[The physiopathologic bases of the neurotoxicity of phosphorus chelating agents containing soluble aluminum salts in patients with renal insufficiency].
To what extent can damage to the central and peripheral nervous systems be ascribed to chronic aluminum (Al) intoxication taken as a chelating agent for phosphorus, to limit hyperphosphatemia in uremic patients? Since Al is normally eliminated by the renal route, its accumulation in uremia has to be ascribed to a reduced or abolished renal clearance of the metal, which results in preferential toxicity for certain tissues, especially nervous tissue, which shows difficulty in eliminating Al, even after intake has been stopped. This review discusses, on the basis of toxicologic, experimental and clinical data, the possible pathogenic steps of Al neurotoxicity in uremia, considering: the damage to axonal transport in which Al intoxication tends to affect the components of the cytoskeleton, the polymerization phase of the alpha and beta tubulin constituents of neurotubules, and the normal translocation of neurofilaments from the perikaryon to more distal positions of the axon; the abnormalities in the brain pool of adrenergic, cholinergic and GABA neurotransmitters; the increase in permeability and changes in perm-selectivity of the blood-brain-barrier, with further loss of neurotransmitters and with acquisition, from the systemic circulation, of neurotransmitter-like substances such as hormones, monoamines and peptides, which may adversely modulate synaptic and membrane functions; the cerebral energy metabolism and particularly the hexokinase reaction, by Al replacement of the Mg-ion in the Mg-ATP complex, so that phosphorylation of glucose to G6P is blocked; the interaction of Al with calmodulin by displacement of the Ca-ion and subsequent formation of a stable Al-calmodulin complex with a cytotoxic effect due to the increase in the intracellular calcium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
Savazzi
G M
GM
Allegri
L
L
Bocchi
B
B
Celendo
M T
MT
Garini
G
G
Raimondi
C
C
Vinci
S
S
Borghetti
A
A
D000535:Aluminum / Q000009:adverse effects*; D002614:Chelating Agents / Q000009:adverse effects*; D006801:Humans; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000503:physiopathology; D014511:Uremia / Q000503:physiopathology*
D002614:Chelating Agents; D000535:Aluminum
Le basi fisiopatologiche della neurotossicità dei chelanti del fosforo contenenti sali solubili di alluminio nel paziente con insufficienza renale.