CORRESPONDENCE: LETTER TO THE EDITOR
Renal Protective Effects and Prevention of Contrast-Induced Nephropathy by Atrial Natriuretic PeptideCan It Work?
Michael Haase, MD*,
Anja Haase-Fielitz, PharmD,
Dirk Habedank, MD and
Stefan D. Anker, MD, PhD
* Department of Nephrology and Intensive Care, Charité, Campus Virchow-Klinikum, Augustenburger Platz 1, D-13353 Berlin, Germany (Email: michael.haase{at}charite.de).
We congratulate Morikawa et al. (1) on this important paper on therapeutic prevention of contrast-induced nephropathy, and Chen (2) for his editorial comment putting this research into perspective. The editorial comment already mentioned many positive aspects of the study.
Contrast-induced nephropathy frequently complicates primary percutaneous coronary intervention (3). In the present study, Morikawa et al. (1) chose an intermediate dose of atrial natriuretic peptide (ANP) at 0.042 µg/kg/min to prevent contrast-induced nephropathy and found—corresponding with the physiological effect of "natriuretic" peptide—increased diuresis associated with a statistically significant but clinically perhaps not meaningful change of glomerular markers (serum creatinine, estimated glomerular filtration rate, cystatin C) at 1 month after the procedure compared with control, for example, a reduced loss of estimated glomerular filtration rate  1 ml/min/1.73 m2. The relevance of this finding is further questioned by the lack of an effect of ANP on markers of tubular damage (urinary microglobulin and N-acetyl-D-glucosaminidase), although contrast-induced nephropathy has been described involving tubular damage.
A previous randomized controlled trial using nesiritide presented during the Congress of the American Society of Nephrology 2008 (4) showed an absolute reduction in the incidence of acute kidney injury after cardiac surgery similar to that of the present study (1), but although powered for it, the former study could not demonstrate a reduced need for dialysis and was discontinued after an interim analysis (4).
It would strengthen the message further to discuss why, in the study by Morikawa et al. (1), N-acetylcysteine has not been used for nephroprotection although N-acetylcysteine has been shown to reduce the incidence of contrast-induced nephropathy and the mortality associated with it (5,6). N-acetylcysteine does not artificially reduce serum creatinine concentration (7), which was a previous concern (8), and its use is current clinical practice for patients undergoing angiography who present with chronic kidney disease at many European centers.
Last, patients of the present study were hospitalized for at least 48 h after the procedure, which deviates from clinical practice, at least in the U.S. and in Europe—the additional potential risks (thrombosis, infection) and costs need to be considered.
We hope that the authors can further elucidate the issue of 272 patients assessed for eligibility, with only 4 patients who did not fulfill the inclusion criteria (serum creatinine  1.3 mg/dl), suggesting that almost all patients presenting for angiography at this hospital have chronic renal impairment with an average estimated glomerular filtration rate of 30 ml/min/1.73 m2. Additional comment on this issue may provide more complete insight into the local patient population.
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1. Morikawa S, Sono T, Tsuboi H, et al. Renal protective effects and the prevention of contrast-induced nephropathy by atrial natriuretic peptide J Am Coll Cardiol 2009;53:1040-1046.[Abstract/Free Full Text]2. Chen HH. Atrial natriuretic peptide for the prevention of contrast-induced nephropathy: what's old is new but at the right dose and duration of therapy! J Am Coll Cardiol 2009;53:1047-1049.[Free Full Text] 3. Marenzi G, Lauri G, Assanelli E, et al. Contrast-induced nephropathy in patients undergoing primary angioplasty for acute myocardial infarction J Am Coll Cardiol 2004;44:1780-1785.[Abstract/Free Full Text] 4. Ejaz AA, Martin TD, Johnson RJ, et al. Decreased incidence of acute kidney injury associated with prophylactic use of nesiritide in cardiac surgery patients Paper presented at: Congress of the American Society of Nephrology. Philadelphia, PA. November 4, 2008. 5. Baker CS, Wragg A, Kumar S, et al. A rapid protocol for the prevention of contrast-induced renal dysfunction: the RAPPID study J Am Coll Cardiol 2003;41:2114-2118.[Abstract/Free Full Text] 6. Marenzi G, Assanelli E, Marana I, et al. N-acetylcysteine and contrast-induced nephropathy in primary angioplasty N Engl J Med 2006;354:2773-2782.[Abstract/Free Full Text] 7. Haase M, Haase-Fielitz A, Ratnaike S, et al. N-acetylcysteine does not artifactually lower plasma creatinine concentration Nephrol Dial Transplant 2008;23:1581-1587.[Abstract/Free Full Text] 8. Hoffmann U, Fischereder M, Krüger B, et al. The value of N-acetylcysteine in the prevention of radiocontrast agent-induced nephropathy seems questionable J Am Soc Nephrol 2004;15:407-410.[Abstract/Free Full Text]
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