PMC8476786_01
Clinical history of the patient. CG-eGFR, estimated glomerular filtration rate by the Cockcroft-Gault; KT, kidney transplantation; IS, immunosuppressant; Tac, tacrolimus; MMF, mycophenolate mofetil; PRED, prednisone; EC-MPS, mycophenolate sodium enteric-coated tablets; CsA, cyclosporine; BKPyV, BK polyomavirus; UTI, urinary tract infection.
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F1
And the postoperative glomerular filtrate rate (GFR) was summarized in Figure 1. Biopsy of the graft kidney and bladder lesions revealed cryptococcal granulomas, with cystoscopy results provided in Supplementary Figure 1.
FDG-FDG-PET/CT images. Full-body PET-maximum intensity projection (MIP) (D1-4, H1-4) show several space-occupying hypermetabolic lesions; they also indicate the positions (magenta arrows) of the slice shown (A1-4, B1-4, C1-4, and E1-4, F1-4, G1-4, respectively); an axial CT image (A1-4 and E1-4, respectively), axial PET image (B1-4 and F1-4, respectively), and axial FDG-PET/CT fusion image (C1-4 and G1-4, respectively) from a single plane show a mass of hypermetabolic lesions in the transplanted kidney and bladder respectively; the largest of which (A1-2, B1-2, and C1-2, red arrows), ~4.3 x 4.9 x 4.1 cm and 6.0 x 4.0 x 4.7 cm in size, with maximal standardized uptake value (SUVmax) of 20.3 and 31.0 and average standardized uptake value (SUVave) of 8.8 and 17.4 respectively; the largest of which (E1-3, F1-3, and G1-3, red arrows), ~4.7 x 4.1 x 5.5 cm, 3.8 x 2.3 x 3.6 cm, and 2.8 x 1.4 x 2.5 cm in size, with SUVmax of 21.9, 21.4, and 6.4 and SUVave of 8.7, 8.9, and 4.3 respectively.
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FDG-PET/CT examination in August 2019 showed that although the area of bladder lesion was significantly reduced from 4.7 x 4.1 x 5.5 cm to 3.8 x 2.3 x 3.6 cm, the lesion in the transplanted kidney was enlarged from 4.3 x 4.9 x 4.1 cm to 6.0 x 4.0 x 4.7 cm, with the cryptococcoma and malacoplakia in the upper pole of the transplanted kidney protruding into the adjacent Gerota's fascia (Figures 2A2-H2). Fluconazole was given at 100 mg BID against cryptococcal infection while the anti-Escherichia coli as well as the anti-tuberculosis regimen was maintained, as described in Phase I. After 2 months, a follow-up FDG-PET/CT showed that the lesions in the urogenital system and lung were significantly reduced compared with the last examination (Figures 2A3-H3). Six months post-transplant nephrectomy, the lesions in the genitourinary system were eventually eliminated (Figures 2A4-H4). Cryptococcus neoformans JEC21 (ATCC@96910) in vitro, the Cryptococcus counts in the control group (without E. coli filtrate) and the experimental group (adding 80, 160, 320, 640, and 1,280 mul E. coli filtrate, respectively) were respectively 2.46 +- 0.52 x 105/mL, 2.30 +- 0.57 x 105/mL, 2.83 +- 0.72 x 105/mL, 3.13 +- 0.76 x 105/mL, 3.09 +- 0.61 x 105/mL, and 2.60 +- 0.63 x 105/mL. Comparison between the control group and the experimental Group III (320 mul E. coli filtrate) and Group IV (640 mul E. coli filtrate) showed a statistically significant difference (P < 0.05) (Supplementary Figure 2), indicating that E. coli at these concentrations may stimulate cryptococcal growth.
Pathology of the masses of the transplanted kidney, and gross photograph of the allograft nephrectomy specimen. Periodic acid-Schiff staining and Grocott methenamine silver staining of renal mass at 100 x (A,C) and at 1,000 x (B,D) show granuloma caused by Cryptococcus (arrows). Electron microscopy of renal mass (E) shows the Cryptococcus (arrow). (F) Renal cryptococcoma (black arrow) and enlarged renal crptococcoma (white arrow).
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Based on the imaging and pathological findings, the patient was diagnosed with cryptococcoma and malacoplakia of the genitourinary system including transplanted kidney, bladder, prostate and seminal vesicles (Figures 2A1-H1 and Figure 3), accompanied by an UTI of E. coli. After 2 months, a follow-up FDG-PET/CT showed that the lesions in the urogenital system and lung were significantly reduced compared with the last examination (Figures 2A3-H3). Six months post-transplant nephrectomy, the lesions in the genitourinary system were eventually eliminated (Figures 2A4-H4). Another 5.0 x 2.5 x 2.5 cm yellow mass was found in the hilar sinus fat (Figure 3F). The pathological changes of the transplanted kidney lesions were consistent with Cryptococcus infection (Figures 3A-E).