Recurrence of Proliferative Glomerulonephritis with Monoclonal Immunoglobulin G Deposits with a Striated Ultrastructure

This is the peer-reviewed but unedited manuscript version of the following article: Nephron 2020;144(suppl 1):43–48 (DOI: 10.1159/000512330)]. The final, published version is available at http://www.karger.com/?doi=10.1159/000512330

Obesity-related proximal tubulopathy: an emerging threat to kidney health

Our previous studies have demonstrated that lipid overload leads to lysosomal dysfunction and autophagic stagnation in kidney proximal tubular epithelial cells (PTECs), which contributes to the renal lipotoxicity and eventually leading to the development of an obesity-related kidney disease. Here we identified that TFEB (transcription factor EB) is a modulator of PTECs lipotoxicity. Exposure to saturated fatty acid enhanced TFEB dephosphorylation and nuclear translocation in PTECs. In a mouse model fed with a high-fat diet (HFD), activated TFEB counteracted phospholipid accumulation in lysosomes by promoting lysosomal exocytosis in PTECs. Conversely, HFD-fed, PTECs-specific tfeb−/− deficient mice exhibited increased phospholipid accumulation and autophagic stagnation, which made kidney vulnerable to injury following ischemia-reperfusion. Moreover, a higher body mass index was correlated to reductions in TFEB nuclear translocation in PTECs of chronic kidney disease patients. These data suggest that PTECs are involved in the pathogenesis of obesity-related kidney disease, which is called obesity-related proximal tubulopathy. Abbreviations: EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; GAP: GTPase activating protein; HFD: high-fat diet; I/R: ischemia-reperfusion; LMP: lysosomal membrane permeabilization; LRP2: low density lipoprotein receptor-related protein 2; MLBs: multilamellar bodies; MTORC1: mechanistic target of rapamycin kinase complex 1; ORT: obesity-related proximal tubulopathy; PA: palmitic acid; PTEC: proximal tubular epithelial cell; RRAG: Ras related GTP binding; RPS6KB1, ribosomal protein S6 kinase B1; TFEB: transcription factor EB

Blood levels of d-amino acids reflect the clinical course of COVID-19

d-Amino acids, rare enantiomers of amino acids, have been identified as biomarkers and therapeutic options for COVID-19. Methods for monitoring recovery are necessary for managing COVID-19. On the other hand, the presence of SARS-CoV2 virus in the blood is associated with worse outcomes. We investigated the potential of d-amino acids for assessing recovery from severe COVID-19. In patients with severe COVID-19 requiring artificial ventilation, the blood levels of d-amino acids, including d-alanine, d-proline, d-serine, and d-asparagine, which were lower than the normal range before treatment, quickly and transiently increased and surpassed the upper limit of the normal range. This increase preceded the recovery of respiratory function, as indicated by ventilation weaning. The increase in blood d-amino acid levels was associated with the disappearance of the virus in the blood, but not with inflammatory manifestations or blood cytokine levels. d-Amino acids are sensitive biomarkers that reflect the recovery of the clinical course and blood viral load. Dynamic changes in blood d-amino acid levels are key indicators of clinical course