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Purpose: Membranous nephropathy (MN) is the most frequent cause of nephrotic syndrome in adults and the disease course is characterized by the "rule of third", with one-third of patients experiencing complete remission and the remaining experiencing relapses or progression of the disease. Additionally, the therapeutic approach is not standardized, leading to further heterogeneity in terms of response and outcome., Experimental Design: In this pilot study, MALDI-MSI analysis is performed on renal biopsies (n = 13) obtained from two homogeneous groups of patients, which differentially responded to the immunosuppressive treatments (Ponticelli regimen)., Results: A signal at m/z 1303 displays the greatest discriminatory power when comparing the two groups and is observed to be of higher intensity in the glomeruli of the non-responding patients. The corresponding tryptic peptide is identified as macrophage migration inhibitory factor (MIF)., Conclusions and Clinical Relevance: Despite much effort being made in recent years to understand the pathogenesis of MN, a biomarker able to predict the outcome of these patients following therapeutic treatment is still lacking. Here, a protein (MIF), verified by immunohistochemistry, that can differentiate between these MN patients and could be a valuable starting point for a further study focused on verifying its predictive role in therapy response is highlighted., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Purpose: Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) technology has advanced rapidly during recent years with the development of instruments equipped with low-diameter lasers that are suitable for high spatial resolution imaging. This may provide significant advantages in certain fields of molecular pathology where more specific protein fingerprints of individual cell types are required, such as renal pathology., Experimental Design: Here MALDI-MSI analysis of a cohort of membranous nephropathy (MN) patients is performed among which patients either responded favorably (R; n = 6), or unfavorably (NR; n = 4), to immunosuppressive treatment (Ponticelli Regimen), employing a 10 µm laser spot diameter., Results: Specific tryptic peptide profiles of the different cellular regions within the glomerulus can be generated, similarly for the epithelial cells belonging to the proximal and distal tubules. Conversely, specific glomerular and sub-glomerular profiles cannot be obtained while using the pixel size performed in previous studies (50 µm). Furthermore, two proteins are highlighted, sonic hedgehog and α-smooth muscle actin, whose signal intensity and spatial localization within the sub-glomerular and tubulointerstitial compartments differ between treatment responders and non-responders., Conclusions and Clinical Relevance: The present study exemplifies the advantage of using high spatial resolution MALDI-MSI for the study of MN and highlights that such findings have the potential to provide complementary support in the routine prognostic assessment of MN patients., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)