Analgesic nephropathy

Analgesic nephropathy
Classically caused by mixed analgesics containing phenacetin, analgesic nephropathy was once a common cause of acute kidney injury.
Specialty	Nephrology

Analgesic nephropathy is injury to the

Analgesic nephropathy was once a common cause of kidney injury and end-stage kidney disease in parts of Europe, Australia, and the United States. In most areas, its incidence has declined sharply since the use of phenacetin fell in the 1970s and 1980s.^{[citation needed]}

Presentation

Common findings in people with analgesic nephropathy include headache, anemia, high blood pressure (hypertension), and white blood cells in the urine (leucocyturia, pyuria).^[1] Some individuals with analgesic nephropathy may also have protein in their urine (proteinuria).^[2]

Complications

Complications of analgesic nephropathy include

The scarring of the small blood vessels, called capillary sclerosis, is the initial lesion of analgesic nephropathy.[7] 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.^[8][7]

How phenacetin and other analgesics lead to this damage is incompletely understood. It is currently thought that the kidney toxicities of

NSAIDs caused no adverse effects on renal function in healthy dogs subjected to anesthesia.[11]^[12][13] 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 analgesic nephropathy.^{[citation needed]}

Phenacetin and paracetamol

It is unclear how phenacetin induces injury to the kidney.^[10] Bach and Hardy have proposed that phenacetin's metabolites lead to lipid peroxidation that damages cells of the kidney.^[14]

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).^[15] NAPQI depletes glutathione via non-enzymatic conjugation with glutathione, a naturally occurring antioxidant.^[16] With depletion of glutathione, cells of the kidney become particularly sensitive to oxidative damage.^{[citation needed]}

Diagnosis

Diagnosis is traditionally based on the clinical findings above in combination with excessive analgesic use. Once suspected, analgesic nephropathy can be confirmed with relative accuracy using

Treatment of analgesic nephropathy begins with the discontinuation of analgesics, which often halts the progression of the disease and may even result in normalization of kidney function.[5] In Stage 5 chronic kidney disease patients renal replacement therapy may become necessary.^{[citation needed]}

History

In the 1950s, Spühler and Zollinger reported an association between kidney injury and the chronic use of phenacetin.[21] They noted that chronic users of phenacetin had an increased risk of developing specific kidney injuries, namely renal papillary necrosis and chronic interstitial nephritis. This condition was dubbed analgesic nephropathy and was attributed to phenacetin, although no absolute causative role was demonstrated. With further reports of the increased risk of kidney injury with prolonged and excessive phenacetin use, however, phenacetin was banned in several countries between the 1960s and 1980s.^[20]

As the use of phenacetin declined, so too did the prevalence of analgesic nephropathy as a cause of end-stage kidney disease. Data from Switzerland, for example, demonstrated a decline in the prevalence of analgesic nephropathy among people with end-stage kidney disease, from 28% in 1981 to 12% in 1990.^[4] An autopsy study performed in Switzerland suggested that the prevalence of analgesic nephropathy in the general population has likewise decreased; the prevalence was 3% in 1980 and 0.2% in 2000.^[8]

While these data demonstrate that analgesic nephropathy has been all but eliminated in some regions, in other regions the condition persists. Notably, in Belgium, the prevalence of analgesic nephropathy among people having dialysis was 17.9% in 1984 and 15.6% in 1990.^[22][23] Michielsen and de Schepper suggest that analgesic nephropathy persists among people in Belgium having dialysis not due to non-phenacetin analgesics, but because Belgium accepts a higher proportion of elderly people for dialysis. According to these authors, a greater proportion have analgesic nephropathy because a greater percentage of people in Belgium having dialysis have been exposed to long-term use of phenacetin.^[24]

Terminology

The term analgesic nephropathy usually refers to damage induced by excessive use of combinations of these medications, specifically combinations that include phenacetin. For this reason, it is also called analgesic abuse nephropathy. Murray prefers the less judgmental analgesic-associated nephropathy.^[1] Both terms are abbreviated to the acronym AAN, by which the condition is also commonly known.^{[citation needed]}

References