Fatal Pneumococcus Sepsis after Treatment of Late Antibody-Mediated Kidney Graft Rejection

Abstract

Antibody-mediated rejection (ABMR) is a major cause of late renal allograft dysfunction and graft loss. Risks and benefits of treatment of late ABMR have not been evaluated in randomized clinical trials. We report on a 35-year-old patient with deterioration in renal function and progressive proteinuria 15 years after transplantation. Recurrent infections after a splenectomy following traumatic splenic rupture 3 years earlier had led to reduction of immunosuppression. Renal transplant biopsy showed glomerular double contours, 40% fibrosis/tubular atrophy, peritubular capillaritis, and positive C4d staining indicating chronic-active ABMR. ABMR treatment was initiated with steroids, plasmapheresis, and rituximab. Fourteen days later, she presented to the emergency department with fever, diarrhea, vomiting, and hypotension. Despite antibiotic treatment she deteriorated with progressive hypotension, capillary leak with pleural effusion, peripheral edema, and progressive respiratory insufficiency. She died due to septic shock five days after admission. Blood cultures showed Streptococcus pneumoniae, consistent with a diagnosis of overwhelming postsplenectomy infection syndrome, despite protective pneumococcus vaccination titers. We assume that the infection was caused by one of the strains not covered by the Pneumovax 23 vaccination. The increased immunosuppression with B cell depletion may have contributed to the overwhelming course of this infection.

Figure 1

Renal function and proteinuria over time. Renal function remained largely stable over 15 years, with intermittent decreases in renal function that led to transplant biopsies.

Figure 2

Histologic assessment of renal transplant biopsy. The biopsy showed signs of chronic-active antibody-mediated rejection with severe tubular damage, interstitial edema, and peritubular capillaritis ((a) arrowheads); glomerulitis with double contours ((b) arrowheads); diffuse positive C4d staining in peritubular capillaries (c); and interstitial fibrosis with severe arteriosclerosis (d). ((a) H&E, (b) and (d) Jones methenamine, and (c) C4d immunohistochemistry; original magnification: (a) and (b) ×60, (c) ×20, and (d) ×40).

Figure 3

Effect of plasmapheresis on immunoglobulin concentration. We measured the concentration of immunoglobulin G in the patient's serum before and after the first and second plasma exchanges and in the plasma waste bag. Serum concentration dropped significantly during the course of treatment.