Glomerular atrophy

The fact that M-T7 binds not only to IFN-y from rabbit but also to chemokines from various species has allowed its use as a vCKBP in mouse models. The ability of low amounts of recombinant M-T7 protein to attenuate restenosis after balloon angioplasty in rats has been described to be similar to that of the M3 and 35-kDa proteins, as mentioned before. Whether this effect is due to direct inhibition of chemokine activity is not dear at present [25]. Using a rat renal allograft model, chronic rejection was attenuated by M-T7 protein, with significant reduction in tubular and glomerular atrophy, scarring and lymphocyte infiltration [52]. 

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). 

Long-term lithium therapy is associated with a 10% to 20% risk of morphologic renal changes (e.g., glomerular sclerosis, tubular atrophy, and interstitial nephritis). 

Renal function impairment Morphologic changes with glomerular and interstitial fibrosis and nephron atrophy have occurred in patients on chronic lithium therapy. The relationship between such changes and renal function has not been established. 

Morphologic studies of radiation nephropathy have documented injury to blood vessels, glomeruh, tubular epithelium and interstitium. Recent ultrastructural studies indicate that glomerular endothelium is an early site of visible injury [236] with endothehal disruption and leukocyte adherence. Later, tubular degeneration and atrophy occur. The second pathophysiologic hypothesis holds vascular injury as the main initial event [237] which helps understand the hypertension occurring in radiation nephritis but does not account for the glomerular lesions. 

Chronic exposure to low levels of lead results in lead accumulation within the body. Workers who have been chronically exposed to lead develop interstitial fibrosis, vascular and glomerular sclerosis, and tubular atrophy and/or hypertrophy. Although acute lead nephropathy is reversible with chelator therapy and/or removal from exposure, chronic effects may be irreversible. In addition, chronic exposure to lead may result in a gouty nephropathy as lead reduces uric acid excretion and elevates blood uric acid levels. 

Renal 1.9 M (marked thickening of glomerular and tubular basement membranes degeneration and atrophy of tubule epithelium) ... 

Acute renal toxicity may occur within days of initiating therapy. Serum creatinine concentration rises and creatinine clearance decreases. Hypertension, hyperkalemia, sodium avidity, and hypomagnesemia may occur. No urine sediment abnormalities are seen. Urinary enzyme excretions increase, but are not reliable indicators of toxicity. Renal biopsy reveals thickening of arterioles, mild focal glomerular sclerosis, proximal tubular epithelial cell vacuolization and atrophy, and interstitial fibrosis. Biopsy is useful to distinguish acute cyclosporine nephrotoxicity from renal allograft rejection, the latter being evidenced by cellular infiltration. ... 

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