Reviews & Analysis

Low nephron number is a risk factor for the development of hypertension, chronic kidney disease and kidney failure. This Review describes the mechanisms that modulate nephrogenesis and the timing of nephrogenesis cessation, focusing on environmental and intrinsic pathways that may be manipulated to enhance nephron endowment in susceptible individuals.

Chronic kidney disease (CKD) is associated with an elevated risk of cardiovascular disease (CVD). Here, the authors examine CKD-associated risk factors for CVD and consider the prediction and management of CVD risk in patients with CKD, including research and implementation gaps.

Sterile inflammation triggered by activation of the innate immune system is an important driver of chronic kidney disease (CKD) and its associated cardiovascular disease. Here, Speer et al. summarize current understanding of the role of inflammation in the pathogenesis of CKD and CKD-associated cardiovascular disease, and how these insights may translate into novel therapeutic strategies.

In this Review, the authors summarize the challenges associated with the care of patients with kidney disease during the COVID-19 pandemic. They describe the major challenges and missed opportunities, global inequalities in health care, and offer a framework for future pandemic preparedness.

Effective vaccination strategies are crucial to mitigate the high risk of infection-associated morbidity and mortality in patients with kidney failure. Here, the authors examine vaccine-induced immunity in these patients, in particular their responses to COVID-19 vaccination, in the context of the immune impairment induced by kidney dysfunction and the use of immunosuppressive medications.

In this Review, the authors provide an overview of the roles of miRNAs in the development of chronic kidney disease, acute kidney injury and allograft injury. They also discuss the utilization of miRNAs as biomarkers and their potential as therapeutic targets in kidney disease.

Chronic kidney disease (CKD) is often well advanced before it is detected. Although polygenic scores may enable the early stratification of patients at risk of CKD, the transferability of polygenic scores for the prediction of CKD to populations of non-European ancestry was limited. A new cross-ancestry polygenic score for CKD overcomes these issues, demonstrating good performance across ancestries.

Cellular senescence has beneficial functions in embryonic development, wound healing and tumour suppression but can also be maladaptive, contributing to cancer development and disease. This Review describes the mechanisms, hallmarks and consequences of senescence, as well as the therapeutic potential of senescence-targeting interventions.

Two recent randomized trials provide evidence to guide the management of sepsis. The CLASSIC trial reports that restrictive fluid therapy has no mortality benefit compared to a standard regimen in patients with septic shock, whereas the LOVIT trial reports that high-dose intravenous vitamin C might be harmful in patients with severe sepsis.

Necroptosis is a form of regulated necrosis in which RIPK3 is activated by binding to RIP homotypic interaction motif (RHIM)-containing proteins. Now, researchers describe a non-canonical pathway of RIPK3 activation that is triggered by osmotic stress and NHE1-mediated cytosol alkalinization. This previously undescribed mechanism of osmotic stress-induced necroptosis might have implications for treating cancer and other diseases.

Alloimmune T cell responses have a crucial role in graft rejection. Here, the authors examine the factors that regulate T cell activation, differentiation and function in secondary lymphoid organs and in the graft, including the different pathways of allorecognition, innate–adaptive immunity crosstalk and the role of survival cytokines.

Our understanding of nephrogenesis has been aided by studies that have compared features of human and mouse nephrogenesis, and by technological advances in single-cell omics and high-resolution imaging techniques. This Review describes current understanding of nephron patterning, focusing on the processes by which nephron progenitors are recruited into the developing nephron.

The interplay between immunological and metabolic processes is important in a variety of processes. This Review describes how changes in lipid and energy metabolism, driven by receptors of the innate immune system, contribute to the response of tubule epithelial cells to injury and the functional consequences of these intersecting pathways in kidney health and disease.

The fibrogenic niche is a unique tissue microenvironment that promotes fibroblast activation in organ fibrosis. This Review discusses the composition, function and mechanisms of action of the fibrogenic niche in kidney fibrosis, as well as the potential implications of the fibrogenic niche hypothesis for the future diagnosis and treatment of kidney diseases.

The cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) pathway not only is involved in host defence against infection but can lead to immune dysregulation. Here, the authors examine the biology and biochemistry of cGAS–STING and discuss its role in disease and potential approaches to therapeutic targeting.

Hypoxia-dependent changes in cellular metabolism have important implications for the effective functioning of multiple immune cell subtypes. This Review describes the inputs that shape the hypoxic response in individual cell types and contexts, and the implications of this response for cellular metabolism and associated alterations in immune cell function.

Meaningful involvement of patients in clinical trial design could lead to improvements in participant recruitment and retention, the uptake of the tested intervention and the impact of the findings. Here, the authors discuss the involvement of patients at all stages of trial design.

In this Review, the authors discuss the roles of extracellular vesicles in kidney physiology and disease as well as the beneficial effects of stem cell-derived extracellular vesicles in preclinical models of acute kidney injury and chronic kidney disease. They also highlight current and future clinical applications of extracellular vesicles in kidney diseases.

Chronic kidney disease is associated with an increased risk of cardiovascular disease, such as heart failure. Here, the authors examine myocardial metabolic remodelling in chronic kidney disease, including changes in energy substrate use, mitochondrial dysfunction and the role of cardiotonic steroids, and discuss potential metabolic therapies.

A post hoc analysis of the COAPT trial suggests that transcatheter mitral valve repair for secondary mitral regurgitation is efficacious in patients with heart failure and chronic kidney disease. The intervention also reduced the risk of kidney failure, raising hypotheses regarding the mechanisms that link heart failure and loss of kidney function.