A High-salt diet induces renal dysfunction and alters cardiometabolic homeostasis through elevation of circulating PCSK9 levels in Wistar rats
Paper Details
A High-salt diet induces renal dysfunction and alters cardiometabolic homeostasis through elevation of circulating PCSK9 levels in Wistar rats
Abstract
There is increasing evidence in support of a decisive role played by the diet in the development of non-communicable diseases. The present study aimed to assess the effect of salt overfeeding on renal function and on the cardiovascular system in Wistar rats. Four groups of rats were exposed to diets with various salt levels, 0.8% for control, and 2%, 4% and 8% for overfed rats during 12 weeks. Blood Glucose, Triglycerides, Total cholesterol, LDL cholesterol (LDL-c) and HDL cholesterol (HDL-c) levels were determined by enzymatic method and serum PCSK9 by ELISA. Kidneys’ histology sections were treated with hematoxylin-eosin staining. Serum creatinine (17.54±2.35 mg/L vs. 11.06±0.95 mg/L; p<0.05) and urea (1.48±0.37 g/L vs. 0.48±0.04 g/L; p<0.05) were significantly increased in overfed rats compared to control. Structural alteration of glomeruli and extensive tubular lesions were observed in rats fed with 4% and 8% salt. High salt intake caused a significant increase in Na+ (171.9±2.1 mEq/L vs. 148.4±2.6 mEq/L; p<0.01), K+ (8.3±0.4 mEq/L vs. 7.2±0.1 mEq/L; p<0.05), and Cl– (109.9±5.1 mEq/L vs. 96.0±1.6 mEq/L; p <0.01) levels at week 12 compared to control. Triglycerides (1.49±0.31 g/L vs. 0.89±0.05 g/L; p <0.05), LDL-c (0.59±0.09 g/L vs. 0.31±0.03 g/L; p <0,05) and serum PCSK9 (10.28±3.21 ng/ml vs. 0.98±0.11 g/L; p <0.001) were significantly increased in salt overfed rats compared to control. Our results suggest that high salt intake impairs renal morphology and function and increases the risks of cardiovascular disease through circulating PCSK9 level increasing.
Abujrad H, Mayne J, Ruzicka M, Cousins M, Raymond A, Cheesman J. 2014. Chronic kidney disease on hemodialysis is associated with decreased serum PCSK9 levels. Atherosclerosis 233, 123–129.
Ayodele OE, Alebiosu CO. 2010. Burden of Chronic Kidney Disease: An International Perspective. Advances in Chronic Kidney Disease 17, 215–224.
Cariou B, Le May C, Costet P. 2011. Clinical aspects of PCSK9. Atherosclerosis 216, 258–265.
Chapman MJ, Ginsberg HN, Amarenco P, Andreotti F, Borén J, Catapano AL. 2011. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. European Heart Journal 32, 1345–1361.
Charan J, Kantharia N. 2013. How to calculate sample size in animal studies? Journal of Pharmacology and Pharmacotherapeutics 4, 303–306.
de Borst MH, Navis G. 2016. Sodium intake, RAAS-blockade and progressive renal disease. Pharmacological Research 107, 344–351.
du Cailar G, Ribstein J, Mimran A. 2002. Dietary sodium and target organ damage in essential hypertension. American Journal of Hypertension 15, 222–229.
Earley A, Miskulin D, Lamb EJ, Levey AS, Uhlig K. 2012. Estimating equations for glomerular filtration rate in the era of creatinine standardization: a systematic review. Annals of Internal Medicine 156, 785–795.
Festing MFW, Altman DG. 2002. Guidelines for the design and statistical analysis of experiments using laboratory animals. ILAR journal 43, 244–258.
Fonseca-Alaniz MH, Brito LC, Borges-Silva CN, Takada J, Andreotti S, Lima FB. 2007. High dietary sodium intake increases white adipose tissue mass and plasma leptin in rats. Obesity (Silver Spring) 15, 2200–2208.
Garofalo C, Borrelli S, Provenzano M, De Stefano T, Vita C, Chiodini P. 2018. Dietary Salt Restriction in Chronic Kidney Disease: A Meta-Analysis of Randomized Clinical Trials. Nutrients 10, 732.
Graudal NA, Hubeck-Graudal T, Jurgens G. 2017. Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride. The Cochrane Database of Systematic Reviews 4, CD004022.
Guo Y, Yan B, Gui Y, Tang Z, Tai S, Zhou S. 2021. Physiology and role of PCSK9 in vascular disease: Potential impact of localized PCSK9 in vascular wall. Journal of Cellular Physiology 236, 2333–2351.
Haas ME, Levenson AE, Sun X, Liao W-H, Rutkowski JM, Nephrotic Syndrome Study Network. 2016. The Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Nephrotic Syndrome-Associated Hypercholesterolemia. Circulation 134, 61–72.
Harsha DW, Sacks FM, Obarzanek E, Svetkey LP, Lin PH, Bray GA. 2004. Effect of Dietary Sodium Intake on Blood Lipids: Results From the DASH–Sodium Trial. Hypertension 43, 393–398.
He FJ, Markandu ND, Sagnella GA, MacGregor GA. 2001. Effect of Salt Intake on Renal Excretion of Water in Humans. Hypertension 38, 317–320.
He FJ, Tan M, Ma Y, MacGregor GA. 2020. Salt Reduction to Prevent Hypertension and Cardiovascular Disease. Journal of the American College of Cardiology 75, 632–647.
Hosohata K. 2017. Biomarkers for Chronic Kidney Disease Associated with High Salt Intake. International Journal of Molecular Sciences 18, 2080.
Huang F, Yu P, Yuan Y, Li Q, Lin F, Gao Z. 2016. The relationship between sodium excretion and blood pressure, urine albumin, central retinal arteriolar equivalent. BMC Cardiovascular Disorders 16, 194.
Jackson EK, Gillespie DG, Mi Z, Cheng D. 2018. Adenosine Receptors Influence Hypertension in Dahl Salt-Sensitive Rats: Dependence on Receptor Subtype, Salt Diet, and Sex. Hypertension 72, 511–521.
James MT, Hemmelgarn BR, Tonelli M. 2010. Early recognition and prevention of chronic kidney disease. Lancet 375, 1296–1309.
Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Plattner B. 2013. Chronic kidney disease: global dimension and perspectives. Lancet 382, 260–272.
Jin K, Park BS, Kim YW, Vaziri ND. 2014. Plasma PCSK9 in Nephrotic Syndrome and in Peritoneal Dialysis: A Cross-sectional Study. American Journal of Kidney Diseases 63, 584–589.
Kitada K, Daub S, Zhang Y, Klein JD, Nakano D, Pedchenko T. 2017. High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation. The Journal of Clinical Investigation 127, 1944–1959.
Koh KH. 2018. Study of low salt diet in hypertensive patients with chronic kidney disease. Medical Journal of Malaysia 73, 376–381.
Konarzewski M, Szolkiewicz M, Sucajtys-Szulc E, Blaszak J, Lizakowski S, Swierczynski J. 2014. Elevated Circulating PCSK-9 Concentration in Renal Failure Patients is Corrected by Renal Replacement Therapy. American Journal of Nephrology 40, 157–163.
Kwakernaak AJ, Lambert G, Slagman MCJ, Waanders F, Laverman GD, Petrides F. 2013. Proprotein convertase subtilisin–kexin type 9 is elevated in proteinuric subjects: Relationship with lipoprotein response to antiproteinuric treatment. Atherosclerosis 226, 459–465.
Levenson AE, Shah AS, Khoury PR, Kimball TR, Urbina EM, de Ferranti SD. 2017. Obesity and type 2 diabetes are associated with elevated PCSK9 levels in young women. Pediatric Diabetes 18, 755–760.
Levey AS, Inker LA, Coresh J. 2014. GFR Estimation: From Physiology to Public Health. American Journal of Kidney Diseases 63, 820–834.
Liu S, Vaziri ND. 2014. Role of PCSK9 and IDOL in the pathogenesis of acquired LDL receptor deficiency and hypercholesterolemia in nephrotic syndrome. Nephrology Dialysis Transplantation 29, 538–543.
Maack T, Johnson V, Kau ST, Figueiredo J, Sigulem D. 1979. Renal filtration, transport, and metabolism of low-molecular-weight proteins: A review. Kidney International 16, 251–270.
MacGregor GA, de Wardener HE. 1999. Salt, diet, and health. Lancet 353, 1709–1710.
MacGregor GA, Markandu ND, Roulston JE, Jones JC, Morton JJ. 1981. Maintenance of blood pressure by the renin-angiotensin system in normal man. Nature 291, 329–331.
MacGregor GA, Markandu ND, Sagnella GA, Singer DR, Cappuccio FP. 1989. Double-blind study of three sodium intakes and long-term effects of sodium restriction in essential hypertension. Lancet 2, 1244–1247.
McMahon EJ, Bauer JD, Hawley CM, Isbel NM, Stowasser M, Johnson DW. 2013. A randomized trial of dietary sodium restriction in CKD. Journal of the American Society of Nephrology 24, 2096–2103.
Mills KT, Xu Y, Zhang W, Bundy JD, Chen C-S, Kelly TN. 2015. A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010. Kidney International 88, 950–957.
Morena M, Le May C, Chenine L, Arnaud L, Dupuy A-M, Pichelin M. 2017. Plasma PCSK9 concentrations during the course of nondiabetic chronic kidney disease: Relationship with glomerular filtration rate and lipid metabolism. Journal of Clinical Lipidology 11, 87–93.
Nakazawa Y, Inoue S, Nakamura Y, Iida Y, Ishigaki Y, Miyazawa K. 2019. High‐salt diet promotes crystal deposition through hypertension in Dahl salt‐sensitive rat model. International Journal of Urology 26, 839–846.
Ohta Y, Tsuchihashi T, Kiyohara K, Oniki H. 2013. High salt intake promotes a decline in renal function in hypertensive patients: a 10-year observational study. Hypertension Research 36, 172–176.
OMS. 2017. Suivi des progrès dans la lutte contre les maladies non transmissibles. Organisation Mondiale de la Santé, Genève.
OMS. 2014. Situation mondiale des maladies non transmissibles. Organisation Mondiale de la Santé, Genève.
Oyebode O, Oti S, Chen YF, Lilford RJ. 2016. Salt intakes in sub-Saharan Africa: a systematic review and meta-regression. Population Health Metrics 14, 1–14.
Palmer SC, Maggo JK, Campbell KL, Craig JC, Johnson DW, Sutanto B. 2017. Dietary interventions for adults with chronic kidney disease. Cochrane Database of Systematic Reviews CD011998.
Park SW, Moon YA, Horton JD. 2004. Post-transcriptional Regulation of Low Density Lipoprotein Receptor Protein by Proprotein Convertase Subtilisin/Kexin Type 9a in Mouse Liver. Journal of Biological Chemistry 279, 50630–50638.
Powles J, Fahimi S, Micha R, Khatibzadeh S, Shi P, Ezzati M. 2013. Global, regional and national sodium intakes in 1990 and 2010: a systematic analysis of 24 h urinary sodium excretion and dietary surveys worldwide. BMJ open 3, e003733.
Radhakrishnan J, Remuzzi G, Saran R, Williams DE, Rios-Burrows N, Powe N. 2014. Taming the chronic kidney disease epidemic: a global view of surveillance efforts. Kidney International 86, 246–250.
Ramachandran CD, Gholami K, Lam SK, Mustafa MR, Hoe SZ. 2019. Effect of high-salt diet on mean arterial pressure, renal epithelial sodium channels and aquaporin subunits expression levels in Spontaneously Hypertensive Rats. Physiology 5, 1–30.
Ritz E, Koleganova N, Piecha G. 2009. Role of sodium intake in the progression of chronic kidney disease. Journal of Renal Nutrition 19, 61–62.
Rogacev KS, Heine GH, Silbernagel G, Kleber ME, Seiler S, Emrich I. 2016. PCSK9 Plasma Concentrations Are Independent of GFR and Do Not Predict Cardiovascular Events in Patients with Decreased GFR. PLOS ONE 11, e0146920.
Rosa AC, Rattazzi L, Miglio G, Collino M, Fantozzi R. 2012. Angiotensin II induces tumor necrosis factor-α expression and release from cultured human podocytes. Inflammation Research 61, 311–317.
Shannon JA. 1935. The renal excretion of creatinine in man. Journal of Clinical Investigation 14, 403–410.
Sharotri V, Collier DM, Olson DR, Zhou R, Snyder PM. 2012. Regulation of Epithelial Sodium Channel Trafficking by Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9). Journal of Biological Chemistry 287, 19266–19274.
Sucajtys-Szulc E, Szolkiewicz M, Swierczynski J, Rutkowski B. 2016. Up-regulation of liver Pcsk9 gene expression as a possible cause of hypercholesterolemia in experimental chronic renal failure. Molecular and Cellular Biochemistry 411, 281–287.
Susic D, Frohlich ED, Kobori H, Shao W, Seth D, Navar LG. 2011. Salt-induced renal injury in SHRs is mediated by AT1 receptor activation. Journal of Hypertension 29, 716–723.
Thout SR, Santos JA, McKenzie B, Trieu K, Johnson C, McLean R. 2019. The Science of Salt: Updating the evidence on global estimates of salt intake. The Journal of Clinical Hypertension 21, 710–721.
Tipping PG. 2008. Are podocytes passive or provocative in proteinuric glomerular pathology? Journal of the American Society of Nephrology 19, 651–653.
Verhave JC, Hillege HL, Burgerhof JGM, Janssen WMT, Gansevoort RT, Navis GJ. 2004. Sodium intake affects urinary albumin excretion especially in overweight subjects. Journal of Internal Medicine 256, 324–330.
Vlad CE, Foia L, Popescu R, Ivanov I, Luca MC, Delianu C. 2019. Apolipoproteins A and B and PCSK9: Nontraditional Cardiovascular Risk Factors in Chronic Kidney Disease and in End-Stage Renal Disease. Journal of Diabetes Research 2019, 1–17.
Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A. 2016. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 388, 1459–1544.
Wang Y, Huang Y, Hobbs HH, Cohen JC. 2012. Molecular characterization of proprotein convertase subtilisin/kexin type 9-mediated degradation of the LDLR. Journal of Lipid Research 53, 1932–1943.
Washino S, Hosohata K, Jin D, Takai S, Miyagawa T. 2018. Early urinary biomarkers of renal tubular damage by a high-salt intake independent of blood pressure in normotensive rats. Clinical and Experimental Pharmacology and Physiology 45, 261–268.
WHO. 2016. Guideline: Sodium intake for adults and children. World Health Organization.
Xu W, Liu L, Hornby D. 2012. c-IAP1 binds and processes PCSK9 protein: linking the c-IAP1 in a TNF-α pathway to PCSK9-mediated LDLR degradation pathway. Molecules 17, 12086–12101.
Zheng-Lin B, Ortiz A. 2018. Lipid Management in Chronic Kidney Disease: Systematic Review of PCSK9 Targeting. Drugs 78, 215–229.
J.C.K. Ligan, T.C.M. Medehouenou, A.G.J. Segbo, E.M.S. Fiogbe, F.E.E. Kougnimon, A.A.E. Anago, D.D.J. Mensah, K.M. Obossa, S.E.R. Tcheoubi, C. Agbangla, D.C. Akpovi (2022), A High-salt diet induces renal dysfunction and alters cardiometabolic homeostasis through elevation of circulating PCSK9 levels in Wistar rats; IJB, V20, N2, February, P255-267
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