Interestingly, in 2012, Forbes et al. serum creatinine, not determined, Intravenous immunoglobulin Open in a separate window Fig. 1 Low esophageal two-chamber view. Shown is large vegetation (arrow) on the Xanthone (Genicide) posterior leaflet of the mitral valve, which prolapses into the left ventricle during sistole Open in a separate window Fig. 2 Three-dimensional trans-esophageal view of the mitral valve C viewed from the atrial side. Shown is large branched vegetation (asteriks), which adheres to the P2 scallop of the posterial mitral leaflet The pathohistological report of the kidney biopsy revealed uneven proliferative (70%), exudative (32%), necrotizing (10%) and crescentic (13%) glomerulonephritis with mixed inflammatory interstitial infiltration. Immunofluorescence showed glomerular deposits of C3, IgG and IgM, suggesting infection-related immunocomplex GN (Fig.?3). Electron microscopy confirmed electron dense mesangial and segmental subendothelial deposits, without large subepithelial deposits (humps) usually found in infection-related GN. Open in a separate window Fig. 3 Diffuse proliferative glomerulonephritis (a) with focal glomerular necrosis Keratin 18 (phospho-Ser33) antibody (b) and extracapillary crescent formation (c) in 13% glomeruli Given our uncertainty of reliably excluding an ANCA driven mechanism of disease, high dose methylprednisolone was introduced (3 pulses 7?mg/kg bw followed by oral methylprednisolone 0.8?mg/kg bw for 1?month with stepwise lowering and exclusion after the second biopsy), which resulted in a gradual improvement of kidney function and general condition. A week later, the patient underwent elective surgical treatment of mitral valve endocarditis. Mitral valve repair with resection of Xanthone (Genicide) the P1-P2 Xanthone (Genicide) scallops and mitral valve annuloplasty was performed. After the surgical intervention, his kidney function further improved. At discharge (1?month after the mitral valve operation) his serum creatinine (131 umol/l) and PR3-ANCA titer (32?IU/mL) were still increased, while blood cryoglobulin level had normalized (100?mg/l) (Table ?(Table1).1). In addition, abdominal ultrasound showed a reduction of spleen size, and the vertigo had disappeared. However, unilateral hearing loss remained. Six months after the first biopsy, laboratory tests and a second biopsy were performed. Improvement of kidney function (serum creatinine 100?mol/l), negative PR3 ANCA levels, restituted serum complement levels, and persistent minimal glomerular erythrocituria were observed. The second kidney biopsy revealed complete kidney resolution, including an absence of immune deposits (Fig.?4). Today, 4?years after the 1st biopsy the patient has persistent unilateral hearing loss but stable renal function (serum creatinine 98 umol/l), negative PR3 ANCA and cryoglobulins levels, and unremarkable urine sediment (Table ?(Table11). Open in a separate window Fig. 4 (a) Immune complex glomerulonephritis (IgG+, IgM+, C32+) in the 1st biopsy disappeared in the 2nd biopsy (IgG-, IgM?+??, C3?+?-). b Renal parenchyma looked normal Discussion and conclusions The principal aim of this case report is to highlight the diagnostic and treatment challenge in patients with ANCA-PR3 GN, nervous system involvement, hepatosplenomegaly and clinically silent subacute/chronic infectious endocarditis. It is nowadays well established that ANCA is a clinically relevant diagnostic marker for systemic ANCA vasculitis, also predictive of renal disease activity [1, 3]. However, recent publications report that ANCA seropositivity (MPO or PR3) also develops in adults with infection-related GN [2]. One of the largest studies addressing the association of ANCA vasculitis and chronic infection discovered that the majority of patients with previously confirmed ANCA vasculitis accompanied with chronic infections were finally re-diagnosed as subacute bacterial endocarditis [4]. In addition,.