Use of the low-dose desferrioxamine test to diagnose and differentiate between patients with aluminium-related bone disease, increased risk for aluminium toxicity, or aluminium overload.
BACKGROUND
Aiming at a safe method in the diagnosis of aluminium-related bone disease (ARBD)/aluminium overload the low-dose desferrioxamine (DFO) test was developed. In a multicentre study histological and histochemical data and aluminium bulk analysis of bone biopsies of 77 dialysis patients were correlated with the results of both the 5 mg/kg and 10 mg/kg DFO tests.


METHODS
ARBD was considered to be present when > 15% of the bone surface was positively stained for aluminium and the bone formation rate was below 220 microns 2/mm2/day. Patients in which the Aluminon staining was positive (> 0%) were considered at an increased risk for aluminium toxicity independent of the type of renal osteodystrophy. Patients were considered aluminium overloaded when the bone aluminium content was > 15 micrograms/g wet weight and/or the Aluminon staining was positive (> 0%).


RESULTS
Using the proposed criteria 15 patients were found to have ARBD; 13 of them presenting with a serum iPTH below 150 ng/l. In conjunction with an iPTH measurement the DFO test had a more than acceptable sensitivity and specificity in the diagnosis of ARBD. The test was considered positive when a post-DFO serum aluminium increment (delta sA1) above 50 micrograms/l (5 mg/kg) or 70 micrograms/l (10 mg/kg) together with a serum iPTH below 150 ng/l was found. Using these cut-off levels the 5 and 10 mg/kg tests in the diagnosis of ARBD had a sensitivity of 87% and a specificity of 95% and 92% respectively whereas the predictive value for a positive test for the population under study was 80% (5 mg/kg). Not a single patient with a serum iPTH > 650 ng/l had a positive staining (> 0%) even when the bone aluminium level was elevated (> 15 micrograms/g wet weight). In the detection of patients at risk for aluminium toxicity delta sA1 thresholds of 50 micrograms/l (5 mg/kg) and 70 micrograms/l (10 mg/kg) in combination with a serum iPTH < 650 ng/l had a sensitivity of 92% and specificity of 86% and 84% respectively. In the clinical setting of aluminium overload, threshold delta sA1 levels of 50 micrograms/l (5 mg/kg) and 70 micrograms/l (10 mg/kg) had a sensitivity of 91% and a specificity of 95% and 90% respectively.


CONCLUSIONS
The low-dose DFO test is a reliable test for the detection of aluminium overload; however, it is not specific enough to differentiate between ARBD, increased risk of aluminium toxicity, and aluminium overload unless it is used in combination with a serum iPTH measurement. In conjunction with a serum iPTH measurement it is an important tool in the differential diagnosis and may avoid the necessity of a bone biopsy in the majority of patients. Data obtained in the present study have allowed us to update the strategies for monitoring, diagnosis and patient follow-up proposed at the Consensus Conference on Diagnosis and Treatment of Aluminium Overload in End-Stage Renal Failure; Paris, 1992.
D'Haese
P C
PC
Department of Nephrology-Hypertension, University of Antwerp, Belgium.
Couttenye
M M
MM
Goodman
W G
WG
Lemoniatou
E
E
Digenis
P
P
Sotornik
I
I
Fagalde
A
A
Barsoum
R S
RS
Lamberts
L V
LV
De Broe
M E
ME
D000328:Adult; D000368:Aged; D000535:Aluminum / Q000009:adverse effects* / Q000097:blood / Q000506:poisoning; D001847:Bone Diseases / Q000139:chemically induced* / Q000175:diagnosis*; D003676:Deferoxamine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D012307:Risk Factors; D012680:Sensitivity and Specificity
D000535:Aluminum; D003676:Deferoxamine