Abstract
Abstract Background and Aims Fibrosis is responsible for the loss of kidney function as a result of several insults, such as ischemia-reperfusion injury or hyperfiltration. This process can continue even after cessation of the primary insult, as documented in acute kidney injury to chronic kidney disease. Recently, we discovered that iron accumulation is a hallmark of fibrotic diseases [1]. We found that in mouse models, iron deposition in the kidney accompanies the progression of the disease. Based on these results, we propose that chronic-low grade hemolysis produced in situation like ischemia-reperfusion injury may be one of the drivers of fibrosis through the damage that the filtrated hemolytic iron cause to the kidneys. Early detection of this iron could help the detection of ongoing fibrogenesis and improve the outcomes by prompt intervention. The challenge of this approach is the lack of non-invasive markers of fibrosis. We evaluated if magnetic resonance image (MRI)-based detection of iron levels in the kidney are correlated to fibrosis in biopsies from kidney transplant recipients. Method After approval from the Institutional Revision Board, we carried out a transversal study in our center between 2020 and 2021. We evaluated iron deposits through MRI in patients who underwent a kidney biopsy (per protocol or by clinical indication) and its association with histological parameters. MRI was performed at the same period the biopsy was done. Iron deposits were estimated by using the R2* sequence considering the Grassedonio protocol [2]. Results We collected data from 15 kidney transplant recipients. Mean age was 58.3 years old. Mean time from kidney transplant to the biopsy was 4.3 years and mean eGFR was 44.4 ml/min/1.73 m2.We analyzed by MRI the R2* signal in the kidney cortex, and their level of fibrosis measured on the biopsies (IFTA score, interstitial fibrosis and tubular atrophy). We found that patients with high IFTA score (2 and 3) presented with significantly higher R2* signal (p = 0.005), than patients with low IFTA score (0 and 1). We also found positive and significant correlation between IFTA (0-3) and iron deposits (Spearman correlation index: r = 0.7537, p = 0.0012). Conclusion Iron deposits in the kidney are higher in patients with more fibrosis, and its detection through MRI could be considered a non-invasive marker.
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