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Published in: International Urology and Nephrology 8/2017

01-08-2017 | Nephrology – Review

Anticoagulant-related nephropathy: a case report and review of the literature of an increasingly recognized entity

Authors: Rigas G. Kalaitzidis, Anila Duni, Georgios Liapis, Olga Balafa, Sofia Xiromeriti, Paulos Karolos Rapsomanikis, Moses S. Elisaf

Published in: International Urology and Nephrology | Issue 8/2017

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Abstract

Treatment with oral anticoagulants has been associated with worsening kidney function in patients with chronic kidney disease (CKD) as well as among patients without underlying CKD. Thus, anticoagulant-related nephropathy (ARN) is an increasingly recognized entity nowadays, mainly associated with warfarin anticoagulation. Recent evidence indicates that patients treated with the direct anticoagulants may also be at risk of ARN. However, the true incidence of anticoagulant-related nephropathy is difficult to determine. The typical histological lesion involves renal tubular occlusion by red blood cells (RBCs), tubular red blood cell casts on light microscopy and dysmorphic RBCs in the glomerulus on electron microscopy. In the absence of active glomerulonephritis or other inflammatory changes that could account for glomerular hemorrhage, the above findings confirm the diagnosis. Dabigatran etexilate was the first direct oral anticoagulant approved for stroke prevention in patients with non-valvular atrial fibrillation. In this article, we describe a rare case of dabigatran etexilate-induced nephropathy in a patient with preexisting IgA nephropathy and review the recent literature regarding this increasingly recognized entity.
Literature
1.
go back to reference Moreno JA, Martin-Cleary C, Gutierrez E et al (2012) AKI associated with macroscopic glomerular hematuria: clinical and pathophysiologic consequences. Clin J Am Soc Nephrol 7:175–184CrossRefPubMed Moreno JA, Martin-Cleary C, Gutierrez E et al (2012) AKI associated with macroscopic glomerular hematuria: clinical and pathophysiologic consequences. Clin J Am Soc Nephrol 7:175–184CrossRefPubMed
2.
go back to reference Praga M, Gutierrez-Millet V, Navas JJ et al (1985) Acute worsening of renal function during episodes of macroscopic hematuria in IgA nephropathy. Kidney Int 28:69–74CrossRefPubMed Praga M, Gutierrez-Millet V, Navas JJ et al (1985) Acute worsening of renal function during episodes of macroscopic hematuria in IgA nephropathy. Kidney Int 28:69–74CrossRefPubMed
3.
go back to reference Delclaux C, Jacquot C, Callard P, Kleinknecht D (1993) Acute reversible renal failure with macroscopic haematuria in IgA nephropathy. Nephrol Dial Transpl 8:195–199 Delclaux C, Jacquot C, Callard P, Kleinknecht D (1993) Acute reversible renal failure with macroscopic haematuria in IgA nephropathy. Nephrol Dial Transpl 8:195–199
4.
go back to reference Abt AB, Carroll LE, Mohler JH (2000) Thin basement membrane disease and acute renal failure secondary to gross hematuria and tubular necrosis. Am J Kidney Dis 35:533–536CrossRefPubMed Abt AB, Carroll LE, Mohler JH (2000) Thin basement membrane disease and acute renal failure secondary to gross hematuria and tubular necrosis. Am J Kidney Dis 35:533–536CrossRefPubMed
5.
go back to reference Martin CC, Moreno JA, Fernandez B et al (2010) Glomerular haematuria, renal interstitial haemorrhage and acute kidney injury. Nephrol Dial Transpl 25:4103–4106CrossRef Martin CC, Moreno JA, Fernandez B et al (2010) Glomerular haematuria, renal interstitial haemorrhage and acute kidney injury. Nephrol Dial Transpl 25:4103–4106CrossRef
6.
go back to reference Tracz MJ, Alam J, Nath KA (2007) Physiology and pathophysiology of heme: implications for kidney disease. J Am Soc Nephrol 18:414–420CrossRefPubMed Tracz MJ, Alam J, Nath KA (2007) Physiology and pathophysiology of heme: implications for kidney disease. J Am Soc Nephrol 18:414–420CrossRefPubMed
7.
go back to reference Moreno JA, Martin-Cleary C, Gutierrez E et al (2012) Haematuria: the forgotten CKD factor? Nephrol Dial Transplant 27:28–34CrossRefPubMed Moreno JA, Martin-Cleary C, Gutierrez E et al (2012) Haematuria: the forgotten CKD factor? Nephrol Dial Transplant 27:28–34CrossRefPubMed
8.
go back to reference Gutierrez E, Egido J, Rubio-Navarro A et al (2012) Oxidative stress, macrophage infiltration and CD163 expression are determinants of long-term renal outcome in macrohematuria-induced acute kidney injury of IgA nephropathy. Nephron Clin Pract 121:c42–c53CrossRefPubMed Gutierrez E, Egido J, Rubio-Navarro A et al (2012) Oxidative stress, macrophage infiltration and CD163 expression are determinants of long-term renal outcome in macrohematuria-induced acute kidney injury of IgA nephropathy. Nephron Clin Pract 121:c42–c53CrossRefPubMed
9.
go back to reference Gutierrez E, Gonzalez E, Hernandez E et al (2007) Factors that determine an incomplete recovery of renal function in macrohematuria-induced acute renal failure of IgA nephropathy. Clin J Am Soc Nephrol 2:51–57CrossRefPubMed Gutierrez E, Gonzalez E, Hernandez E et al (2007) Factors that determine an incomplete recovery of renal function in macrohematuria-induced acute renal failure of IgA nephropathy. Clin J Am Soc Nephrol 2:51–57CrossRefPubMed
10.
go back to reference Brodsky SV, Satoskar A, Chen J et al (2009) Acute kidney injury during warfarin therapy associated with obstructive tubular red blood cell casts: a report of 9 cases. Am J Kidney Dis 54:1121–1126CrossRefPubMed Brodsky SV, Satoskar A, Chen J et al (2009) Acute kidney injury during warfarin therapy associated with obstructive tubular red blood cell casts: a report of 9 cases. Am J Kidney Dis 54:1121–1126CrossRefPubMed
11.
go back to reference Ryan M, Ware K, Qamri Z et al (2014) Warfarin-related nephropathy is the tip of the iceberg: direct thrombin inhibitor dabigatran induces glomerular hemorrhage with acute kidney injury in rats. Nephrol Dial Transpl 29:2228–2234CrossRef Ryan M, Ware K, Qamri Z et al (2014) Warfarin-related nephropathy is the tip of the iceberg: direct thrombin inhibitor dabigatran induces glomerular hemorrhage with acute kidney injury in rats. Nephrol Dial Transpl 29:2228–2234CrossRef
12.
go back to reference Limdi NA, Beasley TM, Baird MF et al (2009) Kidney function influences warfarin responsiveness and hemorrhagic complications. J Am Soc Nephrol 20:912–921CrossRefPubMedPubMedCentral Limdi NA, Beasley TM, Baird MF et al (2009) Kidney function influences warfarin responsiveness and hemorrhagic complications. J Am Soc Nephrol 20:912–921CrossRefPubMedPubMedCentral
13.
go back to reference Brodsky SV, Collins M, Park E et al (2010) 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 115:c142–c146CrossRefPubMedPubMedCentral Brodsky SV, Collins M, Park E et al (2010) 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 115:c142–c146CrossRefPubMedPubMedCentral
14.
go back to reference Brodsky SV, Nadasdy T, Rovin BH et al (2011) Warfarin-related nephropathy occurs in patients with and without chronic kidney disease and is associated with an increased mortality rate. Kidney Int 80:181–189CrossRefPubMedPubMedCentral Brodsky SV, Nadasdy T, Rovin BH et al (2011) Warfarin-related nephropathy occurs in patients with and without chronic kidney disease and is associated with an increased mortality rate. Kidney Int 80:181–189CrossRefPubMedPubMedCentral
15.
go back to reference An JN, Ahn SY, Yoon CH et al (2013) The occurrence of warfarin-related nephropathy and effects on renal and patient outcomes in korean patients. PLoS ONE 8:e57661CrossRefPubMedPubMedCentral An JN, Ahn SY, Yoon CH et al (2013) The occurrence of warfarin-related nephropathy and effects on renal and patient outcomes in korean patients. PLoS ONE 8:e57661CrossRefPubMedPubMedCentral
16.
go back to reference Ware K, Brodsky P, Satoskar AA et al (2011) Warfarin-related nephropathy modeled by nephron reduction and excessive anticoagulation. J Am Soc Nephrol 22:1856–1862CrossRefPubMedPubMedCentral Ware K, Brodsky P, Satoskar AA et al (2011) Warfarin-related nephropathy modeled by nephron reduction and excessive anticoagulation. J Am Soc Nephrol 22:1856–1862CrossRefPubMedPubMedCentral
17.
go back to reference Ozcan A, Ware K, Calomeni E et al (2012) 5/6 nephrectomy as a validated rat model mimicking human warfarin-related nephropathy. Am J Nephrol 35:356–364CrossRefPubMedPubMedCentral Ozcan A, Ware K, Calomeni E et al (2012) 5/6 nephrectomy as a validated rat model mimicking human warfarin-related nephropathy. Am J Nephrol 35:356–364CrossRefPubMedPubMedCentral
18.
go back to reference Husted S, de Caterina R, Andreotti F et al (2014) Non-vitamin K antagonist oral anticoagulants (NOACs): no longer new or novel. Thromb Haemost 111:781–782CrossRefPubMed Husted S, de Caterina R, Andreotti F et al (2014) Non-vitamin K antagonist oral anticoagulants (NOACs): no longer new or novel. Thromb Haemost 111:781–782CrossRefPubMed
19.
go back to reference Hauel NH, Nar H, Priepke H, Ries U, Stassen JM, Wienen W (2002) Structure-based design of novel potent nonpeptide thrombin inhibitors. J Med Chem 45:1757–1766CrossRefPubMed Hauel NH, Nar H, Priepke H, Ries U, Stassen JM, Wienen W (2002) Structure-based design of novel potent nonpeptide thrombin inhibitors. J Med Chem 45:1757–1766CrossRefPubMed
20.
go back to reference Turpie AG, Kreutz R, Llau J, Norrving B, Haas S (2012) Management consensus guidance for the use of rivaroxaban—an oral, direct factor Xa inhibitor. Thromb Haemost 108:876–886CrossRefPubMed Turpie AG, Kreutz R, Llau J, Norrving B, Haas S (2012) Management consensus guidance for the use of rivaroxaban—an oral, direct factor Xa inhibitor. Thromb Haemost 108:876–886CrossRefPubMed
21.
22.
go back to reference Wong PC, Crain EJ, Xin B et al (2008) Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies. J Thromb Haemost 6:820–829CrossRefPubMed Wong PC, Crain EJ, Xin B et al (2008) Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies. J Thromb Haemost 6:820–829CrossRefPubMed
23.
go back to reference Dager WE, Gosselin RC, Kitchen S, Dwyre D (2012) Dabigatran effects on the international normalized ratio, activated partial thromboplastin time, thrombin time, and fibrinogen: a multicenter, in vitro study. Ann Pharmacother 46:1627–1636CrossRefPubMed Dager WE, Gosselin RC, Kitchen S, Dwyre D (2012) Dabigatran effects on the international normalized ratio, activated partial thromboplastin time, thrombin time, and fibrinogen: a multicenter, in vitro study. Ann Pharmacother 46:1627–1636CrossRefPubMed
24.
go back to reference Pollack CV Jr, Reilly PA, Eikelboom J et al (2015) Idarucizumab for dabigatran reversal. N Engl J Med 373:511–520CrossRefPubMed Pollack CV Jr, Reilly PA, Eikelboom J et al (2015) Idarucizumab for dabigatran reversal. N Engl J Med 373:511–520CrossRefPubMed
25.
go back to reference Chai-Adisaksopha C, Hillis C, Isayama T, Lim W, Iorio A, Crowther M (2015) Mortality outcomes in patients receiving direct oral anticoagulants: a systematic review and meta-analysis of randomized controlled trials. J Thromb Haemost 13:2012–2020CrossRefPubMed Chai-Adisaksopha C, Hillis C, Isayama T, Lim W, Iorio A, Crowther M (2015) Mortality outcomes in patients receiving direct oral anticoagulants: a systematic review and meta-analysis of randomized controlled trials. J Thromb Haemost 13:2012–2020CrossRefPubMed
26.
go back to reference Stangier J, Rathgen K, Stahle H, Mazur D (2010) Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet 49:259–268CrossRefPubMed Stangier J, Rathgen K, Stahle H, Mazur D (2010) Influence of renal impairment on the pharmacokinetics and pharmacodynamics of oral dabigatran etexilate: an open-label, parallel-group, single-centre study. Clin Pharmacokinet 49:259–268CrossRefPubMed
27.
go back to reference Berger R, Salhanick SD, Chase M, Ganetsky M (2013) Hemorrhagic complications in emergency department patients who are receiving dabigatran compared with warfarin. Ann Emerg Med 61:475–479CrossRefPubMed Berger R, Salhanick SD, Chase M, Ganetsky M (2013) Hemorrhagic complications in emergency department patients who are receiving dabigatran compared with warfarin. Ann Emerg Med 61:475–479CrossRefPubMed
28.
go back to reference Hernandez I, Baik SH, Pinera A, Zhang Y (2015) Risk of bleeding with dabigatran in atrial fibrillation. JAMA Intern Med 175:18–24CrossRefPubMed Hernandez I, Baik SH, Pinera A, Zhang Y (2015) Risk of bleeding with dabigatran in atrial fibrillation. JAMA Intern Med 175:18–24CrossRefPubMed
29.
go back to reference Harel Z, Mamdani M, Juurlink DN et al (2016) Novel oral anticoagulants and the risk of major hemorrhage in elderly patients with chronic kidney disease: a nested case-control study. Can J Cardiol 32:986–1017CrossRefPubMed Harel Z, Mamdani M, Juurlink DN et al (2016) Novel oral anticoagulants and the risk of major hemorrhage in elderly patients with chronic kidney disease: a nested case-control study. Can J Cardiol 32:986–1017CrossRefPubMed
30.
go back to reference Carlile-Klusacek M, Rizzo V (2007) Endothelial cytoskeletal reorganization in response to PAR1 stimulation is mediated by membrane rafts but not caveolae. Am J Physiol Heart Circ Physiol 293:H366–H375CrossRefPubMed Carlile-Klusacek M, Rizzo V (2007) Endothelial cytoskeletal reorganization in response to PAR1 stimulation is mediated by membrane rafts but not caveolae. Am J Physiol Heart Circ Physiol 293:H366–H375CrossRefPubMed
31.
go back to reference Rondeau E, Vigneau C, Berrou J (2001) Role of thrombin receptors in the kidney: lessons from PAR1 knock-out mice. Nephrol Dial Transplant 16:1529–1531CrossRefPubMed Rondeau E, Vigneau C, Berrou J (2001) Role of thrombin receptors in the kidney: lessons from PAR1 knock-out mice. Nephrol Dial Transplant 16:1529–1531CrossRefPubMed
32.
go back to reference Moeckel G, Luciano R, Brewster U (2013) Warfarin-related nephropathy in a patient with mild IgA nephropathy on dabigatran and aspirin. Clin Kidney J 0:1–3 Moeckel G, Luciano R, Brewster U (2013) Warfarin-related nephropathy in a patient with mild IgA nephropathy on dabigatran and aspirin. Clin Kidney J 0:1–3
33.
go back to reference Kadiyala D, Bum G (2012) Dabigatran induced acute kidney injury The American Society of Nephrology Annual Meeting, San Diego, CA, 1–4 Nov 2012. p. FR-PO1122 [abstract] Kadiyala D, Bum G (2012) Dabigatran induced acute kidney injury The American Society of Nephrology Annual Meeting, San Diego, CA, 1–4 Nov 2012. p. FR-PO1122 [abstract]
34.
go back to reference Shafi ST, Negrete H, Roy P, Julius CJ, Sarac E (2013) A case of dabigatran-associated acute renal failure. WMJ 112:173–175PubMed Shafi ST, Negrete H, Roy P, Julius CJ, Sarac E (2013) A case of dabigatran-associated acute renal failure. WMJ 112:173–175PubMed
35.
go back to reference Caldeira D, Goncalves N, Pinto FJ, Costa J, Ferreira JJ (2015) Risk of renal failure with the non-vitamin K antagonist oral anticoagulants: systematic review and meta-analysis. Pharmacoepidemiol Drug Saf 24:757–764CrossRefPubMed Caldeira D, Goncalves N, Pinto FJ, Costa J, Ferreira JJ (2015) Risk of renal failure with the non-vitamin K antagonist oral anticoagulants: systematic review and meta-analysis. Pharmacoepidemiol Drug Saf 24:757–764CrossRefPubMed
36.
go back to reference Bohm M, Ezekowitz MD, Connolly SJ et al (2015) Changes in renal function in patients with atrial fibrillation: an analysis from the RE-LY Trial. J Am Coll Cardiol 65:2481–2493CrossRefPubMed Bohm M, Ezekowitz MD, Connolly SJ et al (2015) Changes in renal function in patients with atrial fibrillation: an analysis from the RE-LY Trial. J Am Coll Cardiol 65:2481–2493CrossRefPubMed
Metadata
Title
Anticoagulant-related nephropathy: a case report and review of the literature of an increasingly recognized entity
Authors
Rigas G. Kalaitzidis
Anila Duni
Georgios Liapis
Olga Balafa
Sofia Xiromeriti
Paulos Karolos Rapsomanikis
Moses S. Elisaf
Publication date
01-08-2017
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 8/2017
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-017-1527-9

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