8b83989d6d05c5701b60800cef70a441 pmc_34067039.pdf 3cdd64055a536a109059ca0c5a95491733247e0a pmc_34067039.pdf 794714c215fe5a5c8d44f70f07fb80261629f68c54f0477562f0ca2e9d7f5c5b pmc_34067039.pdf Title: Clinical Relevance of Corticosteroid Withdrawal on Graft Histological Lesions in Low-Immunological-Risk Kidney Transplant Patients Subject: The impact of corticosteroid withdrawal on medium-term graft histological changes in kidney transplant (KT) recipients under standard immunosuppression is uncertain. As part of an open-label, multicenter, prospective, phase IV, 24-month clinical trial (ClinicalTrials.gov, NCT02284464) in low-immunological-risk KT recipients, 105 patients were randomized, after a protocol-biopsy at 3 months, to corticosteroid continuation (CSC, n = 52) or corticosteroid withdrawal (CSW, n = 53). Both groups received tacrolimus and MMF and had another protocol-biopsy at 24 months. The acute rejection rate, including subclinical inflammation (SCI), was comparable between groups (21.2 vs. 24.5%). No patients developed dnDSA. Inflammatory and chronicity scores increased from 3 to 24 months in patients with, at baseline, no inflammation (NI) or SCI, regardless of treatment. CSW patients with SCI at 3 months had a significantly increased chronicity score at 24 months. HbA1c levels were lower in CSW patients (6.4 1.2 vs. 5.7 0.6%; p = 0.013) at 24 months, as was systolic blood pressure (134.2 14.9 vs. 125.7 15.3 mmHg; p = 0.016). Allograft function was comparable between groups and no patients died or lost their graft. An increase in chronicity scores at 2-years post-transplantation was observed in low-immunological-risk KT recipients with initial NI or SCI, but CSW may accelerate chronicity changes, especially in patients with early SCI. This strategy did, however, improve the cardiovascular profiles of patients.14pt Keywords: subclinical inflammation; kidney transplant; protocol biopsy; corticosteroids withdrawal; low immunological risk; rejection; borderline lesions; chronic graft histological changes Author: Domingo Hernández, Juana Alonso-Titos, Teresa Vázquez, Myriam León, Abelardo Caballero, María Angeles Cobo, Eugenia Sola, Verónica López, Pedro Ruiz-Esteban, Josep María Cruzado, Joana Sellarés, Francesc Moreso, Anna Manonelles, Alberto Torío, Mercedes Cabello, Juan Delgado-Burgos, Cristina Casas, Elena Gutiérrez, Cristina Jironda, Julia Kanter, Daniel Serón and Armando Torres Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri May 7 12:04:44 2021 CEST ModDate: Fri May 7 12:20:42 2021 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 18 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1061558 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- IJLLXV+VnURWPalladioL Type 1 Custom yes yes no 10 0 NDTLAH+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 NZEVYD+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 MIRUOI+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 JGMOZW+CMSY10 Type 1 Builtin yes yes no 28 0 JYPLJJ+VnURWPalladioL-Bold Type 1 Custom yes yes no 32 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 40 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 43 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 65 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 69 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 73 0 KGJGOL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 97 0 KGJGOM+PalatinoLinotype CID TrueType Identity-H yes yes yes 100 0 KGJGON+PalatinoLinotype TrueType WinAnsi yes yes no 106 0 KGJGOP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 109 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 119 0 KGJGOL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 139 0 KGJGOM+PalatinoLinotype CID TrueType Identity-H yes yes yes 142 0 KGJGON+PalatinoLinotype TrueType WinAnsi yes yes no 148 0 KGJGOP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 151 0 KGJJMP+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 154 0 KGJGOL+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 168 0 KGJGON+PalatinoLinotype TrueType WinAnsi yes yes no 171 0 KGJGOP+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 174 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:15:40 CEST RepresentationInformation: pmc_34067039.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:14:01 CEST Size: 1061558 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 425 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Methods Destination: section.2 Children: Item: Title: Study Design Destination: subsection.2.1 Item: Title: Randomization, Immunosuppression Protocol and Interventions Destination: subsection.2.2 Item: Title: Protocol Biopsies and Histological Assessment Destination: subsection.2.3 Item: Title: Testing for dnDSA Destination: subsection.2.4 Item: Title: Cardiovascular and Renal Assessment Destination: subsection.2.5 Item: Title: Statistical Analysis Destination: subsection.2.6 Item: Title: Results Destination: section.3 Children: Item: Title: Baseline Clinical and Histological Data Destination: subsection.3.1 Item: Title: Acute Rejection during Follow-Up Destination: subsection.3.2 Item: Title: Histological Data Evolution Destination: subsection.3.3 Item: Title: De Novo DSA Destination: subsection.3.4 Item: Title: Clinical and Biochemical Data Destination: subsection.3.5 Item: Title: Safety and Graft and Patient Survival Destination: subsection.3.6 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Clinical Relevance of Corticosteroid Withdrawal on Graft Histological Lesions in Low-Immunological-Risk Kidney Transplant Patients Author: Domingo Hernández, Juana Alonso-Titos, Teresa Vázquez, Myriam León, Abelardo Caballero, María Angeles Cobo, Eugenia Sola, Verónica López, Pedro Ruiz-Esteban, Josep María Cruzado, Joana Sellarés, Francesc Moreso, Anna Manonelles, Alberto Torío, Mercedes Cabello, Juan Delgado-Burgos, Cristina Casas, Elena Gutiérrez, Cristina Jironda, Julia Kanter, Daniel Serón and Armando Torres Subject: The impact of corticosteroid withdrawal on medium-term graft histological changes in kidney transplant (KT) recipients under standard immunosuppression is uncertain. As part of an open-label, multicenter, prospective, phase IV, 24-month clinical trial (ClinicalTrials.gov, NCT02284464) in low-immunological-risk KT recipients, 105 patients were randomized, after a protocol-biopsy at 3 months, to corticosteroid continuation (CSC, n = 52) or corticosteroid withdrawal (CSW, n = 53). Both groups received tacrolimus and MMF and had another protocol-biopsy at 24 months. The acute rejection rate, including subclinical inflammation (SCI), was comparable between groups (21.2 vs. 24.5%). No patients developed dnDSA. Inflammatory and chronicity scores increased from 3 to 24 months in patients with, at baseline, no inflammation (NI) or SCI, regardless of treatment. CSW patients with SCI at 3 months had a significantly increased chronicity score at 24 months. HbA1c levels were lower in CSW patients (6.4 1.2 vs. 5.7 0.6%; p = 0.013) at 24 months, as was systolic blood pressure (134.2 14.9 vs. 125.7 15.3 mmHg; p = 0.016). Allograft function was comparable between groups and no patients died or lost their graft. An increase in chronicity scores at 2-years post-transplantation was observed in low-immunological-risk KT recipients with initial NI or SCI, but CSW may accelerate chronicity changes, especially in patients with early SCI. 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