Inhibition of pyruvate dehydrogenase kinase 4 ameliorates kidney ischemia-reperfusion injury by reducing succinate accumulation during ischemia and preserving mitochondrial function during reperfusion.
Ischemia-reperfusion (IR) injury, a leading cause of acute kidney injury (AKI), is still without effective therapies. Succinate accumulation during ischemia followed by its oxidation during reperfusion leads to excessive reactive oxygen species (ROS) and severe kidney damage. Consequently, the targeting of succinate accumulation may represent a rational approach to the prevention of IR-induced kidney injury. Since ROS are generated primarily in mitochondria, which are abundant in the proximal tubule of the kidney, we explored the role of pyruvate dehydrogenase kinase 4 (PDK4), a mitochondrial enzyme, in IR-induced kidney i...
Source: Kidney International - July 1, 2023 Category: Urology & Nephrology Authors: Chang Joo Oh, Min-Ji Kim, Ji-Min Lee, Dong Hun Kim, Il-Young Kim, Sanghee Park, Yeongmin Kim, Kyung-Bok Lee, Sang-Hee Lee, Chae Won Lim, Myeongjin Kim, Jung-Yi Lee, Haushabhau S. Pagire, Suvarna H. Pagire, Myung Ae Bae, Dipanjan Chanda, Themis Thoudam, Ah Tags: basic research Source Type: research

Beyond UPR: Cell-specific Roles of ER Stress Sensor IRE1 α in Kidney Ischemic Injury and Transplant Rejection
Kidney damage due to ischemia or rejection results in the accumulation of unfolded and misfolded proteins in the endoplasmic reticulum (ER) lumen, a condition known as “ER stress”. Inositol-requiring enzyme 1α (IRE1α), the first ER stress sensor found, is a type I transmembrane protein with kinase and endoribonuclease activity. Upon activation, IRE1α non-conventionally splices an intron from unspliced X-box binding protein 1 (XBP1u) mRNA to produce XBP1s mR NA that encodes the transcription factor, XBP1s, for the expression of genes encoding proteins that mediate the unfolded protein response (UPR). (Source: Kidney International)
Source: Kidney International - June 28, 2023 Category: Urology & Nephrology Authors: Longhui Qiu, Xin Zheng, Dinesh Jaishankar, Richard Green, Deyu Fang, Satish Nadig, Zheng Jenny Zhang Tags: mini review Source Type: research

Development of an adaptive clinical web-based prediction tool for kidney replacement therapy in children with chronic kidney disease
Clinicians need improved prediction models to estimate time to kidney replacement therapy (KRT) for children with chronic kidney disease (CKD). Here, we aimed to develop and validate a prediction tool based on common clinical variables for time to KRT in children using statistical learning methods and design a corresponding online calculator for clinical use. Among 890 children with CKD in the Chronic Kidney Disease in Children (CKiD) study, 172 variables related to sociodemographics, kidney/cardiovascular health, and therapy use, including longitudinal changes over one year were evaluated as candidate predictors in a rand...
Source: Kidney International - June 28, 2023 Category: Urology & Nephrology Authors: Derek K. Ng, Matthew B. Matheson, George J. Schwartz, Frances M. Wang, Susan R. Mendley, Susan L. Furth, Bradley A. Warady, CKiD investigators Tags: clinical investigation Source Type: research

A prospective controlled, randomized clinical trial of kidney transplant recipients developed personalized tacrolimus dosing using model-based Bayesian Prediction
For three decades, tacrolimus (Tac) dose adjustment in clinical practice has been calculated empirically according to the manufacturer's labeling based on a patient's body weight. Here, we developed and validated a Population pharmacokinetic (PPK) model including pharmacogenetics (cluster CYP3A4/CYP3A5), age, and hematocrit. Our study aimed to assess the clinical applicability of this PPK model in the achievement of Tac Co (therapeutic trough Tac concentration) compared to the manufacturer's labelling dosage. (Source: Kidney International)
Source: Kidney International - June 28, 2023 Category: Urology & Nephrology Authors: N úria Lloberas, Josep M. Grinyó, Helena Colom, Anna Vidal-Alabró, Pere Fontova, Raul Rigo, Ariadna Padró, Oriol Bestard, Edoardo Melilli, Núria Montero, Ana Coloma, Ana Manonelles, Maria Meneghini, Alex Favà, Joan Torras, Josep M. Cruzado Tags: clinical trial Source Type: research

Age and memory B cells at baseline are associated with risk of relapse and memory B-cell reappearance following anti-CD20 treatment in pediatric frequently-relapsing/steroid-dependent nephrotic syndrome
B-cell depleting anti-CD20 monoclonal antibodies, mainly rituximab, have proven efficacy in children with frequently-relapsing/steroid-dependent nephrotic syndrome (FR/SDNS). However, drug-free remission is variable and specific baseline markers predictive of relapse after anti-CD20 treatment are still being defined. To clarify this, we performed a bicentric observational study in a large cohort of 102 children and young adults with FR/SDNS treated with anti-CD20 monoclonal antibodies (rituximab and ofatumumab). (Source: Kidney International)
Source: Kidney International - June 27, 2023 Category: Urology & Nephrology Authors: Manuela Colucci, Andrea Angeletti, Federica Zotta, Rita Carsetti, Francesca Lugani, Lucilla Rava, Pietro Ravani, Francesco Emma, Gian Marco Ghiggeri, Marina Vivarelli Tags: clinical investigation Source Type: research