Review Articles in 2021

Mutations in ~35 genes have been identified as monogenic causes of kidney stone disease, and gene variants have been associated with stone disease in the general population. Here, the authors discuss the genetic and molecular basis of kidney stone disease and nephrocalcinosis.

This Review examines the concept of kidney lifespan and how increases in haemodynamic and metabolic demands in the kidney can lead to nephron overload, which is a common feature of progressive kidney disease and therefore represents a therapeutic target.

Here, the authors discuss how structural racism underlies many of the health disparities that affect individuals from minority racial groups. They also examine how the use of race coefficients in estimated glomerular filtration rate equations might contribute to health inequities in Black patients with kidney disease.

Loss of muscle protein is a deleterious consequence of chronic kidney disease (CKD) that results in decreased muscle strength and function. This Review summarizes the cellular mechanisms that lead to reductions in muscle protein in patients with CKD and highlights commonalities with other catabolic conditions such as cancer and diabetes.

RNA-binding proteins are involved in every stage of the RNA life cycle and have a major impact on cellular biology. Here, the authors discuss current knowledge of RNA-binding proteins, their interactions with RNAs and proteins, their roles in kidney diseases and their potential as novel therapeutic targets.

Novel non-steroidal mineralocorticoid receptor antagonists have a better safety profile than steroidal formulations. This Review examines the pro-inflammatory and profibrotic activity of mineralocorticoid receptor activation and discusses the therapeutic potential of MRAs in the treatment of diabetic kidney disease to improve kidney and cardiovascular outcomes.

Endothelial cells in the kidney microvasculature have an intrinsic molecular and phenotypic heterogeneity and respond to sepsis-induced acute kidney injury conditions in a segment-specific manner. This Review discusses the roles of these cells and the molecular systems that control endothelial functions in the development of sepsis-induced acute kidney injury.

Pain management in patients with haemodialysis-dependent kidney failure might involve the use of opioids. This Review discusses the safe implementation of opioid therapy in these patients, including specific pharmacological considerations, drug choice and opioid use monitoring.

Dyslipidaemia is a hallmark of chronic kidney disease (CKD), with insights from lipidomics studies suggesting that alterations in free fatty acid partitioning may contribute to CKD progression. This Review provides an introduction to lipidomics and discusses insights from lipidomics studies of relevance to CKD.

Studies of lineage relationships in the mouse have advanced the understanding of kidney development and repair. Here, the authors discuss these advances as well as how the application of lineage tools to kidney organoids will facilitate studies of human lineage relationships.

Here, the authors provide an overview of the evolutionary processes that have implications for our understanding of kidney disease development and progression. They describe data derived from studies of ancient and archaic genomes and how population migration and genetic admixture have shaped the current landscape of human kidney-associated diseases, as well as the potential impact of environmental influences on evolutionary genetics and the adaptation of kidneys.

The actions of immune cells within the kidney are of fundamental importance to kidney homeostasis and disease. This Review describes how live imaging of the kidney microvasculature in animal models has advanced our understanding of leukocyte behaviour in healthy and diseased kidneys.

This Review examines the unique biological characteristics of unconventional T cells, including γδ T cells, mucosal-associated invariant T cells and natural killer T cells, and their roles in kidney injury, glomerulopathies and fibrosis. The authors also discuss the potential clinical applications of these cells, including in patients with kidney failure treated with dialysis or transplantation.

Analyses of single-cell, multi-omics datasets have potential to provide new insights into biological processes; however, the integration of these complex datasets represents a considerable challenge. This Review describes the principles underlying the integration of multimodal data measured on the same cell (that is, matched data) and on different cells (unmatched data), outlining developments in computational methods and data visualization approaches.

The apelin system is a broad regulator of physiology that has beneficial cardiovascular and renal effects. This Review focuses on the role of this system in kidney and cardiovascular health and disease and its potential as a therapeutic target.

CircRNAs have been implicated in the pathogenesis of kidney diseases, cardiovascular complications of chronic kidney disease and kidney cancer. This Review describes the roles of circRNAs in the pathophysiology of these diseases and highlights their potential as therapeutic targets and prognostic or diagnostic biomarkers.

The clinical course of diabetic kidney disease can follow different trajectories of albuminuria and glomerular filtration rate. In this Review, the authors discuss these trajectories and their underlying factors, as well as their correlation with histopathological changes in the kidney and patient outcomes.

Inflammation is a known driver of diabetes and obesity-associated kidney disease. This Review describes the role of endogenous lipid mediators — specialized pro-resolving lipid mediators and branched fatty acid esters of hydroxy fatty acids — in the resolution of inflammation and explores how insights into their function could identify new targets for therapeutic intervention.

Acute kidney injury (AKI) is a common complication of COVID-19. This Review describes current understanding of the pathophysiology of COVID-19-associated AKI, examining potential mechanisms by which SARS-CoV-2 infection might induce direct and indirect effects on the kidney and non-specific factors, including haemodynamic changes and/or organ crosstalk, that may adversely influence kidney function.

Aquaporin 2 has an essential role in water reabsorption in the collecting duct. Here, the authors discuss novel insights in the field of aquaporin 2 regulation and how they might have implications for the treatment not only of water balance disorders but also of patients with autosomal dominant polycystic kidney disease.