Correlation of drug-related aluminum intake and dialysis treatment with deposition of argyrophilic aluminum-containing inclusions in CNS and in organ systems of patients with dialysis-associated encephalopathy.
CNS tissue and peripheral organs of 50 autopsy cases with chronic renal failure (CRF) and dialysis treatment were evaluated for aluminum- (Al) containing argyrophilic inclusions using the Howell and Black method modified by Reusche. Morphological alterations were correlated with the duration of hemodialysis (HD) and to the amount of prescribed Al-containing drugs for better control of hyperphosphatemia. Significant correlations were found between the degree of morphological alterations and Al intake up to 2.5 kg (p = 0.0003), as well as for morphology and duration of longterm HD up to 178 months (p = 0.001). Most sensitive structure for CNS deposits were choroid epithelia, followed by glial cells and neurons. Autonomic ganglia, heart, ovary/testis, parathyroid, adrenal, and pituitary demonstrated reliably peripheral deposits. Al-containing drugs, administered preferentially during HD, explain the additional significance of Al uptake and duration of dialysis (R-Qu. = 0.6697). The deposition of Al-containing proteinaceous inclusions is apparently irreversible. After renal transplantation, with termination of drug-related Al intake and normalized renal Al excretion, the Al-induced argyrophilic degradation products remained in the cellular cytoplasm in unchanged fashion up to 10 years.
Reusche
E
E
Institute of Pathology, Medical University, Lübeck, Germany.
Koch
V
V
Friedrich
H J
HJ
Nünninghoff
D
D
Stein
P
P
Rob
P M
PM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000535:Aluminum / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000032:analysis; D001927:Brain Diseases / Q000209:etiology*; D002490:Central Nervous System / Q000737:chemistry* / Q000473:pathology; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D006435:Renal Dialysis / Q000009:adverse effects*; D012834:Silver / Q000032:analysis*
D015415:Biomarkers; D004364:Pharmaceutical Preparations; D012834:Silver; D000535:Aluminum