HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bräutigam, M. Articles by Katzberg, R. Search for Related Content PubMed PubMed Citation Articles by Bräutigam, M. Articles by Katzberg, R.

Do Iodinated Contrast Media Interfere with Renal Tubular Creatinine Secretion?

Matthias Bräutigam, PhD^* and Pontus B. Persson, PhD

Schering, CRBA Diagnostics & Radiopharmaceuticals, Müllerstrasse 178, D-13353 Berlin, Germany*
Institut für Vegetative Physiologie, Humboldt Universität, Berlin, Medizinische Fakultät (Charité), Berlin, Germany
e-mail: matthias.braeutigam{at}schering.de

Editor:

The intriguing editorial by Dr Katzberg (1) in the June 2005 issue of Radiology reminds us of the importance of tubular function for the effects of iodinated contrast media on overall kidney function.

Contrast medium–induced nephropathy (CIN) is typically defined as change in plasma creatinine concentrations, which is a widely used surrogate marker of glomerular filtration rate (GFR). The rise in creatinine plasma concentration after examination with contrast medium is typically limited to 1–2 weeks and is more frequently observed in patients with impaired kidney function (2).

Unfortunately, it is not consistently appreciated that overall renal creatinine excretion is achieved by tubular secretion, in addition to the quantitatively more important glomerular filtration.

Is there evidence that the high-dose contrast media could also interfere with the tubular creatinine secretion? We believe there is:

1. All iodinated contrast media are "enriched" in the tubular cells and may interfere with tubular function (eg, review by Dr Katzberg [3]).

2. Paraaminohippurate (PAH) is excreted by the tubular secretion, and, as reviewed by Dr Katzberg (1), there are several studies with results that clearly show considerable, short-lasting decrease in PAH excretion during contrast media applications in animal studies.

3. In 1947, Crawford (4) measured creatinine clearance and inulin-thiosulfate clearance (equivalent to GFR) after administration of an ionic contrast medium (iodopyracet; Diodrast) in humans; Crawford clearly showed that the creatinine clearance is decreased but that there is no influence of iodopyracet on the inulin-thiosulfate clearance (equivalent to GFR). Thus, the noteworthy conclusion from Crawford (4):

We are therefore inclined to accept the simpler interpretation; namely, that the inulin and thiosulfate clearances are at the level of glomerular filtration and that the exogenous creatinine clearance exceeds both the other clearances because of the tubular excretion of creatinine, the tubular excretion being depressed and the creatinine clearance being reduced to or toward the inulin and thiosulfate clearance by Diodrast and PAH in consequence of some type of intracellular competition.

 4. Jakobsen et al (5) in 1996 compared the effect of iohexol and iodixanol in patients with impaired kidney function by measuring GFR (technetium 99m diethylenetriaminepentaacetic acid) and creatinine clearance. They observed little difference between the two contrast media regarding GFR, yet serum creatinine level tended to increase (and creatinine clearance tended to decrease) in the iohexol group. Maintained GFR despite reduced creatinine tubular secretion suggests that iohexol merely feigns impaired GFR (as known for cimetidine and trimethoprim).

Taken together, it seems that tubular creatinine excretion is somewhat blunted by contrast media, thus leading to a small transient increase in plasma creatinine level. This interference of contrast media with the tubular creatinine secretion is more apparent in patients with impaired glomerular filtration (higher proportion tubular creatinine excretion compared with the glomerular creatinine excretion; longer half-life of the contrast medium because of the impaired urinary excretion). Iohexol in particular may interfere with tubular creatinine excretion.

In conclusion, serum creatinine levels are not sufficient to assess CIN (6). Indeed, since it has never really been possible to induce CIN in animal models with clinically relevant doses, the occurrence of nephropathies induced directly by the contrast media (and not by the interventional procedure) may be lower, as stated by Dr Katzberg (7): "There is a real possibility that the null hypothesis [of no CIN in clinical standard doses] may represent the truth."

	References

TOP References

 

1. Katzberg RW. Contrast medium-induced nephrotoxicity: which pathway? [editorial]. Radiology 2005;235:752–755.[Free Full Text]
2. Morcos SK, Thomsen HS, Webb JAW. Contrast-media-induced nephrotoxicity: a consensus report. Eur Radiol 1999;9:1602–1613.[CrossRef][Medline]
3. Katzberg RW. Urography into the 21st century: new contrast media, renal handling, imaging characteristics, and nephrotoxicity. Radiology 1997;204:297–312.[Free Full Text]
4. Crawford B. Depression of the exogenous creatinine/inulin or thiosulfate clearance ratios in man by diodrast and p-aminohippuric acid. J Clin Invest 1948;27(2):171–175.[Medline]
5. Jakobsen JA, Berg KJ, Kjaersgaard P, et al. Angiography with nonionic x-ray contrast media in severe chronic renal failure: renal function and contrast retention. Nephron 1996;73(4):549–556.[Medline]
6. Persson PB, Hansell P, Liss P. Pathophysiology of contrast medium–induced nephropathy. Kidney Int 2005;68:14–22.[CrossRef][Medline]
7. Katzberg RW. What do we really know about contrast medium-induced acute renal failure? Invest Radiol 1989;24:219–220.[CrossRef][Medline]

Response

Department of Radiology, University of California Davis Medical Center, 4860 Y Street, Suite 3100, Sacramento, CA 95817
e-mail: richard.katzberg{at}ucdmc.ucdavis.edu

I thank Drs Bräutigam and Persson for their important and extremely interesting insights into the specific effects of contrast media on tubular mechanisms. Their observations have important clinical implications that, hopefully, will be more fully recognized and investigated.

The adverse outcomes reported in the cardiology literature are alarming. However, it is as yet unclear to what extent these outcomes can actually be attributed to the contrast media, per se.

This Article Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bräutigam, M. Articles by Katzberg, R. Search for Related Content PubMed PubMed Citation Articles by Bräutigam, M. Articles by Katzberg, R.