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Review
. 2017 Nov 16;377(20):1964-1975.
doi: 10.1056/NEJMra1703100.

Diuretic Treatment in Heart Failure

David H Ellison  1 , G Michael Felker  1
Affiliations
Review

Diuretic Treatment in Heart Failure

David H Ellison et al. N Engl J Med. .

Erratum in

  • Diuretic Treatment in Heart Failure.
    [No authors listed] [No authors listed] N Engl J Med. 2018 Feb 1;378(5):492. doi: 10.1056/NEJMx180001. N Engl J Med. 2018. PMID: 29385375 No abstract available.
No abstract available

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Figures

Figure 1
Figure 1
Mechanisms of loop diuretic action and resistance. Loop diuretics circulate bound to protein, and are secreted into the tubule lumen by organic anion transporters (OAT1 and OAT2) at the basolateral membrane, and Multidrug Resistant Protein-4 (and others) at the apical membrane. Diuretics compete with chloride for binding to NKCC2, which is also present at the macula densa. Enhanced salt absorption along proximal tubules limits diuretic-sensitive transport. Each step can mediate diuretic resistance (see text). PT: proximal tubule; TAL: thick ascending limb; MD: macula densa; DCT: distal convoluted tubule; CD: collecting duct; G: glomerulus.
Figure 2
Figure 2
Pharmacokinetic and Pharmacodynamic properties of loop diuretics. Panel A: acute decompensated heart failure shifts the dose-response curve to the right (R) and reduces the maximal natriuresis (D). B: plasma concentration of loop diuretic [Diuretic]P, as a function of time after intravenous (IV) or oral dose. The natriuretic threshold (as in A) in normal individuals and in acute decompensated heart failure is shown. Note that a higher concentration may be required for patients with acute decompensated heart failure. C: effects of repeated daily doses of loop diuretic (LD) on Na+ excretion comparing post-diuretic Na+ retention and the braking phenomenon. To be effective, natriuresis (dotted area) must exceed antinatriuresis (hatched area). These relationships may be altered, however, in acute decompensated heart failure.
Figure 3
Figure 3
Nephron remodeling as a mechanism of diuretic resistance. When high doses of loop diuretics are used chronically, the distal nephron undergoes remodeling, with hypertrophy and hyperplasia of distal convoluted tubule cells, principal cells and intercalated cells. This increases the reabsorptive capacity of the distal nephron, through mechanisms discussed in the text.
See this image and copyright information in PMC

Comment in

  • Diuretic Treatment in Heart Failure.
    Schranz D. Schranz D. N Engl J Med. 2018 Feb 15;378(7):683. doi: 10.1056/NEJMc1716477. N Engl J Med. 2018. PMID: 29446295 No abstract available.
  • Diuretic Treatment in Heart Failure.
    Berczeller PH. Berczeller PH. N Engl J Med. 2018 Feb 15;378(7):683. doi: 10.1056/NEJMc1716477. N Engl J Med. 2018. PMID: 29446296 No abstract available.
  • Diuretic Treatment in Heart Failure.
    Tuttolomondo A, Parrinello G, Pinto A. Tuttolomondo A, et al. N Engl J Med. 2018 Feb 15;378(7):683-4. doi: 10.1056/NEJMc1716477. N Engl J Med. 2018. PMID: 29446297 No abstract available.

References

    1. Gheorghiade M, Follath F, Ponikowski P, et al. Assessing and grading congestion in acute heart failure: a scientific statement from the acute heart failure committee of the heart failure association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine. Eur J Heart Fail. 2010;12:423–33. - PubMed
    1. Faris RF, Flather M, Purcell H, Poole-Wilson PA, Coats AJ. Diuretics for heart failure. Cochrane Database Syst Rev. 2012:Cd003838. - PubMed
    1. Somasekharan S, Tanis J, Forbush B. Loop diuretic and ion binding residues revealed by scanning mutagenesis of transmembrane helix 3 (TM3) of the Na-K-Cl Cotransporter (NKCC1) The Journal of biological chemistry. 2012 - PMC - PubMed
    1. Palmer LG, Schnermann J. Integrated control of Na transport along the nephron. Clinical journal of the American Society of Nephrology : CJASN. 2015;10:676–87. - PMC - PubMed
    1. Anders HJ, Davis JM, Thurau K. Nephron Protection in Diabetic Kidney Disease. The New England journal of medicine. 2016;375:2096–8. - PubMed

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