Vol. 9, No 1, 2002 pp. 1 - 6
UC 616.61-004 616.613-006 616.617-006 616.62-006
ANALGESIC NEPHROPATHY, BALKAN ENDEMIC
NEPHROPATHY AND CHINESE HERBS NEPHROPATHY:
SEPARATE TUBULOINTERSTITIAL KIDNEY DISEASES
ASSOCIATED WITH UROTHELIAL MALIGNANCY
Vladisav Stefanović
Institute of Nephrology and Hemodialysis, Faculty of Medicine, Niš,
Serbia
E-mail: stefan@ni.ac.yu
Summary. 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.
Key words: Analgesic nephropathy, Balkan endemic nephropathy,
Chinese herbs nephropathy, tubulointerstitial kidney disease, urothelial
cancer, analgesic drugs, aristolochic acid, nephrotoxicity
