RESUMO
Functional and morphological changes developed rapidly in rats after the intravenous administration of the organic nephrotoxin p-aminophenol. Proximal intratubular pressure remained close to its mean control value of 14.9 +/- 0.9 mm Hg up to 40 min after injection of the nephrotoxin then rose rapidly over the following 50 min to a maximum of 38.7 +/- 7.4 mm Hg. Distal tubular pressure also rose in the same manner. Renal blood flow remained constant, but GFR fell to 11% of control values while fractional excretion of sodium and water rose 12 and five times, respectively. Morphological changes developed in parallel with the functional changes. They were widespread, varied in intensity from cell to cell, were more severe in the distal third of the proximal convoluted tubule and consisted of cytoplasmic swelling, reduced organelle concentration, reduction or loss of basal infoldings, widening of lateral intercellular spaces, extrusion of bubbles of cell sap into the tubular lumen; brush borders were preserved. No casts were present up to 90 min. Similar results were seen when p-aminophenol was added to the perfusate of the isolated perfused kidney. It is proposed that metabolic and morphological damage leads rapidly to both impairment of proximal tubular sodium reabsorption and increased flow resistance in the cortical collecting system. Both effects contribute to a rise in tubular pressures which oppose glomerular filtration.
Assuntos
Injúria Renal Aguda/induzido quimicamente , Aminofenóis/toxicidade , Necrose Tubular Aguda/induzido quimicamente , Animais , Taxa de Filtração Glomerular/efeitos dos fármacos , Capacidade de Concentração Renal/efeitos dos fármacos , Necrose Tubular Aguda/patologia , Necrose Tubular Aguda/fisiopatologia , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/patologia , Túbulos Renais Proximais/fisiopatologia , Masculino , Microscopia Eletrônica , Natriurese/efeitos dos fármacos , Organoides/efeitos dos fármacos , Perfusão , Pressão , Ratos , Ratos Endogâmicos , Circulação Renal/efeitos dos fármacos , Fatores de TempoRESUMO
The uninephrectomised homozygous Gunn rat is more sensitive than other experimental animals to the nephrotoxic effects of analgesics. Phenacetin derivatives produce severe necrosis of proximal convoluted tubules and aspirin and phenazone renal papillary necrosis. The observations suggest that the components of compound analgesic preparations have separate and complementary nephrotoxic effects, and this is a possible factor contributing to the association of analgesic nephropathy with abuse of such preparations.