Clinical manifestations and diagnosis of analgesic nephropathy

INTRODUCTION

Analgesic nephropathy is a renal disease characterized by papillary necrosis and chronic interstitial nephritis, and caused by the long-term consumption of analgesic agents [1]. According to one definition, analgesic nephropathy results from the use of combination agents that contain two or more analgesics agents, and usually codeine or caffeine [2]. However, many believe that analgesic nephropathy may result from ingestion of any single analgesic agent that is taken long term [2]. The use of phenacetin, which is no longer available, was particularly associated with analgesic nephropathy [3].

The manifestations, diagnosis, differential diagnosis, and prognosis of analgesic nephropathy are reviewed here. The epidemiology, risk factors, and the associations with urinary tract malignancy and atherosclerotic cardiovascular disease are discussed separately. (See "Risk factors for and pathogenesis of analgesic nephropathy", section on 'Importance of phenacetin' and "Urinary tract malignancy and atherosclerotic disease in patients with chronic analgesic abuse".)

EPIDEMIOLOGY

Analgesic nephropathy used to be one of the more common causes of chronic kidney disease, particularly in Australia and parts of Europe and the United States, but there was a marked decline in prevalence in the 1990s [4]. The decrease in prevalence was likely due to the withdrawal of phenacetin from the market and to legislation that made combined analgesics available only by prescription [5-7]. As an illustrative example, a Swiss autopsy study performed between 2000 and 2002, revealed medullary findings characteristic of analgesic nephropathy in only 0.2 percent of autopsies [5], compared with a prevalence of 3 percent cited by the same group in a study performed in 1983 [8]. It is not clear whether the marked decline in prevalence was due to the withdrawal of phenacetin in 1983, or to subsequent legislation that mandated the requirement for a prescription for combination agents [9].

CLINICAL FEATURES

Clinical manifestations — Most patients who present with analgesic nephropathy are older than 45 years of age [10]. Usually patients have no symptoms and the disease is incidentally detected by laboratory studies that are performed for an unrelated problem and show an elevated creatinine or abnormal urinalysis.

Patients often have a history of chronic headaches or low back pain that leads to the analgesic use. Other common problems include somatic complaints such as malaise and weakness, and a history of peptic ulcer disease that may be related, in part, to aspirin and/or nonsteroidal antiinflammatory drug ingestion [1]. The frequency of reported history varies between studies [1]. In a review of studies from Europe and the United States, headache was present in 35 to 100 percent and gastrointestinal symptoms were reported in 40 to 60 percent of patients [1,11-15].