Changing concepts in pathogenesis and morphology of analgesic nephropathy as seen in Europe

Abstract

A detailed analysis of 60 autopsy cases of AN is presented. Renal papillary necrosis is the hallmark of AN. Special emphasis is given to early changes in the basement membranes and the ground substance of the renal papilla observed by light and electron microscopy. The "interstitial nephritis" in the renal cortex is secondary to papillary changes. The histologic picture of the cotex is often complicated by bacterial infection and, therefore, is complex. An unusual hyalinization of small vessels beneath the urothelium of the mucosa of the urinary tract, similar to that seen in the inner medullary zone, has been called "analgesic microangiopathy". Its significance is not clear. The renal papillae, the mucosal membranes of the urinary tract, the liver, the cartilages, and the skin often display a striking brownish discoloration caused by a lipid-containing pigment. Statistical data from out autopsies in Switzerland show no decrease in death rates of AN. This is in contrast to reports from Denmark and Sweden where the sale of phenacetin has been restricted by prescription.

Renal Papillary Necrosis—40 Years On

“…2 141 microscopic hematuria, ureteral colic, and lower back pains. It is now agreed that the primary lesion of analgesic abuse is in the medulla, where the "fine elements" such as the interstitial cells, endothelia, and loops of Henle are the earliest affected parts, leading to cortical degeneration and then leading to renal functional compromise and end-stage renal disease (13,32,78), changes that cannot currently be identified noninvasively. Some of the key pathological features include loss of the fine elements of the medulla (interstitial cells and microvasculature), changes in the medullary mucopolysaccharide staining, lipid accumulations as shown by Oil Red 0, tubular dilatation and tubular casts, cortical scarring and glomerular sclerosis (13,32,78).…”

“…There are few clinical symptoms associated with the early development of analgesicassociated RF" (13,32,78,171,203,204). The progression of renal damage is insidious and renal function may be severely compromised before the condition becomes obvious (13,32,78,171,203,204). 2 141 microscopic hematuria, ureteral colic, and lower back pains.…”

“…The progression of renal failure in analgesic-associated nephropathy has been well documented (13,32,47,78,96,142,170,171,203,204). Analgesic nephropathy is a degenerative condition leading to renal failure following long-term analgesic abuse.…”

Enzyme Histochemical Changes in an Acutely Induced Renal Papillary Necrosis

“…The thickening of the ATPase stained areas, to the point where the lumen of the vessel was occluded, suggests that a capillary sclerosis had occurred. A microangiopathy, with a progressive narrowing ofthe capillaries due to basement membrane thickening and the deposit oflipid material, has been described in humans with RPN (12,20,21,25). These changes are thought to be pathognomonic in human analgesic abusers, but have not been reported previously in animal models of RPN (14) and, therefore, warrant further investigation.…”

“…Relatively little is known about the histochemical changes that are associated with the genesis of analgesic-related renal papillary necrosis in man (2). Some studies have shown an increase (7-9) or a decrease (12) in the medullary mucopolysaccharide matrix staining in analgesic abusers. Similar changes have been reported in animals following aspirin-induced RPN (22,23) and treatment with BEA (1).…”