There is currently no technique to unambiguously diagnose antemortem kidney injury on postmortem examination since postmortem tissue damage and autolysis are common. We assessed the ability to detect kidney injury molecule-1 (KIM-1) expression in adult and fetal kidneys examined at autopsy. In adult kidneys (n=52 subjects), we found that the intensity of KIM-1 staining significantly correlated with the antemortem level of serum creatinine, and this was independent of the extent of tissue autolysis. Kidneys from a total of 52 fetal/neonatal subjects, 30 stillborns and 22 liveborns, were assessed for KIM-1 staining. Given that serum creatinine is unreliable and often unavailable in fetuses and newborns, we assessed pre-terminal hypoxia in fetuses by the presence of squames in pulmonary alveoli and by required intubation. KIM-1 expression correlated with these clinical indices of hypoxia. The expression of KIM-1 was seen in a majority of the fetal and neonatal autopsy kidneys (77%, 40/52) as early as 16 weeks of gestation, even in the presence of autolysis. Thus, KIM-1 is a specific and stable marker of antemortem tubular injury in adult and fetuses, despite postmortem autolysis.
A rat model of antineutrophil cytoplasmic antibody (ANCA) associated vasculitides reveals crescentic glomerulonephritis as seen in human renal biopsies and diffuse lung hemorrhage that is not well documented in human lung biopsies. A 64-year-old male, with shortness of breath and mild elevation of serum creatinine, was found to have a positive serum test for ANCA, but negative antiglomerular basement membrane antibody. A renal biopsy showed pauci-immune type of crescentic glomerulonephritis and focal arteritis. The prior lung wedge biopsy was retrospectively reviewed to show diffuse hemorrhage and hemosiderosis with focal giant cells. In addition, small arteries revealed subtle neutrophil aggregation, and margination along vascular endothelium, but no definitive vasculitis. The pathology of ANCA associated vasculitides results from activated neutrophils by ANCA and subsequent activation of the alternative complement cascade with endothelial injury, neutrophil aggregation and margination. Our findings, after the correlation between lung biopsy and renal biopsy, imply that the top differential diagnosis in the lung biopsy should be microscopic polyangiitis when diffuse pulmonary hemorrhage and hemosiderosis are present in this ANCA-positive patient.
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