18FDG PET/CT imaging of adenovirus‐associated acute interstitial nephritis after allogeneic bone marrow transplantation

Abstract

Key Clinical Message

Adenovirus‐associated acute interstitial nephritis (AAIN) should always be considered in the differential diagnosis of acute kidney failure following allogeneic bone marrow transplant. Although not intended for the definitive diagnosis of AAIN, ¹⁸FDG PET/CT can be a helpful noninvasive diagnostic tool, especially when a biopsy is not feasible.

CASE PRESENTATION

A 49-year-old woman presented with grade III hematuria, flank pain, fever, diffuse skin rash, and painful lumbar percussion 3 months after receiving an allogeneic hematopoietic stem cell transplant (HSCT). At transplant time, she was in first complete remission of an acute myeloid leukemia (AML) of intermediate prognosis. Conditioning regimen was myeloablative, based on total body irradiation. Early complication was acute skin graft-versus-host disease (aGVHD). She had no other relevant medical or family history and no allergies. Her immunosuppressive treatment consisted of mycophenolate mofetil and tacrolimus. At presentation, blood tests showed acute kidney failure (AKF) with creatinine of 3.72 mg/dL and C-reactive protein of 226 mg/dL. Abdominal CT scan without contrast and urinary tract ultrasonography were normal. Viral infection screening (urine and blood) was performed and piperacillin/tazobactam was started (4 g twice daily) until negative culture confirmation. Glucocorticosteroids were also resumed because of aGVHD relapse suspicion. Due to persistent fever and pending quantitative polymerase chain reaction (qPCR) results, ¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (¹⁸FDG PET/CT) was performed as part of the work-up for fever of undetermined origin. It showed corticomedullary thickening associated with bilateral avid ¹⁸FDG uptake within the renal parenchyma (Figure 1A). The qPCRs were finally positive for adenovirus viruria (estimated viral load: 70 × 10⁶ copies/mL) and adenovirus viremia (5 × 10⁶ copies/mL). Among with rapid glucocorticosteroids tapering, cidofovir treatment was initiated (3 mg/kg) once weekly for overall two doses, resulting in rapid and complete symptom resolution, kidney function correction (Table 1), as well as viremia and viruria normalization (Figure 1, lower panel). To exclude other differential diagnoses (e.g., extramedullary relapse of AML), ¹⁸FDG PET/CT was repeated 6 weeks posttreatment, displaying complete morpho-metabolic kidney normalization (Figure 1B).

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TABLE 1 Evolution of C-reactive protein and creatinine levels following treatment with cidofovir.

	Hospital admission	1st 18FDG Pet/CT (A)	2nd dose of cidofovir	2nd 18FDG Pet/CT (B)	3 months follow-up
C-reactive protein (mg/dL)	226	132,3	20,8	1,3	1,0
Creatinine (mg/dL)	3,72	2,36	1,42	1,24	1,05

DISCUSSION

Adenovirus infection following HSCT has an estimated incidence of 0 to 20%.¹ Clinical presentation ranges from asymptomatic viremia to life-threatening disseminated disease. Various organs can be affected, resulting in clinical manifestations of varying severity, including pneumonia, hepatitis and hemorrhagic enteritis or cystitis.¹ Adenovirus-associated interstitial nephritis (AAIN) is well-known following kidney transplantation but has rarely been described after HSCT. Clinical presentation of AAIN is unspecific, consisting of the association of AKF, gross hematuria, flank pain, or fever. Diagnosis of AAIN post-HSCT is challenging and must be considered as part of a broad differential diagnosis, including viral infection, bladder involvement of aGVHD, or extramedullary relapse of AML involving the kidney. Proven diagnosis of adenovirus-organ infection is based on documented adenovirus infection associated with clinical signs or symptoms consistent with the infection and histological documentation of organ involvement.² Probable disease refers to the absence of histological evidence.² Without specific clinical features, laboratory tests, or imaging findings, most cases remain probable in the absence of histological examination. Interestingly, recent cases have highlighted the potential interest of ¹⁸FDG PET/CT in the evaluation of acute interstitial nephritis (AAIN).³ In our case, ¹⁸FDG PET/CT provided an interesting image which, combined with clinical presentation and biological analyses, led to the prompt initiation of effective treatment. Biopsy was initially considered but not performed given the work-up results and favorable evolution with treatment.

AUTHOR CONTRIBUTIONS

G. Jadot: Conceptualization; investigation; resources; writing – original draft. X. Poire: Supervision; validation; writing – review and editing. R. Lhommel: Investigation; writing – review and editing. G. Dachy: Investigation; supervision; validation; writing – original draft; writing – review and editing.

ACKNOWLEDGMENTS

None.

FUNDING INFORMATION

No funding was received regarding the preparation of this manuscript.

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

CONSENT

Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.

References

Cesaro S. Adenovirus infection in allogeneic hematopoietic cell transplantation. Transpl Infect Dis. 2023;25(1): [eLocator: e14173]. doi:10.1111/tid.14173

Matthes‐Martin S, Feuchtinger T, Shaw PJ, et al. European guidelines for diagnosis and treatment of adenovirus infection in leukemia and stem cell transplantation: summary of ECIL‐4 (2011). Transpl Infect Dis. 2012;14(6):555‐563. doi:10.1111/tid.12022

Qualls D, Seethapathy H, Bates H, et al. Positron emission tomography as an adjuvant diagnostic test in the evaluation of checkpoint inhibitor‐associated acute interstitial nephritis. J Immunother Cancer. 2019;7(1):356. doi:10.1186/s40425-019-0820-9