Inclusion bodies lead nephropathy

Renal Effects. The characteristics of early or acute lead-induced nephropathy in humans include nuclear inclusion bodies, mitochondrial changes, and cytomegaly of the proximal tubular epithelial cells dysfunction of the proximal tubules (Fanconi s syndrome) manifested as aminoaciduria, glucosuria, and phosphaturia with hypophosphatemia and increased sodium and decreased uric acid excretion. These effects appear to be reversible. Characteristics of chronic lead nephropathy include progressive interstitial fibrosis, dilation of tubules and atrophy or hyperplasia of the tubular epithelial cells, and few or no nuclear inclusion bodies, reduction in glomerular filtration rate, and azotemia. These effects are irreversible. The acute form is reported in lead-intoxicated children, whose primary exposure is via the oral route, and sometimes in lead workers. The chronic form is reported mainly in lead workers, whose primary exposure is via inhalation. Animal studies provide evidence of nephropathy similar to that which occurs in humans, particularly the acute form (see Section 2.2.3.2). 

Acute exposure to inorganic lead can cause reversible damage to the kidneys, manifested as tubular dysfunction. Chronic exposure to lead, however, causes permanent interstitial nephropathy, which involves tubular cell atrophy, pathological changes in the vasculature, and fibrosis. The most pronounced changes occur in the proximal tubules. Indeed, lead-protein complexes are seen as inclusion bodies in tubular cells, and the mitochondria in such cells have been shown to be altered with impaired oxidative phosphorylation. Clearly, this will influence the function of the proximal tubular cells in reabsorption and secretion of solutes and metabolites. Consequently, one indication of renal dysfunction is amino aciduria, glycosuria, and impairment of sodium reabsorption. 

Cyclosporine is a macrolide antibiotic and has been used as an immunosuppressive agent. Cyclosporine can cause both renal and nonrenal toxicity. Clinically renal toxicity consists of four discrete syndromes which include acute reversible renal functional impairment, delayed renal allograft function, acute vasculopathy, and chronic nephropathy with interstitial fibrosis. Proximal tubular epithelium is uniquely sensitive to the toxic effect. The toxic effect is characterized by isometric cytoplasmic vacuolations (several small equally sized vacuoles in cytoplasm), necrosis with or without subsequent mineralization, inclusion bodies (giant mitochondria), and giant lysosomes. Acute vasculopathy consists of vacuolization of the arteriolar smooth muscles and endothelial cells leading to necrosis. In some cases, thrombotic microangiopathy develops, characterized by thrombosis of the renal micro vasculature. Long-term treatment with cyclosporine results in chronic nephropathy with interstitial fibrosis (Chamey et al., 2004). 

Clinically, lead nephropathy is seen as either reversible tubular dysfunction or as an irreversible interstitial nephropathy. Tubular toxicity occurs most commonly in children following acute exposure and is characterized by glucosuria, phosphaturia, aminoaciduria, and occasionally proteinuria. One unique morphological feature of lead exposure is the formation of nuclear inclusion bodies within renal tubular cells. These bodies are complexes between lead... 

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