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Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

PGC1α protects against kidney injury by upregulating enzymes that enhance nicotinamide adenine dinucleotide (NAD) and driving local accumulation of the fatty acid breakdown product β-hydroxybutyrate, which leads to increased production of the renoprotective prostaglandin E₂.

Impaired NAD⁺ biosynthesis may be a common feature of high-risk hospitalizations for which NAD⁺ augmentation could improve therapeutic outcome.

Acute tubular injury (ATI) significantly contributes to many kidney diseases. Here, the authors identify several immune response and cellular stress plasma proteins linked to ATI severity and acute kidney injury, which may aid in non-invasive ATI assessment.

A new study provides cogent evidence that fluid overload—measured using bioimpedance spectroscopy—promotes progression of chronic kidney disease (CKD). A prospective randomized trial is warranted to assess the effect of interventions to reduce fluid overload on disease progression in patients with CKD.

The coenzyme NAD⁺ can be produced from the amino acid tryptophan. It emerges that inhibiting an enzyme that degrades an intermediate in this pathway can help to combat kidney and liver diseases in mouse models.

A high-resolution kidney cellular atlas of 51 main cell types, including rare and previously undescribed cell populations, represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

Women with pre-eclampsia, a potentially deadly complication of pregnancy, produce agonistic autoantibodies against angiotensin receptor-1, a transmembrane protein that regulates blood pressure. Findings in mice suggest how these antibodies might help trigger the condition (pages 855–862).

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Healthy mitochondria are essential for normal kidney function and mitochondrial dysfunction has been implicated in various types of renal disorders, both inherited and acquired. In this article, the authors review mitochondrial cytopathies with renal manifestations and the role of mitochondrial dysfunction in acute kidney injury (AKI).

AKR1A1-regulated protein S-nitrosylation protects against kidney injury through PKM2-mediated metabolic reprogramming.

Systemic capillary leak syndrome occurs when there is systemically dysregulated fluid homeostasis. This can lead to hypotensive shock, widespread tissue oedema and multi-organ dysfunction syndrome. In this Primer, Druey and colleagues summarize the epidemiology, pathophysiology, diagnosis and management of this condition.

Fatty acid transport from blood vessels to skeletal muscle, across endothelial cells, is regulated by the branched chain amino acid metabolite 3-hydroxy-isobutyrate. This finding provides a mechanistic explanation for the link between high levels of branched chain amino acids and diabetes.

This paper describes mini-XPerT, a multiplexed screen to simultaneously measure cellular contraction, endothelial barrier function, and cytoskeletal and cell-cell junctional changes. It is the unique combination of these measurements that has enabled the authors to unveil the distinct biophysical mechanisms of barrier defense conferred by Y-27632 and Angpt-1. Mini-XPerT is likely to be applicable across the spectrum of basic and translational science - in mechanistic studies of the endothelium across numerous diseases, and for high-throughput drug discovery.

Staphylococcus infection-associated glomerulonephritis (SAGN) and acute post-streptococcal glomerulonephritis (APSGN) are the two main types of bacterial infection-associated glomerulonephritis. In this Review, the authors discuss the epidemiology of these diseases, common histopathology findings and the complexities of clinical diagnosis, as well as patient management and renal outcomes.

Here, the authors discuss evidence for a role of NAD⁺ imbalance in the pathogenesis of acute kidney injury (AKI) and chronic kidney disease (CKD). They suggest that disruption of NAD⁺ metabolism may contribute to mechanistic links among AKI, CKD and ageing.

Raza et al. report a naturally occurring animal model that recapitulates cardinal features of Systemic Capillary Leak Syndrome and map its histamine-triggered vascular leak trait to Chromosome 6. They suggest that the predisposition to develop vascular hyperpermeability has a strong genetic component conserved between humans and mice.

Tissue cytometry is a promising new microscopy technique that can be used to enumerate and characterize each cell in a tissue. Here the authors describe a complete and accessible pipeline, including methods of sample preparation, microscopy, image analysis, and data analysis for large-scale three-dimensional tissue cytometry of human kidney tissues.

Lutnick et al. develop a cloud-based deep learning tool for whole slide image segmentation. The authors provide several examples of its application in renal pathology, for segmenting glomeruli, interstitial fibrosis and other features of interest.