Effects of impaired renal function on levels and performance of D-dimer in patients with suspected pulmonary embolism

Summary

Clinical probability and D-dimer measurement play an essential role in the non-invasive diagnostic strategies for pulmonary embolism (PE). PE can be ruled out without further imaging in patients with non-high clinical probability and negative D-dimer. D-dimer level is increased in patients with renal impairment. Whether its diagnostic usefulness is maintained in these patients is not well determined. We aimed to evaluate the effects of renal impairment on diagnostic performances of D-dimer in patients with suspected PE. A retrospective analysis of 1,625 patients with suspected PE included in a multicentre prospective study was performed. D-dimer levels and percentages of patients with a negative D-dimer were compared between three subgroups according to glomerular filtration rate (GFR) estimated by the MDRD formula: ≥90 ml/min (normal renal function), 60–89 ml/min (mild renal impairment), 30–59 ml/min (moderate renal impairment). D-dimer levels increased and the proportion of negative D-dimer decreased significantly according to renal status: 46% negative D-dimer in patients with normal GFR, 31% in patients with mild renal impairment, 11% in those with moderate renal impairment, corresponding to number of patients needed to test to obtain one negative test of 2.2, 3.2 and 9, respectively. In conclusion, the clinical usefulness of D-dimer decreases with renal impairment. However, PE can still be ruled out by negative D-dimer in a substantial proportion of patients with non-high clinical probability, avoiding exposure to contrast media.

Keywords

Creatinine - glomerular filtration rate - D-dimer - pulmonary embolism - renal insufficiency

• References

• 1 Perrier A, Desmarais S, Miron MJ. et al. Non-invasive diagnosis of venous thromboembolism in outpatients. Lancet 1999; 353: 190-195.
• 2 Righini M, Perrier A, De Moerloose P. et al. D-Dimer for venous thromboembolism diagnosis: 20 years later. J Thromb Haemost 2008; 06: 1059-1071.
• 3 van Belle A, Buller HR, Huisman MV. et al. Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. J Am Med Assoc 2006; 295: 172-179.
• 4 Righini M, Le Gal G, Aujesky D. et al. Diagnosis of pulmonary embolism by multidetector CT alone or combined with venous ultrasonography of the leg: a randomised non-inferiority trial. Lancet 2008; 371: 1343-1352.
• 5 Di Nisio M, Squizzato A, Rutjes AW. et al. Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism: a systematic review. J Thromb Haemost 2007; 05: 296-304.
• 6 Raimondi P, Bongard O, de Moerloose P. et al. D-dimer plasma concentration in various clinical conditions: implication for the use of this test in the diagnostic approach of venous thromboembolism. Thromb Res 1993; 69: 125-130.
• 7 Chabloz P, Reber G, Boehlen F. et al. TAFI antigen and D-dimer levels during normal pregnancy and at delivery. Br J Haematol 2001; 115: 150-152.
• 8 Righini M, Le Gal G, De Lucia S. et al. Clinical usefulness of D-dimer testing in cancer patients with suspected pulmonary embolism. Thromb Haemost 2006; 95: 715-719.
• 9 Righini M, Goehring C, Bounameaux H. et al. Effects of age on the performance of common diagnostic tests for pulmonary embolism. Am J Med 2000; 109: 357-361.
• 10 Miron MJ, Perrier A, Bounameaux H. et al. Contribution of non-invasive evaluation to the diagnosis of pulmonary embolism in hospitalized patients. Eur Respir J 1999; 13: 1365-1370.
• 11 Righini M, Nendaz M, Le Gal G. et al. Influence of age on the cost-effectiveness of diagnostic strategies for suspected pulmonary embolism. J Thromb Haemost 2007; 05: 1869-1877.
• 12 Le Gal G, Righini M, Roy PM. et al. Value of D-dimer testing for the exclusion of pulmonary embolism in patients with previous venous thromboembolism. Arch Intern Med 2006; 166: 176-180.
• 13 Le Gal G, Righini M, Roy PM. et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Ann Intern Med 2006; 144: 165-171.
• 14 Gordge MP, Faint RW, Rylance PB. et al. Plasma D dimer: a useful marker of fibrin breakdown in renal failure. Thromb Haemost 1989; 61: 522-525.
• 15 Catena C, Zingaro L, Casaccio D. et al. Abnormalities of coagulation in hyper-tensive patients with reduced creatinine clearance. Am J Med 2000; 109: 556-561.
• 16 Wannamethee SG, Shaper AG, Lowe GD. et al. Renal function and cardiovascular mortality in elderly men: the role of inflammatory, procoagulant, and endothelial biomarkers. Eur Heart J 2006; 27: 2975-2981.
• 17 Shlipak MG, Fried LF, Crump C. et al. Elevations of inflammatory and procoagulant biomarkers in elderly persons with renal insufficiency. Circulation 2003; 107: 87-92.
• 18 Dubin R, Cushman M, Folsom AR. et al. Kidney function and multiple hemostatic markers: cross sectional associations in the multi-ethnic study of atherosclerosis. BMC Nephrol 2011; 12: 3.
• 19 Sharain K, Hoppensteadt D, Bansal V. et al. Progressive increase of inflammatory biomarkers in chronic kidney disease and end-stage renal disease. Clin Appl Thromb Hemost 2013; 19: 303-308.
• 20 Tanaka H, Sonoda M, Kashima K. et al. Impact of decreased renal function on coagulation and fibrinolysis in patients with non-valvular atrial fibrillation. Circ J 2009; 73: 846-850.
• 21 Klok FA, Mos IC, Nijkeuter M. et al. Simplification of the revised Geneva score for assessing clinical probability of pulmonary embolism. Arch Intern Med 2008; 168: 2131-2136.
• 22 Levey AS, Bosch JP, Lewis JB. et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999; 130: 461-470.
• 23 K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39: S1-266.
• 24 Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31-41.
• 25 Douma RA, le Gal G, Sohne M. et al. Potential of an age adjusted D-dimer cutoff value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts. Br Med J 2010; 340: c1475.
• 26 Mehran R, Aymong ED, Nikolsky E. et al. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. J Am Coll Cardiol 2004; 44: 1393-1399.
• 27 Calvin AD, Misra S, Pflueger A. Contrast-induced acute kidney injury and diabetic nephropathy. Nat Rev Nephrol 2010; 06: 679-688.
• 28 McCullough PA, Adam A, Becker CR. et al. Risk prediction of contrast-induced nephropathy. Am J Cardiol 2006; 98: 27K-36K.
• 29 Karami-Djurabi R, Klok FA, Kooiman J. et al. D-dimer testing in patients with suspected pulmonary embolism and impaired renal function. Am J Med 2009; 122: 1050-1053.