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.
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.
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DOI：
10.1093/ndt/10.10.1874
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发表时间：
1995-10
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通讯作者：
P. D’Haese;M. Couttenye;W. Goodman;E. Lemoniatou;P. Digenis;I. Sotorník;A. Fagalde;R. Barsoum;L. Lamberts;M. Broe
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作者：
P. D’Haese;M. Couttenye;W. Goodman;E. Lemoniatou;P. Digenis;I. Sotorník;A. Fagalde;R. Barsoum;L. Lamberts;M. Broe
背景为了寻找一种安全的方法来诊断铝相关性骨病（ARBD）/铝超载，开发了低剂量去铁胺（DFO）试验。在一项多中心研究中，77例透析患者骨活检的组织学和组织化学数据以及铝体积分析与5 mg/kg和10 mg/kg DFO试验的结果相关。方法：当> 15%的骨表面铝染色阳性且骨形成率低于220 μ m 2/mm 2/天时，认为存在ARBD。铝染色阳性（> 0%）的患者被认为铝毒性的风险增加，与肾性骨营养不良的类型无关。当骨铝含量> 15微克/克湿重和/或Aluminon染色呈阳性（> 0%）时，患者被认为是铝超载。结果：使用提出的标准，15例患者被发现有ARBD，其中13例血清iPTH低于150 ng/l。结合iPTH测量，DFO测试在ARBD诊断中具有超过可接受的灵敏度和特异性。当DFO后血清铝增加时，该试验被视为阳性（Δ sA 1）高于50微克/升（5毫克/千克）或70微克/升以10 mg/kg为界值，诊断ARBD的敏感性为87%，特异性为95%，特异性为92%而对研究人群阳性试验的预测值为80%（5 mg/kg）。即使骨铝水平升高（> 15 μ g/g湿重），血清iPTH > 650 ng/l的患者中也没有一个阳性染色（> 0%）。在检测铝中毒风险患者时，δ sA 1阈值为50微克/升（5 mg/kg）和70微克/升（10 mg/kg），同时血清iPTH < 650 ng/l，灵敏度为92%，特异性分别为86%和84%。在铝超负荷的临床环境中，50微克/升（5 mg/kg）和70微克/升（10 mg/kg）的阈值Δ sA 1水平的灵敏度分别为91%，特异性分别为95%和90%。结论：低剂量DFO试验是检测铝过载的可靠试验;然而，除非与血清iPTH测量联合使用，否则其特异性不足以区分ARBD、铝毒性风险增加和铝过载。结合血清iPTH测量，它是鉴别诊断的重要工具，可以避免大多数患者进行骨活检的必要性。本研究中获得的数据使我们能够更新1992年巴黎终末期肾衰竭铝超载诊断和治疗共识会议上提出的监测、诊断和患者随访策略。
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.