Wiener klinische Wochenschrift

, Volume 130, Issue 13–14, pp 436–445 | Cite as

Renal function in patients with mechanical prosthetic valves

Long-term effects of anticoagulation and over-anticoagulation with warfarin
  • Yiğit ÇangaEmail author
  • Tolga Sinan Güvenç
  • Ali Nazmi Çalık
  • Mehmet Baran Karataş
  • Evliya Akdeniz
  • Gizem Yüksel
  • Ayşe Emre
original article



Warfarin-related nephropathy (WRN) is a complication of warfarin over-anticoagulation that is associated with acute and/or chronic renal dysfunction and increased mortality. The long-term effects of warfarin on renal function has not been adequately studied in patients with a mechanical prosthetic valve (MPV).


To study the time-dependent effects of over-anticoagulation on renal function in patients with a MPV.


A total of 193 patients who underwent MPV implantation and were followed up in this study were eligible for inclusion. Time above therapeutic international normalized ratio (INR) range (TATR) was calculated by dividing the number of INR measurements above target in a year by the total number of INR measurements within a year. Patients were divided into quartiles according to average TATR at 60 months.


At 60 months more patients within the 4th quartile had a ≥20% reduction in the estimated glomerular filtration rate (eGFR, 25.0%, p = 0.04) and chronic kidney disease (CKD, 33.0%, p = 0.07) compared to patients within the 1st quartile. High TATR remained a significant determinant for reduction in eGFR (odds ratio OR: 7.50, 95% confidence interval CI:1.55–36.32) and CKD (OR:5.15, 95% CI: 1.26–20.62) after adjusting for other variables. Longitudinal analysis revealed that the change in eGFR was related to the duration of warfarin use (p < 0.001) and the interaction between the duration of warfarin use and TATR (p = 0.03). Similar findings were observed in patients without CKD at baseline, but not in those with CKD before the index operation.


Anticoagulation over targeted INR values is associated with a steeper decline in eGFR and an increased frequency of CKD in patients with a MPV.


Warfarin Chronic kidney disease Mechanical prosthetic valve 


Conflict of interest

Y. Çanga, T.S. Güvenç, A.N. Çalık, M.B. Karataş, E. Akdeniz, G. Yüksel, and A. Emre declare that they have no competing interests.


  1. 1.
    Brodsky SV, Collins M, Park E, Rovin BH, Satoskar AA, Nadasdy G, Wu H, Bhatt U, Nadasdy T, Hebert LA. Warfarin therapy that results in an international normalization ratio above the therapeutic range is associated with accelerated progression of chronic kidney disease. Nephron Clin Pract. 2010;115:c142–6.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Wheeler DS, Giugliano RP, Rangaswami J. Anticoagulation-related nephropathy. J Thromb Haemost. 2016;14(3):461–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Fanola CL, Mooney D, Cowan AJ, Ko D, Sisson EK, Henault LE, Tripodis Y, Hylek EM. Incidence of severe renal dysfunction among individuals taking warfarin and implications for non-vitamin K oral anticoagulants. Am Heart J. 2017;184:150–5.CrossRefPubMedGoogle Scholar
  4. 4.
    Krishna VN, Warnock DG, Saxena N, Rizk DV. Oral anticoagulants and risk of nephropathy. Drug Saf. 2015;38(6):527–523.CrossRefGoogle Scholar
  5. 5.
    Logan I, Sheerin NS. Anticoagulation and kidney injury: rare observation or common problem? J Nephrol. 2013;26:603–5.CrossRefPubMedGoogle Scholar
  6. 6.
    An JN, Ahn SY, Yoon CH, Youn TJ, Han MK, Kim S, Chin HJ, Na KY, Chae DW. The occurrence of warfarin-related nephropathy and effects on renal and patient outcomes in Korean patients. PLoS ONE. 2013;8(4):e57661.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Eikelboom JW, Connolly SJ, Brueckmann M, Granger CB, Kappetein AP, Mack MJ, Blatchford J, Devenny K, Friedman J, Guiver K, Harper R, Khder Y, Lobmeyer MT, Maas H, Voigt JU, Simoons ML, RE-ALIGN Investigators. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369:1206–14.CrossRefPubMedGoogle Scholar
  8. 8.
    Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2017;38(36):2739–91. Scholar
  9. 9.
    Levey AS, Stevens LA, Schmid CH, Zhang Y, Castro AF, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150:604–12.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Vittinghoff E, McCulloch CE. Relaxing the rule of ten events per variable in logistic and Cox regression. Am J Epidemiol. 2007;165:710–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Rizk DV, Warnock DG. Warfarin-related nephropathy: another newly recognized complication of an old drug. Kidney Int. 2011;80:131–3.CrossRefPubMedGoogle Scholar
  12. 12.
    Brodsky SV, Satoskar A, Chen J, Nadasdy G, Eagen JW, Hamirani M, Hebert L, Calomeni E, Nadasdy T. Acute kidney injury during warfarin therapy associated with obstructive tubular red blood cell casts: a report of 9 cases. Am J Kidney Dis. 2009;54(6):1121–6.CrossRefPubMedGoogle Scholar
  13. 13.
    Yanagita M. Gas6, warfarin, and kidney diseases. Clin Exp Nephrol. 2004;8(4):304–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Kapoor KG, Bekaii-Saab T. Warfarin-induced allergic interstitial nephritis and leucocytoclastic vasculitis. Intern Med J. 2008;38:281–3.CrossRefPubMedGoogle Scholar
  15. 15.
    Moll S, Huffman J. Cholesterol emboli associated with warfarin treatment. Am J Hematol. 2004;77(2):194–5.CrossRefPubMedGoogle Scholar
  16. 16.
    Brodsky SV, Nadasdy T, Rovin BH, Satoskar AA, Nadasdy GM, Wu HM, Bhatt UY, Hebert LA. Warfarin-related nephropathy occurs in patients with and without chronic kidney disease and is associated with an increased mortality rate. Kidney Int. 2011;80(2):181–9.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Najjar M, Yerebakan H, Sorabella RA, Guglielmetti L, Vandenberge J, Kurlansky P, Williams MR, Argenziano M, Smith CR, George I. Reversibility of chronic kidney disease and outcomes following aortic valve replacement. Interact Cardiovasc Thorac Surg. 2015;21(4):499–505.CrossRefPubMedGoogle Scholar
  18. 18.
    Thongprayoon C, Cheungpasitporn W, Kittanamongkolchai W, Srivali N, Greason KL, Kashani K. Changes in kidney function among patients undergoing transcatheter aortic valve replacement. J Renal. Inj Prev. 2017;6(3):216–21.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of CardiologyDr. Siyami Ersek Cardiovascular and Thoracic Surgery Research and Training HospitalKadıköy, IstanbulTurkey

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