Severe adenovirus-associated pneumonia complicated by biopsy-evaluated acute kidney injury in an immunocompetent adult: a case report

Abstract

Background

Adenovirus infection is typically self-limited in immunocompetent individuals. Severe adenovirus-associated pneumonia with renal involvement is uncommon and has been predominantly reported in immunocompromised hosts. Acute kidney injury (AKI) during viral infections may occur through inflammatory or tubular mechanisms even in the absence of immune-complex–mediated glomerular disease.

Case presentation

An 18-year-old previously healthy immunocompetent woman presented with severe pneumonia. Upper respiratory tract PCR was positive for adenovirus, while blood and urine cultures were negative. Laboratory findings showed marked systemic inflammation (CRP 256 mg/L; procalcitonin 15 ng/mL). Serum creatinine was elevated to 4.0 mg/dL prior to antibiotic therapy. Urinalysis revealed leukocyturia, microscopic hematuria, and proteinuria below the nephrotic range. Due to severe acute kidney injury at presentation and diagnostic uncertainty, a kidney biopsy was performed. Light microscopy demonstrated preserved glomerular architecture without proliferative or crescentic changes. Immunofluorescence staining was negative for IgG, IgA, IgM, C3, and C1q. Mild tubular alterations, including focal granular-hyaline casts, were observed, without specific vascular pathology. Overall findings were compatible with infection-associated acute kidney injury. Mini-pulse corticosteroid therapy and empirical broad-spectrum antibiotics were administered. Renal function subsequently improved, with complete recovery during hospitalization.

Conclusion

Severe adenovirus-associated pneumonia may be complicated by acute kidney injury even in immunocompetent adults. In the absence of immune-complex deposition or overt glomerular pathology, renal dysfunction may reflect infection-associated tubular injury or systemic inflammatory mechanisms.

Introduction

Adenovirus infections are generally mild and self-limited in immunocompetent adults [1]. Severe pulmonary involvement is uncommon and occurs more frequently in immunocompromised individuals and transplant recipients [2]. Renal complications associated with adenovirus are rare and have been described predominantly in immunosuppressed populations [3].

Acute kidney injury (AKI) during viral infections may result from multiple mechanisms, including systemic inflammatory response, hemodynamic alterations, or tubular injury. Immune-complex–mediated glomerular disease is uncommon in adenovirus infection, particularly in immunocompetent adults. Reports describing biopsy-evaluated renal involvement in this population remain limited [4].

Here, we describe a case of severe adenovirus-associated pneumonia complicated by biopsy-evaluated acute kidney injury in a previously healthy woman.

Case presentation

An 18-year-old previously healthy woman with no history of chronic disease, immunodeficiency, or regular medication use was admitted with progressive dyspnea, cough, and intermittent hemoptysis. Approximately one week before admission, the patient developed progressive dyspnea and cough. A few days later, intermittent hemoptysis occurred, and she subsequently presented to the emergency department. On admission, the patient was dyspneic and tachypneic, with an oxygen saturation of 88%, heart rate of 130 beats/min, and blood pressure of 140/128 mmHg. Arterial blood gas analysis showed metabolic acidosis with pH 7.22, pCO₂ 28 mmHg, bicarbonate 11.5 mmol/L, and lactate 10 mmol/L. She required nasal oxygen support, but did not require inotropic support or invasive mechanical ventilation. Chest computed tomography demonstrated bilateral multifocal ground-glass opacities, consolidative lesions, multiple nodular cavitary lesions, and loculated left pleural effusion, radiologically compatible with severe pneumonia (Fig. 1).

Fig. 1.

Chest imaging findings in severe adenovirus-associated pneumonia. (A) Axial chest computed tomography showing bilateral multifocal nodular consolidative lesions, some with cavitary appearance, and loculated left pleural effusion. (B) Chest radiography demonstrating bilateral pulmonary infiltrates and prominent left-sided pleural/parenchymal opacity

A comprehensive respiratory PCR panel was performed using an upper respiratory tract/nasopharyngeal swab sample. SARS-CoV-2 (COVID-19), influenza A/B, respiratory syncytial virus, parainfluenza virus, and other common respiratory pathogens were negative; adenovirus was the only detected pathogen. The respiratory PCR panel included common respiratory viral pathogens and atypical respiratory agents. Bacterial and fungal etiologies were evaluated separately using blood, urine, and pleural fluid cultures, cytological examination, and fungal staining. Blood and urine cultures were also negative. Alternative infectious etiologies were also investigated. In particular, mycobacterial infection was considered in the differential diagnosis because of the nodular cavitary pulmonary lesions; however, sputum acid-fast bacilli testing and QuantiFERON-TB testing did not support tuberculosis. Given the patient’s young age and severe clinical presentation, Legionella urinary antigen testing was also performed and was negative. Bronchoalveolar lavage was performed later during the clinical course as part of the extended pulmonary evaluation, but it was not the source of adenovirus PCR. Because of loculated pleural effusion, percutaneous pleural drainage was performed; the aspirated pleural fluid was purulent, and cytological examination showed dense bacterial clusters, whereas fungal staining was negative. Pleural fluid culture showed no growth.

Laboratory evaluation revealed marked systemic inflammation (C-reactive protein 256 mg/L; procalcitonin 15 ng/mL). At admission, serum creatinine was elevated to 4.0 mg/dL from previously normal baseline levels. Notably, renal dysfunction developed prior to the initiation of antibiotic therapy. Urinalysis demonstrated leukocyturia (7 leukocytes per high-power field), microscopic hematuria (5 erythrocytes per high-power field), and proteinuria below the nephrotic range (860 mg/24 h), without clinical features suggestive of primary glomerular disease. No overt oliguria was documented during hospitalization, and urine output remained preserved during clinical follow-up. Urinary tract imaging showed normal-sized kidneys without collecting system dilatation, hydronephrosis, or urinary tract stones. Intravesical hematoma or clot retention was not documented. There was no evidence of post-renal acute kidney injury.

A percutaneous kidney biopsy was performed during the first week of hospitalization, after partial clinical stabilization, because severe AKI at admission was accompanied by microscopic hematuria, leukocyturia, subnephrotic proteinuria, hemoptysis, and marked systemic inflammation. Although serum creatinine had already begun to improve by the time of biopsy, the underlying renal mechanism remained uncertain; therefore, biopsy was pursued to exclude glomerulonephritis, vasculitis, thrombotic microangiopathy, interstitial nephritis, or obstructive cast-related pathology. Light microscopy demonstrated preserved glomerular architecture without proliferative, necrotizing, or crescentic lesions. The biopsy contained up to 17 glomeruli, all showing preserved architecture. In the medullary area, a small number of tubules contained hematoxylinophilic granular amorphous material and hyaline casts, involving approximately < 5% of the sampled tubules. No granuloma formation, immune-complex deposition, or specific vascular pathology was identified. Congo red staining was negative for amyloid deposition. Immunofluorescence staining was negative for IgG, IgA, IgM, C3, C1q, fibrinogen, kappa, and lambda light chains. Overall, the findings were compatible with infection-associated acute kidney injury with limited tubular cast formation/tubular injury (Fig. 2.A/B).

Fig. 2.

(A) Light microscopy showing renal cortical tissue with preserved glomerular architecture. (B) Light microscopy demonstrating a small number of tubules containing granular/hyaline casts. No granuloma formation, immune-complex deposition, amyloid deposition, or specific vascular pathology was identified. Periodic acid–Schiff stain; scale bars: 100 μm and 200 μm

The initial severity of presentation, including hypoxemia, marked systemic inflammation, metabolic acidosis, cavitary nodular pulmonary lesions, purulent loculated pleural effusion, and a high National Early Warning Score (NEWS), supported early escalation of empirical antimicrobial therapy. Although the patient was immunocompetent, the radiological appearance and pleural findings raised concern for severe bacterial pneumonia, empyema, atypical infection, or culture-negative coinfection [5]. Therefore, broad-spectrum antimicrobial therapy was administered according to infectious disease recommendations during the early critical phase. Vancomycin 1 g every 24 h and meropenem 500 mg twice daily were initiated initially and were dose-adjusted after improvement in renal function. Levofloxacin 750 mg/day, doxycycline 100 mg twice daily, and trimethoprim-sulfamethoxazole were subsequently administered because atypical infection and nocardiosis were considered during the extended differential diagnosis.

Mini-pulse corticosteroid therapy was initiated because of severe systemic inflammation, acute kidney injury, and progressive pulmonary involvement; it was not administered as targeted treatment for suspected nocardiosis. Intravenous methylprednisolone 250 mg/day was given initially, followed by dose reduction to 80 mg/day for 3 days. The administered treatments were tolerated without documented treatment-related adverse events. Serum creatinine decreased from 4.0 mg/dL at admission to 3.55 mg/dL on hospital day 2, 1.22 mg/dL on hospital day 3, and 0.77 mg/dL on hospital day 4, consistent with rapid and complete renal recovery during the early hospital course.

Discussion

Acute kidney injury (AKI) during systemic infections may result from multiple mechanisms, including hemodynamic instability, systemic inflammatory response, cytokine-mediated tubular stress, or, less commonly, immune-mediated processes [6]. Infection-associated renal injury may occur even in the absence of immune-complex–mediated glomerular disease [7].

Adenovirus-associated renal involvement has predominantly been described in immunocompromised individuals, particularly hematopoietic stem cell and solid organ transplant recipients, in whom direct viral cytopathic effects may be demonstrated in renal tissue [2, 8]. In contrast, renal complications in immunocompetent adults are rare and are usually reported as transient or mild renal dysfunction rather than biopsy-evaluated renal involvement.

In the present case, the patient was previously healthy and immunocompetent, with no history of chronic illness or immunodeficiency. Acute kidney injury was already present at admission and developed in the setting of severe systemic infection and inflammation. Blood and urine cultures were negative, and an extensive respiratory viral panel excluded alternative viral pathogens, supporting adenovirus as a possible major contributor to the clinical presentation rather than proving it as the sole causative pathogen.

The pulmonary findings in our patient were also consistent with the reported radiological spectrum of adenovirus pneumonia in immunocompetent adults. Zhang et al. reported that consolidation is the predominant CT finding in adenovirus pneumonia among immunocompetent adults, often accompanied by ground-glass opacities, multilobar involvement, and pleural effusion [9]. Similarly, our patient had bilateral ground-glass opacities, consolidations, nodular cavitary lesions, and loculated pleural effusion. Although cavitary nodular lesions are not specific for adenovirus infection and initially prompted an extensive search for alternative infectious and noninfectious etiologies, no additional causative microorganism was isolated from blood, urine, or pleural fluid cultures. In this context, the radiological findings, microbiological results, and clinical course could support the diagnosis of severe adenovirus-associated pneumonia.

The markedly elevated procalcitonin level, purulent pleural fluid, and cytological detection of dense bacterial clusters supported probable concomitant bacterial infection or empyema, although cultures remained negative. Negative cultures may have been influenced by empirical antimicrobial therapy. Therefore, this case should not be interpreted as proven isolated adenoviral pneumonia. Rather, the pulmonary and renal manifestations were most likely related to severe adenovirus-associated pneumonia complicated by probable culture-negative bacterial coinfection, empyema, and systemic inflammatory response.

Recent data also indicate that adenoviral community-acquired pneumonia (CAP) in immunocompetent adults may clinically and radiologically mimic bacterial pneumonia and may be accompanied by elevated inflammatory markers, including procalcitonin. Gjurasin et al. reported that all hospitalized immunocompetent adults with adenoviral CAP initially received empirical antibiotics, highlighting the diagnostic difficulty and antimicrobial stewardship challenges in this setting [10].

Histopathological evaluation demonstrated preserved glomerular architecture without immune-complex deposition or proliferative changes. Mild tubular alterations, including focal granular-hyaline casts, were observed, while no specific vascular pathology was identified. The renal biopsy findings argue against immune-complex–mediated glomerulonephritis, thrombotic microangiopathy, vasculitis, and diffuse obstructive cast nephropathy. Instead, the limited tubular cast formation and absence of major glomerular or vascular pathology support infection-associated acute kidney injury, probably mediated by systemic inflammation and tubular injury during severe pneumonia.

Although adenovirus infection may be associated with hemorrhagic cystitis, particularly in immunocompromised patients, our patient had only microscopic hematuria, with no evidence of urinary tract obstruction, clot retention, intravesical hematoma, or post-renal acute kidney injury [11].

Because adenoviral PCR or immunohistochemical staining was not performed on renal tissue, direct viral invasion of the kidney could not be confirmed. Moreover, no viral cytopathic inclusions were identified on renal biopsy. Therefore, the renal injury in this case should be interpreted cautiously as infection-associated acute kidney injury, probably mediated by systemic inflammatory response and tubular injury, rather than proven direct adenoviral nephropathy.

The use of corticosteroids in severe adenovirus infection remains controversial because of the potential risk of further immunosuppression. In the present case, corticosteroids were administered as a short course because the patient was young but had a severe and rapidly progressive systemic inflammatory presentation accompanied by acute kidney injury. Therefore, the favorable clinical course should not be interpreted as evidence supporting routine corticosteroid therapy for adenovirus pneumonia. Clinical improvement following supportive management and short-course corticosteroid therapy further suggests a potentially reversible inflammatory component.

This case broadens the clinical spectrum of adenovirus-associated renal injury in immunocompetent adults and highlights the importance of considering infection-associated AKI in patients presenting with renal dysfunction during severe viral pneumonia.

Conclusion

Although adenovirus was not demonstrated in renal tissue and could not be proven as the sole cause of pneumonia, the clinical course suggests infection-associated AKI occurring in the setting of severe adenovirus-associated pneumonia, probable culture-negative bacterial coinfection, empyema, and systemic inflammation.

Severe adenovirus-associated pneumonia may be complicated by acute kidney injury even in immunocompetent adults. In the absence of immune-complex deposition or overt glomerular pathology, renal dysfunction may reflect infection-related tubular injury rather than classic immune-mediated interstitial nephritis. Early recognition and appropriate supportive management are essential to optimize renal outcomes.

Author contributions

N.N.O.S. conceived the study, collected the clinical data, and wrote the main manuscript text, Y.A. contributed to clinical interpretation, supervised the study, and critically revised the manuscript.

Funding

No funding was received for this case report.

Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Declarations

Ethical approval

was not required for this retrospective single case report according to the institutional policy of the University of Health Sciences, Bursa City Training and Research Hospital.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and accompanying clinical information.

Competing interests

The authors declare no competing interests.