Case Studies
Case 9.5 Antineutrophil cytoplasmic antibody-associated necrotizing crescentic glomerulonephritis
A 64-year-old man presented with a 1-month history of nausea and malaise and a 1-week history of flu-like symptoms, rigors and vomiting. Eight weeks earlier, whilst on holiday, he developed infected insect bites around his left ankle and was treated with erythromycin. He had no urinary or joint symptoms and no family history of renal disease. On examination, he was pale with mild pitting oedema of both ankles and a blood pressure of 170/90. Analysis of a mid-stream urine specimen showed proteinuria (3+) with microscopic haematuria and granular casts. His haemoglobin was 92g/l with a white-cell count of 17.7 x 109/l and an erythrocyte sedimentation rate (ESR) of 122mm/h. His blood urea was 42.6mmol/l (NR 2.5-7.5) and serum creatinine 1094µmol/l (NR 60-120). Malarial parasites and hepatitis B surface antigen were not detected in his blood. Over the next 72h, his urine output fell to 30ml/day with further increases in his blood urea and serum creatinine.
Ultrasound examination showed bilaterally enlarged kidneys but no evidence of obstruction. Serum immunoglobulin levels were normal but C3 (1.56g/l; NR 0.8-1.40) and C4 (0.46g/l; NR 0.2-0.4) were raised. There was no paraproteinaemia and no free monoclonal light chains in his urine. Antinuclear, anti-dsDNA, and anti-GBM antibodies were negative. However, the patients's serum contained IgG antibodies which reacted strongly with cytoplasmic antigens of alcohol-fixed neutrophils, producing a granular pattern characteristic of classical antineutrophil cytoplasmic antibodies (cANCA). Further analysis showed antibodies to a neutrophil enzyme called serine proteinase 3 (PR3) by enzyme-linked immunosorbent assay (ELISA) (see Chapter 19).
A renal biopsy was performed to confirm the cause of his rapidly progressive glomerulonephritis. The biopsy specimen contained 30 glomeruli: one-third of these were totally sclerosed and all but one of the remainder showed necrotizing, crescentic glomerulonephritis. Cellular crescents, with extensive tuft necrosis, were seen in most glomeruli. The diagnosis was that of ANCA-associated, necrotizing crescentic glomerulonephritis.
He was treated with pulse cyclophosphamide (500mg/m2) and pulse methylprednisolone (1g daily for 3 days), followed by 60mg of prednisolone daily. For the next 12 days he required peritoneal dialysis until his renal function improved. He was discharged on maintenance therapy of prednisolone 40mg/day with pulse intravenous cyclophosphamide at monthly intervals. He continued on this regimen until his cANCA became negative; his treatment was then changed to oral prednisolone and azathioprine.
|
