Visual Abstract
Keywords: transplantation
Case Description
A 30-year-old man with a medical history of presumed IgA nephropathy (IgAN) subjected to a five-antigen mismatched deceased donor kidney transplant 6 years ago was brought to our emergency department in an acute confusional state progressing over the past week. His maintenance immunosuppressive regimen consisted of prednisolone (5 mg/d), mycophenolic acid (MPA) (540 mg/twice daily), and tacrolimus (TAC) (trough levels in the previous 6 months of 6 ng/ml). Since transplantation, his allograft function had been stable with an estimated glomerular filtration rate of 60 ml/min per 1.73 m2.
On emergency department admission, blood analysis revealed a mild elevation of C-reactive protein (30 mg/L) and brain magnetic resonance imaging (Figure 1) displayed multiple white matter lesions, raising a suspicion of central nervous system infection. After collecting blood and cerebrospinal fluid samples for microbiologic study, empirical treatment with ceftriaxone plus ampicillin plus acyclovir was initiated, MPA was interrupted, and TAC was reduced to target trough levels of 4–5 ng/ml. However, because of lack of clinical improvement and failure to identify any infectious, autoimmune, or malignant process, brain biopsy was performed (Figure 2). Only a positive Nocardia PCR assay in the cerebral tissue was diagnostic.
Figure 1.
Brain magnetic resonance imaging. Axial T2 image reveals multiple supratentorial hyperintense tumefactive lesions. A possible infectious etiology was raised.
Figure 2.
Histological findings observed in the brain biopsy. (A) White matter with diffuse inflammatory infiltrate mainly composed of macrophages with xanthelasmized cytoplasm, focally with perivascular aggregation. Scattered reactive astrocytes with dense cytoplasm were identified (arrow) (hematoxylin and eosin staining, 200×). (B) Immunohistochemistry for CD68 highlighting the macrophagic inflammatory infiltrate. (C) Glial fibrillary acidic protein immunohistochemistry stained scattered reactive astrocytes with wide dense cytoplasm.
Immediately after cotrimoxazole plus imipenem introduction, clinical and radiologic improvement was noted. Unfortunately, after 2 months of reduced immunosuppressive therapy, de novo anti-HLA donor-specific antibodies were detected with an magnetic resonance imaging over 8000 units and allograft biopsy revealed recurrent IgAN with crescents and probable active humoral rejection. No rescue immunosuppressive treatment was attempted because of the risk of exacerbating the serious underlying infection. After 2 months of intravenous antimicrobial therapy, the patient was discharged on chronic hemodialysis.
Discussion
Typically occurring in the first year after transplantation, nocardiosis is an opportunistic disease with a mortality rate of approximately 20%.1,2 Except for TAC use, this case is highlighted by the young age at presentation and the absence of prior rejection episodes or cytomegalovirus infection, which are well-known risk factors of severe disease.2
Although a positive microbiological culture from the infected site remains the gold standard method to establish nocardiosis, the recent use of PCR-based assays has facilitated faster diagnosis and species identification.1,3
Cotrimoxazole is the first-line therapy for disease management; however, successful treatment also requires immunosuppression adjustments, particularly in severe cases.1 Similar to other post-transplant infections, where a profound reduction of immunosuppression is linked to a higher incidence of an alloimmune phenomenon,4 in our case, we hypothesize that the humoral alloimmune response triggered by TAC reduction and MPA suspension may have been a risk factor of clinically significant IgAN recurrence and graft loss.5
Teaching Points
Nocardiosis can cause life-threatening complications in kidney transplant recipients. Although typically described in the first year, it can occur later after transplantation, particularly in patients with risk factors.
Tissue biopsies of the affected organs are frequently required to confirm the diagnosis and facilitate timely initiation of antibiotherapy.
Antibiotic-related toxicity and immunosuppression adjustments associated with the treatment of this entity can lead to graft loss.
Acknowledgments
A special acknowledgment to Dr. Luís Albuquerque from the neuroradiology department of Centro Hospitalar de São João and Dr. Jorge Pinheiro from the pathology department of Centro Hospitalar e Universitário de São João for their image support.
Informed consent was obtained from the patient.
Disclosures
All authors have nothing to disclose.
Funding
None.
Author Contributions
Writing – original draft: Adriana Santos.
Writing – review & editing: Manuela Bustorff, Ana Rocha.
References
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