Kidney Lipidomics by Mass Spectrometry Imaging: A Focus on the Glomerulus

Abstract

Lipid disorders have been associated with glomerulopathies, a distinct type of renal pathologies, such as nephrotic syndrome. Global analyses targeting kidney lipids in this pathophysiologic context have been extensively performed, but most often regardless of the architectural and functional complexity of the kidney. The new developments in mass spectrometry imaging technologies have opened a promising field in localized lipidomic studies focused on this organ. In this article, we revisit the main works having employed the Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) technology, and the few reports on the use of TOF-Secondary Ion Mass Spectrometry (TOF-SIMS). We also present a first analysis of mouse kidney cortex sections by cluster TOF-SIMS. The latter represents a good option for high resolution lipid imaging when frozen unfixed histological samples are available. The advantages and drawbacks of this developing field are discussed.

Keywords: MALDI-TOF; MSI; TOF-SIMS; glomerulopathies; nephrotic syndrome.

Figure 1

Representative section of a mouse kidney cortex, showing the spatial distribution of several ions (sum of cholesterol peaks, sum of α-tocopherol peaks, sum of phosphatidylcholine (PC) peaks, sum of sulfatides (ST 40:1, ST 40:2, ST 40:3), sum of sphingomyelin (SM) 34:1 peaks, and the total ion current) at a spatial resolution of 2 µm per pixel. The scale on the right (gray levels or colors) indicates the relative abundance. Yellow or white denote higher abundances, while blue or black denote lower abundances. The two lower panels have been constructed by attributing one color (red or green) to each compound. Glomerular regions of interest are selected and depicted by the dashed white line. Bar length: 100 µm. The name of the compound, the maximal number of counts in a pixel (MC), and the total number of counts (TC) are written below each image.

Figure 2

Representative spectra of a mouse kidney cortex, showing the relative intensities of peaks corresponding to cholesterol ions (in positive-top- and negative-bottom-mode) in glomerular and non-glomerular regions. The spectra are normalized to the total primary ion dose.