The need for careful interpretation of animal data on lanthanum

Abstract

To the Editor: Lacour et al [1.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: 1062-1069Abstract Full Text Full Text PDF PubMed Scopus (168) Google Scholar] describe reductions in organ weights in uremic rats given lanthanum carbonate, those for liver and kidney being highlighted as significant because differences remained after normalisation for femur length. Adjustment using femur length is unconventional, as drug effects on body mass (unless they affect growth) do not influence this parameter. Normalization using body mass is the standard method, and in our view should have been used due to the differences in body weight between lanthanum-treated and -untreated rats. When kidney and liver weights are normalized in this way, group differences are abolished (see Table 1 above).Table 1Absolute (mg) and body weight adjusted (mg/g) liver and kidney weights in normal and uremic ratsTreatment groupBody weight (g)aNonfasted preterminal body weight (day 38) extracted from Figure 1 of Lacour et al [1].Liver wt (mg)Liver wt (mg/g)Kidney wt (mg)Kidney wt (mg/g)La[-] control47211,63224.614893.2La[+] control46311,00423.814303.1La[-] adenine340900326.524207.1La[+] adenine307711423.220926.8La[-] Nx330889927.08102.5La[+] Nx307782925.57272.4Abbreviations: [-], no lanthanum treatment; [+], 3% lanthanum in diet; Nx, 5/6th nephrectomized renal failure model; adenine, adenine induced renal failure model (adenine given 0.3% of diet); control, normal renal function. Body weight adjustment abolishes differences in organ weight between lanthanum-treated and -untreated groups within each renal failure model.a Nonfasted preterminal body weight (day 38) extracted from Figure 1 of Lacour et al [1.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: 1062-1069Abstract Full Text Full Text PDF PubMed Scopus (168) Google Scholar]. Open table in a new tab Abbreviations: [-], no lanthanum treatment; [+], 3% lanthanum in diet; Nx, 5/6th nephrectomized renal failure model; adenine, adenine induced renal failure model (adenine given 0.3% of diet); control, normal renal function. Body weight adjustment abolishes differences in organ weight between lanthanum-treated and -untreated groups within each renal failure model. The authors also note qualitative differences in tissue lanthanum deposition between normal and uremic rats, and between different uremia models. No hypotheses were put forward to suggest why lanthanum might deposit in brain, heart, and skeletal muscle in one disease model, but not in another, or in normal rats. The extent to which these differences were artefacts of contamination is unclear, as lanthanum was administered at very high concentrations in the diet (probably powdered), and plasma concentrations were extraordinarily high both in control and lanthanum-treated groups [2.Behets G.J. Dams G. Vercauteren S.R. et al.Does the phosphate binder lanthanum carbonate affect bone in rats with chronic renal failure.J Am Soc Nephrol. 2004; 15: 2219-2228Crossref PubMed Scopus (86) Google Scholar]. Lung deposition is also unusual in our experience and may reflect inhalation of lanthanum from the diet. Furthermore, the authors report major intestinal pathology in the adenine uremia model, but not the nephrectomized model, yet paradoxically rule out any influence of this on the absorption and deposition of lanthanum. Extrapolation of the Lacour et al [1.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: 1062-1069Abstract Full Text Full Text PDF PubMed Scopus (168) Google Scholar] findings to human lanthanum exposure appears unwarranted at this time.