro Mimura
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  4. Machiko Tanaka
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  5. Takeyuki Ohshita
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  6. Mayumi Yano
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  7. Yasuji Ishimaru
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  8. Junko Ono
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Corresponding author

Correspondence to Junko Ono.

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Sakamoto, M., Akehi, Y., Mimura, G. et al. The suppressive effects of dietary protein restriction on the progression of renal impairment in OLETF rats. Clin Exp Nephrol 10, 244–252 (2006). https://doi.org/10.1007/s10157-006-0434-7

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  • DOI: https://doi.org/10.1007/s10157-006-0434-7

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