Renal and urinary lipid changes associated with an acutely induced renal papillary necrosis in rats

Renal Papillary Necrosis—40 Years On

“…The morphological and histochemical changes (8,15,19,82,85) support distinct pathological changes following a papillotoxic insult. The primary morphological changes occur in the interstitial cells in acute (13,16,82,85), subchronic (92), and chronic (13) papillary necrosis.…”

“…The lipid staining of epithelial and microvascular cells for neutral lipid appears to be pathognomonic for RPN, as it also occurs in the pig (83), baboon, and marmoset following BEA (Bach and Gregg, unpublished observations) and aspirin-induced (160) RPN. By contrast, chemicals that affect the cortex (e.g., hexachlorobutadiene and cis-platin) do not produce specific localized lipid changes in the medullary epithelial cells (19).…”

“…The earliest change in the papilla was marked pyknosis of the renal medullary interstitial cells at a time when other cells were normal or near normal. Other investigations using lower doses of BEA and shorter time intervals (15,16,19,82,85) were unable to show any role for microvasculature injury in the pathogenesis of RPN. The only microvascular effects seen were platelet adhesion well after interstitial necrosis had occurred.…”

“…Papillary necrosis is associated with the progressive deposition of neutral lipid material in the capillaries, collecting duct, and covering epithelial cells. Lipid staining extends into the outer medulla that would appear as normal by routine staining (15,16,19). The lipid staining of epithelial and microvascular cells for neutral lipid appears to be pathognomonic for RPN, as it also occurs in the pig (83), baboon, and marmoset following BEA (Bach and Gregg, unpublished observations) and aspirin-induced (160) RPN.…”

Renal Papillary Necrosis—40 Years On

“…The morphological and histochemical changes (8,15,19,82,85) support distinct pathological changes following a papillotoxic insult. The primary morphological changes occur in the interstitial cells in acute (13,16,82,85), subchronic (92), and chronic (13) papillary necrosis.…”

“…The lipid staining of epithelial and microvascular cells for neutral lipid appears to be pathognomonic for RPN, as it also occurs in the pig (83), baboon, and marmoset following BEA (Bach and Gregg, unpublished observations) and aspirin-induced (160) RPN. By contrast, chemicals that affect the cortex (e.g., hexachlorobutadiene and cis-platin) do not produce specific localized lipid changes in the medullary epithelial cells (19).…”

“…The earliest change in the papilla was marked pyknosis of the renal medullary interstitial cells at a time when other cells were normal or near normal. Other investigations using lower doses of BEA and shorter time intervals (15,16,19,82,85) were unable to show any role for microvasculature injury in the pathogenesis of RPN. The only microvascular effects seen were platelet adhesion well after interstitial necrosis had occurred.…”

“…Papillary necrosis is associated with the progressive deposition of neutral lipid material in the capillaries, collecting duct, and covering epithelial cells. Lipid staining extends into the outer medulla that would appear as normal by routine staining (15,16,19). The lipid staining of epithelial and microvascular cells for neutral lipid appears to be pathognomonic for RPN, as it also occurs in the pig (83), baboon, and marmoset following BEA (Bach and Gregg, unpublished observations) and aspirin-induced (160) RPN.…”

Biomarkers of Collecting Duct Injury in Han-Wistar and Sprague-Dawley Rats Treated with N-Phenylanthranilic Acid

“…N-phenylanthranilic acid (NPAA) is a biphenyl analogue of fenamic acid and chloride channel blocker that causes renal papillary necrosis (RPN) in rats after repeated oral dosing for fourteen days (Williams et al 2003). Animal models of RPN have used agents such as 2-bromethanamine and nonsteroidal anti-inflammatory drugs including cyclooxygenase inhibitors (Bach and Bridges 1985a; Bach and Bridges 1985b; Bach et al 1991; Bach and Nguyen 1998; Kahn et al 1998), but NPAA provides a better model of chronic RPN free of gastrointestinal toxicity (Hardy and Bach 1984; Thanh et al 2001; Williams 2003). Further, RPN induced by NPAA after repeated dosing is considered more representative of drug-induced RPN than the very acute effect resulting from administration of the widely used 2-bromoethanamine.…”

Renal Papillary Necrosis—40 Years On

“…The morphological and histochemical changes (8,15,19,82,85) support distinct pathological changes following a papillotoxic insult. The primary morphological changes occur in the interstitial cells in acute (13,16,82,85), subchronic (92), and chronic (13) papillary necrosis.…”

“…The lipid staining of epithelial and microvascular cells for neutral lipid appears to be pathognomonic for RPN, as it also occurs in the pig (83), baboon, and marmoset following BEA (Bach and Gregg, unpublished observations) and aspirin-induced (160) RPN. By contrast, chemicals that affect the cortex (e.g., hexachlorobutadiene and cis-platin) do not produce specific localized lipid changes in the medullary epithelial cells (19).…”

“…The earliest change in the papilla was marked pyknosis of the renal medullary interstitial cells at a time when other cells were normal or near normal. Other investigations using lower doses of BEA and shorter time intervals (15,16,19,82,85) were unable to show any role for microvasculature injury in the pathogenesis of RPN. The only microvascular effects seen were platelet adhesion well after interstitial necrosis had occurred.…”

“…Papillary necrosis is associated with the progressive deposition of neutral lipid material in the capillaries, collecting duct, and covering epithelial cells. Lipid staining extends into the outer medulla that would appear as normal by routine staining (15,16,19). The lipid staining of epithelial and microvascular cells for neutral lipid appears to be pathognomonic for RPN, as it also occurs in the pig (83), baboon, and marmoset following BEA (Bach and Gregg, unpublished observations) and aspirin-induced (160) RPN.…”

Biomarkers of Collecting Duct Injury in Han-Wistar and Sprague-Dawley Rats Treated with N-Phenylanthranilic Acid

“…N-phenylanthranilic acid (NPAA) is a biphenyl analogue of fenamic acid and chloride channel blocker that causes renal papillary necrosis (RPN) in rats after repeated oral dosing for fourteen days (Williams et al 2003). Animal models of RPN have used agents such as 2-bromethanamine and nonsteroidal anti-inflammatory drugs including cyclooxygenase inhibitors (Bach and Bridges 1985a; Bach and Bridges 1985b; Bach et al 1991; Bach and Nguyen 1998; Kahn et al 1998), but NPAA provides a better model of chronic RPN free of gastrointestinal toxicity (Hardy and Bach 1984; Thanh et al 2001; Williams 2003). Further, RPN induced by NPAA after repeated dosing is considered more representative of drug-induced RPN than the very acute effect resulting from administration of the widely used 2-bromoethanamine.…”

Renal Papillary Necrosis—40 Years On

“…The morphological and histochemical changes (8,15,19,82,85) support distinct pathological changes following a papillotoxic insult. The primary morphological changes occur in the interstitial cells in acute (13,16,82,85), subchronic (92), and chronic (13) papillary necrosis.…”

“…The lipid staining of epithelial and microvascular cells for neutral lipid appears to be pathognomonic for RPN, as it also occurs in the pig (83), baboon, and marmoset following BEA (Bach and Gregg, unpublished observations) and aspirin-induced (160) RPN. By contrast, chemicals that affect the cortex (e.g., hexachlorobutadiene and cis-platin) do not produce specific localized lipid changes in the medullary epithelial cells (19).…”

“…The earliest change in the papilla was marked pyknosis of the renal medullary interstitial cells at a time when other cells were normal or near normal. Other investigations using lower doses of BEA and shorter time intervals (15,16,19,82,85) were unable to show any role for microvasculature injury in the pathogenesis of RPN. The only microvascular effects seen were platelet adhesion well after interstitial necrosis had occurred.…”

“…Papillary necrosis is associated with the progressive deposition of neutral lipid material in the capillaries, collecting duct, and covering epithelial cells. Lipid staining extends into the outer medulla that would appear as normal by routine staining (15,16,19). The lipid staining of epithelial and microvascular cells for neutral lipid appears to be pathognomonic for RPN, as it also occurs in the pig (83), baboon, and marmoset following BEA (Bach and Gregg, unpublished observations) and aspirin-induced (160) RPN.…”

Biomarkers of Collecting Duct Injury in Han-Wistar and Sprague-Dawley Rats Treated with N-Phenylanthranilic Acid

“…N-phenylanthranilic acid (NPAA) is a biphenyl analogue of fenamic acid and chloride channel blocker that causes renal papillary necrosis (RPN) in rats after repeated oral dosing for fourteen days (Williams et al 2003). Animal models of RPN have used agents such as 2-bromethanamine and nonsteroidal anti-inflammatory drugs including cyclooxygenase inhibitors (Bach and Bridges 1985a; Bach and Bridges 1985b; Bach et al 1991; Bach and Nguyen 1998; Kahn et al 1998), but NPAA provides a better model of chronic RPN free of gastrointestinal toxicity (Hardy and Bach 1984; Thanh et al 2001; Williams 2003). Further, RPN induced by NPAA after repeated dosing is considered more representative of drug-induced RPN than the very acute effect resulting from administration of the widely used 2-bromoethanamine.…”