A 57-year old male with a history of neurofibromatosis type 1 and mitral valve prolapse with moderate mitral regurgitation was admitted to a regional hospital due to prolonged dry cough, anemia, hepatosplenomegaly and 6 months non-intentional weight loss. Physical examination revealed many skin neurofibromatomas, a pre-existing holosystolic murmur and enlarged spleen. Laboratory tests showed increased serum creatinine (236 μmol/l), erythrocituria and proteinuria (1.7 g/day), anemia, thrombocytopenia. On admission, immunoserology (HEp-2, ANCA, anti-GBM) was negative. In hospital, he experienced sudden unilateral hearing loss and severe vertigo. Head CT and MRI revealed diffused chronic bilateral microscopic cerebral hemorrhages. Since the clinical course suggested glomerulonephritis associated with systemic disease, he was referred to the nephrology department. Cystoscopic evaluation performed due to an episode of macrohematuria was unremarkable. Viral hepatitis and HIV serology were negative. Abdominal ultrasound and CT confirmed hepatosplenomegaly with no signs of neoplastic process in the abdomen. Repeated immunoserological tests revealed cANCA/PR3 antibodies (84 IU/mL), low C3 complement fraction and mixed cryoglobulinemia. Electrophoresis of serum and urine was normal. Bone marrow biopsy performed due to haematologic abnormalities and enlarged spleen excluded potential hematologic disorder. Due to neurologic and haematologic disorders, the patient was incapable for a kidney biopsy procedure. Since the diagnosis was uncertain, he was initially treated with intravenous immunoglobulins at a dosage of 2 g/kg body weight. His condition finally improved enough to perform an urgent kidney biopsy. However, immediately after the biopsy, signs of sepsis appeared and a further deterioration of kidney function was observed. Streptoccus cristatus was isolated from blood cultures. Transesophageal echocardiography revealed mitral valve endocarditis with very large (3,5 X 0.5 cm), mobile pedunculated vegetation arising from the atrial side of the prolapsing P1-P2 scallops and moderate mitral regurgitation. In accordance with these findings, treatment with crystalline penicillin was started. 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. Electron microscopy confirmed electron dense mesangial and segmental subendothelial deposits, without large subepithelial deposits (humps) usually found in infection-related GN. 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 the P1-P2 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). 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 μmol/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. 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.