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Article
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Longitudinal tracking of acute kidney injury reveals injury propagation along the nephron
The mechanisms of failed tubule repair after acute kidney injury are incompletely understood. Here, the authors show spatial and temporal analysis of cycling cells relative to initial necrosis and postulate pronounced injury expansion into non-necrotic tissue regions, predictive of tubule atrophy.
- Luca Bordoni
- , Anders M. Kristensen
- & Ina Maria Schiessl
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Article
| Open Access
HCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy
The authors previously reported HCK was associated with kidney inflammation and fibrosis. Here, they further unravel a mechanism of HCK regulating autophagy within macrophages, altering their polarization, proliferation, and migration and they also developed a more selective HCK inhibitor.
- Man Chen
- , Madhav C. Menon
- & Chengguo Wei
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Article
| Open Access
Direct mapping of kidney function by DCE-MRI urography using a tetrazinanone organic radical contrast agent
Current clinical methods for assessing kidney function report an aggregate value for both kidneys, and lack the ability to say which kidney is dysfunctioning or even to localize the dysfunction to a region of renal pathology. Here, the authors show that an injectable dye can be used to map kidney function by magnetic resonance imaging, offering a safer alternative than existing dyes for the spatial evaluation of kidney health.
- Nicholas D. Calvert
- , Alexia Kirby
- & Adam J. Shuhendler
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Article
| Open Access
Predicting in-hospital outcomes of patients with acute kidney injury
Early prediction of AKI-related clinical events and timely intervention for high-risk patients could improve outcomes. Here, the authors show a deep learning model that can identify patients with acute kidney injury (AKI) who are at high risk of death or dialysis at certain time points.
- Changwei Wu
- , Yun Zhang
- & Guisen Li
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Article
| Open Access
A randomized clinical trial assessing the effect of automated medication-targeted alerts on acute kidney injury outcomes
In a multicenter randomized trial, researchers found that electronic alerts increased the rate of discontinuation of potential nephrotoxins. This did not translate into improved clinical outcomes, except among those exposed to proton-pump inhibitors.
- F. Perry Wilson
- , Yu Yamamoto
- & Ugochukwu Ugwuowo
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Article
| Open Access
Inhibition of ALKBH5 attenuates I/R-induced renal injury in male mice by promoting Ccl28 m6A modification and increasing Treg recruitment
m6A modification has been reported to play roles in many developmental and pathological processes, but its role in AKI remains poorly understood. Here, the authors show the role and the mechanism of the m6A demethylase, ALKBH5 on IRI induced AKI.
- Juntao Chen
- , Cuidi Xu
- & Tongyu Zhu
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Article
| Open Access
Targeting endogenous kidney regeneration using anti-IL11 therapy in acute and chronic models of kidney disease
Repair processes in kidney are impaired in severe disease. Here, the authors show that in kidney failure, genetic or pharmacologic inhibition of IL11 releases the brake on regeneration, reverses tissue damage and restores kidney function.
- Anissa A. Widjaja
- , Sivakumar Viswanathan
- & Stuart A. Cook
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Article
| Open Access
Chromatin accessibility dynamics dictate renal tubular epithelial cell response to injury
Renal tubular epithelial cells (TECs) can initiate an adaptive or maladaptive response after injuries of different severity. Here, the authors elucidate a chromatin-mediated mechanism underlying the responses of TECs to varying kidney injuries.
- Xinyi Cao
- , Jiuchen Wang
- & Lirong Zhang
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Article
| Open Access
Circular RNA circBNC2 inhibits epithelial cell G2-M arrest to prevent fibrotic maladaptive repair
G2/M arrest of epithelial cells leads to fibrosis with unclear mechanisms. This study identifies a protein-encoding circRNA, circBNC2, which inhibits epithelial cells G2/M arrest to prevent fibrotic maladaptive repair in damaged kidney and liver, revealing a potential intervention target for fibrosis.
- Peng Wang
- , Zhitao Huang
- & Fan Fan Hou
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Article
| Open Access
Immune-mediated tubule atrophy promotes acute kidney injury to chronic kidney disease transition
Acute kidney injury can lead to chronic kidney disease. Here the authors show that the transition is related to a macrophage-mediated second wave of inflammatory cells that promote late tubule injury, dedifferentiation and fibrosis. Suppressing this second wave reduced tubular loss and kidney atrophy.
- Leyuan Xu
- , Jiankan Guo
- & Lloyd G. Cantley
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Article
| Open Access
Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 infection
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to acute kidney injury. The authors describe that SARS-COV-2 can directly infect human kidney, possibly mediating tubular pathogenesis.
- Bo Diao
- , Chenhui Wang
- & Yongwen Chen
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Article
| Open Access
Catalytic activity tunable ceria nanoparticles prevent chemotherapy-induced acute kidney injury without interference with chemotherapeutics
Reactive oxygen species management is a practical strategy that can reduce the risk of chemotherapy-induced acute kidney injury, but at the cost of chemotherapeutic efficacy. Here the authors report catalytic activity tunable ceria nanoparticles as context-dependent reactive oxygen species scavengers, which can prevent chemotherapy-induced acute kidney injury without interfering with chemotherapeutic agents.
- Qinjie Weng
- , Heng Sun
- & Daishun Ling
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Article
| Open Access
Cross-site transportability of an explainable artificial intelligence model for acute kidney injury prediction
Artificial intelligence (AI) has demonstrated promise in predicting acutekidney injury (AKI), however, clinical adoption of these models requires interpretability and transportability across sites. Here, the authors develop an AKI prediction model and a measure for model transportability across six independent health systems.
- Xing Song
- , Alan S. L. Yu
- & Mei Liu
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Article
| Open Access
Explainable artificial intelligence model to predict acute critical illness from electronic health records
Acute critical illness is often preceded by deterioration of routinely measured clinical parameters, e.g., blood pressure and heart rate. Here, the authors develop an explainable artificial intelligence early warning score system for its early detection.
- Simon Meyer Lauritsen
- , Mads Kristensen
- & Bo Thiesson
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Article
| Open Access
Enhancer and super-enhancer dynamics in repair after ischemic acute kidney injury
Acute kidney injury is a major health problem amongst hospitalized patients. Here the authors provide a comprehensive characterization of enhancer and super-enhancer elements, and the transcription factor motifs associated with these elements in response to kidney injury in vivo; providing insight into the regulation of kidney repair.
- Julia Wilflingseder
- , Michaela Willi
- & Joseph V. Bonventre
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Article
| Open Access
Ultrasmall copper-based nanoparticles for reactive oxygen species scavenging and alleviation of inflammation related diseases
Oxidative stress is involved in several diseases and is a target for intervention. Here, the authors report on the synthesis of ultrasmall copper-based nanozymes as reactive oxygen species scavengers and demonstrate improved treatment outcomes in acute liver and kidney injury and wound healing in vivo.
- Tengfei Liu
- , Bowen Xiao
- & Jun Deng
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Article
| Open Access
A kinome-wide screen identifies a CDKL5-SOX9 regulatory axis in epithelial cell death and kidney injury
Protein kinases have emerged as critical regulators of disease pathogenesis. Here, the authors have utilized kinome-wide screening approaches to reveal a pathogenic role of CDKL5 kinase in acute kidney injury, which is dependent on suppression of a SOX9-associated transcriptional network.
- Ji Young Kim
- , Yuntao Bai
- & Navjot Singh Pabla
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Article
| Open Access
TMEM33 regulates intracellular calcium homeostasis in renal tubular epithelial cells
Polycystin-2 (PC2) is an ion channel commonly found mutated in autosomal dominant polycystic kidney disease. Here Arhatte et al. identify transmembrane protein 33 (TMEM33) as a regulator of PC2 function at the endoplasmic reticulum, and find that deletion of TMEM33 protects mice from acute kidney injury.
- Malika Arhatte
- , Gihan S. Gunaratne
- & Amanda Patel
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Article
| Open Access
Molybdenum-based nanoclusters act as antioxidants and ameliorate acute kidney injury in mice
There are currently no effective therapies available for acute kidney injury (AKI). Here the authors generate molybdenum-based polyoxometalate nanoclusters and show that these have preferential renal uptake and can ameliorate AKI pathology in mice by scavenging reactive oxygen species.
- Dalong Ni
- , Dawei Jiang
- & Weibo Cai
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Article
| Open Access
Endocycle-related tubular cell hypertrophy and progenitor proliferation recover renal function after acute kidney injury
The recovery of function upon acute kidney injury is thought to involve tubular cell dedifferentiation and proliferation. Here the authors show that Pax2+ progenitors regenerate tubules via cell division while other tubular cells support function recovery by undergoing hypertrophy through endoreplication.
- Elena Lazzeri
- , Maria Lucia Angelotti
- & Paola Romagnani
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Article
| Open Access
The CPLANE protein Intu protects kidneys from ischemia-reperfusion injury by targeting STAT1 for degradation
Intu is a planar cell polarity protein known to regulate ciliogenesis during embryonic development. Here, Wang et al. identify a role for Intu in adult kidneys, where they find it promotes degradation of STAT1 and thus prevents cilia loss and cell death upon ischemia-reperfusion injury.
- Shixuan Wang
- , Aimin Liu
- & Zheng Dong
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Article
| Open Access
Protective role of fructokinase blockade in the pathogenesis of acute kidney injury in mice
The polyol pathway, which converts glucose into sorbitol and fructose, is active in chronic conditions like hepatic steatosis and chronic kidney disease. Here, Andres-Hernandoet al. show that fructose production promotes renal injury and fructokinase inhibition protects against kidney damage during ischaemic acute kidney disease.
- Ana Andres-Hernando
- , Nanxing Li
- & Miguel A. Lanaspa
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Article
| Open Access
Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis
Kidney stone disease is caused by accumulation of oxalate crystals, which trigger tissue injury, inflammation and cell death. Mulay et al. show that crystals induce cell death in the kidney through necroptosis, and propose that this pathway may be a target for the treatment of crystal-induced disease.
- Shrikant R. Mulay
- , Jyaysi Desai
- & Hans-Joachim Anders
Predicting proximal tubule failed repair drivers through regularized regression analysis of single cell multiomic sequencing