Update of aristolochic acid nephropathy in Korea

Abstract

Background/aims: The true incidence of aristolochic acid nephropathy (AAN) is thought to be underestimated because numerous ingredients known or suspected to contain aristolochic acid (AA) are used in traditional medicine in Korea.

Methods: We collected data on cases of AAN since 1996 via a database in Korea. We evaluated the year of AAN development, route to obtaining AA-containing herbal medicine, gender, reason for taking AA-containing herbal medicine, clinical manifestations, histological findings, phytochemical analysis, and prognosis of patients with AAN.

Results: Data on 16 cases of AAN were collected. Thirteen cases developed AAN before and three cases after the prohibition of AA-containing herbal medicine by the Korea Food and Drug Administration. Patients were prescribed AA-containing herbal medicine from oriental clinics or had purchased it from traditional markets. AAN was distributed in all age groups. Young females were most commonly exposed to AA-containing herbal medicine for slimming purposes and postpartum health promotion, while older adults took AA-containing compounds for the treatment of chronic diseases. The most common symptoms presented at hospitalization were nausea and vomiting, and acute kidney injury was accompanied by Fanconi syndrome in almost half of the patients. Phytochemical analysis of AA in herbal medicine was available in six cases. Progression to end stage renal disease (ESRD) was observed in seven patients (43.8%), and five patients (31.3%) had progressed to ESRD within 6 months of diagnosis.

Conclusion: Our report shows that patients were still exposed to AA-containing herbal medicine and that there is a possibility of underdiagnosis of AAN in Korea. A stronger national supervision system of herbal ingredients and remedies in oriental medicine is needed to prevent AAN.

Keywords: Aristolochic acid; Chinese herbal medicine; Renal toxicity.

Figure 1.

Occurrence of aristolochic acid nephropathy (AAN) and routes for obtaining herbal medicine in Korea. (A) Occurrence of AAN over a period of 20 years. (B) Routes for obtaining Chinese herbal remedies. The arrow indicates the year that Korea Food and Drug Administration prohibited AA-containing herbal medicine in Korea.

Figure 2.

Age distribution of patients with aristolochic acid nephropathy (AAN) and reasons for taking herbal medicine. (A) The distribution of AAN patients in each age decade. (B) The reasons for taking Chinese herbal remedies. AAN was most commonly observed in females in the fourth or fifth decade of age.

Figure 3.

Symptoms and diagnosis of aristolochic acid nephropathy patients at initial hospitalization. (A) Initial patient symptoms. (B) Initial patient diagnosis. Note that acute gastrointestinal symptoms were the most common symptoms, and almost 50% of acute kidney injury (AKI) cases were accompanied by Fanconi syndrome (FS). NS, nephrotic syndrome.

Figure 4.

Representative renal histopathologic findings of aristolochic acid nephropathy (AAN). Kidney biopsy was performed in 35-year-old female patient suspected AAN. Her initial estimated glomerular filtration rate was 5.3 mL/min/1.73 m² and she underwent emergent hemodialysis with uremic symptoms. (A) Interstitial inflammatory cell infiltration (H&E, ×400). (B) Severe interstitial fibrosis and tubular atrophy (Trichrome, ×400). (C) Relatively preserved glomeruli (H&E, ×40).