NDT Advance Access originally published online on April 3, 2007
Nephrology Dialysis Transplantation 2007 22(6):1788-1789; doi:10.1093/ndt/gfm033
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Lanthanum carbonate, body lanthanum accumulation and potential liver toxicity
Email: bernard.lacour{at}nck.ap-hop-paris.frSir,
We read with interest the article in the Journal by Ben-Dov et al. [1] and the accompanying Editorial by Cozzolino and Brancaccio [2], on possible effects of lanthanum carbonate on the liver. Ben-Dov et al. [1] reported that lanthanum (La) carbonate administration to uraemic rats for 4 weeks was not associated with signs of hepatotoxicity using light microscopy, magnetic resonance imaging and serum biochemistry methods. They were unable to confirm our previous finding of reduced liver weight [3]. They provided two different possible explanations for this discrepancy. First, they reasoned that we might have used an incorrect expression of liver weight, namely corrected for femur length. Second, they speculated that the rats of our study might have been exposed to heavy external La contamination. Cozzolino and Brancaccio [2] echoed these hypotheses in their Editorial.
We had already answered similar remarks, by other authors, in a previous correspondence in Kidney International [4–6]. Since the aforementioned authors are apparently not aware of our previous Letter-and-Reply exchange, we would like to clarify these points again.
First of all, we observed that the mean liver weight of uraemic rats given La carbonate for 4 weeks was significantly lower than that of uraemic rats given no La supplementation, be the liver weight corrected for femur length or body weight. We provided this clarification after having done a reanalysis of our data in response to the comment by Rambeck [7], by proceeding to a formal comparison of liver weight after normalization for total body weight using ANOVA. This analysis showed a significant group effect for body weights, that is lower body weights in uraemic vs non-uraemic groups (P < 0.001), and also a significant treatment effect, that is lower body weights in La vs no La treatment (P < 0.022), with no interaction. Moreover, ANOVA also showed significant effects of both group and La treatment on liver weight (P < 0.001 and <0.001).
Second, we do not agree with the hypothesis that the rats of our study were heavily intoxicated by exogenous La contamination, in addition to the oral overload route. It is true that in our study, rats received La carbonate with food in the form of powder, not by gavage as in the study by Behets et al. [8]. Nevertheless, La tissue concentrations found in our study were of the same order of magnitude as those of the latter study, as we pointed out previously [6]. Thus the mean bone La content was near 300 ng/g (= µg/kg) wet weight in the La carbonate-overloaded uraemic rats of our study and near 1500 µg/kg wet weight in the La carbonate-overloaded uraemic rats of Behets et al. [8] One must consider that the animals of our study ingested approximately 1800 mg/kg La carbonate per day for a time period of only 4 weeks, whereas the rats of their study were gavaged with a maximal daily dose of 1000 mg/kg La carbonate for a time period of 3 months. When correcting for this time factor, it is fair to conclude that the measurements in the two studies yielded comparable results. The La measurement techniques were the same, namely inductively coupled plasma emission spectrometry.
Conflict of interest statement. The authors declare having received grant support from Genzyme. T.D. also declares having received lecture fees, consulting fees and honoraria from Genzyme.
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References
- Ben-Dov IZ, Pappo O, Sklair-Levy M, et al. Lanthanum carbonate decreases PTH gene expression with no hepatotoxicity in uraemic rats. Nephrol Dial Transplant (2007) 22:362–368.
[Abstract/Free Full Text] - Cozzolino M, Brancaccio D. Lanthanum carbonate—new data on parathyroid hormone control without liver damage. Nephrol Dial Transplant (2007) 22:316–318.
[Free Full Text] - Lacour B, Lucas A, Auchere D, et al. Chronic renal failure is associated with increased tissue deposition of lanthanum after 28-day oral administration. Kidney Int (2005) 67:1062–1069.[CrossRef][Web of Science][Medline]
- Lacour B, Drueke T. Reply from the author. Kidney Int (2005) 68:2906–2907.[Web of Science][Medline]
- Lacour B, Drueke T. Reply from the authors. Kidney Int (2005) 68:2908–2909.[CrossRef][Web of Science]
- Lacour B, Drueke T. Reply from the authors. Kidney Int (2005) 68:2909–2910.[Web of Science][Medline]
- Rambeck W. The need for careful interpretation of animal data on lanthanum. Kidney Int (2005) 68:2909. author reply 2909–2910.[Web of Science][Medline]
- Behets GJ, Dams G, Vercauteren SR, et al. Does the phosphate binder lanthanum carbonate affect bone in rats with chronic renal failure? J Am Soc Nephrol (2004) 15:2219–2228.
[Abstract/Free Full Text]
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