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Prevention of Contrast-induced Nephropathy in High-risk Patients with Hemofiltration

      To the Editor:
      We believe the study by Marenzi and colleagues
      • Marenzi G.
      • Lauri G.
      • Campodonico J.
      • et al.
      Comparison of two hemofiltration protocols for prevention of contrast-induced nephropathy in high-risk patients.
      possesses several shortcomings. First, as the authors point out, a major confounder of the beneficial results of pre- and posthemofiltration may have been the alkalinizing effect of the bicarbonate-based replacement solution during hemofiltration. The omission of bicarbonate-based fluids in the control group is understandable because the results of the study by Merten and colleagues
      • Merten G.J.
      • Burgess W.P.
      • Gray L.V.
      • et al.
      Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial.
      were published just as enrollment in Marenzi et al’s
      • Marenzi G.
      • Lauri G.
      • Campodonico J.
      • et al.
      Comparison of two hemofiltration protocols for prevention of contrast-induced nephropathy in high-risk patients.
      study was concluding. However, given that the prophylactic benefits of bicarbonate therapy were so robust in Merten et al’s study, and that posthemofiltration alone provided far less protection against contrast-induced nephropathy in this current study, it is completely plausible that most, if not all, of the benefits in the pre- and posthemofiltration group were attributable to alkalization precontrast administration and not hemofiltration itself.
      Second, the authors did not administer n-acetylcysteine to the control group in conjunction with intravenous hydration. Although the true benefits of n-acetylcysteine are still not fully conclusive, it remains part of the standard of care in prevention of contrast-induced nephropathy.
      • Fishbane S.
      • Durham J.H.
      • Marzo K.
      • Rudnick M.
      N-acetylcysteine in the prevention of radiocontrast-induced nephropathy.
      It is routinely administered because of its low cost and lack of side effects, along with its potential beneficial effects, as evidenced by positive results (point estimates of relative risk reductions ranging from 0.37-0.73) in several published meta-analyses.
      • Alonso A.
      • Lau J.
      • Jaber B.L.
      • Weintraub A.
      • Sarnak M.J.
      Prevention of radiocontrast nephropathy with N-acetylcysteine in patients with chronic kidney disease: a meta-analysis of randomized, controlled trials.
      • Birck R.
      • Krzossok S.
      • Markowetz F.
      • Schnulle P.
      • van der Woude F.J.
      • Braun C.
      Acetylcysteine for prevention of contrast nephropathy: meta-analysis.
      • Isenbarger D.W.
      • Kent S.M.
      • O’Malley P.G.
      Meta-analysis of randomized clinical trials on the usefulness of acetylcysteine for prevention of contrast nephropathy.
      • Nallamothu B.K.
      • Shojania K.G.
      • Saint S.
      • et al.
      Is acetylcysteine effective in preventing contrast-related nephropathy? A meta-analysis.
      • Pannu N.
      • Manns B.
      • Lee H.
      • Tonelli M.
      Systematic review of the impact of N-acetylcysteine on contrast nephropathy.
      Third, iopentol, a nonionic, low-osmolality contrast agent, was used in this study. There is evidence that the rate of contrast nephropathy is much lower in high-risk patients when a nonionic iso-osmolar agent is used (3% vs 26% in nonionic low-osmolality contrast).
      • Aspelin P.
      • Aubry P.
      • Fransson S.G.
      • Strasser R.
      • Willenbrock R.
      • Berg K.J.
      Nephrotoxic effects in high-risk patients undergoing angiography.
      Therefore, we think the control group was “handicapped” in 3 ways: lack of bicarbonate-containing fluids, lack of n-acetylcysteine prophylaxis, and lack of nonionic iso-osmolar contrast. Before this costly and invasive technique were ever to become adopted for prevention of contrast-induced nephropathy in high-risk individuals, a trial comparing hemofiltration versus the current standards of care would need to be performed.
      Finally, the authors strongly suggest that the benefits of pre- and posthemofiltration may have been obtained because of “controlled high-volume hydration” that may have resulted in an “increase in effective circulating volume, renal perfusion pressure, and glomerular filtration.” However, it is difficult to imagine an increase in any of these 3 parameters when using a completely isovolemic protocol as described in the “Methods” section of the article. If the hypothesis of the authors is correct, then urine volume should have increased. Do the authors have any data on urine output pre- and posttreatments in the 3 groups?

      References

        • Marenzi G.
        • Lauri G.
        • Campodonico J.
        • et al.
        Comparison of two hemofiltration protocols for prevention of contrast-induced nephropathy in high-risk patients.
        Am J Med. 2006; 119: 155-162
        • Merten G.J.
        • Burgess W.P.
        • Gray L.V.
        • et al.
        Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomized controlled trial.
        JAMA. 2004; 291: 2328-2334
        • Fishbane S.
        • Durham J.H.
        • Marzo K.
        • Rudnick M.
        N-acetylcysteine in the prevention of radiocontrast-induced nephropathy.
        J Am Soc Nephrol. 2004; 15: 251-260
        • Alonso A.
        • Lau J.
        • Jaber B.L.
        • Weintraub A.
        • Sarnak M.J.
        Prevention of radiocontrast nephropathy with N-acetylcysteine in patients with chronic kidney disease: a meta-analysis of randomized, controlled trials.
        Am J Kidney Dis. 2004; 43: 1-9
        • Birck R.
        • Krzossok S.
        • Markowetz F.
        • Schnulle P.
        • van der Woude F.J.
        • Braun C.
        Acetylcysteine for prevention of contrast nephropathy: meta-analysis.
        Lancet. 2003; 362: 598-603
        • Isenbarger D.W.
        • Kent S.M.
        • O’Malley P.G.
        Meta-analysis of randomized clinical trials on the usefulness of acetylcysteine for prevention of contrast nephropathy.
        Am J Cardiol. 2003; 92: 1454-1458
        • Nallamothu B.K.
        • Shojania K.G.
        • Saint S.
        • et al.
        Is acetylcysteine effective in preventing contrast-related nephropathy? A meta-analysis.
        Am J Med. 2004; 117: 938-947
        • Pannu N.
        • Manns B.
        • Lee H.
        • Tonelli M.
        Systematic review of the impact of N-acetylcysteine on contrast nephropathy.
        Kidney Int. 2004; 65: 1366-1374
        • Aspelin P.
        • Aubry P.
        • Fransson S.G.
        • Strasser R.
        • Willenbrock R.
        • Berg K.J.
        Nephrotoxic effects in high-risk patients undergoing angiography.
        N Engl J Med. 2003; 348: 491-499

      Linked Article

      • The Reply:
        The American Journal of MedicineVol. 120Issue 8
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          We wish to address the apparent limitations of our report pointed out by Coca and Perazella. Bicarbonate was not used because the Merten study was published after we designed our trial. The same is true for the contrast agent, given that the Nephrotoxic Effects in High-Risk Patients Undergoing Angiography (NEPRHIC) study with iodixanol was published in 2003, and for N-acetylcysteine, whose first meta-analyses were published in 2003 and 2004. However, neither of our study groups received these prophylactic measures, and, therefore, both shared the lack of any potential benefit.
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