Combination analgesic involvement in the pathogenesis of analgesic nephropathy: the European perspective

Analgesic nephropathy (AN) is a chronic renal disease characterized by renal papillary necrosis and interstitial nephritis caused by excessive consumption of analgesic mixtures. In a recent study, diagnostic criteria for AN, based on a computed tomography scan investigation without contrast, were presented. The observation of a decreased renal mass of both kidneys combined with either bumpy contours or papillary calcifications was found to have a high diagnostic performance. Although several case control studies and two prospective studies demonstrated the association between analgesic abuse and nephropathy, the nephrotoxicity of the different analgesic products had not been clearly established. Analgesic abuse can be defined as a daily consumption of analgesic mixtures over a several-year period. Abuse of single analgesics is rare; it has been clearly demonstrated that abusers prefer analgesic mixtures. In Belgium, the prevalence of AN was positively related to the sales of analgesic mixtures containing two analgesic components plus caffeine and/or codeine. This relationship could not be observed for analgesics containing only one analgesic component plus caffeine and/or codeine. Moreover, during a European multicenter study, nephrotoxicity of different combinations of analgesic mixtures (all containing caffeine and/or codeine) could be documented in the absence of any previous phenacetin consumption. Epidemiologic observations in Sweden, France, and Belgium regarding incidence of AN, sales figures of analgesics, and legislative measurements concerning analgesic consumption supported the previous observations.