Late-Onset Adenovirus-Induced Achalasia in a Kidney Transplant Recipient: A Case Report

Abstract

Patient: Male, 60-year-old

Final Diagnosis: Adenovirus infection with achalasia

Symptoms: Dysuria • gross hematuria • diarrhea • progressive dysphagia

Clinical Procedure: —

Specialty: Transplantology

Objective: Unusual clinical course

Background

Adenovirus infection in kidney transplant recipients, although rare, represents a potentially life-threatening complication that typically manifests early after transplantation. Late-onset adenovirus infection is uncommon and presents substantial diagnostic and therapeutic challenges, particularly in cases of atypical organ involvement. Esophageal involvement is exceptionally rare and has not been extensively characterized in solid-organ transplant recipients.

Case Report

A 60-year-old male kidney transplant recipient presented with a 1-week history of dysuria, gross hematuria, diarrhea, and worsening graft function 5 years after transplantation. Progressive dysphagia developed after admission. Laboratory testing confirmed adenovirus infection in the blood, with a viral load of 779 000 IU/mL. Adenovirus was also detected in urine and stool samples, whereas cytomegalovirus and polyomavirus testing yielded negative results. Gastroscopy and barium swallow studies demonstrated achalasia-like features. Esophageal biopsy specimens did not show viral cytopathic changes. Management consisted of immunosuppression reduction, intravenous immunoglobulin administration, and low-dose cidofovir therapy. Clinical and virologic recovery was achieved within 3 weeks, with complete resolution of gastrointestinal symptoms and stabilization of graft function.

Conclusions

This case underscores the atypical late presentation of adenovirus infection in a kidney transplant recipient and illustrates the potential for extremely rare esophageal involvement manifesting as achalasia. Despite the absence of direct viral confirmation in esophageal tissue, the clinical course and therapeutic response support adenovirus as the most likely etiology. Early recognition, confirmation by polymerase chain reaction testing, and timely immunosuppression adjustment combined with antiviral therapy are essential to optimize patient outcomes.

Introduction

Human adenoviruses (HAdVs) are nonenveloped, double-stranded DNA viruses capable of infecting multiple organ systems and causing a broad spectrum of diseases. In immunocompetent individuals, HAdV infections are typically mild and self-limited, most commonly manifesting as upper respiratory tract infections, conjunctivitis, or gastroenteritis [1]. In contrast, the clinical course in immunocompromised patients – particularly recipients of solid organ or hematopoietic stem cell transplants – may be severe, rapidly progressive, and associated with substantial morbidity and mortality [2,3].

Among kidney transplant recipients, adenovirus infection remains an uncommon but important cause of allograft dysfunction. The disease spectrum ranges from localized urinary tract involvement, including hemorrhagic cystitis and tubulointerstitial nephritis, to disseminated disease with multiorgan involvement [4,5]. Disseminated adenovirus infection is particularly concerning because it may present insidiously and progress to viremia, hepatitis, pneumonia, enterocolitis, or neurologic involvement; these manifestations are frequently followed by rapid clinical deterioration. Adenovirus-associated hepatic failure is a particularly devastating complication that often progresses to death, despite early diagnosis and aggressive antiviral therapy [6].

Disease severity is strongly influenced by the degree of immunosuppression. Agents such as anti-thymocyte globulin, mycophenolate mofetil, and calcineurin inhibitors impair viral clearance and predispose patients to persistent or disseminated infection [7]. In transplant recipients, infection may manifest early after transplantation as viral reactivation or may develop later as de novo infection, particularly among individuals with prolonged immunosuppressive exposure [8–10] or those who recently underwent intensification of immunosuppression [11].

Diagnosis primarily relies on molecular testing, most commonly polymerase chain reaction (PCR) assessments of blood, urine, or tissue that permit early detection and longitudinal monitoring of viral load [8]. Histopathologic confirmation through immunohistochemistry may be required to differentiate viral infection from allograft rejection, particularly in cases with renal involvement [12].

Management remains challenging because no targeted antiviral therapies are currently approved. Cidofovir is widely used but is hindered by nephrotoxicity [13,14]. Brincidofovir, a lipid-conjugated derivative with reduced renal toxicity, has shown promise but remains unavailable in many settings [15]. Supportive strategies, including immunosuppression reduction and intravenous immunoglobulin (IVIG) administration, are integral to management; however, outcomes remain poor in cases complicated by hepatic failure or multiorgan involvement [16].

Here, we describe a rare case of late-onset adenovirus infection in a kidney transplant recipient who exhibited esophageal involvement manifesting as achalasia. Our report emphasizes the importance of timely recognition and tailored immunosuppressive management in preventing life-threatening complications of adenoviral disease.

Case Report

A 60-year-old Middle Eastern man with end-stage kidney disease secondary to chronic glomerulonephritis underwent deceased-donor kidney transplantation in January 2020. The allograft was obtained from an expanded-criteria donor, and the postoperative course was complicated by delayed graft function. Induction immunosuppression included anti-thymocyte globulin; maintenance therapy consisted of tacrolimus, mycophenolate mofetil, and prednisone.

The patient’s medical history was notable for mitral valve replacement with a mechanical prosthesis, which required maintenance warfarin therapy, and prior parathyroidectomy due to secondary hyperparathyroidism. The patient denied tobacco use, alcohol consumption, or illicit drug use. In May 2020, he had been diagnosed with biopsy-proven polyomavirus (BK) nephropathy and received immunosuppression reduction therapy, with a target tacrolimus trough level of 5 ng/mL and discontinuation of mycophenolate mofetil. Despite chronic allograft dysfunction, renal function remained stable, with baseline serum creatinine levels of approximately 3.0 to 3.3 mg/dL until September 2025.

In early September 2025, the patient presented with a 1-week history of dysuria, gross hematuria, diarrhea, and worsening allograft function. He reported recent exposure to a family member with fever and diarrhea, 10 days before his symptoms began. Based on this presentation, the initial differential diagnosis included sepsis secondary to pyelonephritis, obstructive uropathy, viral infections such as cytomegalovirus or BK virus, and – less likely – acute allograft rejection or urinary tract malignancy. Laboratory evaluation on admission demonstrated acute allograft dysfunction, with a serum creatinine level of 4.9 mg/dL that subsequently peaked at 9.2 mg/dL, normal white blood cell count (6000/μL), lymphopenia (lymphocyte count, 300/μL), thrombocytopenia (platelet count, 94 000/μL), and hypoalbuminemia (2.7 g/dL) (Table 1). Urinalysis showed gross hematuria, and urine microscopy demonstrated monomorphic red blood cells. Blood and urine culture findings were negative, and urine cytology revealed no malignant cells. Ultrasonography of the transplanted kidney demonstrated a normal-sized allograft exhibiting pronounced uroepithelial thickening and hyperemia of the transplanted ureter, consistent with ureteritis.

Table 1.

Laboratory tests at admission and discharge demonstrating improvement in allograft function, hematologic indices, and viral clearance.

Laboratory test (normal range)	At admission	At discharge
Creatinine (0.66–1.25 mg/dL)	4.9	3.3
White blood cell count (4000–10 000/μL)	6000	6300
Lymphocyte count (900–4900/μL)	300	1300
Hemoglobin (13.5–17.5 g/dL)	11.4	9.8
Platelets (150 000–450 000/μL)	94 000	200 000
Albumin (3.5–5.2 g/dL)	2.7	3.5
International normalized ratio	2.5–3	3.2
Polyomavirus (BK virus) DNA (IU/mL)	<22	Undetected
Cytomegalovirus DNA (IU/mL)	Undetected	Undetected
Blood adenovirus DNA (IU/mL)	779 000	Undetected
Urine adenovirus DNA	Positive	Undetected

DNA – deoxyribonucleic acid.

A renal allograft biopsy was considered as part of the diagnostic evaluation for rejection or viral nephritis; however, the procedure was deferred because the patient’s anticoagulation therapy for a mechanical mitral valve conferred a high bleeding risk. Given the negative results from early assessments for common etiologies and the presence of hemorrhagic cystitis, diarrhea, lymphopenia, and ureteral inflammation, adenovirus emerged as a key diagnostic consideration. Thus, targeted virologic testing was initiated.

Virologic studies demonstrated PCR positivity for adenovirus in urine and stool samples, whereas cytomegalovirus and BK virus DNA were not detected. Quantitative adenoviral DNA PCR testing of blood obtained on admission revealed a viral load of 779 000 IU/mL, confirming adenovirus viremia. Qualitative urine and stool samples also showed adenovirus DNA positivity. Although adenovirus serotype 11 is most commonly associated with hemorrhagic cystitis [17], serotyping was unavailable at our institution; therefore, the specific serotype could not be determined.

Three days after admission, the patient developed new-onset dysphagia and retrosternal discomfort. The differential diagnosis was expanded to include infectious esophagitis (viral or fungal), reflux-related inflammation, and early esophageal motility disorders. Gastrointestinal evaluation via gastroscopy revealed a stricture with mucosal friability suggestive of achalasia. Multiple biopsies showed mild esophageal mucosal inflammation with reflux-related changes but no viral cytopathic effects. Immunostaining results were negative for Candida species, cytomegalovirus, adenovirus, and herpes simplex virus. A subsequent barium swallow study demonstrated dilation of the distal esophagus with mild contrast stasis and abrupt tapering at the lower esophageal sphincter, producing a “bird-beak” appearance consistent with achalasia (Figure 1). A barium swallow study performed 2 months earlier (July 2025) for reflux evaluation had revealed no evidence of achalasia or esophageal narrowing, indicating that these findings were of recent onset.

Figure 1.

Barium swallow study demonstrating dilation of the distal esophagus with “bird-beak” tapering at the lower esophageal sphincter, consistent with achalasia.

The patient was treated with IVIG at a dose of 0.5 g/kg/day for 2 consecutive days, followed by intravenous cidofovir at a reduced dose of 0.5 mg/kg, administered twice at 1-week intervals. To minimize nephrotoxicity, adequate hydration was provided via 500 mL of 0.9% sodium chloride solution before and after each infusion. Additionally, 2 g of probenecid were administered 3 h before cidofovir, followed by 1 g at 2 and 8 h after administration. During this period, the immunosuppressive regimen was adjusted by reducing tacrolimus trough levels to 3 to 5 ng/mL.

The patient’s clinical condition progressively improved. Follow-up gastroscopy and barium swallow studies performed 2 weeks later demonstrated complete resolution of esophagitis and a normal, patent gastroesophageal junction, without endoscopic or radiologic features of achalasia (Figure 2). At discharge, 3 weeks after initial presentation, the serum creatinine level had returned to baseline (3.3 mg/dL), the lymphocyte count had increased to 1300/μL (Figure 3), the platelet count had risen to 200 000/μL, the albumin level had improved to 3.5 g/dL, and adenovirus DNA was undetectable in blood samples (Table 1).

Figure 2.

Follow-up barium swallow study demonstrating complete resolution of the radiologic features of achalasia.

Figure 3.

Trends in serum creatinine level (A) and lymphocyte count (B) demonstrating improvement in allograft function and lymphocyte recovery after therapy.

At follow-up 10 days after discharge, the patient was asymptomatic without recurrence of dysuria, hematuria, or dysphagia. Allograft function remained stable, with a serum creatinine level of 3.0 mg/dL.

Discussion

Adenovirus infection is a rare but clinically significant complication in kidney transplant recipients. This case is distinguished by both the late onset (5 years after transplantation) and the presence of transient achalasia, an esophageal motility disorder that – to our knowledge – has not yet been reported in relation to adenovirus infection in solid organ transplant recipients. These observations expand the recognized spectrum of adenoviral disease manifestations in immunocompromised hosts.

Most reported cases occur within the first year after transplantation, corresponding to the period of greatest immunosuppressive vulnerability [1,2]. However, late-onset adenovirus infections have also been documented [18–20]. In the present case, immunosuppression had already been reduced due to prior BK virus nephropathy, with a tacrolimus trough level of approximately 5 ng/mL and discontinuation of mycophenolate therapy. Despite this reduced immunosuppressive burden, adenovirus infection developed several years after transplantation, suggesting a de novo infection rather than viral reactivation. This delayed presentation underscores the need for continued vigilance during long-term post-transplant follow-up, even when apparent immunologic stability has been achieved.

The patient’s clinical presentation with hematuria and allograft dysfunction was consistent with previously reported cases of adenoviral nephritis. Although adenoviral gastrointestinal disease is well described, esophageal motility disorders mimicking achalasia are extremely rare and represent a distinctive manifestation in transplant recipients. Given the onset of progressive dysphagia in our patient, we performed further evaluation. Endoscopy revealed a distal esophageal stricture without erosions or ulcerations. Histologic examination showed nonspecific chronic inflammation, and adenovirus staining results were negative. Although positive staining results would have provided stronger diagnostic confirmation, a negative result does not exclude adenoviral involvement because detection is highly dependent on sampling adequacy, tissue depth, and the focal nature of viral infiltration.

Esophageal motility disorders after viral infections, including herpes simplex virus, varicella-zoster virus, human papillomavirus, measles virus, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been designated post-viral achalasia and are thought to result from virus-induced injury to esophageal smooth muscle, the myenteric plexus, or inhibitory neuronal pathways [21,22]. Although adenovirus has not previously been linked to this phenomenon, a similar mechanism is plausible given its known mucosal and neural tropism. In the present case, complete resolution of dysphagia after antiviral therapy and clearance of viremia, along with the absence of alternative infectious etiologies, strongly supports adenovirus as the most likely cause of reversible achalasia. Our findings suggest that motility abnormalities are reversible with appropriate antiviral therapy and immune modulation.

Another notable feature of the present case was pronounced lymphopenia at presentation, which gradually improved as the patient’s viral load declined. Lymphopenia, a common finding in adenovirus infection, often reflects profound T-cell depletion related to immunosuppressive therapy [1]. Lymphopenia severity has been associated with increased disease severity and adverse outcomes in transplant recipients [7]. The recovery of lymphocyte counts during antiviral therapy, as observed in this case, may serve as a favorable prognostic marker of immune reconstitution and viral control. Similar patterns have been identified among hematopoietic stem cell transplant recipients, in whom increased absolute lymphocyte counts were associated with declining viral loads and improved survival [23]. Serial lymphocyte monitoring, in conjunction with PCR testing, may provide additional clinical insight to evaluate treatment response and disease course.

Therapeutic management relies on a multimodal approach that combines immunosuppression reduction, IVIG administration, and low-dose cidofovir. Cidofovir remains the most commonly used antiviral agent for severe adenovirus infection in transplant recipients, despite its well-known nephrotoxicity. Previous reports, including those by Yang et al [3] and Mihaylov et al [6], have emphasized the delicate balance between viral suppression and preservation of allograft function. In the present case, successful use of a low-dose cidofovir regimen (0.5 mg/kg), combined with probenecid to limit tubular reabsorption and adequate hydration, suggests a safer therapeutic window for kidney transplant recipients.

From a diagnostic perspective, differentiation between viral nephritis and allograft rejection remains a major clinical challenge. Misinterpretation of adenoviral cytopathic changes as rejection may prompt inappropriate escalation of immunosuppression, exacerbating viral replication and organ injury [12]. Integration of quantitative PCR testing and – when indicated – tissue immunohistochemistry is critical for accurate diagnosis and therapeutic guidance.

The rarity of late-onset adenovirus infection with esophageal involvement raises important questions regarding viral latency and reactivation versus de novo infection in patients receiving chronic immunosuppression therapy. Further investigation is warranted to clarify mechanisms of viral persistence and to assess the efficacy of newer, less nephrotoxic antiviral agents and adoptive T-cell therapy in preventing severe complications [13–15].

This report has some limitations. First, despite systemic adenovirus infection, direct virologic confirmation from esophageal tissue could not be obtained because immunohistochemical staining results were negative. Although negative results do not exclude adenoviral involvement, the absence of tissue-level confirmation limits definitive attribution. Second, the diagnosis of adenovirus-associated esophageal dysmotility was primarily based on the temporal relationships concerning viremia, symptom onset, and subsequent resolution after antiviral therapy. Although this sequence may support a causal relationship, alternative transient or immune-mediated mechanisms cannot be excluded. Finally, esophageal manometry was not performed due to the patient’s clinical status, which hindered precise characterization of the motility abnormality. These limitations underscore the need for cautious interpretation of rare post-viral esophageal dysmotility and highlight the importance of diagnostic flexibility when evaluating immunocompromised patients.

Conclusions

This case highlights an unusual presentation of adenovirus infection manifesting as reversible achalasia in the late post-transplant period. Although direct virologic confirmation in esophageal tissue was not achieved, the temporal association with high-level viremia, absence of alternative pathogens, and complete resolution of dysphagia after antiviral therapy collectively support adenovirus as the most likely etiology. Clinicians should recognize that adenovirus infection may manifest as esophageal dysmotility even in the absence of positive tissue staining, particularly given sampling limitations. Importantly, this case demonstrates that virus-associated esophageal motility disorders may be fully reversible with timely immunosuppression adjustment and administration of low-dose cidofovir and IVIG. Awareness of this manifestation may facilitate early recognition, appropriate diagnostic evaluation, and prompt management in transplant recipients.