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we report here the first case of spontaneous rupture of kidney resulting from mixed cryoglobulinemia .
a 44-year - old man presented with sudden onset of fever , acute pulmonary edema , left flank abdominal pain unassociated with trauma , and rapidly progressive renal failure requiring dialysis . computed tomography of the abdomen revealed a large perirenal hematoma of the left kidney . during conservative surgery , the patient underwent renal biopsy that showed renal vasculitis and membranoproliferative glomerulonephritis with intracapillary microthrombi .
the patient was better after immunosuppressive therapy , with the disappearance of clinical symptoms and the recovery of baseline renal function .
we report on this case and discuss a possible link between spontaneous rupture of kidney and mixed cryoglobulinemia - associated sjgren s syndrome .
spontaneous rupture of kidney ( srk ) is uncommon . in most cases , it was a complication of benign or malignant kidney tumors .
only a few cases are a result of systemic vasculitis , particularly polyarteritis nodosa ( pan ) , microscopic polyangiitis , and in sporadic reports , wegener s granulomatosis . to our knowledge
a 44-year - old white man was admitted to our hospital because of acute pulmonary edema .
his past medical history was significant for chronic tobacco use and recurrent episodes of arthralgias over the course of 2 years , which were treated symptomatically by the patient by self - medication with analgesics , without any specific medical management .
the patient had been well until 2 months earlier , when he began to have worsening of his physical state , anorexia , weakness , weight loss , and diffuse myalgias .
three days before admission , he complained of acute left flank pain unassociated with trauma .
in addition , the patient reported a significant decrease of urine volume ( < 0.5 l urine in 24 hours ) and dyspnea .
physical examination showed high blood pressure ( 170/100 mmhg ) , his temperature was 38.7c , and his respiratory rate was 34 breaths per minute .
the abdomen was tender , mainly over the left upper quadrant , and had no palpable hepatosplenomegaly .
exam of the lower limb found petechial purpura on his left leg , with livedo reticularis . otherwise , the examination was normal .
laboratory findings revealed a rapidly progressive renal failure with a serum creatinine level of 1.71 mg / dl ( normal value , 0.61.2 mg / dl ) , which increased to 4.02 mg / dl over the next 2 days ; a blood urea nitrogen level of 57 mg / dl ( normal value , 720 mg / dl ) , which also increased to 123 mg / dl ; a hypervolemic hyponatremia of 124 meq / l ( normal value , 135145 meq / l ) ; and normal serum electrolytes otherwise .
twenty - four hour urinary protein levels were 0.6 g/24 hours ( normal value , < 0.03 g/24 hours ) , and urinary sediment was positive for microscopic hematuria .
hemoglobin was 9.7 g / dl ( normal value , 1316 g / dl ) , white blood cell count was 18,300/mm ( normal value , 4,0001,000/mm ) , and platelets were 626,000/mm ( normal value , 150,000300,000/mm ) .
erythrocyte sedimentation rate was 80 mm / hour ( normal value , < 15 mm / hour ) , with a c - reactive protein level of 11.3 mg / l ( normal value , 612 mg / l ) .
lactate dehydrogenase levels were elevated ( 1,243 u / l ; normal value , < 250 u / l ) .
ch50 was not checked , but complement component c3 was normal , at 80 mg / dl ( normal , 80170 mg / dl ) , and c4 was strongly reduced , at 6 mg / dl ( normal , 1640 mg / dl ) .
there was no monoclonal paraprotein detected both on serum and urine protein immuno - electrophoresis .
in addition , five blood samples for cultures ( both aerobic and anaerobic ) were sent to the laboratory in view of the patient s fever , leukocytosis , and high erythrocyte sedimentation rate , all of which were negative .
renal ultrasound showed normal - sized kidneys without evidence of hydronephrosis , but it allowed us to identify a subcapsular renal hematoma that measured 6352 mm in the upper pole of the left kidney , which was confirmed by abdominal computed tomography ( ct ) scan ( figure 1a ) .
multislice computed angiotomography scanning identified the hematoma and ruled out microaneurysms of the main renal arteries , other vascular abnormalities , and renal tumors ( figure 1b ) .
hemodialysis therapy was started because of oliguria , continuous decrease of renal function , and persisting pulmonary edema despite high doses of furosemide ( 500 mg / day ) , and then the patient was operated on with conservative surgery for renal hematoma .
renal biopsy was performed , during surgery , the third day after admission and was submitted for light microscopic and immunofluorescence examination ( figure 2 ) . the specimen consisted of renal medulla and cortex with 14 glomeruli .
there was significant hypercellularity of glomeruli with numerous infiltrating neutrophils , minimal endocapillary proliferation , and one cellular crescent .
there were thickening and reduplication of the glomerular basal membrane , suggesting membranoproliferative glomerulonephritis . in two glomeruli , we noted intracapillary amorphous deposits compatible with microthrombi .
the laboratory tests were sent immediately after we received the kidney biopsy results , 72 hours after the biopsy had been performed .
serological studies for antineutrophil cytoplasmic antibodies , antiglomerular basement membrane antibodies , anti - double - stranded dna antibodies , and anti - smith antibodies were negative , excluding respectively pauci - immune vasculitis , goodpasture s syndrome , and lupus vasculitis .
skin - biopsy specimen of a purpuric lesion showed leukocytoclastic vasculitis without immunoglobulin a deposition , and therefore did not support the diagnosis of henoch - schnlein purpura .
tests for cryoglobulinemia were positive , including the presence of cryocrit ( 12% ) with type ii mixed cryoglobulin ( immunoglobulin g / immunoglobulin m kappa ) .
we made additional investigations to determine the cause of mixed cryoglobulinemia , and assessment for hepatitis c virus ( hcv ) rna and hepatitis b virus dna by polymerase chain reaction was negative .
tests for sjgren s syndrome were positive with the presence of anti - ro ( ss - a ) , anti - la ( ss - b ) , lymphocytic infiltrate in minor salivary gland biopsy ( grade 3 according to chisholm and mason grading system ) , and positive schirmer s test . screening for lymphoma remained negative despite initial elevated lactate dehydrogenase levels .
all these data confirmed that the patient had srk caused by type ii mixed cryoglobulinemia - associated sjgren s syndrome .
the patient received 3 days of pulses of methylprednisolone ( 1 g / day ) , followed by oral prednisone ( 1 mg / kg / day ) with a decreasing regimen and 6 monthly pulses of intravenous cyclophosphamide ( 1 g ) as induction of remission .
the patient remained febrile during hospitalization , with temperatures ranging between 38.5c and 38.8c , until he received the third pulse of methyl prednisolone , which was administered 12 days after admission .
arthralgias and the other symptoms disappeared , proteinuria fell to only trace amounts , and renal function returned to its baseline value ( 0.9 mg / dl ) over the next 2 weeks , and c4 levels were again normal .
ethical approval was not needed in the present case report , because it did nt include research or experiments .
there was no risk of causing harm or violating the patient s right , since it was presented in a way that respected the patient s privacy and confidentiality .
it was first reported by bonet in 1700 and later described in more detail by wnderlich in 1856.1,2 to date , more than 200 cases have been reported in world literature . to the best of our knowledge ,
tumors , particularly renal cell carcinoma and angiomyolipoma , are the most common cause of srk , occurring in 57%73% of cases.3,4 vascular disease was reported in a meta - analysis of spontaneous renal hemorrhage as the next most common offender , with pan occurring most frequently.5 other vasculitis was also reported to be associated with srk , especially microscopic polyangiitis and wegener s granulomatosis.68 our patient had srk , probably as a result of vasculitis ; however , he had neither pan nor pauci - immune vasculitis .
furthermore , the patient had also neither renal tumor , both in radiologic and histologic findings , nor renal infection . on the basis of clinical context and laboratory findings , we suggest that srk was a result of cryoglobulinemic vasculitis associated with sjgren s syndrome .
prevalence of hcv infection in patients with mixed cryoglobulinemia ranges from 30% to 96%.9,10 the etiologies of negative - hcv mixed cryoglobulinemia are  essential  mixed cryoglobulinemia ( 27% ) ; lymphoproliferative disorders , especially b - non - hodgkin s lymphoma and myeloma ( 26% ) ; autoimmune diseases , particularly sjgren s disease and lupus ( 34% ) ; and infectious disease ( 13% ) , including hepatitis b virus and hiv.11 in the study of trejo et al,12 of 443 patients with cryoglobulinemia , 10% had sjgren s syndrome .
inversely , in large series of patients with sjgren s syndrome , mixed cryoglobulinemia , especially type ii , was present in 20% of cases and was characterized by a low ch50 , cutaneous vasculitis , and poor prognosis resulting from more severe internal organ involvement and frequent evolution to malignant lymphomas.1315 vasculitis in sjgren s syndrome can occur either as a cutaneous localized form ( leukocytoclastic vasculitis ) or as systemic necrotizing vasculitis involving small - sized and medium - sized arteries of various organs related to the presence of cryoglobulinemia.16 it is well known that in sjgren s syndrome type b , there is aneurysmal dilatation of arteries .
, there are only three reports : achkar et al described first a ruptured aneurysm of the inferior pancreaticoduodenal artery in the setting of rheumatoid vasculitis - associated sjgren s
syndrome,17 curi et al reported a contained rupture of the visceral aorta in a patient with sjgren s syndrome associated with osteoarthritis,18 and klingler et al reported a rupture of a spinal artery aneurysm attributable to exacerbated sjgren syndrome - associated cryoglobulinemic vasculitis.19 in contrast , it is also known that cryoglobulinemic vasculitis may induce injuries in the vascular wall .
herold et al described cryoglobulinemic vasculitis associated with aortic aneurysms in pediatric cases of kawasaki disease,20 and au et al reported structural aortic abnormalities in four patients with negative - hcv cryoglobulinemia , including multiple dissections , aneurysms , and congenital aortic arch abnormalities.21 therefore , we presume that an exacerbation of the sjgren s syndrome - induced cryoglobulinemic vasculitis with necrotizing arteritis and fibrinoid necrosis of the vessel s media led to weakening of the arterial wall , formation of kidney aneurysm , and spontaneous rupture .
this mechanism may also explain the occurence of microaneurysms and srk in pan and in rare cases of microscopic polyangiitis and wegener s granulomatosis.2226
backgroundspontaneous rupture of the kidney is uncommon and is mainly caused by renal tumors . 
 only a few cases are caused by vasculitis . 
 we report here the first case of spontaneous rupture of kidney resulting from mixed cryoglobulinemia.case presentationa 44-year - old man presented with sudden onset of fever , acute pulmonary edema , left flank abdominal pain unassociated with trauma , and rapidly progressive renal failure requiring dialysis . 
 computed tomography of the abdomen revealed a large perirenal hematoma of the left kidney . during conservative surgery , the patient underwent renal biopsy that showed renal vasculitis and membranoproliferative glomerulonephritis with intracapillary microthrombi . 
 tests were positive for mixed cryoglobulinemia caused by sjgren s syndrome . 
 the patient was better after immunosuppressive therapy , with the disappearance of clinical symptoms and the recovery of baseline renal function.conclusionwe report on this case and discuss a possible link between spontaneous rupture of kidney and mixed cryoglobulinemia - associated sjgren s syndrome .