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 μm 2 /mm 2 /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 μg/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 (ΔsAl) above 50 μg/l (5 mg/kg) or 70 μg/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 μg/g wet weight). In the detection of patients at risk for aluminium toxicity ΔsAl thresholds of 50 μg/l (5 mg/kg) and 70 μg/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 ΔsAl levels of 50 μg/l (5 mg/kg) and 70 μg/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.