Low-Protein Diet for CKD: Comparison
Please note this is a comparison between Version 2 by Bruce Ren and Version 1 by Shaw Watanabe.

The epidemiology of chronic kidney disease (CKD) shows increasing trends in prevalence and mortality and has become the leading health problem worldwide. Reducing the amount of proteins ingested from rice is an easy way to control the total intake of proteins, saving energy sources, particularly in rice-eating countries. 

  • low-protein rice
  • processed low-protein brown rice
  • CKD
  • dietary therapy
  • lactobacillus

Note: The entry will be online only after author check and submit it.

1. Increasing Trends of CKD in the World

In addition to cardiovascular diseases and cancer, chronic kidney disease (CKD) contributes to increased mortality in many industrialized countries [1,2,3,4][1][2][3][4]. The prevalence of CKD is estimated to be 8–16% worldwide [5,6,7][5][6][7]. CKD leads to kidney failure, requiring hemodialysis or renal transplantation. Recently, 20–40% of diabetic patients have developed CKD as a late complication [8,9,10][8][9][10]. Adequate interventions are necessary [11,12,13][11][12][13].
In Japan, peritoneal dialysis and hemodialysis are the most current treatments for advanced renal failure, and transplantation is rare. The medical cost is enormous [14,15][14][15]: 96% of dialyzed patients receive hemodialysis, and only 3–4% undergo peritoneal dialysis [16,17][16][17]. The number of patients treated with hemodialysis in Japan exceeded 344,640 in 2019, including 40,885 newcomers.
To improve patients’ quality of life and decrease medical costs, it is essential to delay the onset of conditions necessary for hemodialysis.

2. Effects of a Low-Protein Diet on CKD

In 1918, von Noorden W. and Volhard F. reported that a protein-reduced diet (Homburg diet) had suppressed uremic symptoms [18]. Since then, many studies have shown that a low-protein diet (LPD) reduced uremia symptoms, delayed the progression of renal failure, and extended life expectancy [19,20][19][20]. In 1963, Giordano reported that a low-protein diet could improve uremic patients’ azotemia and shifted the nitrogen balance from negative to positive [21]. In 1964, Giovannetti also defined a diet whereby animal proteins and energy sources were provided by cereals [19].
In 1983, Brenner reported that excess protein intake imposed a load on glomerular hemodynamics and caused glomerular disorders [22]. After that, the mechanisms of renal damage due to excessive protein intake were rapidly elucidated [23]. Early intervention through LPD could decrease proteinuria in CKD [24,25,26,27,28][24][25][26][27][28].
For 50 years, a LPD has been employed to treat chronic renal failure in Japan. It is now recognized that a LPD is almost certainly effective [29,30][29][30]. However, large-scale studies conducted by Locatelli et al. did not detect the same effect of a LPD inhibiting renal disease progression [31]. Although low-protein diets have proven very effective for CKD patients, many physicians have failed to control renal dysfunction in RCT; they fail to ensure patients keep to a LPD and maintain their energy intake simultaneously [32,33,34,35][32][33][34][35]. A recent meta-analysis of RCT showed inconclusive results, and the appropriate protein intake is still an issue of debate [36].
Even though excess protein intake promotes glomerular overfiltration and adversely affects renal function, the Japanese guidelines for CKD patients recommend as standard a daily protein intake of 0.8 to 1.0 g/kg for stage G3a and 0.6 to 0.8 g/kg normal weight/day for stage G3b and later [37]. This dose does not seem to be effective, as described below. An extreme LPD was poorly judged to reduce the various risks involved and more work is needed to confirm efficacy and safety in future studies.

3. Adequate Amount of Protein Intake by CKD Patients

Historically, the first recommendation on protein intake was 118 g/day/person in the so-called essential diet by German physiologist Professor Voit in 1881 [38]. Professor R.H. Chittenden (Yale University) took a different position. He began to experiment with reduced protein intake in November 1902 on his own body. He first quit breakfast, had only a light lunch, and had a regular supper for seven months until June 1904 [39]. In that time, his intake of protein was progressively reduced. After carefully analyzing nitrogen in his food and urine, Chittenden proved that taking 30–35 g of protein a day was sufficient to maintain his nitrogen balance. This diet also helped Chittenden control rheumatoid arthritis and mild nonspecific complaints.
Different results had been reported, but from almost all studies, it appeared that simultaneous intake of the right balance of energy and protein seemed to be difficult. In Japan, the dietary reference intake (DRI) uses the reference value of 0.8 g/kg body weight for healthy people. The average protein intake of Japanese people is 0.65 g/kg/day. Adding two standard deviations yields a figure of 0.87 g/kg/day. So, the Japanese DRI was set at 60 g daily for healthy men and 50 g for women [40]. In 1973, the FAO Protein Requirement Committee reported that the minimum physiological input was 0.35 g/kg body weight. So, the lowest acceptable protein intake would be 0.3 to 0.4 g/kg body weight. The experience of Chittenden practicing on his own body and getting better with 30 g a day was substantial evidence in the age of personalized nutrition. After all, Zen priests used to remain healthy with a minimal intake of protein!

4. Effect of Prolonged Intake of Low-Protein Diet

Many physicians did not adopt LPD therapy, especially after the Evaluation of Modification of Diet in Renal Disease Study (MDRD), in which a LPD resulted in a worse prognosis [41]. Those regimens failed to maintain an adequate energy intake, so malnutrition seemed to worsen the prognosis.
We carried out a case study to confirm the effect of more than six years of treatment with a LPD. We enrolled ten patients with LPD and hemodialysis patients (0.39 g/kg in CKD and 0.55 g/kg in the hemodialysis group, respectively) or families of the patients and supportive dieticians [42]. The daily protein intake of families was 1.17 g/kg and 1.25 g/kg in the dietician groups, respectively. The recommended protein intake during hemodialysis was 1.2–1.5 g/kg body weight in the guideline, but 0.55 g/kg was enough to maintain body weight and serum protein. Important was the energy intake, being 32 kcal/kg body weight.
Intake of vitamins and minerals was less than half of the DRI, but none of the patients showed signs of deficiency. Study groups did not show any significant difference either in tests using dual-energy X-ray absorptiometry (DEXA), bone mineral density, and non-fatty tissue weight. CKD patients did not complain of sarcopenia, osteoporosis, hyperkalemia, hypo-phosphatemia, or high uric acid. Even lower intakes could reduce the frequency of dialysis in some cases [43].
In another retrospective analysis on 241 CKD patients who participated in the “Low-Protein Diet Practice for advanced CKD” program [44], patients started with serum creatinine levels around 5 mg/dL. Proteinuria improved within a relatively short period, with urinary protein output decreasing by 1.1 g/day after reducing protein intake to 0.5 g/kg body weight. Thus, we recommended LPD protocols, starting with a low-protein diet (0.5 g/kg body weight) from the earliest stage of the disease (eGFR < 60 mL/1.73 m2). Blood urea nitrogen (BUN) is a good index for healthy people based on how much they eat protein. A target value was under 15 mg/dL in our population-based cohort study. The substitution of meat with vegetable proteins improved the prognosis in diabetic renal disease [45].

References

  1. Couser, W.G.; Remuzzi, G.; Mendis, S.; Tonelli, M. The contribution of chronic kidney disease to the global burden of major non-communicable diseases. Kidney Int. 2011, 80, 1258–1270.
  2. Jha, V.; Garcia, G.G.; Iseki, K.; Li, Z.; Naicker, S.; Plattner, B.; Saran, R.; Wang, A.Y.-M.; Yang, C.-W. Chronic kidney disease: Global dimension and perspectives. Lancet 2013, 382, 260–272.
  3. Global Burden of Disease Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: A systemat ic analysis for the Global Burden of Disease study 2017. Lancet 2020, 395, 709–732.
  4. Carney, E.F. The impact of chronic kidney disease on global health. Nat. Rev. Nephrol. 2020, 16, 251.
  5. Zhang, Q.-L.; Rothenbacher, D. Prevalence of chronic kidney disease in population-based studies: Systematic review. BMC Public Health 2008, 8, 117.
  6. Imai, E.; Horio, M.; Iseki, K.; Yamagata, K.; Watanabe, T.; Hara, S.; Ura, N.; Kiyohara, Y.; Hirakata, H.; Moriyama, T.; et al. Prevalence of chronic kidney disease (CKD) in the Japanese general population predicted by the MDRD equation modified by a Japanese coefficient. Clin. Exp. Nephrol. 2007, 11, 156–163.
  7. Takeuchi, M.; Shinkawa, K.; Yanagita, M.; Kawakami, K. Prevalence, recognition and management of chronic kidney disease in Japan: Population-based estimate using a healthcare database with routine health checkup data. Clin. Kidney J. 2021, sfab016.
  8. Zimmet, P.; Alberti, K.G.; Shaw, J. Global and societal implications of the diabetes epidemic. Nature 2001, 414, 782–787.
  9. Atkins, R.C.; Zimmet, P. teWorld kidney day 2010: Diabetic kidney disease—Act now or pay later. Am. J. Kidney Dis. 2010, 55, 205–208.
  10. El Nahas, M. The global challenge of chronic kidney disease. Kidney Int. 2005, 68, 2918–2929.
  11. Bilous, R. Microvascular disease: What does the UKPDS tell us about diabetic nephropathy? Diabet Med. 2003, 20, 25–29.
  12. Low-Protein Diets for Adults Without Diabetes Mellitus Who Have CKD. Available online: www.aafp.org/afp/2020/1201/p665.html (accessed on 5 June 2021).
  13. Kalantar-Zadeh, K.; Joshi, S.; Schlueter, R.; Cooke, J.; Brown-Tortorici, A.; Donnelly, M.; Schulman, S.; Lau, W.-L.; Rhee, C.M.; Streja, E.; et al. Plant-Dominant Low-Protein Diet for Conservative Management of Chronic Kidney Disease. Nutrients 2020, 12, 1931.
  14. Medical Cost of Hemodialysis. Available online: http://www.mhlw.go.jp/toukei/saikin/hw/k-iryohi/J4/dl/kekka.pdf (accessed on 15 June 2021).
  15. CDC: Chronic Kidney Disease Basic. Available online: http://www.cdc.gov/kidneydisease/basics.html (accessed on 15 June 2021).
  16. The Japanese Society for Dialysis Therapy. Available online: https://www.jsdt.or.jp/dialysis/2227.html (accessed on 15 June 2021).
  17. Nomiyama, T.; Kiyohara, Y.; Tokuda, Y.; Doi, Y.; Arima, H.; Harada, A.; Ohashi, Y.; Ueshima, H. Japan arteriosclerosis longitudinal study group. Impact of kidney disease and blood pressure on the development of cardiovascular disease: An overview from the Japan Arteriosclerosis Longitudinal Study. Circulation 2008, 118, 2694–2701.
  18. Von Noorden, C. Clinical Treatises on the Pathology and Therapy of Disorders of Metabolism and Nutrition; EB Treat & Company: New York, NY, USA, 1906.
  19. Giovannetti, S.; Maggiore, Q. A low-nitrogen diet with proteins of high biological value for severe chronic uræmia. Lancet 1964, 283, 1000–1003.
  20. Mariani, G.; Barsotti, S.; Bianchi, G. Nutritional aspects of plasma protein metabolic studies: Long-term treatment of chronic uraemia by a very-low-protein diet supplemented with essential amino acids and keto analogues. In Pathophysiology of Plasma Protein Metabolism; Mariane, G., Ed.; Springer Nature: Cham, Switzerland, 1984; pp. 325–331.
  21. Giordano, C. Use of exogenous and endogenous urea for protein synthesis in normal and uremic subjects. J. Lab. Clin. Med. 1963, 62, 231.
  22. Brenner, B.M.; Meyer, T.W.; Hostetter, T.H. 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, 652–659.
  23. National Research Council (US) Subcommittee on the Tenth Edition of the Recommended Dietary Allowances. Recommended Dietary Allowances: 6 Protein and Amino Acids, 10th ed.; National Academies Press: Washington, DC, USA, 1989.
  24. van der Velde, M.; Halbesma, N.; de Charro, F.T.; Bakker, S.J.; de Zeeuw, D.; de Jong, P.E.; Gansevoort, R.T. Screening for albuminuria identifies individuals at increased renal risk. J. Am. Soc. Nephrol. 2009, 20, 852–862.
  25. Romundstad, S.; Holmen, J.; Kvenild, K.; Hallan, H.; Ellekjaer, H. Microalbuminuria and all-cause mortality in 2089 apparently healthy individuals: A 44-year follow-up study. The Nord-Trondelag Health Study (HUNT), Norway. Am. J. Kidney Dis. 2003, 42, 466–473.
  26. Gansevoort, R.T.; de Jong, P.E. The case for using albuminuria in staging chronic kidney disease. J. Am. Soc. Nephrol. 2009, 20, 465–468.
  27. Verhave, J.C.; Gansevoort, R.; Hillege, H.L.; Bakker, S.J.; De Zeeuw, D.; De Jong, P.E. An elevated urinary albumin excretion predicts de novo development of renal function impairment in the general population. Kidney Int. 2004, 66, S18–S21.
  28. Watanabe, S. Low-protein diet for the prevention of renal failure. Proc. Jpn. Acad. Ser. B 2017, 93, 1–9.
  29. Mitch, W.E.; Remzzi, D. Diets for patients with chronic kidney disease, should we reconsider? BMC Nephrol. 2016, 17, 80.
  30. Rhee, C.M.; Ahmadi, S.-F.; Kovesdy, C.P.; Kalantar-Zadeh, K. Low-protein diet for conservative management of chronic kidney disease: A systematic review and meta-analysis of controlled trials. J. Cachex. Sarcopenia Muscle 2017, 9, 235–245.
  31. Locatelli, F.; Alberti, D.; Graziani, G.; Buccianti, G.; Redaelli, B.; Giangrande, A. Prospective, randomised, multicentre trial of effect of protein restriction on progression of chronic renal insufficiency. Lancet 1991, 337, 1299–1304.
  32. Williams, P.; Stevens, M.; Fass, G.; Irons, L.; Bone, J. Failure of dietary protein and phosphate restriction to retard the rate of progression of chronic renal failure: A prospective, randomized, controlled trial. Qjm Int. J. Med. 1991, 81, 837–855.
  33. Cianciaruso, B.; Pota, A.; Pisani, A.; Torraca, S.; Annecchini, R.; Lombardi, P.; Capuano, A.; Nazzaro, P.; Bellizzi, V.; Sabbatini, M. Metabolic effects of two low protein diets in chronic kidney disease stage 4–5—A randomized controlled trial. Nephrol. Dial. Transplant. 2007, 23, 636–644.
  34. Ihle, B.U.; Becker, G.J.; Whitworth, J.A.; Charlwood, R.A.; Kincaid-Smith, P.S. The effect of protein restriction on the progression of renal insufficiency. N. Engl. J. Med. 1989, 321, 1773–1777.
  35. Rosman, J.B.; Langer, K.; Brandl, M.; Piers-Becht, T.P.; Van Der Hem, G.K.; Ter Wee, P.M.; Donker, A.J. Protein-restricted diets in chronic renal failure: A four year follow-up shows limited indications. Kidney Int. Suppl. 1989, 27, S96–S102.
  36. Harn, D.; Hodson, E.M.; Fouque, D. Low-protein diets for non-diabetic adults with chronic kidney disease. Cochrane Database Syst. Rev. 2018.
  37. Japan Nephrology Society. Japan Nephrology Society dietary recommendations for chronic kidney disease. Jpn. J. Renal Soc. 2014, 56, 553–599.
  38. Wilson, H.E.C. Studies on the physiology of protein retention. J. Physiol. 1931, 72, 327–343.
  39. Vickery, H.B. Biographical Memoir of RUSSELL HENRY CHITTENDEN 1856-1943; National Academy of Sciences: Washington, DC, USA, 1944; pp. 59–104.
  40. Dietary Reference Intake of Japanese 2020. Available online: https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/kenkou_iryou/kenkou/eiyou/syokuji_kijyun.html (accessed on 15 June 2021).
  41. Watanabe, S. Evaluation of Modification of Diet in Renal Disease (MDRD) study. Clin. Funct. Nutr. 2009, 1, 238–241.
  42. Watanabe, S.; Noboru, M.; Yasunari, M.; Ideura, T. A cross-sectional study on the effects of long term very low protein diets in patients with chronic kidney disease. Anti-Aging Med. 2010, 7, 7–13.
  43. Nakao, T.; Kanazawa, Y.; Takahashi, T. Once-weekly hemodialysis combined with low-protein and low-salt dietary treatment as a favorable therapeutic modality for selected patients with end-stage renal failure: A prospective observational study in Japanese patients. BMC Nephrol. 2018, 19, 151–161.
  44. Ideura, T.; Shimazui, M.; Morita, H.; Yoshimura, A. Protein intake of more than 0.5 g/kg BW/day is not effective in suppressing the progression of chronic renal failure. Contrib. Nephrol. 2007, 155, 40–49.
  45. Chauveau, P.; Combe, C.; Fouque, D.; Aparicio, M. Vegetarianism: Advantages and drawbacks in patients with chronic kidney diseases. J. Ren. Nutr. 2013, 23, 399–405.
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