The US Food and Drug Administration (FDA) approved the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine on August 23, 2021. Furthermore, on August 31, 2022, the FDA approved mRNA COVID-19 booster vaccines developed by Pfizer-BioNTech and Moderna for a subset of immunocompromised individuals. This measure was designed to reduce the incidence of COVID-19 infections and deaths.

Vaccine-induced hypermetabolic lymphadenopathy has been reported clinically following the administration of the COVID-19 mRNA vaccine. A recent retrospective cohort study investigated the incidence and pattern of hypermetabolic axillary lymph nodes on 18-fluorodeoxyglucose positron emission tomography-computed tomography in patients who received the Pfizer-BioNTech COVID-19 vaccine [1]. In a separate cohort study, patients who were administered the same vaccine exhibited a high incidence of hypermetabolic axillary lymph nodes. Supraclavicular lymph nodes, while rare, were also noted. Lymphadenopathy was found in 36.4% of patients after the first dose of the COVID-19 vaccine and in 53.9% of patients following the booster dose [2]. Herein, we report a case of graft kidney hydronephrosis due to ureteric compression caused by para-aortic lymphadenopathy after receipt of the COVID-19 booster vaccine.

The patient provided informed consent to include his medical case details in this clinical case report. All identification information was anonymized to ensure the patient's privacy and confidentiality. The patient understood that the information provided would contribute to medical knowledge and research and agreed to publish it.

A 79-year-old man, who had received a booster shot of mRNA COVID-19 vaccine earlier in the day, presented to the emergency department with acute pain and weakness in his lower extremities. The patient had received a kidney transplant 25 years earlier for end-stage renal disease of unknown origin and was maintained on a regimen of immunosuppressive medications, including tacrolimus (2 mg), mizoribine (150 mg), and prednisolone (7.5 mg). He did not have diabetes, although he had developed hypertension posttransplantation. He had no history of adverse events from vaccinations, and his renal function was normal.

The patient’s serum creatinine level was 1.5 mg/dL, and his tacrolimus trough level was maintained at 4–5 ng/mL. He had no history of adverse reactions to vaccinations before receiving the booster dose of the mRNA COVID-19 vaccine. The initial COVID-19 vaccine administered to the patient was the version developed by Oxford/AstraZeneca, while all follow-up vaccinations were mRNA COVID-19 vaccines produced by Pfizer-BioNTech. The booster dose was administered on August 10, which was 30 days following the third dose of COVID-19 vaccination.

In the evening following the administration of the booster dose, the patient experienced a rapid onset of increasing left inguinal pain, scrotal swelling, and weakness in his left leg. He promptly sought care at the emergency room. Laboratory tests revealed that his serum C-reactive protein level was normal, his creatinine level was mildly elevated at 1.9 mg/dL, and his albumin level was 2.1 g/dL. Computed tomography indicated subcapsular and perirenal fluid accumulation around the transplanted kidney. Additional fluid collection was observed along the left posterior pararenal fascia, within the left psoas muscle, and in the perisplenic and pelvic cavities. The scan also showed swelling, hydroureter, and a relatively high density of the transplanted kidney located in the left iliac fossa (Fig. 1).

Doppler ultrasonography of the transplanted kidney revealed a graft measuring 14.2 cm and a resistive index value ranging from 0.69 to 0.71. Percutaneous nephrostomy (PCN) was subsequently performed on the kidney. Despite successful PCN, on the third day of admission, no changes were observed in the swelling of the hydroureter, nor in the relatively high density of the transplanted kidney within the left iliac region, which was accompanied by left pleural effusion. After 5 days of hospitalization, percutaneous abdominal drainage and double J stent insertion were conducted to manage the hydroureter and to drain the accumulated fluid from the left psoas muscle.

Analysis of the fluid obtained through percutaneous abdominal drainage revealed the presence of white blood cells, characterized by lymphocytic dominance (with the percentages of neutrophils, lymphocytes, and histiocytes being 6%, 60%, and 34%, respectively), and a creatinine level of 1.6 mg/dL. These findings suggested that the large-volume ascites represented a direct response to immune system activity, rather than a pathology of the urinary system. Cytology was negative for malignant cells. The source of the percutaneously drained abdominal fluid was identified as the para-aortic lymph node. Similarly, the fluid accumulation within the psoas muscle was lymphatic in nature and was attributed to an immune response to mRNA COVID-19 vaccination.

After 1 week of admission, the patient demonstrated an excellent urinary stream, and no leakage was observed on antegrade pyelography. The PCN was then removed. One month following the booster dose, computed tomography revealed reduced fluid collections in the peritoneal cavity and within the left psoas muscle; the pleural effusion had also resolved. We postulated that the ascites would spontaneously resolve in the following weeks, as it was likely an immune response to the vaccination (Fig. 2).

Lymphadenopathy is a recognized local adverse reaction to vaccines such as those for influenza or papillomavirus [3,4]. However, it has been observed more frequently following administration of novel COVID-19 mRNA vaccines, such as Pfizer and Moderna, which encode the viral spike protein. Lymphocytic infiltration has been repeatedly observed in various regions of the body following COVID-19 vaccination. Most frequently, this lymphadenopathy has been detected in the axilla, but it has also been confirmed in other locations, including the neck, skin, and myocardium [5–8].

Furthermore, lymphadenopathy is more frequent following the administration of a booster dose of the vaccine compared to the first and second doses [9,10]. Several cases of lymphadenopathy that occurred after vaccination with the mRNA COVID-19 vaccine have been verified through fine needle aspiration cytology [11].

Malahe et al. [12] confirmed that T cells and B cells exhibit normal immune responses following COVID-19 vaccination in kidney transplant recipients. Vaccination-associated reactive lymphadenopathy occurs when antigen-presenting cells migrate to regional lymph nodes, triggering both cellular (T cell) and humoral (B cell) immune responses. Consequently, lymphadenopathy is more commonly associated with mRNA vaccines than with protein-based vaccines. The underlying mechanism for this vaccination-associated lymphadenopathy involves robust and swift proliferation of B cells within the germinal centers of lymph nodes, as stimulated by the mRNA vaccine [13]. Sensitization to the vaccine during the initial dose primes the immune system, leading to a dramatic increase in antibody production by memory B cells upon booster vaccination. This suggests that lymphadenopathy is more likely to occur following the administration of a booster dose.

Interactions between vaccines and immunosuppressants require careful consideration. However, due to the urgency of the global pandemic crisis, the COVID-19 mRNA vaccine was not subjected to the full clinical research process. Consequently, scarce research data were available on its interactions with other medications, making it challenging to understand its relationship with immunosuppressants.

Herein, we report a case of a patient who presented with ipsilateral lymphadenopathy that was mistaken for a urinoma. This error can be attributed to the considerable size of the lymphadenopathy and its extensive involvement, as it occupied the peritoneal space around the graft kidney, infiltrated the psoas muscle, and led to ureteric compression and hydronephrosis.

Likewise, in several patients with breast cancer, lymphadenopathy following a booster dose of the COVID-19 vaccine was also misdiagnosed as axillary metastasis, leading to unnecessary biopsies. Consequently, immunocompromised patients should be informed about the incidence and potential severity of lymphadenopathy after booster vaccination.