Seminars in Nephrology
Volume 31, Issue 6 , Pages 475-482 , November 2011

Diuretics and Salt Transport Along the Nephron

  • Paul L. Bernstein, MD

      Affiliations

    • Division of Nephrology, Rochester General Hospital, University of Rochester School of Medicine and Dentistry, Rochester, NY
    • Corresponding Author InformationAddress reprint requests to Paul L. Bernstein, MD, Rochester General Hospital, University of Rochester School of Medicine and Dentistry, 1425 Portland Ave, Rochester, NY 14621
    • ,
  • David H. Ellison, MD

      Affiliations

    • Division of Nephrology and Hypertension, Oregon Health and Science University, Portland, OR

References 

  1. Gitelman H, Grahm J, Walt L. A new familiar disorder characterized by hypokalemia, hypomagnesemia. Trans Assoc Am J Physiol. 1966;79:221–235
  2. Wilson I, Freis E. Relationship between plasma and extracellular fluid volume deprivation and the anti-hypertensive effect of chlorthiazide. Circulation. 1959;20:1028–1036
  3. Gamba G. Molecular physiology and pathophysiology of electroneutral cation-chloride cotransporters. Physiol Rev. 2005;85:423–493
  4. Gamba G. The thiazide-sensitive Na+Cl- cotransporter: molecular biology, functional properties, and regulation by WNKs. Am J Physiol Renal Physiol. 2009;297:F838–F848
  5. Kaplan J. Biochemistry of Na, K-ATPase. Ann Rev Biochem. 2002;71:511–535
  6. McDonough A. Mechanism of proximal tubule sodium transport regulation that link extracellular fluid volume and blood pressure. Am J Physiol Regul Integr Compar Physiol. 2010;298:R851–R861
  7. Singh P, Thomson S. Renal homeostasis and tubuloglomerular feedback. Curr Opin Nephrol Hypertens. 2010;19:59–64
  8. Komoroski B, Vacharajani N, Boulton D, Kornhauser D, Geraldes M, Li L. Dapagliflozin, a novel SGLT2 inhibitor, induces dose-dependent glucosuria in healthy subjects. Clin Pharmacol Ther. 2009;85:520–526
  9. Calado J, Loeffler J, Sakallioglu O, Gok F, Lhotta K, Barata J, et al. Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting. Kidney Int. 2006;69:852–855
  10. Zhang Y, Magyar C, Norian J, Holstein-Rathlou N, Mircheff A, McDonough A. Reversible effects of acute hypertension on proximal tubule sodium transporters. Am J Physiol Cell Physiol. 1998;274:1090–1100
  11. Brater DC. Pharmacology of diuretics. Am J Med Sci. 2000;319:38–50
  12. Sarafidis P, Georgianos P, Lasaridis A. Diuretics in clinical practice (Part I: mechanisms of action, pharmacological effects and clinical indications of diuretic compounds). Expert Opin Drug Saf. 2010;9:243–257
  13. Lytle C, McManus T, Haas M. A model of Na-K-2Cl cotransport based on ordered ion binding and glide symmetry. Am J Physiol. 1998;274:C299–C309
  14. Payne J, Forbush B. Alternatively spliced isoforms of the putative renal Na-K-Cl cotransporter are differentially distributed within the rabbit kidney. Proc Natl Acad Sci U S A. 1994;91:4544–4548
  15. Brunet G, Gagnon E, Simard C, Daigle N, Caron L, Noel M, et al. Novel insights regarding the operational characteristics and teleological purpose of the renal Na-K-Cl2 cotransporter (NKCC2s) splice variants. J Gen Physiol. 2005;126:325–337
  16. Haas M, McManus T. Bumetanide inhibits Na+K+2Cl- co-transport at a chloride site. Am J Physiol Cell Physiol. 1983;245:C235–C240
  17. Gagnon E. Molecular mechanisms of Cl transport by the renal Na-K-Cl cotransporter. J Biol Chem. 2004;279:5648–5654
  18. Anahi-Paredes C, Plata C, Rivera M, et al. Activity of the renal Na-K-2Cl cotransporter is reduced by mutagenesis of N-glycosylation sites: role for protein surface charge in Cl transport. Am J Physiol Renal Physiol. 2006;290:F1094–F1102
  19. Simon D, Nelson-Williams C, Bia M, Ellison D, Karet F, Molina A, et al. Gitelman's variant of Barter's syndrome, inherited hypokalemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. Nat Genet. 1996;12:24–30
  20. Tran J, Farrell M, Fanestil D. Effect of ions on binding of the thiazide-type diuretic metolazone to kidney membrane. Am J Physiol. 1990;258:F908–F915
  21. Obermuller N, Kunchaparty S, Ellison D, Bachmann S. Expression of the Na-K-2Cl cotransporter by macula densa and thick ascending limb cells of rat and rabbit nephron. J Clin Invest. 1996;98:635–640
  22. Meneton P, Loffing J, Warnock D. Sodium and potassium handling by the aldosterone-sensitive distal nephron: the pivotal role of the distal and connecting tubule. Am J Physiol Renal Physiol. 2004;287:F593–F601
  23. Gimenez I. Molecular mechanisms and regulation of furosemide-sensitive Na-K-Cl cotransporters. Curr Opin Nephrol Hypertens. 2006;15:517–523
  24. Yang C-L, Angell J, Mitchell R, Ellison D. WNK kinases regulate thiazide-sensitive Na-Cl cotransport. J Clin Invest. 2003;111:1039–1045
  25. Wilson F. Human Hypertension caused by mutations in WNK-kinases. Science. 2001;293:1107–1112
  26. Lalioti M, Zhang J, Volkman H, Kahle K, Hoffmann K, Toka H, et al. WNK-4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule. Nat Genet. 2006;38:1124–1132
  27. Subramanya A, Ellison D. Sorting out lysosomal trafficking of the thiazide-sensitive Na-Cl Co-transporter. J Am Soc Nephrol. 2010;21:7–9
  28. Chiga M, Rai T, Yang S-S, Ohta A, Takizawa T, Sasaki S, et al. Dietary salt regulates the phosphorylation of OSR1/SPAK-kinases, and the sodium-chloride cotransporter through aldosterone. Kidney Int. 2008;74:1403–1409
  29. Okusa M, Ellison D. Physiology and pathophysiology of diuretic action. In:  Alpern RJ,  Hebert SC editor. Seldin and Giebisch's the kidney. 4th ed.. Philadelphia: Elsevier; 2008;p. 1051–1094
  30. Kellenberger S. Mutations in the epithelial Na channel outer pore disrupt amiloride block by increasing its dissociation rate. Mol Pharmacol. 2003;64:848–856
  31. Funder JW. The nongenomic effects of aldosterone. Endocr Rev. 2005;26:313–321
  32. Berger S, Bleich M, Schmid W, Cole T, Peters J, Watanabe H, et al. Mineralocorticoid receptor knockout mice: pathophysiology of Na metabolism. Proc Natl Acad Sci U S A. 1998;95:9424–9429
  33. Knight K, Olson D, Zhou R, Snyder P. Liddle's syndrome mutations increase Na transport through dual effects on epithelial Na channel surface expression and proteolytic cleavage. Proc Natl Acad Sci U S A. 2006;103:2805–2808
  34. Van der Lubbe N, Lim C, Fenton R, Meima M, Danser A, Zietse R, et al. Angiotensin II induces phosphorylation of thiazide-sensitive sodium chloride cotransporter independent of aldosterone. Kidney Int. 2011;79:66–76
  35. Ellison D. Through a glass darkly: salt transport by the distal tubule. Kidney Int. 2011;79:5–8
  36. Laffi G, La Villa G, Carloni V, Foschi M, Bartoletti L, Quartini M, et al. Loop diuretic therapy in liver cirrhosis with ascites. J Cardiovasc Pharmacol. 1993;22(Suppl 3):S51–S58
  37. Bhave G, Chauder B, Liu W, Dawson E, Kadakia R, Nguyen T, et al. Development of a selective small-molecule inhibitor of Kir1.1, the renal outer medullary potassium channel. Mol Pharmacol. 2011;79:42–50
  38. Glover M, O'Shaughnessy K. SPAK and WNK kinases: a new treatment for blood pressure treatment?. Curr Opin Nephrol Hypertens. 2011;20:16–22
  39. Glover M, Zuber A, O'Shaugnessy K. Hypertension, salt intake, and the role of the thiazide-sensitive sodium chloride transporter NCCT. Cardiovascular therapeutics. 2011;29:68–76

PII: S0270-9295(11)00131-8

doi: 10.1016/j.semnephrol.2011.09.002

Seminars in Nephrology
Volume 31, Issue 6 , Pages 475-482 , November 2011

Article Tools

* Image Usage & Resolution