Myocardial effects of a low-protein diet in experimental kidney dysfunction
https://doi.org/10.36485/1561-6274-2022-26-4-110-118
Abstract
THE AIM: to evaluate the effect of low protein diet supplemented with ketosteril on morphological and epigenomic changes in the myocardium of Wistar rats with simulated kidney dysfunction. MATERIALS AND METHODS. The work was performed on male Wistar rats subjected to 5/6 nephrectomy (NE). The first group after NE received a standard diet (20.16% animal protein), the second – low protein diet (LPD), including 10% ketosteril. Control rats received a standard diet. After 4 months, blood pressure (BP) and left ventricular mass index (LVMI) were assessed in rats, and a histological examination of the myocardium was performed. In the myocardium, the relative expression levels of NF-kB, miRNA-21, miRNA-133, and miRNA-203 were determined. RESULTS. After 4 months in rats with NE on a standard diet, an increase in blood pressure, an increase in the mass index of the LV myocardium was recorded. MBD with the inclusion of 10% Ketosteril slowed down the growth of systolic blood pressure and the development of LV myocardial hypertrophy in rats with kidney dysfunction. At the histological level, the use of LPD provided a decrease in the degree of hypertrophy of cardiomyocytes and degenerative changes in cardiomyocytes. Animals treated with LPD had less pronounced diffuse and perivascular fibrosis compared with animals fed normal food. The use of MBD slowed down the increase in the relative level of expression of the NFκB gene and miRNA-21 in the myocardium of rats with NE and promoted an increase in the expression level of miRNA-133 and miRNA-203 compared to the indices of animals with NE that received standard food. CONCLUSION: long-term use of LPD with the use of ketoanalogues of essential amino acids can have a potential cardioprotective effect in CKD, slowing down the growth of blood pressure, an increase in LV myocardial mass and the formation of structural changes in the myocardium. It is possible that a decrease in the expression of NF-kB and miRNA-21, as well as an increase in the expression of miRNA-203 and 133 in the myocardium, can play a significant role in this.
About the Authors
O. N. BeresnevaRussian Federation
Olga N. Beresneva, PhD, Senior researcher
Pavlov University Institute of Nephrology Laboratory of Clinical Physiology of the Kidney
197022
L.Tolstoy st., 17, build. 54
St-Petersburg
tel.: (812)346-39-26
M. M. Parastaeva
Russian Federation
Marina M. Parastaeva, PhD, Senior researcher
Pavlov University Institute of Nephrology Laboratory of Clinical Physiology of the Kidney
197022
L.Tolstoy st., 17 build. 54
St-Petersburg
tel.: (812)346-39-26
G. T. Ivanova
Russian Federation
Galina T. Ivanova, PhD, Senior researcher
laboratory of physiology of the cardiovascular and lymphatic systems
199034
Makarova Emb., 6
St-Petersburg
tel.: 8 (812) 328-07-01
M. I. Zaraiski
Russian Federation
Mikhail I. Zaraiski, Prof., MD, PhD, DMedSci
Department of Clinical Laboratory Diagnostics with a Course of Molecular Medicine
197022
L. Tolstoy st., 17, build 54
St- Petersburg
S. A. Orlova
Russian Federation
Svetlana A. Orlova, MD, PhD, Assistant prof
Department of Propaedeutics of Internal Diseases
197022
L. Tolstoy st., 17 build. 54
St-Petersburg
tel.: +78123386919
A. G. Kucher
Russian Federation
Prof. Anatoly G. Kucher, MD, PhD, DMedSci, Vice-Director
Research Institute of Nephrology, Research and Сlinical Research Center
197022
L. Tolstoy st., 17, build 54
St-Petersburg
tel.: +7(921)421-18-17
References
1. Sárközy M, Gáspár R, Zvara Á et al. Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212. Sci Rep 2019; 9(1):1302. doi: 10.1038/s41598-018-37690-5
2. Wang Y, ZhangT, Cao X et al. Prostaglandin E 2 induced cardiac hypertrophy through EP2 receptor-dependent activation of β-catenin in 5/6 nephrectomy rats. ESC Heart Fail 2021; 8(3):1979–1989. doi: 10.1002/ehf2.13269
3. Kaesler N, Babler A, Floege J, Kramann R. Cardiac remodeling in chronic kidney disease. Toxins 2020; 12: 161. doi: 10.3390/toxins12030161
4. Verzola D, Picciotto D, Saio M et al. Low protein diets and plant-based low protein diets: do they meet protein requirements of patients with chronic kidney disease? Nutrients 2021; 13: 83. https://doi.org/10.3390/nu13010083
5. Apetrii M, Timofte D, Voroneanu L, Covic A. Nutrition in chronic kidney disease–the role of proteins and specific diets. Nutrients 2021; 13: 956. https://doi.org/10.3390/nu13030956
6. Kalantar-Zadeh K, Joshi S, Schlueter R et al. Plant-dominant low-protein diet for conservative management of chronic kidney disease. Nutrients 2020; 12: 1931. doi:10.3390/nu12071931
7. Koppe L, Cassani de Oliveira M, Fouque D. Ketoacid analogues supplementation in chronic kidney disease and future perspectives. Nutrients 2019; 11: 2071. doi: 10.3390/nu11092071
8. Molina P, Gavela E, Vizcaíno B et al. Optimizing diet to slow CKD progression. J Front Med(Lausanne) 2021; 8:654250. doi: 10.3389/fmed.2021.654250. eCollection 2021
9. Teixeira dos Santos AL, Duarte CK, Santos M et al. Low linolenic and linoleic acid consumption are associated with chronic kidney disease in patients with type 2 diabetes. PLoS One 2018;13(8):e0195249. doi: 10.1371/journal.pone.0195249. eCollection 2018
10. Beresneva ON, Parastaeva MM, Ivanova GT i dr. The role of ketosteril in nephroprotection and cardioprotection in experimental uremia. Nephrology (Saint-Petersburg) 2006;10(1):56–61 (In Russ.). doi: 10.24884/1561-6274-2006-10-1-56-61
11. Noels H, Lehrke M, Vanholder R, Jankowski J. Lipoproteins and fatty acids in chronic kidney disease: molecular and metabolic alterations. Nat Rev Nephrol 2021; 17(8):528–542. doi: 10.1038/s41581-021-00423-5
12. Gao X, Huang L, Grosjean F et al. Low-protein diet supplemented with ketoacids reduces the severity of renal disease in 5/6 nephrectomized rats: a role for KLF15. Kidney Int 2011;79:987–996. doi: 10.1038/ki.2010.539
13. Wang M, Xu H, Shin O et al. Compound α-keto acid tablet supplementation alleviates chronic kidney disease progression via inhibition of the NF-kB and MAPK pathway. J Transl Med 2019; 17:122. https://doi.org/10.1186/s12967-019-1856-9.
14. Wang JY, Gao YB, Zhang N et al. MicroRNA-21 overexpression enhances TGF-β1-induced epithelial-to-mesenchymal transition by target smad7 and aggravates renal damage in diabetic nephropa- thy. Mol Cell Endocrinol 2014;392(1–2):163–172. doi:10.1016/j.mce.2014.05.018
15. He Q, Wang C, Qin J et al. Effect of miR-203 expression on myocardial fibrosis. Eur Rev Med Pharmacol Sci 2017; 21:837–842
16. Sun B, Liu S, Hao R et al. RGD-PEG-PLA delivers MiR133 to infarct lesions of acute myocardial infarction model rats for cardiac protection. Pharmaceutics 2020;12(6):575. doi: 10.3390/pharmaceutics12060575
17. Martínez-Arias L, Panizo-García S, Martín-Vírgala J et al. Contribution of phosphorus and PTH to the development of cardiac hypertrophy and fibrosis in an experimental model of chronic renal failure. Nefrologia (Engl Ed) 2021; S0211-6995(21)00033-3. doi:10.1016/j.nefro.2021.02
18. Di Iorio B, Di Micco L, Torraca S et al. Acute effects of verylow-protein diet on FGF 23 levels: a randomized study. Clin J Am Soc Nephrol 2012;7(4):581–587. doi: 10.2215/CJN.07640711
19. Ivanova GT, Kucher AG, Beresneva ON i dr. Experimental evaluation of the nephroprotective and cardioprotective effects of long-term use of a low-protein diet including ketosteril. Nephrology (Saint-Petersburg) 2011;15(4):45–50 (In Russ.). doi: 10.24884/1561-6274-2011-15-4-45-50
20. Molina P, Gavela E, Vizcaíno B et al. Optimizing Diet to Slow CKD Progression. Front Med (Lausanne) 2021; 8:654250. doi: 10.3389/fmed.2021.654250. eCollection 2021
Review
For citations:
Beresneva O.N., Parastaeva M.M., Ivanova G.T., Zaraiski M.I., Orlova S.A., Kucher A.G. Myocardial effects of a low-protein diet in experimental kidney dysfunction. Nephrology (Saint-Petersburg). 2022;26(4):110-118. (In Russ.) https://doi.org/10.36485/1561-6274-2022-26-4-110-118