A randomized controlled trial comparing hydration therapy to additional hemodialysis or N-acetylcysteine for the prevention of contrast medium-induced nephropathy

The Dialysis-versus-Diuresis (DVD) Trial
  • Holger Reinecke
  • Manfred Fobker
  • Jürgen Wellmann
  • Birgit Becke
  • Jörn Fleiter
  • Christine Heitmeyer
  • Günter Breithardt
  • Hans-Werner Hense
  • Roland M. Schaefer
ORIGINAL PAPER

Summary

Contrast mediuminduced nephropathy (CIN) is a serious complication with increasing frequency and an unfavorable prognosis. Previous analyses of surrogate parameters have suggested beneficial effects of hemodialysis that are assessed in this randomized clinical trial.

We performed a prospective single-center trial in 424 consecutive patients with serum creatinine concentrations between 1.3– 3.5 mg/dl who underwent elective coronary angiography. Patients were randomized to one of three treatment strategies with all patients receiving pre- and postprocedural hydration: One group received no additional therapy, patients in the second group were hemodialyzed once, and the third group received oral N-acetylcysteine. The frequency of CIN (defined as an increase in serum creatinine ≥0.5 mg/dl) from 48 to 72 h after catheterization was 6.1% in the hydration-only group, 15.9% with hemodialysis treatment, and 5.3% in the N-ACC group (intention-to-treat analysis; P = 0.008). There were no differences between the treatment groups with regard to increased (≥ 0.5 mg/dl) serum creatinine concentrations after 30–60 days (4.8%, 5.1%, and 3.1%, respectively; P = 0.700). Analyses of long-term follow-up (range 63 to 1316 days) by Cox regressions models of the study groups found quite similar survival rates (P = 0.500). In contrast to other (retrospective) studies, long-term survival of patients with vs those without CIN within 72 h was not different, but patients who still had elevated creatinine concentrations at 30–60 days suffered from a markedly higher 2-year mortality (46% vs 17%, P = 0.002).

In conclusion, hemodialysis in addition to hydration therapy for the prevention of CIN provided no evidence for any outcome benefit but evidence for probable harm. Increased creatinine concentrations at 30–60 days, but not within 72 h, were associated with markedly reduced long-term survival.

Key words

Contrast mediuminduced nephropathy angiography mortality dialysis 

References

  1. 1.
    K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification (2002) Am J Kidney Dis 39:S1–266CrossRefGoogle Scholar
  2. 2.
    USRDS 2004 annual data report (2005) Am J Kidney Dis 45:8–280Google Scholar
  3. 3.
    Amann B (2006) Diabetic nephropathy and ACE inhibitors. Clin Res Cardiol 95:i83–i87PubMedCrossRefGoogle Scholar
  4. 4.
    Anavekar NS, McMurray JJ, Velazquez EJ et al (2004) Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med 351:1285–1295PubMedCrossRefGoogle Scholar
  5. 5.
    Asif A, Epstein M (2004) Prevention of radiocontrast-induced nephropathy. Am J Kidney Dis 44:12–24PubMedCrossRefGoogle Scholar
  6. 6.
    Aspelin P, Aubry P, Fransson SG et al (2003) Nephrotoxic effects in highrisk patients undergoing angiography. N Engl J Med 348:491–499PubMedCrossRefGoogle Scholar
  7. 7.
    Barrett BJ, Parfrey PS (2006) Clinical practice. Preventing nephropathy induced by contrast medium. N Engl J Med 354:379–386PubMedCrossRefGoogle Scholar
  8. 8.
    Erley CM, Bader BD, Berger ED et al (2004) Gadolinium-based contrast media compared with iodinated media for digital subtraction angiography in azotaemic patients. Nephrol Dial Transplant 19:2526–2531PubMedCrossRefGoogle Scholar
  9. 9.
    Furukawa T, Ueda J, Takahashi S et al (1996) Elimination of low-osmolality contrast media by hemodialysis. Acta Radiol 37:966–971PubMedCrossRefGoogle Scholar
  10. 10.
    Gruberg L, Mintz GS, Mehran R et al (2000) The prognostic implications of further renal function deterioration within 48 h of interventional coronary procedures in patients with preexistent chronic renal insufficiency. J Am Coll Cardiol 36:1542–1548PubMedCrossRefGoogle Scholar
  11. 11.
    Hoffmann U, Fischereder M, Marx M et al (2003) Induction of cytokines and adhesion molecules in stable hemodialysis patients: is there an effect of membrane material? Am J Nephrol 23:442–447PubMedCrossRefGoogle Scholar
  12. 12.
    Hostetter TH (2004) Chronic kidney disease predicts cardiovascular disease. N Engl J Med 351:1344–1346PubMedCrossRefGoogle Scholar
  13. 13.
    Laskey WK, Gellman J (2003) Inflammatory markers increase following exposure to radiographic contrast media. Acta Radiol 44:498–503PubMedCrossRefGoogle Scholar
  14. 14.
    Lehnert T, Keller E, Gondolf K et al (1998) Effect of haemodialysis after contrast medium administration in patients with renal insufficiency. Nephrol Dial Transplant 13:358–362PubMedGoogle Scholar
  15. 15.
    Levey AS, Coresh J, Balk E et al (2003) National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 139:137–147PubMedGoogle Scholar
  16. 16.
    Levy EM, Viscoli CM, Horwitz RI (1996) The effect of acute renal failure on mortality. A cohort analysis. JAMA 275:1489–1494PubMedCrossRefGoogle Scholar
  17. 17.
    Lindsay J, Canos DA, Apple S et al (2004) Causes of acute renal dysfunction after percutaneous coronary intervention and comparison of late mortality rates with postprocedure rise of creatine kinase-MB versus rise of serum creatinine. Am J Cardiol 94:786–789PubMedCrossRefGoogle Scholar
  18. 18.
    Maeder M, Klein M, Fehr T et al (2004) Contrast nephropathy: review focusing on prevention. J Am Coll Cardiol 44:1763–1771PubMedCrossRefGoogle Scholar
  19. 19.
    Marenzi G, Lauri G, Assanelli E et al (2004) Contrast-induced nephropathy in patients undergoing primary angioplasty for acute myocardial infarction. J Am Coll Cardiol 44:1780–1785PubMedCrossRefGoogle Scholar
  20. 20.
    Marenzi G, Marana I, Lauri G et al (2003) The prevention of radiocontrast- agent-induced nephropathy by hemofiltration. The New England Journal of Medicine 349:1333–1340PubMedCrossRefGoogle Scholar
  21. 21.
    Matzkies FK, Reinecke H, Tombach B et al (2000) Influence of dialysis procedure, membrane surface and membrane material on iopromide elimination in patients with reduced kidney function. Am J Nephrol 20:300–304PubMedCrossRefGoogle Scholar
  22. 22.
    McCullough PA, Wolyn R, Rocher LL et al (1997) Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality. Am J Med 103:368–375PubMedCrossRefGoogle Scholar
  23. 23.
    Nallamothu BK, Shojania KG, Saint S et al (2004) Is acetylcysteine effective in preventing contrast-related nephropathy? A meta-analysis. Am J Med 117:938–947PubMedCrossRefGoogle Scholar
  24. 24.
    Reinecke H, Trey T, Matzkies F et al (2003) Grade of chronic renal failure, and acute and long-term outcome after percutaneous coronary interventions. Kidney Int 63:696–701PubMedCrossRefGoogle Scholar
  25. 25.
    Rihal CS, Textor SC, Grill DE et al (2002) Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 105:2259–2264PubMedCrossRefGoogle Scholar
  26. 26.
    Rudnick MR, Goldfarb S (2003) Pathogenesis of contrast-induced nephropathy: experimental and clinical observations with an emphasis on the role of osmolality. Rev Cardiovasc Med 4(Suppl 5):S28–S33PubMedGoogle Scholar
  27. 27.
    Russo D, Minutolo R, Cianciaruso B et al (1995) Early effects of contrast media on renal hemodynamics and tubular function in chronic renal failure. J Am Soc Nephrol 6:1451–1458PubMedGoogle Scholar
  28. 28.
    Smith SC Jr, Dove JT Jacobs AK et al (2001) ACC/AHA guidelines for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation 103:3019–3041PubMedGoogle Scholar
  29. 29.
    Solomon R, Werner C, Mann D et al (1994) Effects of saline, mannitol, and furosemide to prevent acute decreases in renal function induced by radiocontrast agents. N Engl J Med 331:1416–1420PubMedCrossRefGoogle Scholar
  30. 30.
    Tepel M, van der Giet M, Schwarzfeld C et al (2000) Prevention of radiographiccontrast- agent-induced reductions in renal function by acetylcysteine. N Engl J Med 343:180–184PubMedCrossRefGoogle Scholar
  31. 31.
    van Buuren F, Horstkotte D (2006) 21th report of performance data from heart catheterization laboratories in Germany. 2003 results of a collaborative survey by the Committee of Clinical Cardiology and the Interventional Cardiology (for ECS) and Angiology Study Groups of the German Society of Cardiology-Cardiovascular Research. Clin Res Cardiol 95:383–387PubMedCrossRefGoogle Scholar
  32. 32.
    Vogt B, Ferrari P, Schonholzer C et al (2001) Prophylactic hemodialysis after radiocontrast media in patients with renal insufficiency is potentially harmful. Am J Med 111:692–698PubMedCrossRefGoogle Scholar
  33. 33.
    Werner D, Misfeld M, Regenfus M et al (2006) Emergency coronary angiography with gadolinium in a patient with thyrotoxicosis, pulmonary embolism and persistent right atrial thrombi. Clin Res Cardiol 95:418–421PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff-Verlag 2006

Authors and Affiliations

  • Holger Reinecke
    • 1
    • 2
  • Manfred Fobker
    • 2
    • 3
  • Jürgen Wellmann
    • 4
  • Birgit Becke
    • 2
  • Jörn Fleiter
    • 2
  • Christine Heitmeyer
    • 2
  • Günter Breithardt
    • 2
  • Hans-Werner Hense
    • 4
  • Roland M. Schaefer
    • 5
  1. 1.HammGermany
  2. 2.Department of Cardiology and AngiologyUniversity Hospital of MuensterMuensterGermany
  3. 3.Institute of Clinical Chemistry and Laboratory MedicineUniversity Hospital of MuensterMuensterGermany
  4. 4.Institute of Epidemiology and Social MedicineUniversity Hospital of MuensterMuensterGermany
  5. 5.Department of NephrologyUniversity Hospital of MuensterMuensterGermany

Personalised recommendations