A randomized trial of sodium-restriction on kidney function, fluid volume and adipokines in CKD patients

BMC Nephrology

Emma McMahon¹  Goce Dimeski²  Jonathan P Whitehead³  Michael Stowasser⁴  Nicole M Isbel⁴  Carmel M Hawley⁴  Judith D Bauer¹  David W Johnson⁴  Katrina L Campbell⁴ 

[1] University of Queensland, Brisbane, QLD, Australia;Chemical Pathology, Pathology Queensland, Princess Alexandra Hospital, Brisbane, QLD, Australia;Mater Research Institute, The University of Queensland, Brisbane, QLD, Australia;Translational Research Institute, Brisbane, QLD, Australia

关键词: Inflammation;    Kidney function;    Blood pressure;    Cardiovascular disease;    Chronic kidney disease;    Nutrition;    Dietary sodium;   

Others  :  1082704
DOI  :  10.1186/1471-2369-15-57

 received in 2013-10-04, accepted in 2014-03-26,  发布年份 2014

【 摘 要 】

Background

Dietary sodium restriction is a key management strategy in chronic kidney disease (CKD). Recent evidence has demonstrated short-term reduction in blood pressure (BP) and proteinuria with sodium restriction, however the effect on other cardiovascular-related risk factors requires investigation in CKD.

Methods

The LowSALT CKD study involved 20 hypertensive Stage III-IV CKD patients counselled by a dietitian to consume a low-sodium diet (<100 mmol/day). The study was a randomised crossover trial comparing 2 weeks of high-sodium (additional 120 mmol sodium tablets) and low-sodium intake (placebo). Measurements were taken after each crossover arm including BP (peripheral and central), adipokines (inflammation markers and adiponectin), volume markers (extracellular-to-intracellular [E/I] fluid ratio; N-terminal pro-brain natriuretic peptide [NT-proBNP]), kidney function (estimated Glomerular Filtration Rate [eGFR]) and proteinuria (urine protein-creatinine ratio [PCR] and albumin-creatinine ratio [ACR]). Outcomes were compared using paired t-test for each cross-over arm.

Results

BP-lowering benefits of a low-sodium intake (peripheral BP (mean ± SD) 148/82 ± 21/12 mmHg) from high-sodium (159/87 ± 15/10 mmHg) intake were reflected in central BP and a reduction in eGFR, PCR, ACR, NTproBNP and E/I ratio. There was no change in inflammatory markers, total or high molecular weight adiponectin.

Conclusions

Short-term benefits of sodium restriction on BP were reflected in significant change in kidney function and fluid volume parameters. Larger, long-term adequately powered trials in CKD are necessary to confirm these results.

Trial registration

Universal Trial Number U1111-1125-2149 registered on 13/10/2011; Australian New Zealand Clinical Trials Registry Number ACTRN12611001097932 registered on 21/10/2011.

【 授权许可】

   
2014 Campbell et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Vogt L, Waanders F, Boomsma F, de Zeeuw D, Navis G: Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan. J Am Soc Nephrol 2008, 19(5):999-1007.
• [2]McMahon EJ, Bauer JD, Hawley CM, Isbel NM, Stowasser M, Johnson DW, Campbell KL: A Randomized Trial of Dietary Sodium Restriction in CKD. J Am Soc Nephrol 2013, 24(12):2096-2103.
• [3]Guerin AP, Blacher J, Pannier B, Marchais SJ, Safar ME, London GM: Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure. Circulation 2001, 103(7):987-992.
• [4]Aburto NJ, Ziolkovska A, Hooper L, Elliott P, Cappuccio FP, Meerpohl JJ: Effect of lower sodium intake on health: systematic review and meta-analyses. BMJ 2013, 346:f1326.
• [5]Strazzullo P, D’Elia L, Kandala N-B, Cappuccio FP: Salt intake, stroke, and cardiovascular disease: meta-analysis of prospective studies. BMJ 2009, 339:b4567.
• [6]Kanbay M, Chen Y, Solak Y, Sanders PW: Mechanisms and consequences of salt sensitivity and dietary salt intake. Curr Opin Nephrol Hypertens 2011, 20(1):37-43.
• [7]Frisoli TM, Schmieder RE, Grodzicki T, Messerli FH: Salt and Hypertension: Is Salt Dietary Reduction Worth the Effort? Am J Med 2012, 125(5):433-439.
• [8]Fogarty AW, Lewis SA, McKeever TM, Britton JR: Is higher sodium intake associated with elevated systemic inflammation? A population-based study. Am J Clin Nutr 2009, 89(6):1901-1904.
• [9]Lely AT, Krikken JA, Bakker SJ, Boomsma F, Dullaart RP, Wolffenbuttel BH, Navis G: Low dietary sodium and exogenous angiotensin II infusion decrease plasma adiponectin concentrations in healthy men. J Clin Endocrinol Metab 2007, 92(5):1821-1826.
• [10]Koomans HA, Roos JC, Boer P, Geyskes GG, Mees EJ: Salt sensitivity of blood pressure in chronic renal failure. Evidence for renal control of body fluid distribution in man. Hypertension 1982, 4(2):190-197.
• [11]Essig M, Escoubet B, de Zuttere D, Blanchet F, Arnoult F, Dupuis E, Michel C, Mignon F, Mentre F, Clerici C, Vrtovsnik F: Cardiovascular remodelling and extracellular fluid excess in early stages of chronic kidney disease. Nephrol Dial Transplant 2008, 23(1):239-248.
• [12]Slagman MCJ, Waanders F, Vogt L, Damman K, Hemmelder M, Navis G, Laverman GD: Elevated N-terminal pro-brain natriuretic peptide levels predict an enhanced anti-hypertensive and anti-proteinuric benefit of dietary sodium restriction and diuretics, but not angiotensin receptor blockade, in proteinuric renal patients. Nephrol Dial Transplant 2012, 27(3):983-990.
• [13]McMahon EJ, Bauer JD, Hawley CM, Isbel NM, Stowasser M, Johnson DW, Hale RE, Campbell KL: The effect of lowering salt intake on ambulatory blood pressure to reduce cardiovascular risk in chronic kidney disease (LowSALT CKD study): Protocol of a randomized trial. BMC Nephrology 2012, 13(1):137. BioMed Central Full Text
• [14]Chowdhury F, Williams A, Johnson P: Validation and comparison of two multiplex technologies, Luminex® and Mesoscale Discovery, for human cytokine profiling. J Immunol Methods 2009, 340(1):55-64.
• [15]Pogue V, Rahman M, Lipkowitz M, Toto R, Miller E, Faulkner M, Rostand S, Hiremath L, Sika M, Kendrick C, Hu B, Greene T, Appel L, Phillips RA, African American Study of Kidney Disease, Hypertension Collaborative Research Group: Disparate estimates of hypertension control from ambulatory and clinic blood pressure measurements in hypertensive kidney disease. Hypertension 2009, 53(1):20-27.
• [16]Dolan E, Stanton A, Thijs L, Hinedi K, Atkins N, McClory S, Den Hond E, McCormack P, Staessen JA, O'Brien E: Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study. Hypertension 2005, 46:156-161.
• [17]Sharman JE, Laurent S: Central blood pressure in the management of hypertension: soon reaching the goal? J Hum Hypertens 2013, 27(7):405-411.
• [18]Safar ME, Blacher J, Pannier B, Guerin AP, Marchais SJ, Guyonvarc'h PM, London GM: Central pulse pressure and mortality in end-stage renal disease. Hypertension 2002, 39(3):735-738.
• [19]Vlachopoulos C, Aznaouridis K, O'Rourke MF, Safar ME, Baou K, Stefanadis C: Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. Eur Heart J 2010, 31(15):1865-1871.
• [20]Suckling RJ, He FJ, Macgregor GA: Altered dietary salt intake for preventing and treating diabetic kidney disease. Cochrane Database Syst Rev 2010, 12:CD006763.
• [21]Luik PT, Hoogenberg K, Van Der Kleij FG, Beusekamp BJ, Kerstens MN, De Jong PE, Dullaart RP, Navis GJ: Short-term moderate sodium restriction induces relative hyperfiltration in normotensive normoalbuminuric Type I diabetes mellitus. Diabetologia 2002, 45(4):535-541.
• [22]Mallamaci F, Leonardis D, Bellizzi V, Zoccali C: Does high salt intake cause hyperfiltration in patients with essential hypertension? J Hum Hypertens 1996, 10(3):157-161.
• [23]Rudberg S, Persson B, Dahlquist G: Increased glomerular filtration rate as a predictor of diabetic nephropathy–an 8-year prospective study. Kidney Int 1992, 41(4):822-828.
• [24]Mogensen CE: Early glomerular hyperfiltration in insulin-dependent diabetics and late nephropathy. Scand J Clin Lab Invest 1986, 46(3):201-206.
• [25]Thomas MC, Moran J, Forsblom C, Harjutsalo V, Thorn L, Ahola A, Waden J, Tolonen N, Saraheimo M, Gordin D, Groop PH, FinnDiane Study Group: The association between dietary sodium intake, ESRD, and all-cause mortality in patients with type 1 diabetes. Diabetes Care 2011, 34(4):861-866.
• [26]Chen J, Gu D, Huang J, Rao DC, Jaquish CE, Hixson JE, Chen C-S, Chen J, Lu F, Hu D, Rice T, Kelly TN, Hamm LL, Whelton PK, He J: Metabolic syndrome and salt sensitivity of blood pressure in non-diabetic people in China: a dietary intervention study. The Lancet 2009, 373(9666):829-835.
• [27]Liu F, Mu J, Yuan Z, Wu G, Liu E, Zheng S, Lian Q, Ren K, Xu H: High salt intake fails to enhance plasma adiponectin in normotensive salt-sensitive subjects. Nutrition (Burbank, Los Angeles County, Calif) 2012, 28(4):422-425.
• [28]Krikken JA, Dallinga-Thie GM, Navis G, Dullaart RP: Short term dietary sodium restriction decreases HDL cholesterol, apolipoprotein A-I and high molecular weight adiponectin in healthy young men: relationships with renal hemodynamics and RAAS activation. Nutr Metab Cardiovasc Dis 2012, 22(1):35-41.
• [29]Axelsson J, Heimburger O, Lindholm B, Stenvinkel P: Adipose tissue and its relation to inflammation: the role of adipokines. J Ren Nutr 2005, 15(1):131-136.
• [30]Yilmaz MI, Sonmez A, Caglar K, Celik T, Yenicesu M, Eyileten T, Acikel C, Oguz Y, Yavuz I, Vural A: Effect of antihypertensive agents on plasma adiponectin levels in hypertensive patients with metabolic syndrome. Nephrology (Carlton) 2007, 12(2):147-153.
• [31]Larrousse M, Bragulat E, Segarra M, Sierra C, Coca A, de La Sierra A: Increased levels of atherosclerosis markers in salt-sensitive hypertension. Am J Hypertens 2006, 19(1):87-93.