(See also Overview of Tubulointerstitial Diseases Overview of Tubulointerstitial Diseases Tubulointerstitial diseases are clinically heterogeneous disorders that share similar features of tubular and interstitial injury. In severe and prolonged cases, the entire kidney may become... read more .)
Analgesic nephropathy, a type of chronic interstitial nephritis Chronic tubulointerstitial nephritis Tubulointerstitial nephritis is primary injury to renal tubules and interstitium resulting in decreased renal function. The acute form is most often due to allergic drug reactions or to infections... read more , was originally described in conjunction with overuse of combination analgesics containing phenacetin (typically with aspirin, acetaminophen, codeine, or caffeine). However, despite removal of phenacetin from the market, analgesic nephropathy continued to occur. Studies to identify the causal agent are equivocal, but acetaminophen, aspirin, and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been implicated. Mechanism is unclear. Whether cyclooxygenase-2 (COX-2) inhibitors cause analgesic nephropathy is not known, but these drugs probably can cause acute tubulointerstitial nephritis and nephrotic syndrome due to minimal change disease Minimal Change Disease Minimal change disease causes abrupt onset of edema and heavy proteinuria, mostly in children. Renal function is typically normal. Diagnosis is based on clinical findings or renal biopsy. Prognosis... read more or membranous nephropathy Membranous Nephropathy Membranous nephropathy is deposition of immune complexes on the glomerular basement membrane (GBM) with GBM thickening. Cause is usually unknown, although secondary causes include drugs, infections... read more .
Analgesic nephropathy predominates in women (peak incidence, 50 to 55 years) and, in the US, is responsible for 3 to 5% of cases of end-stage renal disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more (13 to 20% in Australia and South Africa).
Patients present with kidney injury and usually non-nephrotic proteinuria with a bland urinary sediment or sterile pyuria. Hypertension, anemia, and impaired urinary concentration are common once renal insufficiency develops.
Flank pain and hematuria and passage of a renal papilla (causing upper urinary tract obstruction) are signs of papillary necrosis that occur late in the course of disease.
Chronic complaints of musculoskeletal pain, headache, malaise, and dyspepsia may be related to long-term analgesic use rather than analgesic nephropathy.
The diagnosis of analgesic nephropathy is based on history of chronic analgesic use and noncontrast CT. CT signs of analgesic nephropathy are the following:
The combination of these findings has a sensitivity of 85% and a specificity of 93% for early diagnosis, but these specificity and sensitivity numbers are based on studies done when use of phenacetin-containing analgesics was widespread.
Renal function stabilizes when analgesics are stopped unless kidney injury is advanced, in which case it may progress to chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more . Patients with analgesic nephropathy are at greater risk of transitional cell carcinomas of the urinary tract.