Reviews & Analysis

Sepsis induces an initial activation of the immune system, which is often followed by a compensatory anti-inflammatory response that can lead to immunosuppression. In this Review, the authors discuss advances in the understanding of sepsis-induced immunosuppression and how this understanding might lead to new, more effective treatments for sepsis.

Complement activation has important physiological and pathological implications for kidney-related and other diseases. Here, the authors discuss the state of the art of complement therapeutics, including the targets, candidate drugs, insights from clinical trials and evolving challenges for the field.

Adipose is an important endocrine and immunologic organ, releasing various adipokines and cytokines that regulate the adipocyte microenvironment and systemic metabolism. Here, the authors discuss the immunologic and endocrine functions of adipose tissue that contribute to kidney disease and the converse effects of kidney dysfunction on adipose tissue.

Dyslipidaemia is a common consequence of nephrotic syndrome, and results in various cardiovascular and metabolic complications. In this Review, the authors discuss the mechanisms that underlie the development of dyslipidaemia, and the treatment options that are available to ameliorate its effects.

The perception of thirst is critical for the control of body fluid homeostasis. In this Review, Gizowski and Bourque discuss the importance of thirst for body fluid balance and describe the central neural networks that regulate thirst, including adaptive changes to systemic processes and feedforward anticipatory responses that precede physiological challenges to maintain body fluid balance.

Extracellular vesicles in the urine have potential as disease biomarkers. This Review discusses the different types of extracellular vesicles and the optimization of approaches to enable their isolation and purification, and to characterize their composition by high-throughput 'omics' technologies.

Animal models that faithfully recapitulate human diabetic nephropathy (DN) are needed to study disease pathogenesis, identify drug targets and test new therapies. Here, the authors review progress in developing mouse models of DN, the limitations of current models, and opportunities for future development.

An increasing body of evidence supports a role for B cells in the pathogenesis of type 1 diabetes mellitus (T1DM). Here, the authors discuss the mechanisms and consequences of B cell activation in T1DM and how these cells might contribute to the development of diabetic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a variable rate of cyst development, variable kidney function decline and variable presentation of renal and extrarenal manifestations. In this Review, the authors discuss pharmacological and non-pharmacological interventions for the treatment of patients with ADPKD and provide recommendations for the management of renal complications.

In this Review, Mark Okusa and colleagues discuss the role of neural circuits in the control of renal inflammation as well as the therapeutic potential of targeting these circuits in the settings of acute kidney injury, kidney fibrosis and hypertension.

Our understanding of endoplasmic reticulum (ER) stress, the unfolded protein response (UPR) and ER stress-induced autophagy in the kidney has increased — using the presence of ER chaperones in the urine as a biomarker of renal ER stress, and using pharmacological agents that improve protein folding or induce the expression of chaperones, may aid in the diagnosis and treatment of kidney disease, respectively.

CD36 has important roles in lipid homeostasis, metabolic inflammation, reprogramming of energy metabolism, apoptosis and kidney fibrosis. Here, the authors discuss these roles as well as the regulation and post-translational modification of CD36 and its potential as a biomarker and a therapeutic target for kidney disease.

Cardiac surgery-associated acute kidney injury (CSA-AKI) is the most common complication in adult patients undergoing open heart surgery. In this Review, the authors discuss the definition, epidemiology, pathophysiology and risk factors of CSA-AKI. The authors also explore the use of novel biomarkers of AKI and their potential utility in preventing or treating CSA-AKI.

The incretin hormone glucagon-like peptide 1 (GLP-1) has been implicated in the gut–renal axis and incretin-based therapies might reduce the burden of diabetic kidney disease. Here, the authors review the physiological roles of GLP-1, the potential renoprotective mechanisms of incretin-based therapies and the available renal outcome data from clinical trials.

Mitochondria provide the kidney with energy to remove waste from the blood and regulate fluid and electrolyte balance. This Review discusses how mitochondrial homeostasis is maintained, the changes in mitochondrial energetics that occur in acute kidney injury and diabetic nephropathy, and how targeting mitochondrial energetics might aid the treatment of renal disease.

Uromodulin is the most abundant urinary protein. Here, the authors discuss the physiological roles of uromodulin, the mechanisms by which mutations in theUMOD gene, which encodes uromodulin, cause autosomal dominant tubulointerstitial kidney disease and the association of common UMODvariants with complex disorders in the general population.

A growing body of evidence supports a key role for T helper type 17 (T_H17) cells in the development of renal damage. This Review discusses the identification, regulation, and function of T_H17 cells and their associated pathways in immune-mediated kidney diseases, with particular focus on the mechanisms underlying renal tissue injury.

Patients with chronic kidney disease have elevated levels of carbamoylated proteins. Here the authors review the mechanisms of carbamoylation, the effects of this post-translational modification on renal function and strategies to reduce the carbamoylation load.

Extracellular vesicles, exosomes and microvesicles are host cell-derived packages of information that are involved in cell–cell communication. This Review discusses how the release and uptake of these vesicles has important physiological functions in renal processes and can contribute to the development of kidney diseases, and how extracellular vesicles might be targeted and used for the treatment of patients with renal diseases.

This Review provides an overview of the molecular determinants of renal cell carcinoma, how understanding the underlying mechanisms of disease has fuelled the development of targeted therapies, and tools to assess the value of these agents.