A 47-year-old male with a past history of nephrolithiasis, irritable bowel syndrome, and mild depression presented to the emergency center with two weeks of flank pain and four days of cola-colored urine. He described a throbbing, stabbing pain in his left flank that persisted and progressively worsened, which was associated with dark urine, nausea, unmeasured fever, chills, and a 10-lb weight loss. He denied dysuria or urinary hesitancy.
On physical exam, vital signs showed a temperature of 37.2°C, blood pressure of 121/55 mmHg, pulse of 95 bpm, and respirations at 20 breaths per minute while saturating at 94% on room air. He was alert and oriented x 3, but in moderate distress from his left-sided flank pain. There was no cervical, axillary, or femoral lymphadenopathy present. On auscultation, he was noted to have bilateral, basilar crackles without rhonchi or wheezing. Cardiac exam showed a regular rate and rhythm, with a 2/6 systolic, crescendo-decrescendo murmur heard best over the left sternal border. There was severe, left CVA tenderness on exam, but his abdomen was soft, nondistended, and nontender. Extremities showed no edema, and skin exam showed no evidence of petechiae or rashes.
Initial laboratory data showed a WBC of 3.8 bil/L, Hgb of 7.7 g/dL, platelet count of 89 bil/L, sodium of 138 mmol/L, potassium of 4.4 mmol/L, chloride of 114 mmol/L, CO2 21 of mmol/L, calcium of 7.4 mg/dL, phosphorus of 3.0 mg/dL, BUN of 19 mg/dL, creatinine of 2.36 mg/dL, and glucose of 97 mg/DL. Urinalysis showed 3+ blood, 1+ protein, > 50 RBC/HPF, 0-5 WBC/HPF, and RBC casts.
Abdominal ultrasound showed a 12.6 cm right kidney, 12.4 cm left kidney with no hydronephrosis, and a spleen with wedge-shaped areas suggestive of infarct. An MRI showed splenomegaly of 17.9 cm and a wedge-shaped infarct (Figure
CT scan showing large splenic infarct.
Further blood test results showed a haptoglobin of 159 mg/DL, LDH of 272 U/L, fibrinogen of 248 mg/dL, an elevated CRP of 4.9 mg/dL, ESR of 25 mm/hr, C3 of 94 mg/dL, C4 of 23 mg/dL, negative antibodies to hepatitis A, B, and C, and negative ANA, ASO, and anticardiolipin antibodies. ANCA testing was negative using an indirect immune-fluorescent assay (IIF) with a positive lab test considered for results greater than 1:20. Myeloperoxidase antibody (MPO-ANCA) was negative, but proteinase-3 (PR3-ANCA) antibody titer was elevated at 160 units, using an enzyme-linked immunosorbent assay (ELISA) with a positive result greater than 21 units. Blood cultures were negative and remained so after 5 days.
A renal biopsy was performed. Light microscopy (Figure
Light microscopy (left) of kidney showing focal proliferation with cellular crescent and electron microscopy (right) showing focal foot process fusion and subendothelial deposits.
Concerned with the heart murmur and renal biopsy results, a transthoracic echocardiogram was performed and was negative for valvular vegetations. A subsequent transesophageal echocardiogram showed a bicuspid aortic valve with a vegetation. Culture-negative endocarditis was diagnosed and valve replacement performed with pathology showing necrosis, neutrophils, and
The patient received 6 weeks of antibiotic therapy with doxycycline and rifampin and clinically improved with decrease in flank pain. Urinalysis also improved showing 4-10 RBC/HPF, 0-5 WBC/HPF, and no visible casts. Creatinine decreased to 1.4 mg/dL, and ESR and CRP normalized within 2 months to 3 mm/hr and <0.4 mg/dL respectively. Repeat proteinase-3 antibodies remained elevated at 121-163 units despite antibiotic therapy.
Initial testing for ANCA-associated vasculitis typically uses IIF-ANCA. The specificity of ANCA testing is very high, with a very low false negative rate, but measurement of PR3-ANCA or MPO-ANCA antibodies with a positive IIF-ANCA improves sensitivity by ruling out false positive tests.
Positive tests for IIF-ANCA, PR3-ANCA, and MPO-ANCA antibodies may be found in patients with subacute bacterial endocarditis. Common organisms include Viridans streptococci, Staphylococcus aureus, and other staph species. The association of infectious endocarditis with these antibodies has led to postulated causal mechanisms for vasculitis. Unmethylated CpG is a constituent of bacterial DNA and has been shown to stimulate ANCA production in B cells of ANCA-associated vasculitis patients. Staph aureus tsst-1 superantigen nasal carriage carries a high rate of relapse in granulomatous polyangiitis patients. Diseases with barrier dysfunction to microbes, such as inflammatory bowel disease, show increased incidence of ANCA positivity. Neutrophil extracellular traps (NETs), which play a role in extracellular killing of microbes, may also release ANCA-associated antigens [
On the other hand, a retrospective review of patients with IIF-ANCA-negative, positive MPO-ANCA, or PR3-ANCA antibody testing such as that found in this case, showed that only 1 of 38 of these patients actually developed ANCA-associated vasculitis. There is evidence for cross-reactivity in the assays, as PR3-ANCA-positive antibodies have also been found in nonvasculitic inflammatory conditions such as rheumatoid arthritis, inflammatory bowel disease, and SLE [
We present a case of culture-negative endocarditis and acute kidney injury due to glomerulonephritis, due to
Case review [
In summary, this case highlights how
This research was presented in poster format at the American Society of Nephrology’s (ASN) Kidney Week 2017 in New Orleans, Louisiana, on November 1, 2017.
The authors declare that they have no conflicts of interest.