Fungal granulomatous interstitial nephritis presenting as acute kidney injury diagnosed by renal histology including PCR assay
A 23-year-old Japanese man was admitted to another hospital for a severe bronchial asthma attack. The patient had a medical history of asthma for more than 10 years; however, no medication had been prescribed. On the day of admission, as his respiratory status worsened, he was intubated and mechanical ventilation was started. Methylprednisolone pulse therapy (1 g/day for 3 days) was administered. Two weeks after admission, the patient's renal function deteriorated and hemodialysis was initiated. Abdominal CT demonstrated enlargement of both kidneys. At the same time, the patient's body temperature rose to 37.5°C. Antifungal therapy (fluconazole, 400 mg on alternate days) was started because C. albicans was detected by blood culture. One month after admission, the patient was transferred to our hospital.\nPhysical examination showed a body temperature of 38.0°C and blood pressure of 133/66 mmHg. Coarse crackles were auscultated in both lungs. Eye examination showed no endophthalmitis and no abnormalities of fundus. Laboratory results were: creatinine, 3.0 mg/dL (265 µmol/L); serum albumin, 1.3 g/dL (13 g/L); and CRP, 13.8 mg/dL. The white blood cell count was 17.7 × 103/µL (17.7 × 109/L) with 72% neutrophils. The hemoglobin level was 7.1 g/dL (71 g/L). The serum level of β-d-glucan was high (>1200 pg/mL), and a titer of Candida antigen was positive. Urinalysis showed 3 (+) proteinuria, too many red blood cells/high-power field and 50–99 white blood cells/high-power field. Abdominal CT showed markedly enlarged kidneys bilaterally. Chest X-ray demonstrated diffuse consolidations and pleural effusions in both lungs. Echocardiography revealed no valvular abnormalities, including vegetation. Sputum and blood cultures were positive for P. aeruginosa. Antibiotics (imipenem/cilastatin, 0.25 g/day) were started. The antifungal medication was changed from fluconazole to amphotericin B because of prolonged elevation of β-d-glucan (>1200 pg/mL). One month after admission, the patient was withdrawn from mechanical ventilation. Despite improvement of the pulmonary infection, the decline in renal function and elevation of β-d-glucan continued. Two months after admission, CT showed multiple low-density areas in both kidneys. Scintigraphy with gallium citrate Ga67 showed strong radionuclide uptake in both kidneys. These findings were considered multiple renal abscesses. Three months after admission, we decided to perform bilateral nephrectomy because eradication of organisms was regarded impossible without the removal of the whole tissue.\nMacroscopic inspection of the patient's removed kidneys found multiple abscesses, mainly in the subcapsular cortical area. Microscopic examination revealed severe interstitial cell infiltration and fibrosis with granulomatous formation. Inflammatory cells included lymphocytes, plasma cells and multinucleated histiocytes. Most of the glomeruli were highly collapsed. The GMS stain showed multiple small, rounded, yeast-like features and branching filamentous features in the interstitium, including at the center of the abscess formation ().\nAn appropriate area of formalin-fixed, paraffin-embedded tissue (FFPE) blocks was selected aligned with GMS stain and a 2 mg of segment was excised and minced using a clean disposable scalpel. DNA was extracted using Genomic DNA purification Kit (Qiagen GmbH, Hilden, Germany). The internal transcribed spacer (ITS) region was amplified with the PCR assay using the universal primer set of the ITS region of the fungi []. Nucleotide sequence analysis and a BLAST (Basic Local Alignment Search Tool) search of the European Molecular Biology Laboratory (EMBL) and GenBank® databases revealed 100% homology with T. laibachii in Patient 1 and C. albicans in Patient 2.