Skip Navigation


NDT Advance Access first published online on September 27, 2009
This version published online on October 5, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp508
This Article
Right arrow Extract
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
24/12/3898    most recent
gfp508v2
gfp508v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Related articles in NDT
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Smyth, M. D. L.
Right arrow Articles by Pratt, R. D.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Smyth, M. D. L.
Right arrow Articles by Pratt, R. D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author [2009]. Published by Oxford University Press [on behalf of ERA-EDTA].
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use distribution, and reproduction in any medium, provided the original work is properly cited.


A confusional state associated with use of lanthanum carbonate in a dialysis patient: a case report

Nephrol Dial Transplant 2009; doi:10.1093/ndt/gfp514

Sir,

Muller and colleagues report a case of febrile confusion and ‘diverticular flare-up’ with abdominal pain and speculate an association with lanthanum carbonate (LC) because discontinuation of LC treatment and initiation of antibiotic therapy led to recovery [1]. They support their argument with the radiographic detection of lanthanum particles in the gastrointestinal tract, a reduction of plasma lanthanum levels following discontinuation of treatment and a selective review of the literature. However, there is no convincing argument for an association with LC treatment.

The only available presentation of LC (FOSRENOL®, Shire Pharmaceuticals, Basingstoke, UK) is a chewable tablet containing no excipients to aid dispersal. Tablets should be taken with or immediately after meals and should be chewed completely; intact tablets should not be swallowed [2]. The size of the lanthanum particles evident in the radiograph is consistent with that of chewed LC, as has been seen in other published reports and not been associated with gastrointestinal obstruction [3,4]. As expected, and noted by the authors, the lanthanum particles ‘continued to migrate through the digestive tract’. In contrast, the case report by Kurtz (sic) et al. (Kongress der Gesellschaft für Nephrologie, Tubingen, Germany, 2008) cited by Muller clearly showed the presence of un-chewed tablets.

Speculation that deposition of lanthanum in the central nervous system (CNS) resulted in the confusional state draws on controversial evidence from in vivo studies [5,6]. Recent data from a study examining the potential for contamination of tissue samples in dietary studies of LC leads one to question the validity of this evidence [7]. In this study comparing dietary, oral gavage and intravenous administration, lanthanum was only detectable in brain tissue from rats administered LC in their diet. It appears that despite stringent efforts to limit contamination, lanthanum is still transferred to tissue samples during autopsy [7]. In another recent study, Bervoets et al. demonstrated no difference in the brain concentrations of lanthanum between healthy rats and those with chronic renal failure treated by oral gavage with LC for 20 weeks [8]. Levels remained around the lower limit of quantification for the assay. The results of these studies add to the weight of evidence in the literature that lanthanum does not cross the blood–brain barrier, even in the uraemic inflammatory and other disease states [8–10]. In the study by Feng et al., which suggests alteration of CNS function with lanthanum treatment, changes in biochemical parameters were not dose dependent and not predictive of effects in humans as discussed in the literature [6,11].

In addition, the authors do not consider the clinical data on the effects of LC on cognitive function [12]. Altmann et al. found no difference in the rate of cognitive decline in dialysis patients randomized to LC or standard phosphate-binder therapy (mainly calcium based) [12]. In this study, the median plasma lanthanum level of LC-treated patients stabilized at ~0.3 (range 0.0–3.1) ng/mL. Therefore, the plasma lanthanum value of 2.13 µg/L noted by Muller et al. is neither ‘higher than normal’ compared with a population treated with LC for 2 years, nor is it associated with excessive cognitive decline. Extrapolation from in vivo tissue deposition data [8] based on human plasma lanthanum levels [13] is not scientifically sound and the conclusion that toxic levels of lanthanum can be reached in patients with renal failure is purely speculative, with no human or animal evidence provided.

This patient was elderly and had diffuse cerebral atrophy on CT scan. Her presenting symptoms included dizziness with falling and confusion. Infection is commonly implicated with the etiology of several conditions that cause confusion in the elderly, and therapy of the underlying condition leads to recovery [14]. Benzodiazepine use is also commonly associated with confusion in the elderly. Either of these factors are plausible explanations for the confusion experienced by this patient.

In summary, this patient with known diverticular disease presented with a febrile episode that responded to antibiotic treatment. The authors noted the expected radio-opaque appearance of lanthanum in the gastrointestinal tract and plasma lanthanum levels within the range observed in pivotal clinical trials. Neither finding has been convincingly linked to the patient's presentation; therefore, there are no grounds for revising the benefit–risk profile for LC.

Conflict of interest statement. MS and RDP are employees of Shire Pharmaceuticals.

Michael D. L. Smyth1 and Raymond D. Pratt2

1 Global Medical Affairs Shire Pharmaceuticals, Basingstoke, UK 2 Research and Development Shire Pharmaceuticals, Wayne, PA, USA E-mail: msmyth{at}shire.com

Notes

The original version was incorrect. The copyright status is now Open Access.

References

  1. Muller C, Chantrel F, Faller B. A confusional state associated with use of lanthanum carbonate in a dialysis patient: a case report. Nephrol Dial Transplant (2009) 24:3245–3247.[Abstract/Free Full Text]
  2. FOSRENOL. Prescribing Information (2008) Wayne, PA: Shire Pharmaceuticals.
  3. Cerny S, Kunzendorf U. Images in clinical medicine. Radiographic appearance of lanthanum. N Engl J Med (2006) 355:1160.[Free Full Text]
  4. Chuang CL, Chiou SY, Li SY, et al. The case: a peritoneal dialysis patient with an unusual abdominal film. Treatment with lanthanum carbonate. Kidney Int (2007) 72:1291–1292.[CrossRef][Web of Science][Medline]
  5. 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]
  6. Feng L, Xiao H, He X, et al. Neurotoxicological consequence of long-term exposure to lanthanum. Toxicol Lett (2006) 165:112–120.[CrossRef][Web of Science][Medline]
  7. Damment SJ, Cox AG, Secker R. Dietary administration in rodent studies distorts the tissue deposition profile of lanthanum carbonate; brain deposition is a contamination artefact? Toxicol Lett (2009) 188:223–229.[CrossRef][Web of Science][Medline]
  8. Bervoets AR, Behets GJ, Schryvers D, et al. Hepatocellular transport and gastrointestinal absorption of lanthanum in chronic renal failure. Kidney Int (2009) 75:389–398.[CrossRef][Web of Science][Medline]
  9. Kato M, Sugihara J, Nakamura T, et al. Electron microscopic study of the blood-brain barrier in rats with brain edema and encephalopathy due to acute hepatic failure. Gastroenterol Jpn (1989) 24:135–142.[Medline]
  10. Xu J, Ling EA. Studies of the ultrastructure and permeability of the blood-brain barrier in the developing corpus callosum in postnatal rat brain using electron dense tracers. J Anat (1994) 184(Pt 2):227–237.[Web of Science][Medline]
  11. Damment SJ, De Broe ME, D’Haese PC, et al. Incredulous effects of lanthanum? Toxicol Lett (2007) 168:186–189.[CrossRef][Web of Science][Medline]
  12. Altmann P, Barnett ME, Finn WF. Cognitive function in Stage 5 chronic kidney disease patients on hemodialysis: no adverse effects of lanthanum carbonate compared with standard phosphate-binder therapy. Kidney Int (2007) 71:252–259.[CrossRef][Web of Science][Medline]
  13. Spasovski GB, Sikole A, Gelev S, et al. Evolution of bone and plasma concentration of lanthanum in dialysis patients before, during 1 year of treatment with lanthanum carbonate and after 2 years of follow-up. Nephrol Dial Transplant (2006) 21:2217–2224.[Abstract/Free Full Text]
  14. Rockwood K. Acute confusion in elderly medical patients. J Am Geriatr Soc (1989) 37:150–154.[Web of Science][Medline]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?

Related articles in NDT:

Reply
Muller Clotilde, Chantrel Francois, and Faller Bernadette
NDT 2009 24: 3899-3900. [Extract] [FREE Full Text]  




This Article
Right arrow Extract
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
24/12/3898    most recent
gfp508v2
gfp508v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Related articles in NDT
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Smyth, M. D. L.
Right arrow Articles by Pratt, R. D.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Smyth, M. D. L.
Right arrow Articles by Pratt, R. D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?