Adenovirus Infection as a Cause of Fever of Unknown Origin and Allograft Dysfunction in a Kidney Transplant Recipient

Abstract

With the recent introduction of more potent modern immunosuppressive regimens in solid-organ transplant, new types of viral infections such as adenovirus are emerging as a potential cause for graft dysfunction and loss. We report a case of 41-year-old male patient with end-stage renal disease from recurrent kidney stones who underwent kidney transplant from a deceased 12-year-old female donor. He developed adenoviral infection with acute cystitis, microscopic hematuria, and necrotizing interstitial nephritis associated with graft dysfunction within the first month of the postoperative period. Diagnosis was made by graft biopsy that showed more than 60% necrosis with tubulointerstitial hemorrhage, thrombotic microangiopathy, and histologic features suggestive of viral infection with negative Cytomegalovirus and polyomavirus stains in the graft and elevated adenovirus PCR in the blood. Simultaneously, the patient had very low absolute total lymphocyte count of 70 cells/μL during which he received supratherapeutic tacrolimus at whole blood trough levels and mycophenolate mofetil. This prompted the tapering of immunosuppression and the discontinuation of all antimicrobial drugs. Within a 2-week period, the immune reconstitution was sufficient for the clearance of the infection and the subsequent gradual recovery of graft function.

Cistitis hemorrágica por adenovirus en trasplante renal: revisión epidemiológica y resultados clínicos

“…La incidencia es entre el 3 y el 5 % aproximadamente. Generalmente se presenta en el primer año, con mayor incidencia entre el segundo y el tercer mes, pero puede presentarse hasta varios años posteriores [6,10]. En un estudio de cohorte retrospectiva, el ADV fue el causante de infección en 24 (3,2 %) de 751 pacientes receptores de trasplante renal, y en 21 (87,5 %) de ellos su presentación clínica fue la cistitis hemorrágica [11].…”

“…Las especies A, B, C, D y E circulan en todo el mundo, sin embargo, más de la mitad de los serotipos de ADV se detectan con poca frecuencia y solo un tercio están asociados con enfermedades humanas [5]. La infección por ADV puede tener un curso clínico que va desde un cuadro asintomático hasta un compromiso sistémico [6]. La incidencia en pacientes trasplantados renales es de aproximadamente un 4,8 %.…”

Literature review of allograft adenovirus nephritis and a case presenting as mass lesions in a transplanted kidney without symptoms of urinary tract infection or acute kidney injury

“…It is speculated that enhanced CT is not considered to be a proper diagnostic tool because most AdVN cases have hemorrhagic cystitis and AKI, which are the strongest clues for diagnosis. However, there may be a tendency in AdVN cases to form focal lesions with hypoperfusion 10‐13 . These lesions can be misdiagnosed as infarcts, abscesses, malignant tumors (especially PTLD), and acute focal bacterial nephritis (AFBN) (so‐called acute lobar nephritis (ALN)) 3 .…”

Disseminated Adenovirus Infection After Combined Liver-Kidney Transplantation

“…We report a case of disseminated HAdV type 21 infection presenting 5 months after combined liver-kidney transplantation. Symptomatic HAdV infections are infrequently reported in adult SOT recipients (Hofland et al, 2004 ; Ison, 2006 ; Kozlowski et al, 2011 ; Storsley and Gibson, 2011 ; Sujeet et al, 2011 ; Dawood et al, 2014 ; Lachiewicz et al, 2014 ; Klein et al, 2015 ; Mehta et al, 2015 ; Saliba et al, 2017 ). An exception to this is the lung transplant population in whom community acquired asymptomatic viremia secondary to HAdV are not infrequent (Humar et al, 2006 ; Bridevaux et al, 2014 ), likely due to the uniqueness of the graft being in direct exposure to the outside environment.…”

“…The natural course of the disease and the severity of the infection are variable. Graft dysfunction and loss can occur (Storsley and Gibson, 2011 ; Sujeet et al, 2011 ; Saliba et al, 2017 ), but data regarding the impact of HAdV on rejection are inconsistent. Fatality rates in disseminated disease in SOT range from 11 to 50% (Echavarría, 2008 ).…”