We herein describe a rare case of an immune-complex-mediated MPGN resulting from a C. burnetii endocarditis of a bicuspid aortic valve.

C. burnetii is a bacterium causing Q fever, a worldwide occurring zoonotic disease. It is an obligate intracellular, pleomorphic, Gram-negative bacterium with high infectivity and worldwide distribution. The main reservoir for human infection consists of farm animals such as sheep, cattle, and goats [4]. Moreover, Celina et al. postulated ticks as a potential risk factor for coxiellosis in livestock [5].

Humans get infected through inhalation of C. burnetii contaminated aerosols expelled by infected animal feces, urine, milk, and birth products [5]. Hence, farm and abattoir workers are exposed to an increased risk of infection. Although a majority of patients stays misdiagnosed or asymptomatic, clinical symptoms can vary from fever, respiratory distress, fatigue, arthralgia, hepatitis, pericarditis, myocarditis, endocarditis, pancreatitis, neurological disorder, skin rash, and others [6].

Life-threatening courses have been primarily described in chronic Q fever with endocarditis [7]. Since people with preexisting valvular heart disease, like the patient reported here, have a considerably increased risk of endocarditis, serological testing for C. burnetii is recommended when blood cultures are negative [8, 9].

Among patients with valvular defects who suffer from Q fever, about 40% develop endocarditis, especially in case of prosthetic valves [10]. But even in native valve diseases, the susceptibility for endocarditis seems to be higher with bicuspid aortic valves compared to secundum atrial septal defect, patent ductus arteriosus, and pulmonary valve stenosis [11].

Infection-related MPGN patterns can be found in various viral and bacterial infections [12, 13]. Bacterial-related immune-complex MPGN have been described in infections including staphylococcus, Mycobacterium tuberculosis, streptococci, Propionibacterium acnes, Mycoplasma pneumoniae, brucella, C. burnetii, nocardia, and meningococcus [1]. In deed only a few cases are known which describe MPGN induced by C. burnetii endocarditis [14,15,16].

A constant light microscopy finding in previous case reports with Q fever and glomerulonephritis is mesangial expansion and glomerular hypercellularity (either mesangial or endocapillary) [15]. Histological changes that are typical for MPGN have been rarely described in Q fever. In our case light microscopy revealed lobulated glomeruli with mesangial proliferation and double contours of the capillary wall as hallmarks of MPGN. Immunohistochemistry showed granular IgG depositions along the capillary walls and the mesangium. Corresponding electron dense subendothelial deposits were detected by electron microscopy. A recently published case by Leclerc et al. described a patient with chronic Q fever and an MPGN with a full house pattern on immunofluorescence with positivity for IgA, IgM, IgG, C3, C1q, kappa and lambda as occasionally found in lupus nephritis [15]. Interestingly, tests for antinuclear and antiphospholipid antibodies showed negative results in their study. In line with these data, the antinuclear antibodies in our study also showed only nonspecific positivity.

Based on the current understanding of the pathological mechanisms, the association between chronic endocarditis caused by C. burnetii and the development of MPGN lies in the persistent antibody formation. These antibodies are produced due to chronic inflammation and deposit as immune precipitates in the glomerulus. An antigen–antibody reaction with glomerular structures has not been described in this context so far.

Previous reports on renal disease in chronic Q fever described proteinuria values in a range from 0.7–4.0 g/d. In our case, urinalysis showed a considerably higher UACR of 8.2 g/g creatinine.

To the best of our knowledge this is the first case of a patient with the coincidence of a chronic C. burnetii-infected native bicuspid aortic valve and a severe MPGN with a UACR of 8.2 g/g creatinine.

This case highlights a C. burnetii-infection causing the destruction of a bicuspid aortic valve and the induction of an immune-complex mediated MPGN. It underscores the importance of considering rare infectious etiologies in patients with blood culture-negative fever, unexplained acute kidney injury and a stay in a high-risk environment. Early recognition and appropriate treatment are crucial for optimizing patient outcomes in such complex cases.