Welcome to Scribd. Sign in or start your free trial to enjoy unlimited e-books, audiobooks & documents.Find out more
Download
Standard view
Full view
of .
Look up keyword
Like this
5Activity
0 of .
Results for:
No results containing your search query
P. 1
Chelation of Gadolinium Oxford 2009

Chelation of Gadolinium Oxford 2009

Ratings: (0)|Views: 125|Likes:
Published by gasfgd
Chelation of gadolinium with deferoxamine in a patient with nephrogenic systemic fibrosis, Mayo

The results of our study showed that deferoxamine is capable of chelating and increasing the renal clearance of gadolinium by more than twofold. A dose-dependent relationship was also suggested, but unfortunately not enough data were available to performa statistical analysis. Despite our positive results, deferoxamine is unlikely to be clinically useful because its chelation of gadolinium is tooweak. Studies with dimeglumine gadopentetate (Gd-DTPA) showed that patients with a creatinine clearance
Chelation of gadolinium with deferoxamine in a patient with nephrogenic systemic fibrosis, Mayo

The results of our study showed that deferoxamine is capable of chelating and increasing the renal clearance of gadolinium by more than twofold. A dose-dependent relationship was also suggested, but unfortunately not enough data were available to performa statistical analysis. Despite our positive results, deferoxamine is unlikely to be clinically useful because its chelation of gadolinium is tooweak. Studies with dimeglumine gadopentetate (Gd-DTPA) showed that patients with a creatinine clearance

More info:

Categories:Types, Research
Published by: gasfgd on Apr 01, 2012
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as PDF, TXT or read online from Scribd
See more
See less

04/27/2013

pdf

text

original

 
 NDT Plus (2009) 1 of 3doi: 10.1093/ndtplus/sfp042
Case Report 
Chelation of gadolinium with deferoxamine in a patientwith nephrogenic systemic fibrosis
 Nelson Leung
1
, Mark R. Pittelkow
2
, Christine U. Lee
3
, Jonathan A. Good 
4
, Matthew M. Hanley
4
and Thomas P. Moyer 
4
1
Division of Nephrology and Hypertension,
2
Department of Dermatology,
3
Department of Radiology and 
4
Department of LaboratoryMedicine & Pathology, Mayo Clinic Rochester, Rochester, MN, USA
Correspondence and offprint requests to
: Nelson Leung; E-mail: leung.nelson@mayo.edu
Abstract
A 65-year-old female with biopsy-confirmed nephrogenicsystemic fibrosis (NSF) received a kidney transplanta-tion. Despite good kidney function, her symptoms con-tinued to progress. Deferoxamine was administered intra-muscularly at 500 mg/day and later 1000 mg/day after 1 week with no adverse effects. Urine excretion of gadolin-ium increased from 6.0
μ
g/day to 11.6
μ
g/day and subse-quently to 13.0
μ
g/day with 500 mg/day and 1000 mg/dayof deferoxamine, respectively. Serum levels, however, re-main unchanged from 1.7 ng/ml to 1.4 ng/ml. Althoughchelation therapy may have a role in the treatment of  NSF, deferoxamine is too weak and a stronger chelator isneeded.
Keywords:
chelation; deferoxamine; gadolinium
Introduction
 Nephrogenic systemic fibrosis (NSF) is a debilitating dis-order characterized by oedema, plaques, discoloration and severe thickening of the skin resulting in contractures and immobility. Currently, exposure to gadolinium-based con-trast agents (GBCA) during low glomerular filtration rate(GFR) states appears to be the most consistent risk fac-tor [1]. Since GBCA is excreted by the kidney, exposureis prolonged in patients with renal insufficiency [2]. Theextended exposure permits transmetallation to occur whichallows free gadolinium to come in contact with proteinsand other cellular components. At the present time, thedownstream effects leading to NSF are still not well un-derstood [3]. No standard treatment currently exists for  NSF.In the past, dialysis patients were commonly plagued with iron or aluminium overload. Deferoxamine was used to chelate the excess metals in their trivalent state [4]. Thechelated metals were excreted in the urine or removed withdialysis. Since gadolinium exists in a trivalent state, wehypothesizethatdeferoxaminemaychelategadolinium.Wereport our experience with a patient who underwent defer-oxamine treatment for her NSF.
Case report
A 65-year-old female kidney transplant recipient presented with worsening symptoms of NSF. The patient had chronicglomerulonephritis for many years and was started ondialysis in February 2003. In October 2005, she devel-oped a fungal peritonitis secondary to microperforationfrom colonoscopy. A MR angiogram was performed with20 cc of a GBCA (estimated 0.13 mmol/kg). Details of thespecific agent were unavailable from her outside records.Within a month, the patient began to notice hardening of her legs and hips making walking extremely difficult. Thesymptoms later spread to her waist and hands. NSF wasconfirmed by a skin biopsy. The patient underwent UVA-1 phototherapythatseemedtoslowtheprogressionofherdis-ease but did not improve it. In August 2007, she received aliving-related donor kidney transplantation from her sister.Despite excellent renal allograft function (Scr 
=
0.9 mg/dl and GFR 
=
65 ml/min/1.73 m
2
), her skin symptomscontinued to progress. The patient was experiencing more pain and was having increasing difficulty walking due tocontractures in her legs. She agreed to undergo chelationtherapy in January 2008.Deferoxamine 500 mg intramuscularly was given daily(except during the weekend) for seven doses. After a week-endbreakwherenoadverseeventswerenoted,thedosewasincreased to 1000 mg/day for five additional doses. Base-line serum and urine samples were collected along withsamples during the two treatment periods. Urine gadolin-ium was measured from 24 h collections. Renal clearancewas calculated using the UV/P method.Gadolinium was quantified by inductively couple plasma mass spectrometry (Perkin-Elmer Life and Ana-lytical Sciences, Shelton, CO, USA). Aqueous acidic cal-ibrating standards and patient samples were diluted with
C
The Author [2009]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.For Permissions, please e-mail: journals.permissions@oxfordjournals.org
 
NDT Plus Advance Access published April 23, 2009
  b  y g u e  s  t   on O c  t   o b  e  , 0  t   t   p :  /   /  n d  t   pl   u s  . oxf   o d  j   o un a l   s  . o g /  D o wnl   o a  d  e  d f   om 
 
.
 No standard treatment currently exists as no clinical trialhas been conducted for the treatment of NSF. Most would agree that physical therapy should be a part of any treat-ment programme, and steroids (topical or systemic) areineffective [5]. Beyond that, controversies exist for nearlyevery treatment. Available treatments can be sorted intothree categories. First is therapies that were reported onlyonce without further confirmation or rebuttal. These med-ications include pentoxifylline, thalidomide and high-doseintravenousimmunoglobulin[6].Thenextcategoryistreat-ments whose success has been challenged in the litera-ture. These include phototherapy (UVA-1, psoralen plusUVA-1, photopheresis), sodium thiosulfate, plasmaphere-sis, sirolimus, calcipotriene and cyclophosphamide [5–8].The third category involves therapies that have been con-firmed but not refuted. The only medication in this cate-gory so far is imatinib, a specific inhibitor of BCR/ABLtyrosine kinase that is approved for treatment of chronicmyelogenous leukaemia [9,10]. Activity against systemicsclerosis, a separate chronic fibrotic disease of unknownetiology, in an animal model makes imatinib a promisingtherapy [11].Despite the promising results, relapse has been reported when treatment is discontinued [9]. One possibility is thatthefibroticreactioncanrecuraslongasacriticalamountof gadolinium remains in the tissue. Elimination or reductionofthegadoliniummaybethemosteffectiveformoftherapy.This explains the reports of spontaneous improvement in NSF after recovery of renal function especially in cases of acute renal failure where the exposure is limited [5]. Thismay also account for some of the differences in responsesreported with some of the therapies.The results of our study showed that deferoxamine iscapable of chelating and increasing the renal clearance of gadolinium by more than twofold. A dose-dependent rela-tionship was also suggested, but unfortunately not enoughdatawereavailabletoperformastatisticalanalysis.Despiteourpositiveresults,deferoxamineisunlikelytobeclinicallyusefulbecauseitschelationofgadoliniumistooweak.Stud-ies with dimeglumine gadopentetate (Gd-DTPA) showed that patients with a creatinine clearance
<
  b  y g u e  s  t   on O c  t   o b  e  , 0  t   t   p :  /   /  n d  t   pl   u s  . oxf   o d  j   o un a l   s  . o g /  D o wnl   o a  d  e  d f   om 

Activity (5)

You've already reviewed this. Edit your review.
1 hundred reads
gasfgd liked this
gasfgd liked this
muennemann liked this
gasfgd liked this

You're Reading a Free Preview

Download
scribd
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->