Background: Acute tubular necrosis (ATN) in renal allograft biopsies correlates poorly with delayed graft function (DGF). Factors involved in the pathogenesis of DGF were evaluated in biopsies in an attempt to refine the recognition of DGF.
Methods: Anti-cubulin and anti-AE-1/AE-3 antibodies identified proximal and distal tubules, respectively. The terminal deoxynucleotide transferase-mediated dUTP nick-end labeling technique and active caspase-3 staining were used to demonstrate apoptosis. Antibodies against superoxide dismutase (SOD) were used as markers of the protective tubular response. Tubular regeneration was evaluated using anti-ki 67 and antivimentin antibodies.
Results: Of a total of 40 biopsies, 9 were associated with DGF. ATN was seen in 16 biopsies; 5 were associated with DGF. The finding of ATN in the biopsy of a graft predicted DGF in only 56% of cases. Absence of distal caspase-3 staining predicted the absence of ATN in 87% of cases. The presence of caspase-3 predicted ATN in 54% of cases. The detection of manganese-SOD in distal tubules predicts the absence of DGF in 76% of the cases.
Conclusions: The use of immunohistochemical staining on posttransplant renal biopsies improved its predictive value with respect to ATN and DGF: The absence of active caspase-3 in distal tubular epithelium predicts the absence of ATN in 87% of cases, whereas its presence predicts ATN in 54% of cases. The presence of manganese-SOD in distal tubules predicts the absence of DGF in 76% of cases.
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http://dx.doi.org/10.1097/01.tp.0000156166.60218.c7 | DOI Listing |
FASEB J
January 2025
Department of Hematology, Nephrology, and Rheumatology, Graduate School of Medicine, Akita University, Akita, Japan.
Various tubular diseases in patients with multiple myeloma (MM) are caused by monoclonal immunoglobulin light chains (LCs). However, the physicochemical characteristics of the disease-causing LCs contributing to the onset of MM-associated tubular diseases remain unclear. We herein report a rare case of MM-associated combined tubulopathies: non-crystalline light chain proximal tubulopathy (LCPT) and crystalline light chain cast nephropathy (LCCN).
View Article and Find Full Text PDFFEBS Lett
January 2025
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Soluble, circulating Klotho (sKlotho) is essential for normal health and renal function. sKlotho is shed from the renal distal convoluted tubule (DCT), its primary source, via enzymatic cleavage. However, the physiologic mechanisms that control sKlotho production, trafficking, and shedding are not fully defined.
View Article and Find Full Text PDFUnlabelled: The With No lysine (WNK) kinases regulate processes such as cell volume and epithelial ion transport through the modulation of Cation Chloride Cotransporters such as the NaCl cotransporter, NCC, present in the distal convoluted tubule (DCT) of the kidney. Recently, the interaction of WNKs with Nuclear Receptor Binding Protein 1 (NRBP1) and Transforming Growth Factor β-Stimulated Clone 22 Domain (TSC22D) proteins was reported. Here we explored the effect of NRBP1 and TSC22Ds on WNK signaling in vitro and in the DCT.
View Article and Find Full Text PDFJ Immunother Cancer
January 2025
National Translational Science Center for Molecular Medicine & Department of Cell Biology, Fourth Military Medical University, Xi'an, Shaanxi, China
Background: Clear cell renal cell carcinoma (ccRCC) is the most common histologic type of RCC. However, the spatial and functional heterogeneity of immunosuppressive cells and the mechanisms by which their interactions promote immunosuppression in the ccRCC have not been thoroughly investigated.
Methods: To further investigate the cellular and regional heterogeneity of ccRCC, we analyzed single-cell and spatial transcriptome RNA sequencing data from four patients, which were obtained from samples from multiple regions, including the tumor core, tumor-normal interface, and distal normal tissue.
Am J Physiol Renal Physiol
January 2025
Department of Pharmacology, New York Medical College, Valhalla, NY.
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