Analgesic Nephropathy, Balkan Endemic Nephropathy and Chinese Herbs Nephropathy: Separate Tubulointerstitial Kidney Diseases Associated with Urothelial Malignancy

Analgesic nephropathy (AN) was described in 1953 as tubulointerstitial kidney disease associated with chronic abuse of analgetic mixtures. Chinese herbs nephropathy (CHN), another tubulointerstitial kidney disease, on the basis of morphological and clinical grounds, was found similar to Balkan endemic nephropathy (BEN), and a common etiologic agent, aristolochic acid, was suspected. However, several different features of BEN, AN and CHN are demonstrated. Progression to end stage renal disease is much faster in CHN than in AN and BEN. In CHN the fibrotic process is not confined to kidneys only but was extended to renal pelvis and ureter, peritoneal membrane and aortic valve. Kidney atrophy in BEN is symmetric with a smooth outline; in CHN kidneys are asymmetric in 54%, with irregular outline. In CHN extensive fibrosis develops with marked tubular atrophy and disappearance of atrophic tubules. Kidney papillary necrosis is the landmark of AN. Classical AN appears to be markedly less common than 20 years ago. Reduction in exposure to phenacetin and combination preparations, however, has not eliminated AN. The exact prevalence of this disease in various countries all over the world is still unclear fifty years after the original description of this entity. The magnitude of analgesic exposure-related renal disease today is unclear both as a primary cause of disease and as a cofactor of renal disease of known etiology. National studies to evaluate the prevalence of AN among incident ESRD patients, leading to national programs to combat this preventable kidney disease are awaited. Etiology remains the major problem for research in BEN. In BEN the results of molecular biological investigations will allow the discovery of genetic markers of BEN, permitting early detection of BEN-predisposing mutations and identification of susceptible individuals who may be at risk of exposure to the environmental agents. CHN has now been reported in several countries all over the world. Aristolochic acid causes a rapid, progressive tubulointerstitial nephritis and urothelial cancer. There is a trend to speak about the aristolochic acid nephropathy instead of CHN. Aristolochic acid is included in a number of Chinese herbs, and all herbal preparations designated for human use should be subjected to stringent pharmacological and toxicological testing as conventional treatments. On the basis of clinical, morphological and up-to-date etiologic studies AN, CHN and BEN are separate chronic tubulointerstitial kidney diseases, frequently associated with urothelial malignancy.