Medullary Ischaemia in Experimental Analgesic Nephropathy—The Pathogenesis of Renal Papillary Necrosis*

Summary: Medullary blood flow has been assessed in 29 analgesic‐fed rats and nine matched control animals and has been correlated with renal medullary histological changes and tests of glomerular and tubular function. The animals were gavage‐fed a variety of common non‐steroid anti‐inflammatory analgesic compounds over 20 weeks. Medullary perfusion was significantly reduced in analgesic‐fed animals and was further lowered in animals subjected to hypovolaemic shock. Dehydration, however, did not appear to influence medullary blood flow in analgesic‐fed rats. Medullary ischaemia appeared to be the earliest analgesic induced renal damage and developed before histological renal papillary necrosis. Ischaemia correlated with tests of medullary dysfunction — renal concentrating capacity and sodium conservation, but not with tests of glomerular function. On the basis of these findings the pathogenesis of analgesic induced renal papillary necrosis is discussed.