Reviews & Analysis

Glucocorticoid exposure remains a major contributor to morbidity and mortality in patients with immune-mediated kidney disease. Recent clinical trials have tested novel potential therapies for these patients and showed that glucocorticoid doses can be reduced without compromising efficacy.

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.

The dramatic increase in advocacy and scholarly work on the impact of structural racism on health inequities that began in 2020 has been sustained in the past year. In response to the call for action on these issues, the nephrology community has developed policy-based mitigation strategies and continues to examine our role in promoting health equity and justice in the care of patients with kidney disease.

Patients with kidney disease are particularly vulnerable to COVID-19. In 2021, key studies demonstrated the safety of renin–angiotensin blockade in patients with kidney failure and COVID-19, and provided new data on the therapeutic potential of soluble angiotensin-converting enzyme, COVID-19 vaccine responses and the long-term effects of COVID-19 on kidney function.

In 2021, extreme weather and climate events caused preventable injuries, illnesses and deaths. A clear imperative exists to reduce greenhouse gas emissions and increase the sustainability and climate resilience of health systems. Countries and communities must implement strategies to mitigate climate change and invest in health systems to protect their populations.

New DAPA-CKD trial analyses have confirmed the outstanding renoprotective benefits of sodium–glucose co-transporter 2 inhibitors, independently of the presence of diabetes or the stage of kidney disease. Moreover, the non-steroidal mineralocorticoid receptor antagonist finerenone provides renal and cardiovascular protection in diabetic kidney disease when combined with renin–angiotensin–aldosterone system inhibitors.

We saw impressive progress in our understanding of the genetics of kidney function and disease in 2021. Genome-wide association studies defined key common variants for kidney function and disease, and multi-omics methods, including quantitative trait analyses and single cell studies, illuminated key genes and cell types responsible for disease development.

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.

Four new reports uncover the lineage relationships between cells throughout the body using mutations in the genome as cellular barcodes. The mutational composition of different tissues provides insights into both developmental processes and organ homeostasis, and may have important implications for our understanding of hereditary diseases such as polycystic kidney disease.

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.

A new study reports that common mitochondrial DNA variants in specific haplogroups induce metabolic alterations that affect the onset of common age-related diseases. Unravelling the role of this subtle, long-lasting burden of mitochondrial DNA variants on kidney homeostasis could provide novel insights into the pathophysiology of chronic kidney disease.

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.