Kidney Res Clin Pract > Volume 42(2); 2023 > Article
Barrera-Herrera, Gonzalez-Rojas, Perissinotti, Larque, Cofan, Diekmann, and Cucchiari: Rejection of a kidney graft revealed by positron emission tomography
A 66-year-old man with end-stage renal disease due to cryoglobulinemia who was on hemodialysis received a kidney graft from a deceased donor. His prior medical history included human immunodeficiency virus (HIV) treated with dolutegravir and darunavir/cobicistat, past hepatitis C virus infection, and Child-Pugh-A-cirrhosis. Induction was based on basiliximab and maintenance on tacrolimus, mycophenolate, and prednisone. Transplantation was complicated by delayed graft function and irregular tacrolimus level due to antiretroviral interactions, with a final creatinine level of 3.5 mg/dL.
The patient was readmitted 2 months after transplantation for fever and vomiting with coffee-ground-appearing vomit. A diagnosis of urinary tract infection due to resistant Klebsiella pneumoniae was based on isolation of the microorganism both in the blood and urine; this infection was treated with meropenem. A blood analysis showed initial stability of renal function (creatinine, 3.3 mg/dL), low platelets (56,000/mL), leukocytes (5,900/µL), and elevated procalcitonin (11.66 ng/mL) and C-reactive-protein (CRP; 26.65 mg/dL). Urine sediment at admission was one to five red blood cells, leukocytes (20–30/µL), and positive nitrites and proteins (100–150 mg/dL) using test strips. Tacrolimus level was 12.8 ng/mL, and the patient was negative for cytomegalovirus. The results showed a BK virus charge and a nonreplicating HIV viral charge, with a CD4 level of 60 cells/μL. Upper endoscopy revealed esophageal candidiasis and an esophageal ulcer with Epstein-Barr virus replication. In consideration of the sepsis and the potential for opportunistic infections, the mycophenolic acid and tacrolimus were temporally suspended, while the steroid dose was increased.
After an initial improvement on day 10 with negative new blood cultures, the patient’s fever recurred; he became oliguric and required hemodialysis on day 16. While the procalcitonin decreased after antibiotic administration to 0.5 ng/mL on day 18, the CRP value remained elevated (7–13 mg/dL) and was classified as reactant without bacterial inflammation signs. Donor-specific human leukocyte antigen antibodies were not isolated by a Luminex test.
The differential diagnosis based on ultrasound, computed tomography (CT) scanning, and blood cultures was inconclusive, so an 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT scan was performed. It revealed intense and diffuse FDG uptake of the renal parenchyma (maximum standardized uptake value, 12.76), and there were no signs of infectious foci in the remainder of the study (Fig. 1A–C). A kidney biopsy was performed and revealed an acute T cell-mediated rejection of type IIB (Fig. 1D, E). By the time the biopsy was performed, urine sediment was negative for nitrites and bacteriuria, and there also was evidence of leukocyturia resolution, persistent microhematuria, and proteinuria of 150 to 300 mg/dL.
Immunosuppression was restarted with tacrolimus and mycophenolate, and three boluses of 500 mg methylprednisolone were administered without clinical response. Antilymphocyte therapy was not considered due to the general state of the patient, and chronic dialysis was reinitiated.
In conclusion, even though further studies are needed, FDG-PET/CT could have a potential role in the diagnosis of kidney graft rejection as a noninvasive imaging method.

Notes

Conflicts of interest

The authors have no conflicts of interest to declare.

Data sharing statement

The data presented in this study are available on request from the corresponding author.

Authors’ contributions

Conceptualization: ABH, AGR, DC

Data curation: all authors

Methodology: AP, ABL

Writing–original draft: ABH, AGR, AP, ABL

Writing–review & editing: FC, FD, DC

All authors read and approved the final manuscript.

Figure 1.

Relationship between PET/TC image and kidney biopsy result.

Coronal images (A, B) and sagittal images (C) of FDG-PET/CT showing a kidney transplant with intense radiotracer uptake due to biopsy-proven acute rejection. (D) Light microscopy (×40) shows widespread interstitial inflammation in the nonsclerotic cortical parenchyma, which corresponds an i3 Banff Classification. There is an artery in the cross section (center) with active intimal mononuclear cell infiltration (v2) that is accompanied by fibrointimal thickening. In addition, three glomeruli are visible; one normal without glomerulitis and two with global sclerosis. Note the moderate periodic acid-Schiff (PAS)-positive hyaline thickening in one arteriole. (E) Light microscopy showing mononuclear infiltrates in a tubule (tubulitis data T2 foci with 10 leukocytes per tubular cross section; PAS staining, ×100). The Banff Classification score was as follows: artery number, 3; glomeruli number, 6; I 3, t 2, g 0*, ah 1, ptc 0, ti 3 i-IFTA NV aah 1; ci 0, ct 0, cv 1, cg 0, mm 0; C4d (frozen), 0. Diagnosis: a partially representative sample due to the low number of glomeruli. Acute rejection mediated by T cells (grade IIB).
CT, computed tomography; PET, positron emission tomography; FDG, 18F-fluorodeoxyglucose.
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ORCID iDs

Aidana Barrera-Herrera
https://orcid.org/0000-0002-4990-5789

Ángela Gonzalez-Rojas
https://orcid.org/0000-0001-7565-2167

Andrés Perissinotti
https://orcid.org/0000-0003-4190-2425

Ana Belen Larque
https://orcid.org/0000-0002-1492-2116

Frederic Cofan
https://orcid.org/0000-0003-4163-9620

Fritz Diekmann
https://orcid.org/0000-0001-6199-3016

David Cucchiari
https://orcid.org/0000-0002-7594-1070

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