Reviews & Analysis

In 2017, progress was made in several aspects of immune-mediated kidney disease. Mechanistic studies provided new insights into the underlying signals that confer risk to, or protection from, immune pathways, whereas new approaches to the treatment of immunological kidney disease will hopefully translate into a move away from the use of toxic corticosteroids.

Studies of cellular energetics have revealed important roles of metabolic pathways in determining cell fate and response to injury. Insights from 2017 into the mechanisms underlying these pathways might identify therapeutic targets to minimize injury and promote repair.

Standardized prevention approaches can decrease the incidence of acute kidney injury among high-risk patients. Now, the INPRESS study demonstrates that a personalized intraoperative blood pressure management strategy guided by risk stratification can improve perioperative practice and reduce the risk of organ dysfunction among high-risk patients undergoing major surgery.

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.

Antiviral treatment options for HCV-infected patients with advanced kidney disease are limited because few clinical trials have tested the efficacy of antiviral drugs in this population. Now, a phase III trial of two pan-genotypic drugs demonstrates excellent viral clearance with minimal adverse events in HCV-infected patients with advanced kidney disease.

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.

Uncontrolled hypertension is an important clinical problem and is associated with considerable morbidity and mortality. A new report from the SPYRAL HTN-OFF MED researchers, which describes the use of renal denervation in patients with uncontrolled hypertension, might reignite enthusiasm for this technique, while a first-in-human description of endovascular baroreflex amplification from the CALM-FIM_EUR investigators highlights the potential of this new approach to inhibit sympathetic activity.

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.

Hypertension is a risk factor for chronic kidney disease (CKD), but the optimal blood pressure (BP) target in patients with stage 3–5 CKD is unclear. Now, a meta-analysis reports that more-intensive BP control is associated with a reduced risk of all-cause mortality compared with less-intensive BP goals in this high-risk population.

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.

Hypoxia-inducible transcription factors (HIFs) are key mediators of several molecular and cellular responses that are activated under hypoxic conditions. New findings demonstrate an important role for the HIF system in mediating the activation and inflammatory responses of neutrophils through tight interaction with their glucose metabolism.

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.

New data from the LEADER trial show that the glucagon-like peptide 1 receptor agonist liraglutide protects against diabetic nephropathy in patients with type 2 diabetes mellitus. The renoprotective efficacy of liraglutide is not, however, as great as that reported for the sodium-glucose cotransporter 2 inhibitor emplagiflozin in the EMPA-REG OUTCOME trial.

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.

Thiazide diuretics lower blood pressure and cardiovascular risk but can cause severe hyponatraemia. Researchers now demonstrate that thiazide-induced hyponatraemia is associated with a genetic variant in a distal nephron prostaglandin transporter. They propose that reduced prostaglandin reabsorption through this transporter facilitates activation of the prostaglandin EP4 receptor to increase water reabsorption.