The scarring of the small blood vessels, called capillary sclerosis, is the initial lesion of<unk> . Found in the renal pelvis, ureter, and capillaries supplying the nephrons, capillary sclerosis is thought to lead to renal papillary necrosis and, in turn, chronic interstitial nephritis. How phenacetin and other<unk> s lead to this damage is incompletely understood. It is currently thought that the kidney toxicities of NSAIDs and the antipyretics phenacetin and paracetamol may combine to give rise to<unk> . A committee of investigators reported in 2000 that there was insufficient evidence to suggest that non-phenacetin<unk> s by themselves are associated with<unk> . Aspirin and NSAIDs Proper kidney function depends upon adequate blood flow to the kidney. Kidney blood flow is a complex, tightly regulated process that relies on a number of hormones and other small molecules, such as prostaglandins. Under normal circumstances, prostaglandin E2 (PGE2) produced by the kidney is necessary to support adequate blood flow to the kidney. Like all prostaglandins, PGE2 synthesis depends upon the cyclooxygenases. Aspirin and other NSAIDs are inhibitors of the cyclooxygenases. In the kidney, this inhibition results in decreased PGE2 concentration causing a reduction in blood flow. Because blood flow to the kidney first reaches the renal cortex (outside) and then the renal medulla (inside), the deeper structures of the kidney are most sensitive to decreased blood flow. Thus the innermost structures of the kidney, known as the renal papillae, are especially dependent on prostaglandin synthesis to maintain adequate blood flow. Inhibition of cyclooxygenases therefore rather selectively damages the renal papillae, increasing the risk of renal papillary necrosis. NSAIDs caused no adverse effects on renal function in healthy dogs subjected to anesthesia. Most healthy kidneys contain enough physiologic reserve to compensate for this NSAID-induced decrease in blood flow. However, those subjected to additional injury from phenacetin or paracetamol may progress to<unk> . Phenacetin and paracetamol It is unclear how phenacetin induces injury to the kidney. Bach and Hardy have proposed that phenacetin's metabolites lead to lipid peroxidation that damages cells of the kidney. Paracetamol is the major metabolite of phenacetin and may contribute to kidney injury through a specific mechanism. In cells of the kidney, cyclooxygenases catalyse the conversion of paracetamol into N-acetyl-p-benzoquinoneimine (NAPQI). NAPQI depletes glutathione via non-enzymatic conjugation with glutathione, a naturally occurring antioxidant. With depletion of glutathione, cells of the kidney become particularly sensitive to oxidative damage.
Analgesic nephropathy
Reflux nephropathy
IgA nephropathy
Contrast-induced nephropathy
Diabetic nephropathy
Shunt nephritis
Phosphate nephropathy
Sickle cell nephropathy