Magnetic resonance-determined sodium removal from tissue stores in hemodialysis patients
Anke Dahlmann, Kathrin Dörfelt, Florian Eicher, Peter Linz, Christoph Kopp, Irina Mössinger, Stephan Horn, Beatrix Büschges-Seraphin, Peter Wabel, Matthias Hammon, Alexander Cavallaro, Kai-Uwe Eckardt, Peter Kotanko, Nathan W Levin, Bernd Johannes, Michael Uder, Friedrich C Luft, Dominik N Müller, Jens M Titze, Anke Dahlmann, Kathrin Dörfelt, Florian Eicher, Peter Linz, Christoph Kopp, Irina Mössinger, Stephan Horn, Beatrix Büschges-Seraphin, Peter Wabel, Matthias Hammon, Alexander Cavallaro, Kai-Uwe Eckardt, Peter Kotanko, Nathan W Levin, Bernd Johannes, Michael Uder, Friedrich C Luft, Dominik N Müller, Jens M Titze
Abstract
We have previously reported that sodium is stored in skin and muscle. The amounts stored in hemodialysis (HD) patients are unknown. We determined whether (23)Na magnetic resonance imaging (sodium-MRI) allows assessment of tissue sodium and its removal in 24 HD patients and 27 age-matched healthy controls. We also studied 20 HD patients before and shortly after HD with a batch dialysis system with direct measurement of sodium in dialysate and ultrafiltrate. Age was associated with higher tissue sodium content in controls. This increase was paralleled by an age-dependent decrease of circulating levels of vascular endothelial growth factor-C (VEGF-C). Older (>60 years) HD patients showed increased sodium and water in skin and muscle and lower VEGF-C levels compared with age-matched controls. After HD, patients with low VEGF-C levels had significantly higher skin sodium content compared with patients with high VEGF-C levels (low VEGF-C: 2.3 ng/ml and skin sodium: 24.3 mmol/l; high VEGF-C: 4.1 ng/ml and skin sodium: 18.2 mmol/l). Thus, sodium-MRI quantitatively detects sodium stored in skin and muscle in humans and allows studying sodium storage reduction in ESRD patients. Age and VEGF-C-related local tissue-specific clearance mechanisms may determine the efficacy of tissue sodium removal with HD. Prospective trials on the relationship between tissue sodium content and hard end points could provide new insights into sodium homeostasis, and clarify whether increased sodium storage is a cardiovascular risk factor.
Conflict of interest statement
Disclosure statement
The authors have no interest conflicts and nothing to disclose.
Figures
References
- Guyton AC, Coleman TC, Cowley AW, Jr, et al. A systems analysis approach to understanding long-range arterial blood pressure control and hypertension. Circ Res. 1974;35:159–176.
- Levin NW, Kotanko P, Eckardt KU, et al. Blood pressure in chronic kidney disease stage 5D-report from a Kidney Disease: Improving Global Outcomes controversies conference. Kidney international. 2010;77:273–284.
- Agarwal R, Alborzi P, Satyan S, et al. Dry-weight reduction in hypertensive hemodialysis patients (DRIP): a randomized, controlled trial. Hypertension. 2009;53:500–507.
- Al-Hilali N, Al-Humoud H, Ninan VT, et al. Blood pressure control in haemodialysis patients: an audit. Nephrology. 2006;11:100–104.
- Davenport A. Audit of the effect of dialysate sodium concentration on inter-dialytic weight gains and blood pressure control in chronic haemodialysis patients. Nephron Clinical practice. 2006;104:c120–125.
- Krautzig S, Janssen U, Koch KM, et al. Dietary salt restriction and reduction of dialysate sodium to control hypertension in maintenance haemodialysis patients. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 1998;13:552–553.
- Chazot C. Can chronic volume overload be recognized and prevented in hemodialysis patients? Use of a restricted-salt diet. Seminars in dialysis. 2009;22:482–486.
- Hur E, Usta M, Toz H, et al. Effect of Fluid Management Guided by Bioimpedance Spectroscopy on Cardiovascular Parameters in Hemodialysis Patients: A Randomized Controlled Trial. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2013
- Kayikcioglu M, Tumuklu M, Ozkahya M, et al. The benefit of salt restriction in the treatment of end-stage renal disease by haemodialysis. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2009;24:956–962.
- Mc Causland FR, Waikar SS, Brunelli SM. Increased dietary sodium is independently associated with greater mortality among prevalent hemodialysis patients. Kidney international. 2012;82:204–211.
- Foley RN, Herzog CA, Collins AJ, et al. Blood pressure and long-term mortality in United States hemodialysis patients: USRDS Waves 3 and 4 Study. Kidney international. 2002;62:1784–1790.
- Wabel P, Moissl U, Chamney P, et al. Towards improved cardiovascular management: the necessity of combining blood pressure and fluid overload. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2008;23:2965–2971.
- Heerspink HL, Ritz E. Sodium chloride intake: is lower always better? Journal of the American Society of Nephrology : JASN. 2012;23:1136–1139.
- Wheeler DC, Becker GJ. Summary of KDIGO guideline. What do we really know about management of blood pressure in patients with chronic kidney disease? Kidney international. 2013;83:377–383.
- Titze J, Bauer K, Schafflhuber M, et al. Internal sodium balance in DOCA-salt rats: a body composition study. Am J Physiol Renal Physiol. 2005;289:F793–802.
- Titze J, Lang R, Ilies C, et al. Osmotically inactive skin Na+ storage in rats. Am J Physiol Renal Physiol. 2003;285:F1108–1117.
- Ziomber A, Machnik A, Dahlmann A, et al. Sodium-, potassium-, chloride-, and bicarbonate-related effects on blood pressure and electrolyte homeostasis in deoxycorticosterone acetate-treated rats. Am J Physiol Renal Physiol. 2008;295:F1752–1763.
- Machnik A, Dahlmann A, Kopp C, et al. Mononuclear phagocyte system depletion blocks interstitial tonicity-responsive enhancer binding protein/vascular endothelial growth factor C expression and induces salt-sensitive hypertension in rats. Hypertension. 2010;55:755–761.
- Machnik A, Neuhofer W, Jantsch J, et al. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat Med. 2009;15:545–552.
- Wiig H, Schroder A, Neuhofer W, et al. Immune cells control skin lymphatic electrolyte homeostasis and blood pressure. J Clin Invest. 2013;123:2803–2815.
- Kopp C, Linz P, Dahlmann A, et al. 23Na Magnetic Resonance Imaging-Determined Tissue Sodium in Healthy Subjects and Hypertensive Patients. Hypertension. 2013;61:635–640.
- Kopp C, Linz P, Wachsmuth L, et al. (23)Na magnetic resonance imaging of tissue sodium. Hypertension. 2012;59:167–172.
- Kopp C, Linz P, Hammon M, et al. Seeing the sodium in a patient with hypernatremia. Kidney international. 2012;82:1343–1344.
- Titze J, Dahlmann A, Lerchl K, et al. Spooky sodium balance. Kidney international; 2013.
- Dhondt AW, Vanholder RC, De Smet RV, et al. Studies on dialysate mixing in the Genius single-pass batch system for hemodialysis therapy. Kidney international. 2003;63:1540–1547.
- Titze J, Shakibaei M, Schafflhuber M, et al. Glycosaminoglycan polymerization may enable osmotically inactive Na+ storage in the skin. Am J Physiol Heart Circ Physiol. 2004;287:H203–208.
- Schafflhuber M, Volpi N, Dahlmann A, et al. Mobilization of osmotically inactive Na+ by growth and by dietary salt restriction in rats. Am J Physiol Renal Physiol. 2007;292:F1490–1500.
- Helle F, Karlsen TV, Tenstad O, et al. High-salt diet increases hormonal sensitivity in skin pre-capillary resistance vessels. Acta physiologica. 2013;207:577–581.
- Kleinewietfeld M, Manzel A, Titze J, et al. Sodium chloride drives autoimmune disease by the induction of pathogenic T17 cells. Nature. 2013
- Ivanova LN, Archibasova VK, Shterental I. Sodium-depositing function of the skin in white rats. Fiziol Zh SSSR Im I M Sechenova. 1978;64:358–363.
- Campisi J. Aging, Cellular Senescence, and Cancer. Annual review of physiology. 2012
- Cavanagh MM, Weyand CM, Goronzy JJ. Chronic inflammation and aging: DNA damage tips the balance. Current opinion in immunology. 2012
- Chertow GM, Johansen KL, Lew N, et al. Vintage, nutritional status, and survival in hemodialysis patients. Kidney international. 2000;57:1176–1181.
- Fouque D, Kalantar-Zadeh K, Kopple J, et al. A proposed nomenclature and diagnostic criteria for protein-energy wasting in acute and chronic kidney disease. Kidney international. 2008;73:391–398.
- Stenvinkel P, Heimburger O, Paultre F, et al. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney international. 1999;55:1899–1911.
- Maynard SE, Min JY, Merchan J, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003;111:649–658.
- Lely AT, Salahuddin S, Holwerda KM, et al. Circulating Lymphangiogenic Factors in Preeclampsia. Hypertens Pregnancy. 2013;32:42–49.
- Pitts RF. Volume and composition of the body fluids. Year Book; Chicago, IL: 1974.
- Bergstrom WH. The participation of bone in total body sodium metabolism in the rat. J Clin Invest. 1955;34:997–1004.
- Edelman IS, Leibman J. Anatomy of body water and electrolytes. Am J Med. 1959:27.
- Farber SJ. Mucopolysaccharides and sodium metabolism. Circulation. 1960;21:941–947.
- Farber SJ, Schubert M, Schuster N. The binding of cations by chondroitin sulfate. J Clin Invest. 1957;36:1715–1722.
- Edelman IS, Leibman J, O’Meara MP, et al. Interrelations between serum sodium concentration, serum osmolarity and total exchangeable sodium, total exchangeable potassium and total body water. J Clin Invest. 1958;37:1236–1256.
- Stewart IJ, Henrich WL. Is there any role for sodium modeling in the prevention of intradialytic hypotension in patients with large interdialytic fluid gains? Seminars in dialysis. 2011;24:422–423.
- Schwenger V, Weigand MA, Hoffmann O, et al. Sustained low efficiency dialysis using a single-pass batch system in acute kidney injury - a randomized interventional trial: the REnal Replacement Therapy Study in Intensive Care Unit PatiEnts. Crit Care. 2012;16:R140.
Source: PubMed