Correspondence

Nephropathy Induced by Contrast Medium

N Engl J Med 2003; 348:2257-2259May 29, 2003

Article

To the Editor:

The article by Aspelin et al. (Feb. 6 issue)1 regarding the lower incidence of contrast-medium–induced nephropathy in patients with diabetes and a serum creatinine concentration of 1.5 to 3.5 mg per deciliter who were treated with iodixanol, as compared with those who received iohexol, is promising. The authors claim that a high ratio of urinary albumin to creatinine did not correlate with a high peak increase in the serum creatinine concentration. Although it is easier to use a single urinary albumin-to-creatinine ratio than a 24-hour urine collection to screen for proteinuria, this approach has its own limitations.2 We would have liked to see more data regarding differences between the two groups in the degree of proteinuria and the presence or absence of retinopathy. Since more than twice as many patients in the iohexol group as in the iodixanol group had proteinuria, such differences might have confounded the results. In addition, we would have liked to see data on the concomitant use of angiotensin-converting–enzyme (ACE) inhibitors and angiotensin-receptor blockers in the two groups.

Steven J. Gruber, M.D.
Craig J. Shapiro, M.D.
Beth Israel Medical Center, New York, NY 10003

2 References

1. 1

   Aspelin P, Aubry P, Fransson S-G, Strasser R, Willenbrock R, Berg KJ. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 2003;348:491-499
   Full Text | Web of Science | Medline

2. 2

   Rodby RA, Rohde RD, Sharon Z, Pohl MA, Bain RP, Lewis EJ. The urine protein to creatinine ratio as a predictor of 24-hour urine protein excretion in type 1 diabetic patients with nephropathy. Am J Kidney Dis 1995;26:904-909
   CrossRef | Web of Science | Medline

To the Editor:

The patients in the randomized trial of Aspelin et al. were probably not a truly high-risk population, since the base-line serum creatinine concentration (mean, 1.49 mg per deciliter) and the base-line creatinine clearance (mean, 50.1 ml per minute) did not indicate the presence of severely impaired renal function. In addition, it is likely that the protective effect of iodixanol was overestimated, since the patients did not receive vigorous hydration (mean volume, 977 ml in the iodixanol group and 934 ml in the iohexol group); vigorous hydration effectively decreases the incidence of contrast-medium–induced nephropathy.1 Hydration regimens used in other randomized trials2,3 have included substantially larger volumes of intravenous saline (mean volumes, 3311 ml and 2022 ml). Finally, rather than prevent a (reversible) increase in the serum creatinine concentration, measures aimed at reducing contrast-medium nephrotoxicity should decrease the incidence of clinically important adverse events. Given these concerns, we would suggest that the study of Aspelin et al. shows mainly a nonsignificant reduction in the rate of adverse events related to the use of contrast medium (2 of 67 patients vs. 8 of 67 patients, P=0.09 with a two-sided Fisher's exact test, according to our calculations).

Claude Braun, M.D., Ph.D.
Rainer Birck, M.D.
University Hospital Mannheim, 68135 Mannheim, Germany
braunc@verw.ma.uni-heidelberg.de

3 References

1. 1

   Trivedi HS, Moore H, Nasr S, et al. A randomized prospective trial to assess the role of saline hydration on the development of contrast nephrotoxicity. Nephron Clin Pract 2003;93:C29-C34
   CrossRef | Web of Science | Medline

2. 2

   Taylor AJ, Hotchkiss D, Morse RW, McCabe J. PREPARED: Preparation for Angiography in Renal Dysfunction: a randomized trial of inpatient vs outpatient hydration protocol for cardiac catheterization in mild-to-moderate renal dysfunction. Chest 1998;114:1570-1574
   CrossRef | Web of Science | Medline

3. 3

   Mueller C, Buerkle G, Buettner HJ, et al. Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med 2002;162:329-336
   CrossRef | Web of Science | Medline

To the Editor:

In the study by Aspelin et al., 17 centers were required to enroll 135 diabetic patients with kidney disease within three years (range, 1 to 18 subjects per center). In contrast, a single institution has reported data, collected over a five-year period, on contrast-medium–induced nephropathy after coronary angiography in 129 (unselected) diabetic patients with a base-line serum creatinine concentration of more than 2.0 mg per deciliter.1 The external validity of the study by Aspelin et al. would improve if they provided information on the number of eligible patients who declined to participate and the number who were screened.

The duration of diabetes was significantly different between the two groups. The inclusion of the duration of diabetes in the regression model might reduce the disadvantage in the iohexol group caused by this difference.

Hydration is a widely accepted practice for reducing contrast-medium nephrotoxicity.2,3 It would be of interest to relate individual hydration volume, adjusted for body weight, to the occurrence or nonoccurrence of subsequent renal failure. Analysis of such information might adjust for the possible contribution of differences in hydration status to renal failure.

Claude M. Bridges, M.D.
Vege Santhi Swaroop, M.B., B.S.
Maria-Teresa Cuddihy, M.D., M.P.H.
Mayo Clinic, Rochester, MN 55905
bridges.claude@mayo.edu

3 References

1. 1

   Rihal CS, Textor SC, Grill DE, et al. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 2002;105:2259-2264
   CrossRef | Web of Science | Medline

2. 2

   Solomon R, Werner C, Mann D, D'Elia J, Silva P. Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents. N Engl J Med 1994;331:1416-1420
   Full Text | Web of Science | Medline

3. 3

   Morcos SK, Thomsen HS, Webb JA. Contrast-media-induced nephrotoxicity: a consensus report. Eur Radiol 1999;9:1602-1613
   CrossRef | Web of Science | Medline

Author/Editor Response

We agree with Gruber and Shapiro that the use of a single urinary albumin-to-creatinine ratio has limitations, but ratios in morning urine correlate well with 24-hour protein excretion.1 We are not aware of any controlled studies correlating contrast-medium–induced nephropathy with protein excretion or retinopathy. The difference in the rate of use of ACE inhibitors (78 percent in the iodixanol group vs. 55 percent in the iohexol group) may explain the difference in proteinuria but not the difference in nephropathy.

Braun and Birck suggest that our patients were not at high risk because their renal impairment was not severe, but the combination of renal impairment and diabetes confers a high risk of contrast-medium–induced nephropathy.2 They suggest that the effect of iodixanol might diminish with increasing hydration; however, no clinical study has determined the optimal rate, route, and volume of hydration to prevent contrast-medium–induced nephropathy. In our study, hydration was the same in both groups, so the effect of iodixanol that we found is valid. We collected data only on intravenous hydration, so we could not relate the hydration volume in a given patient to the risk of nephropathy, as suggested by Bridges et al. Regarding adverse events related to contrast mediums, Braun and Birck seem to ignore the absence of serious adverse events (0 in 67 patients) in the iodixanol group and the presence of such events (7 in 67 patients) in the iohexol group, which included 6 patients with acute renal failure. These six patients did not differ from the rest of the population with regard to hydration volumes.

In response to Bridges et al., patients were randomly assigned to a particular contrast medium only after enrollment. Eleven patients were screened but not included; some declined to participate, but most did not fulfill the criteria for entry. We believe that these facts have no effect on the validity of the study results because of the randomization and the objective end point. Finally, although the duration of diabetes differed between the two groups, this factor is not known to be a predictor of contrast-medium–induced nephropathy.

Peter Aspelin, M.D., Ph.D.
Huddinge University Hospital, 14186 Stockholm, Sweden
peter.aspelin@cfss.ki.se

Knut Joachim Berg, M.D., Ph.D.
Rikshopitalet, N-0027 Oslo, Norway

2 References

1. 1

   Shaw AB, Risdon P, Lewis-Jackson JD. Protein creatinine index and Albustix in assessment of proteinuria. Br Med J (Clin Res Ed) 1983;287:929-932
   CrossRef | Web of Science | Medline

2. 2

   Rudnick MR, Goldfarb S, Wexler L, et al. Nephrotoxicity of ionic and nonionic contrast media in 1196 patients: a randomized trial: the Iohexol Cooperative Study. Kidney Int 1995;47:254-261
   CrossRef | Web of Science | Medline

Citing Articles (5)

Citing Articles

1. 1

   Martin Zo’o, Marcus Hoermann, Csilla Balassy, Francis Brunelle, Robin Azoulay, Danièle Pariente, Michel Panuel, Patrick Dosseur. (2011) Renal safety in pediatric imaging: randomized, double-blind phase IV clinical trial of iobitridol 300 versus iodixanol 270 in multidetector CT. Pediatric Radiology 41:11, 1393-1400
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2. 2

   Norbert Lameire. (2005) The Pathophysiology of Acute Renal Failure. Critical Care Clinics 21:2, 197-210
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3. 3

   Giorgio Savazzi, Simona Detrenis, Michele Meschi, Sabrina Musini. (2005) Low-osmolar and iso-osmolar contrast media in contrast-induced nephropathy. American Journal of Kidney Diseases 45:2, 435
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4. 4

   Norbert Lameire, Wim Van Biesen, Raymond Vanholder. (2005) Acute renal failure. The Lancet 365:9457, 417-430
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5. 5

   (2003) Current awareness: Pharmacoepidemiology and drug safety. Pharmacoepidemiology and Drug Safety 12:8, 699-617
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