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

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.