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.

Introduction: Diabetic nephropathy (DN) and hypertensive nephrosclerosis (HN) represent the most common causes of chronic kidney disease (CKD) and many patients progress to ­end-stage renal disease. Patients are treated primarily through the management of cardiovas­cular risk factors and hypertension; however patients with HN have a more favorable outcome. A noninvasive clinical approach to separate these two entities, especially in hypertensive patients who also have diabetes, would allow for targeted treatment and more appropriate resource allocation to those patients at the highest risk of CKD progression. Meth­ods: In this preliminary study, high-spatial-resolution matrix-assisted laser desorption/ion­ization (MALDI) mass spectrometry imaging (MSI) was integrated with high-mass accuracy MALDI-FTICR-MS and nLC-ESI-MS/MS analysis in order to detect tissue proteins within kidney biopsies to discriminate cases of DN (n = 9) from cases of HN (n = 9). Results: Differences in the tryptic peptide profiles of the 2 groups could clearly be detected, with these becoming even more evident in the more severe histological classes, even if this was not evident with routine histology. In particular, 4 putative proteins were detected and had a higher signal intensity within regions of DN tissue with extensive sclerosis or fibrosis. Among these, 2 proteins (PGRMC1 and CO3) had a signal intensity that increased at the latter stages of the disease and may be associated with progression. Discussion/Conclusion: This preliminary study represents a valuable starting point for a future study employing a larger cohort of patients to develop sensitive and specific protein biomarkers that could reliably differentiate between diabetic and hypertensive causes of CKD to allow for improved diagnosis, fewer biopsy procedures, and refined treatment approaches for clinicians.

The organic acid excretion was studied in urine samples from 26 preterm infants on the 1st and 5th days of life and the results compared to those obtained in 5 samples from full-term neonates. Gas-chromatography-mass spectrometry with a computer system was the method used in this work. The acids tabulated were those more closely related to lactic acidosis and the Krebs cycle. Great variations were found in the excretion of these acids in preterm infants in contrast to the very homogeneous pattern obtained in full-term neonates.

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