A 58-year-old woman with no history of kidney disease was admitted to our hospital for examination and treatment of kidney dysfunction. She had annual medical check-ups and had a history of dyslipidemia, but was not taking any medication. She had no other significant medical history, family history, or allergies.

About 6 weeks prior to admission, she had started taking cholesterol-lowering supplements containing red yeast rice (Benikoji CholesteHelp®). She took the prescribed dosage of three tablets per day (3 mg of rice red yeast polyketide) and noticed mild fever (37 ℃), nausea, and appetite loss 3 weeks after starting the medication. Therefore, she discontinued the medication 1 month later. After that, she visited a local clinic, where blood tests revealed kidney dysfunction with a serum creatinine (Cr) level of 2.75 mg/dL, and she was referred to our hospital. The examinations in our hospital revealed kidney dysfunction with the levels of serum Cr 1.57 mg/dL, urinary β2-microglobulin (β2MG) 126,473 μg/L, and urinary N-acetyl-β-D-glucosaminidase (NAG) 71.7 IU/L.

Upon admission, the patient weight and height were 45.6 kg and 154.5 cm, respectively. The patient’s blood pressure was 132/92 mmHg, pulse rate was 80 beats/min, and body temperature was 36.6 ℃. Chest, heart, and abdominal findings were unremarkable. Ophthalmological examination indicated no uveitis, and no superficial lymphadenopathies or rashes were observed. The electrocardiogram showed no significant abnormal findings. Computed tomography findings did not suggest any post-renal lesions. Table 1 shows the findings of the hospital admission examination. In the urine test, no hematuria was observed, but proteinuria (1.06 g/day) and leukocyturia (10–19 white blood cells/high-power field) were detected. Urinary β2MG and NAG were 126,473 μg/L and 71.7 IU/L, respectively. The white blood cell counts and hemoglobin levels were 3600 cells/μL and 13.0 g/dL, respectively. There were no elevations in laboratory findings suggestive of allergy, such as eosinophils or IgE. The results of blood biochemistry tests indicated that serum Cr was 1.57 mg/dL (estimated glomerular filtration rate, 27.3 mL/min/1.73 m2). The levels of electrolyte, liver function tests, and blood glucose were within the normal range. Immunological tests for C-reactive protein, myeloperoxidase antineutrophil cytoplasmic antibody, proteinase 3 antineutrophil cytoplasmic antibody, antinuclear antibody, anti-SS-A/Ro antibodies, and anti-SS-B/La antibodies were all negative. A kidney biopsy was performed to investigate the causes of kidney dysfunction. The sample of kidney cortex contained 44 glomeruli, 1 of which showed global sclerosis, and the remaining 43 glomeruli were almost normal. A mild infiltration of inflammatory cells, chiefly composed of lymphocytes and plasma cells, were observed along with a small number of eosinophils in the interstitium of the kidney cortex (Fig. 1). Tubulitis, tubular atrophy, flattened and expanded proximal tubular epithelium with areas of foamy cytoplasm, and interstitial fibrosis were mildly observed. Immunofluorescent staining for IgG, IgA, IgM, C3, and C1q was all negative. Electron microscopy showed no deposits, no thickening or thinning of the basement membrane, and little foot process effacement in glomerulus. These findings were basically consistent with those typically observed in tubulointerstitial nephritis (TIN).

Light microscopic (a–c) and electron microscopic (d) findings of kidney biopsy. a, b A mild infiltration of inflammatory cells, chiefly composed of lymphocytes and plasma cells was observed along with a small number of eosinophils in the interstitium of the kidney cortex (hematoxylin–eosin stain). c Fibrosis in the tubulointerstitium was mild (Masson trichrome stain). d Electron microscopy showed no deposits, no thickening or thinning of the basement membrane, and little foot process effacement in the glomerulus

Based ###on a comprehensive consideration of clinical symptoms, blood, urine, and pathological findings, including the absence of fundoscopic abnormalities, we diagnosed acute TIN. Although kidney function tended to improve after discontinuation of Benikoji CholesteHelp®, the patient was treated with prednisolone, considering the residual inflammation in the tubulointerstitium. Oral prednisolone was started at a dose of 20 mg/day and tapered by 5 mg/day every 2 weeks until discontinuation. Considering the risk of side effects, the treatment was limited to about 2 months, all kidney impairment markers were improved with the prednisolone treatment, and there was no relapse observed even after the discontinuation of prednisolone (Fig. 2).

Clinical course of the patient over a period of 3 months, and serum creatinine and urinary NAG, β2MG, PCR (protein/creatinine ratio), glucose, WBC, and RBC are shown