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Long-term calcineurin inhibitor (CNI) administration causes irreversible nephrotoxicity. Therefore, early CNI-induced nephrotoxicity detection is necessary for patients who will need long-term CNI administration. There is no pathological indicator for early CNI-induced nephrotoxicity. Here, serial protocol kidney biopsy specimens from five kidney-transplant patients with severe CNI-induced nephrotoxicity were examined. We observed that the increase in CD44 expression in glomerular parietal epithelial cells (PECs) preceded the chronic pathological changes of CNI-induced nephrotoxicity such as tubular atrophy/interstitial fibrosis, arterial hyaline thickening, and focal segmental glomerulosclerosis (FSGS). This result suggests that CD44-positive PECs have pivotal roles in FSGS development in human CNI-induced nephrotoxicity as well as rodent models. CD44 could be useful as a pathological marker for early CNI-induced nephrotoxicity detection post kidney transplantation.
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http://dx.doi.org/10.2220/biomedres.43.181 | DOI Listing |
Sci Rep
July 2025
Division of Nephrology, Japan Community Health Care Organization Sendai Hospital, 2-1-1, Murasakiyama, Izumi, Sendai, Miyagi, Japan.
Tonicity-responsive enhancer binding protein (TonEBP) protects kidney tubular cells against hypertonicity. Calcineurin inhibitors (CNI) are known to suppress TonEBP by hampering nuclear translocation. Moreover, sodium inversely activates TonEBP.
View Article and Find Full Text PDFClin Transplant
January 2024
Department of Kidney Transplant Surgery and Urology, Sapporo City General Hospital, Sapporo, Hokkaido, Japan.
Introduction: Calcineurin inhibitor (CNI)-induced nephrotoxicity (CNI-T) is a post-transplantation complication that leads to graft dysfunction. Older-donor kidney grafts may be susceptible to chronic CNI exposure because of long-term arteriolar damage. The primary aim of this study was to examine the CNI-T incidence and time-course changes in the graft function according to donor age.
View Article and Find Full Text PDFTransplant Proc
December 2023
Division of Pulmonary, Critical Care, Sleep Medicine and Physiology, School of Medicine, UC San Diego, La Jolla, California.
Background: After lung transplant, 2 common complications are calcineurin inhibitor (CNI) induced nephrotoxicity and bronchiolitis obliterans syndrome. The objective of this study was to investigate the long-term effects of sirolimus conversion after lung transplantation.
Methods: This was a retrospective cohort study of patients who had undergone lung transplantation at a single center from June 2003 to December 2016.
Biomedicines
May 2023
Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari "Aldo Moro", 70121 Bari, Italy.
Kidney transplantation is the first-choice treatment for end-stage renal disease (ESRD). Kidney transplant recipients (KTRs) are at higher risk of experiencing a life-threatening event requiring intensive care unit (ICU) admission, mainly in the late post-transplant period (more than 6 months after transplantation). Urosepsis and bloodstream infections account for almost half of ICU admissions in this population; in addition, potential side effects related to immunosuppressive treatment should be accounted for cytotoxic and ischemic changes induced by calcineurin inhibitor (CNI), sirolimus/CNI-induced thrombotic microangiopathy and posterior reversible encephalopathy syndrome.
View Article and Find Full Text PDFFront Med (Lausanne)
February 2023
Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada.
Background: Calcineurin inhibitors (CNIs) are associated with nephrotoxicity, endothelial cell dysfunction, and thrombotic microangiopathy (TMA). Evolving evidence suggests an important role for complement dysregulation in the pathogenesis of CNI-induced TMA. However, the exact mechanism(s) of CNI-induced TMA remain(s) unknown.
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