A Case of Death Due to Rapidly Progressive Multiple Liver Tumors and Multiple Lung Tumors 13 Years After Living Donor Kidney Transplantation.

A 54-year-old woman had been taking a Hong Kong–manufactured Chinese herbal medicine (Longdan Xiegan Tang) for atopic dermatitis for approximately five years since X–26. In January of X–20, she had appeared sudden onset of lower extremity edema, and she had a medical examination in our hospital. She had be detected proteinuria, microscopic hematuria,  and her serum creatinine level was1.5 mg/dL.  Therefore, it was performed renal biopsy, and she was diagnosed tubulointerstitial nephritis. and based on her past intake of Chinese herbal medicine, the cause of her renal impairment was diagnosed Chinese herbs nephropathy (aristolochic acid nephropathy). Her renal function gradually declined, and started hemodialysis in X–14. In X–13, she was received kidney transplantation with her mother as the donor. After transplantation, her serum creatinine level remained stable at around 0.9–1.0 mg/dL. However, after transplantation, she consistently refused routine systemic examinations, and follow-up was performed without general checkups.

In X year Y-1 month, her appetite has decreased, and in Y month, her body temperature rose to 38°C. On Y month Z day, she presented to our hospital, and mild hepatic impairment and elevating inflammatory markers (CRP 6.77 mg/dL) were noted. Initially, however at a follow-up visit on Z+7 day, her CRP had further increased to 11.51 mg/dL, therefore she was hospitalized for medication and further evaluation and management.

Contrast-enhanced CT on admission demonstrated multiple ring-enhancing hepatic lesions, enlargement of the right renal cyst, progression of hydronephrosis, and irregular wall thickening of the right renal pelvis. MRI showed multiple nodules in the dilated renal pelvic wall and a well-defined low-intensity lesion at the L2 vertebral body. Gallium scintigraphy revealed uptake in the L2 vertebral body and patchy uptake in the liver. She received drainage of right renal cyst, however no bacteria were detected, and the cytology was negative. From the foregoing, it seems that there is some form of malignant tumor, and multiple organ metastases are suspected, however the primary site was unknown. Therefore, to identify the primary site, a liver biopsy was performed on day 14, and a definitive diagnosis of urothelial carcinoma with metastasis was made. Her condition deteriorated rapidly, and she died on hospital day 24. Autopsy revealed atypical cells infiltrating from the cyst wall into the native renal parenchyma, as well as a tumor composed of proliferating atypical cells in the right ureter. These findings confirmed the diagnosis of urothelial carcinoma of the right ureter with multiple metastases.

Because aristolochic acid involved in the onset of both interstitial renal fibrosis urothelial carcinoma in general, the right ureter carcinoma of this case was considered to be related to aristolochic acid taken in the past. We experienced a case of a woman who died of rapidly progressive urothelial carcinoma, diagnosed 13 years after living-donor kidney transplantation, initially presenting with multiple liver and lung tumors. Moreover, it was thought to be caused by herbal medicine taken long ago, and carcinoma was thought to have triggered immunosuppressants taken due to kidney transplantation. We report this instructive case with a review of the literature.