(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). The incidence varied by region (eg, causing up to 10% of cases of end-stage kidney disease in Australia [ 1 References Analgesic nephropathy is chronic tubulointerstitial nephritis caused by cumulative lifetime use of large amounts (eg, ≥ 2 kg) of certain analgesics. Patients present with kidney injury and usually... read more ]), with a female predominance. Since the removal of phenacetin from the market, the incidence of analgesic nephropathy has declined (2 References Analgesic nephropathy is chronic tubulointerstitial nephritis caused by cumulative lifetime use of large amounts (eg, ≥ 2 kg) of certain analgesics. Patients present with kidney injury and usually... read more ). It remains uncertain whether non–phenacetin-containing combination analgesics, including acetaminophen, aspirin, and other nonsteroidal anti-inflammatory drugs (NSAIDs), are still implicated (3 References Analgesic nephropathy is chronic tubulointerstitial nephritis caused by cumulative lifetime use of large amounts (eg, ≥ 2 kg) of certain analgesics. Patients present with kidney injury and usually... read more ). Mechanism is unclear. However, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) may cause acute tubulointerstitial nephritis 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 or 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 .
References
1. Chang SH, Mathew TH, McDonald SP: Analgesic nephropathy and renal replacement therapy in Australia: Trends, comorbidities and outcomes. Clin J Am Soc Nephrol 3(3):768-776, 2008. doi: 10.2215/CJN.04901107
2. Mihatsch MJ, Khanlari B, Brunner FP: Obituary to analgesic nephropathy—An autopsy study. Nephrol Dial Transplant 21(11):3139-3145, 2006. doi: 10.1093/ndt/gfl390
3. Feinstein AR, Heinemann LA, Curhan GC, et al: Relationship between nonphenacetin combined analgesics and nephropathy: A review. Ad Hoc Committee of the International Study Group on Analgesics and Nephropathy. Kidney Int 2000 58(6):2259-64. doi: 10.1046/j.1523-1755.2000.00410.x
Symptoms and Signs of Analgesic Nephropathy
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.
Diagnosis of Analgesic Nephropathy
History of chronic analgesic use
CT
The diagnosis of analgesic nephropathy is based on history of chronic analgesic use and noncontrast CT. CT signs of analgesic nephropathy are the following:
Decreased renal size
Bumpy contours, defined as at least 3 indentations in the normally convex outline of the kidney
Papillary calcifications
The combination of these findings has a sensitivity of 87% and a specificity of 97% for early diagnosis (1 Diagnosis reference Analgesic nephropathy is chronic tubulointerstitial nephritis caused by cumulative lifetime use of large amounts (eg, ≥ 2 kg) of certain analgesics. Patients present with kidney injury and usually... read more ), but these specificity and sensitivity numbers are based on studies done when use of phenacetin-containing analgesics was widespread.
Diagnosis reference
1. Elseviers MM, De Schepper A, Corthouts R, et al: High diagnostic performance of CT scan for analgesic nephropathy in patients with incipient to severe renal failure. Kidney Int 48(4):1316-1323, 1995. doi: 10.1038/ki.1995.416
Treatment of Analgesic Nephropathy
Stopping analgesic use
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.