USE OF THE LOW-DOSE DESFERRIOXAMINE TEST TO DIAGNOSE AND DIFFERENTIATE BETWEEN PATIENTS WITH ALUMINUM-RELATED BONE-DISEASE, INCREASED RISK FOR ALUMINUM TOXICITY, OR ALUMINUM OVERLOAD
Pc. Dhaese et al., USE OF THE LOW-DOSE DESFERRIOXAMINE TEST TO DIAGNOSE AND DIFFERENTIATE BETWEEN PATIENTS WITH ALUMINUM-RELATED BONE-DISEASE, INCREASED RISK FOR ALUMINUM TOXICITY, OR ALUMINUM OVERLOAD, Nephrology, dialysis, transplantation, 10(10), 1995, pp. 1874-1884
Background. Aiming at a safe method in the diagnosis of aluminium-rela
ted bone disease (ARBD)/aluminium overload the low-dose desferrioxamin
e (DFO) test was developed. In a multicentre study histological and hi
stochemical data and aluminium bulk analysis of bone biopsies of 77 di
alysis patients were correlated with the results of both the 5 mg/kg a
nd 10 mg/kg DFO tests. Methods. ARBD was considered to be present when
> 15% of the bone surface was positively stained for aluminium and th
e bone formation rate was below 220 mu m(2)/mm(2)/day. Patients in whi
ch the Aluminon staining was positive (> 0%) were considered at an inc
reased risk for aluminium toxicity independent of the type of renal os
teodystrophy. Patients were considered aluminium overloaded when the b
one aluminium content was > 15 mu g/g wet weight and/or the Aluminon(R
) staining was positive (> 0%). Results. Using the proposed criteria 1
5 patients were found to have BRED; 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 dia
gnosis of ARBD. The test was considered positive when a post-DFO serum
aluminium increment (Delta sA1) above 50 mu g/l (5 mg/kg) or 70 mu g/
l (10 mg/kg) together with a serum iPTH below 150 ng/l was found. Usin
g these cut-off levels the 5 and 10 mg/kg tests in the diagnosis of AR
BD had a sensitivity of 87% and a specificity of 95% and 92% respectiv
ely whereas the predictive value for a positive test for the populatio
n under study was 80% (5 mg/kg). Not a single patient with a serum iPT
H > 650 ng/l had a positive staining (> 0%) even when the bone alumini
um level was elevated (> 15 mu g/g wet weight). In the detection of pa
tients at risk for aluminium toxicity Delta sA1 thresholds of 50 mu g/
l (5 mg/kg) and 70 mu g/l (10 mg/kg) in combination with a serum iPTH
< 650 ng/l had a sensitivity of 92% and specificity of 86% and 84% res
pectively. In the clinical setting of aluminium overload, threshold De
lta sA1 levels of 50 mu g/l (5 mg/kg) and 70 mu g/l (10 mg/kg) had a s
ensitivity of 91% and a specificity of 95% and 90% respectively. Concl
usions. The low-dose DFO test is a reliable test for the detection of
aluminium overload; however, it is not specific enough to differentiat
e between ARBD, increased risk of aluminium toxicity, and aluminium ov
erload 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 bi
opsy in the majority of patients. Data obtained in the present study h
ave allowed us to update the strategies for monitoring, diagnosis and
patient follow-up proposed at the Consensus Conference on Diagnosis an
d Treatment of Aluminium Overload in End-Stage Renal Failure; Paris, 1
992.