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Renal biopsies of two patients from cohort 1 (tacrolimus) who lost their grafts. Patient 1: A, inflammation in areas of interstitial fibrosis and tubular atrophy (i-IFTA) (Masson's trichrome stain, 40Â, scale bar 250 mm); B, chronic cellular rejection due to tubulitis (t3) and interstitial inflammation (i1) (Jones' methenamine silver stain, 400Â, scale bar 100 mm); C, C4d-negative in peritubular capillaries (C4d immunofluorescence stain (40Â, scale bar 250 mm). Patient 2: D, diffuse tubulitis (t3), pericapillaritis (ptc1), and interstitial inflammation (i2) (hematoxylin and eosin stain, 400Â, scale bar 100 mm); E, focal glomerulitis (g1) (hematoxylin and eosin stain, 400Â, scale bar 100 mm); F, C4d-positive peritubular capillaries (C4d immunofluorescence stain, 40Â, scale bar 250 mm).
Source publication
Tacrolimus (TAC), a calcineurin inhibitor, and everolimus (EVL), an mTOR inhibitor, have been used as immunosuppressive (ISS) drugs in post-kidney transplantation therapy. The objective of this study was to compare the efficacy of EVL vs TAC in the ISS maintenance triple therapy. Ninety-seven kidney transplant patients, who received triple maintena...
Context in source publication
Context 1
... renal biopsy results for two patients from C1 who lost their grafts showed that one patient experienced a chronic cellular rejection due to inflammation in areas of interstitial fibrosis and tubular atrophy (i-IFTA), intense tubulitis (t3), and interstitial inflammation (i2) (PAS stain, 40 Â magnification); C4d was negative per immunohistochemistry stain (at 40 Â magnification). The second patient experienced active cellular and humoral rejections characterized by diffuse intense tubulitis (t3), interstitial inflammation (i2), focal glomerulitis (g1), and pericapillaritis (ptc1); C4d was positive (C4d2: 10-50%) according to BANFF (25,26) (Figure 2). Among the C2 patients, three Data are reported as means±SD, number (%), or median and interquartile range (Student's t-test, MannWhitney and Pearson's chi-squared test). ...
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Chronic kidney disease (CKD) is a serious comorbidity affecting liver transplant recipients (LTRs). Calcineurin inhibitor dosing minimization protocols and everolimus use purportedly increased from 2010, potentially impacting CKD development. This systematic literature review was designed to identify CKD incidence in adult LTRs, focusing on studies...
Citations
The mammalian target of rapamycin (mTOR), an evolutionarily highly conserved serine/threonine protein kinase, plays a prominent role in controlling gene expression, metabolism, and cell death. Programmed cell death (PCD) is indispensable for maintaining homeostasis by removing senescent, defective, or malignant cells. Necroptosis, a type of PCD, relies on the interplay between receptor-interacting serine-threonine kinases (RIPKs) and the membrane perforation by mixed lineage kinase domain-like protein (MLKL), which is distinguished from apoptosis. With the development of necroptosis-regulating mechanisms, the importance of mTOR in the complex network of intersecting signaling pathways that govern the process has become more evident. mTOR is directly responsible for the regulation of RIPKs. Autophagy is an indirect mechanism by which mTOR regulates the removal and interaction of RIPKs. Another necroptosis trigger is reactive oxygen species (ROS) produced by oxidative stress; mTOR regulates necroptosis by exploiting ROS. Considering the intricacy of the signal network, it is reasonable to assume that mTOR exerts a bifacial effect on necroptosis. However, additional research is necessary to elucidate the underlying mechanisms. In this review, we summarized the mechanisms underlying mTOR activation and necroptosis and highlighted the signaling pathway through which mTOR regulates necroptosis. The development of therapeutic targets for various diseases has been greatly advanced by the expanding knowledge of how mTOR regulates necroptosis.
