Aristolochic Acid Nephropathy
Shane M. Meehan, MBBCh
Key Facts
Terminology
Progressive tubulointerstitial nephropathy and urothelial carcinoma related to aristolochic acid in herbal remedies
Etiology/Pathogenesis
Patients give history of intake of herbal preparations containing aristolochic acid for weight loss
Severity of renal injury is dose dependent
Microscopic Pathology
Early lesions have acute tubular injury with interstitial myxoid change and scattered mononuclear cell infiltrates
Late interstitial fibrosis tends to be paucicellular and most pronounced in outer cortex
Papillary urothelial carcinoma may arise in pelvis, ureter, or bladder
 Early features of aristolochic acid nephropathy include acute tubular injury, early tubular atrophy, and diffuse fine interstitial fibrosis with little inflammation. Glomeruli are spared. |
 Tubules are shrunken, and there is widening of the interstitial compartment with myxoid matrix accumulation and characteristically minimal infiltrate of mononuclear cells. |
TERMINOLOGY
Abbreviations
Aristolochic acid nephropathy (AAN)
Synonyms
Chinese herb nephropathy
Definitions
Tubulointerstitial nephropathy and urothelial carcinoma associated with exposure to aristolochic acid in herbal remedies
ETIOLOGY/PATHOGENESIS
Plant-derived Toxin from Genus Aristolochia
Used in traditional Chinese, Indian, and European medical preparations
Aristolactams derived from reduction of aristolochic acid (AA) bind adenine and guanine residues on DNA, forming DNA-adducts
Proximal tubule is most affected in animal models of disease
AA-related DNA adducts cause activation of H-ras and p53, and may be important in carcinogenesis
A:T → T:A transversions are signature mutations of p53 from exposure to AA
Severity of renal injury is dose dependent
Cumulative intake of > 100 grams is associated with chronic renal failure
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