R2 and R2* MRI assessment of liver iron content in an undifferentiated diagnostic population with hyperferritinaemia, and impact on clinical decision making.

PURPOSE: To confirm the linear correlation between Ferriscan® R2 (1/T2 Relaxomatry) and R2* (1/T2* Relaxometry) derived 3D Gradient echo (GRE) mDIXON-Quant sequence (Philips) with simultaneous production of a proton density fat fraction (PDFF) in undifferentiated patients with hyperferritinaemia, and to prospectively determine the clinical utility of this tool in these patients by recording the impact on clinical decision-making. MATERIALS AND METHODS: Participants referred to a hospital haematology outpatient clinic for investigation and management of elevated serum ferritin (two serum ferritin levels > 500 µg/L 4 weeks apart) were included in the study. EXCLUSION CRITERIA: contraindications to MRI; clinically relevant investigations for alternative causes of hyperferritinaemia pending; and terminal illness. Thirty-two participants were recruited: 27 men, 5 women. All MRIs performed at 1.5 T. For R2* quantification, 3D six echo GRE sequence (mDIXON-Quant) was acquired. R2 images were acquired over 20 min as dictated and reported by the licensee (Ferriscan®). Clinician interpretation and patient management based on R2* and liver iron content derived from R2 (LICR2) was recorded. Pearson's correlations, linear regression analyses, and ROC curves were calculated. P value <0.05 was considered significant. RESULTS: A high degree of correlation between mean R2* and LICR2 was observed in this novel patient population (slope ±â€¯SE of 43.35 ±â€¯1.88 s-1 permg/g; 95 % CI 39.5-47.2; P < 0.001; R2 = 0.87). Clinical decision making was amended in 14/32 (44 %) patients with hyperferritinaemia following the disclosure of R2* results to clinicians, compared with serum ferritin alone. Liver biopsy was avoided in one patient based on LICR2 and R2*. Unrecognised hepatic steatosis was diagnosed in one patient from the PDFF map. CONCLUSION: We have confirmed the linear correlation between R2 and R2* in a real-world diagnostic population with hyperferritinaemia. Non-invasive assessment of liver iron content (LIC) by R2 and R2* MRI is a useful clinical tool and alters management in these patients.

IL-18 contributes to renal damage after ischemia-reperfusion.

IL-18 is a proinflammatory cytokine produced by macrophages and other cell types present in the kidney during ischemia-reperfusion injury (IRI), but its role in this injury is unknown. Here, compared with wild-type mice, IL-18(-/-) mice subjected to kidney IRI demonstrated better kidney function, less tubular damage, reduced accumulation of neutrophils and macrophages, and decreased expression of proinflammatory molecules that are downstream of IL-18. For determination of the relative contributions of leukocytes and parenchymal cells to IL-18 production and subsequent kidney damage during IRI, bone marrow-chimeric mice were generated. Wild-type mice engrafted with IL-18(-/-) hemopoietic cells showed less kidney dysfunction and tubular damage than IL-18(-/-) mice engrafted with wild-type bone marrow. In vitro, macrophages produced IL-18 mRNA and protein in response to ischemia. These data suggest bone marrow-derived cells are the key contributors to IL-18-mediated effects of renal IRI. Finally, similar to IL-18(-/-) mice, pretreatment of wild-type mice with IL-18-binding protein was renoprotective in this model of IRI. In conclusion, IL-18, derived primarily from cells of bone marrow origin, contributes to the renal damage observed during IRI. IL-18-binding protein may have potential as a renoprotective therapy.