Brucellosis represents the most widespread zoonotic disease globally, with its endemic regions progressively expanding, thereby constituting a major public health concern worldwide (1, 2). The highest incidence of human brucellosis is observed in Asia, particularly in China and Mongolia, which bear the greatest disease burden (3).

Brucella, a Gram-negative bacterium characterized as facultative intracellular, is the etiological agent responsible for brucellosis. Its primary virulence attribute lies in its ability to persist and replicate within host cells over extended periods, thereby evading detection and response by the host immune system. This capability is fundamental to sustaining its chronic infection (1, 2, 4). Humans can contract the disease through various transmission routes, including contact with infected animals and their secretions, consumption of contaminated food, and occupational exposure, among others (5, 6). The disease is often challenging to accurately diagnose and is prone to misdiagnosis (7). Human brucellosis manifests with nonspecific clinical symptoms and is a systemic disease that can affect multiple organs and systems (4, 8–10), with the bones and joints being the most commonly involved (8). The urogenital system is also frequently affected, with orchitis being a common clinical presentation (9). In addition, the disease can manifest as pyelonephritis, acute interstitial nephritis, and acute kidney injury (9–12). However, glomerular diseases are relatively rare and are primarily documented in case reports within the clinical literature. Renal pathology with renal biopsy may present as immunoglobulin A nephropathy (IgAN) (13, 14), as well as diffuse proliferative, mesangiocapillary, membranoproliferative, and crescentic glomerulonephritis (15–20), each with different clinical presentations. Both acute and chronic Brucella infections can result in glomerular lesions. In this paper, we report the first case of IgAN with cellular crescentic lesions secondary to acute Brucella infection in our center.

A 45-year-old man, who worked as a teacher with no past kidney medical history, was hospitalized on September 13, 2023, at the Department of Nephrology, Shenzhen Second People’s Hospital. On September 1, 2023, 12 days prior to admission, the patient presented with a high fever exceeding 39°C, accompanied by chills, generalized myalgia, arthralgia, hyperhidrosis, nausea, and vomiting. Approximately 20 years ago, the patient experienced an abrupt onset of left-sided deafness. Furthermore, he has a 3-year history of untreated hypertension, with systolic blood pressure readings consistently around 140 mmHg.

Upon admission, a physical examination was conducted, which revealed the following vital signs: blood pressure at 145/90 mmHg, pulse rate at 83 bpm, and body temperature at 38.9°C. Clinical examination indicated the absence of edema and no abnormal findings. Laboratory analyses demonstrated a white blood cell count of 20.5 × 10⁹/L, hemoglobin level of 130 g/L, serum albumin concentration of 31.1 g/L, and blood creatinine levels ranging from 220 to 330 μmol/L. The hypersensitivity C-reactive protein (CRP) was measured at 97.3 mg/L, and procalcitonin (PCT) was 1.06 ng/ml. Urinalysis revealed proteinuria at 2+ mg/dl and red blood cells at 2+ per high-power field (HPF), with a 24-h urinary protein excretion of 1.51 g. The erythrocyte sedimentation rate was 35 mm/h. Tests for Plasmodium sanguinis, dengue antigen/antibody, urine bacterial culture, and tuberculosis infection T cells were all within normal limits. In addition, tests for anti-neutrophil cytoplasmic antibody (ANCA), anti-glomerular basement membrane (GBM) antibody, anti-double-stranded DNA (dsDNA), and antinuclear antibody (ANA) were negative. Complement C3 was 0.92 g/L and C4 was 0.22 g/L. The patient was negative for hepatitis B, hepatitis C, syphilis, and HIV.A monoclonal protein fraction was not detected in the serum protein electrophoresis. The virology assays for cytomegalovirus, hepatitis viruses, Epstein–Barr virus, and herpes simplex virus returned negative results. Ultrasonographic evaluation of the kidneys indicated normal morphology and size. The cardiac ultrasound findings revealed an enlargement of the left atrium, while the morphology and structure of the cardiac valves appeared normal. Computed tomography (CT) of the lungs showed no evidence of infection or effusion. The patient was administered piperacillin/tazobactam for anti-infective therapy over the course of 1 week. However, symptoms of fever, nausea, vomiting, and arthralgia recurred. The patient presented with a body temperature of 38.3°C and reported symptoms of urinary urgency, frequency, gross hematuria, and a cough without expectoration.

Meropenem was given as anti-infective treatment. A subsequent physical examination revealed no tenderness at the ureteral points, no percussion pain in the renal area, and no edema in the extremities. Repeat laboratory analyses indicated a white blood cell count of 14.73 × 10⁹/L, hemoglobin level of 96.0 g/L, and blood creatinine concentration of 150.5 μmol/L. Urinalysis demonstrated proteinuria at 2+ mg/dl, red blood cells at 3+ per HPF, and negative urine white blood cells. The blood and bone marrow cultures showed no bacterial growth. The patient was also negative for influenza A/B virus and novel coronavirus.

An abdominal ultrasound revealed enlarged kidneys, with the left kidney measuring 130 mm × 61 mm and the right kidney measuring 132 mm × 57 mm. Enlarged lymph nodes were identified in the right axillary region and the bilateral groin area. A cardiac ultrasound showed no valvular vegetation. CT of the lungs indicated inflammation in both lungs and a small amount of effusion. Abdominal CT demonstrated exudative changes around both kidneys, likely due to inflammation. A bone marrow biopsy revealed markedly active hyperplasia in the granulocyte and megakaryocyte lineages, with decreased erythroid hyperplasia; scattered and clustered platelets were readily observed. The renal biopsy pathology indicated mesangial proliferative IgAN with some glomerular crescent formation, classified as M1E0S0T0C2 according to the Oxford classification. Immunofluorescence analysis showed IgG negativity, IgA (++), IgM (+), C3 (+), and C1q negativity, deposited in the mesangial region. Examination under a light microscope revealed 11 glomeruli, with no evidence of glomerular sclerosis or stage sclerosis.

The glomeruli exhibited variability in size, accompanied by a mild proliferation of glomerular mesangial cells and matrix and deposition of fuchsinophilic material in the mesangial area, without evident endothelial cell proliferation. There was fibroid necrosis in segmental capillary vessels observed in two glomeruli, as well as the presence of five small cellular crescents. Vacuolar degeneration of renal tubular epithelial cells was observed. The renal interstitium demonstrated pronounced inflammation, along with mild fibrosis and a slight thickening of the arteriolar walls. Electron microscopy revealed no significant thickening of the glomerular basement membrane, segmental fusion of foot processes, and a small quantity of electron-dense material in select mesangial regions. There were no obvious subepithelial electron-dense deposits (see Figure 1 ).

Upon reviewing the patient’s medical history, it was noted that the patient had been in contact with raw mutton 2 weeks prior to disease onset, had sustained damage to the skin on his hands, and had consumed cooked mutton. Further diagnostic tests indicated a positive result (+++) for the Rose Bengal test (RBT) and a positive result (1:200+++) for the standard agglutination test (SAT). Magnetic resonance imaging (MRI) revealed scattered patchy, nodular, proton density (PD) fat-suppressed hyperintense signals in the thoracic vertebrae (T4, T5, T7, T9, and T11) and the first lumbar vertebra (L1), with significant lesions observed in L1, which were considered to be infectious in nature, leading to a diagnosis of Brucella spondylitis. Cerebrospinal fluid (CSF) analysis showed no significant abnormalities. The results of the laboratory tests are presented in Table 1 .

The patient was diagnosed with brucellosis, Brucella spondylitis, and brucellosis-related renal impairment. The decision was made to prioritize the treatment of brucellosis, with subsequent treatment plans to be determined based on the efficacy of the initial intervention. A therapeutic regimen consisting of rifampicin (600 mg/day), doxycycline (200 mg/day), and levofloxacin (500 mg/day) was administered, with treatment duration of 4 months. Remarkably, after 7 days of treatment, the patient’s clinical symptoms, including the fever and musculoskeletal pain, were alleviated, although significant sweating persisted. After 1 month, the patient’s sweating had also improved, and the kidney function tests returned to normal. Repeat laboratory analyses revealed a hemoglobin level of 105 g/L, blood albumin of 41.6 g/L, and creatinine at 95.4 μmol/L. Urinalysis indicated negative proteinuria, 69 red blood cells per HPF, and negative urine white blood cells. After 3 months, the creatinine levels decreased to 87.5 μmol/L, and urinalysis showed positive proteinuria, two to four red blood cells per HPF, and a specific gravity of 1.023. The Brucella antibody tube agglutination test was negative. At 11 months of follow-up, the patient’s blood creatinine was 86 μmol/L, and urinalysis indicated resolution of the proteinuria and red blood cells.

In this report, we present the case of a 45-year-old male teacher with no prior history of renal disease. The patient reported exposure to raw mutton 2 weeks prior to the onset of symptoms, during which time the skin on his hands was compromised. It is hypothesized that the patient contracted an infection through direct contact with Brucella-contaminated raw mutton. Subsequently, the patient developed glomerulonephritis following acute Brucella infection, which affected multiple organ systems. Renal biopsy revealed mesangial proliferative IgAN with some glomerular crescent formation, classified as M1E0S0T0C2 according to the Oxford classification, in conjunction with Brucella spondylitis. Following a 4-month regimen of anti-brucellosis therapy, which included doxycycline, levofloxacin, and rifampicin, the patient achieved complete remission. Post-treatment, both the urinalysis abnormalities and the renal function were fully restored. We hypothesize that the patient’s IgAN with cellular crescent formation was induced by the Brucella infection.

Brucella infection affects multiple organ systems, with patients often presenting with nonspecific symptoms such as fever, fatigue, night sweats, vomiting, arthralgia, myalgia, hepatomegaly, and lymphadenopathy (4). The literature indicates that both acute and chronic Brucella infections can lead to Brucella nephropathy, which is characterized by a wide range of clinical manifestations, predominantly resulting in acute kidney injury (16–20). The clinical presentations may include gross hematuria and significant proteinuria, with some patients developing nephrotic syndrome, potentially accompanied by anemia, hypocomplementemia, pleural effusion, and cardiac valve vegetations (21). In addition, two cases of chronic Brucella infection have been associated with cryoglobulinemia and ANCA positivity (20). In our case, the patient exhibited renal manifestations alongside anemia, pleural effusion, and, notably, Brucella spondylitis, without evidence of hypocomplementemia or valvular heart disease. These findings suggest that, in patients with Brucella nephropathy, it is crucial to consider and exclude the possibility of Brucella spondylitis and endocarditis.

Prior studies have demonstrated that the renal biopsy pathology results show that, in addition to IgAN, the renal pathology associated with Brucella nephropathy may encompass minimal lesions, diffuse, mesangial, and membranous proliferative glomerulonephritis, and crescentic glomerulonephritis, among others (see Table 2 ).

In our case, the condition manifested following an acute Brucella infection. The renal biopsy pathology revealed mesangial proliferative IgAN, which was characterized by two instances of glomerular segmental capillary fibrinoid necrosis, five small cell crescents, and a focal area of strong interstitial inflammation. Previous literature has documented two instances of IgAN attributed to acute Brucella infection (13, 14). Compared with these earlier cases, our patient exhibited more pronounced renal pathological changes. Notably, repeated renal biopsies in patients with Brucella-induced IgAN, even after treatment-induced remission, have demonstrated persistent proliferation in the glomerular mesangial region and continued IgA deposition (14).

In our case, the renal pathology also indicated crescentic lesions. Previous studies have reported that acute Brucella infection can lead to rapidly progressive crescentic glomerulonephritis (19), accompanied by acute inflammatory cell infiltration. Previous studies have documented that chronic brucellosis infection is associated with the development of cryoglobulinemia and ANCA-associated vasculitis (20). The renal biopsy of the patient revealed intracapillary proliferative glomerulonephritis with a limited presence of crescents. This finding indicates that Brucella infection may induce alterations in glomerular crescent formation.

Currently, there are no established guidelines or recommendations for the treatment of Brucella nephropathy, with the existing literature limited to case reports. In our case study, the patient received a combination therapy of doxycycline, levofloxacin, and rifampicin over a 4-month period due to complications from Brucella spondylitis and IgAN. The clinical symptoms of the patient showed improvement within 1 week of initiating treatment. After 1 month, the renal function normalized, the proteinuria resolved, and microscopic hematuria decreased. By the end of the 4-month treatment, the hematuria had also resolved. In two previously documented cases of IgAN following Brucella infection, the renal impairment fully resolved after anti-Brucella therapy, with treatment durations of 6 weeks and 3 months, respectively (13, 14). Our observations indicate that while the renal function and proteinuria improved rapidly following anti-Brucella treatment, the hematuria resolved more gradually. This slower resolution of the hematuria may be attributed to the persistent deposition of IgA immune complexes in the mesangial region.

The treatment outcomes for renal glomerular disease secondary to acute brucellosis indicate that the majority of patients achieve complete remission following anti-brucellosis therapy, typically over a period of 6 weeks to 3 months (12, 16, 25). Nonetheless, some patients continue to exhibit persistent proteinuria despite antibacterial treatment alone (17). A subset of these patients has been successfully treated with a combination of corticosteroids and anti-brucellosis agents, leading to full resolution of the glomerular lesions (22, 23). In cases where patients present with concurrent aortic valve endocarditis and pericarditis due to Brucella infection, treatment regimens involving rifampicin, doxycycline, and ceftriaxone (26), or a combination of anti-brucellosis therapy and hormonal therapy (21), have resulted in complete clinical remission. Furthermore, for Brucella-associated rapidly progressive glomerulonephritis, a therapeutic strategy incorporating anti-Brucella agents and immunosuppressive therapies, such as corticosteroids, cyclophosphamide, and azathioprine, has been employed. In certain cases, additional interventions, including rituximab and plasma exchange, have also been utilized (24, 27). These strategies yielded favorable outcomes, with the patients demonstrating good prognosis.

Currently, there are two documented cases of glomerular disease attributed to chronic Brucella infection (18, 20). The clinical manifestations in these patients included nephrotic syndrome, significant renal function impairment, and the presence of cryoglobulinemia. In one case, the renal pathology revealed membranoproliferative glomerulonephritis (18). The patient was treated with doxycycline, rifampicin, and trimethoprim/sulfamethoxazole. After 5 months, the patient’s urinary protein level was 14 g/day, prompting the administration of a reduced dose of corticosteroids, which resulted in partial remission of the proteinuria. The second patient exhibited coexisting cryoglobulinemia and ANCA-associated vasculitis (20) and received treatment with prednisone, doxycycline, and rifampicin for 6 months, leading to the rapid alleviation of all symptoms.

The current therapeutic strategies for Brucella nephropathy primarily target various renal pathological types and associated complications. Different treatment modalities are employed, and most yield favorable prognoses. Nevertheless, there is presently no standardized treatment protocol for Brucella nephropathy (28–30). The glomerular disease induced by Brucella infection is believed to be associated with the production of circulating immune complexes and antibodies (31). The underlying mechanism remains unclear, necessitating further clinical investigation to elucidate both the pathogenesis and the optimal treatment approaches.