Reviews & Analysis

Accumulating evidence indicates that activation of the complement system is crucial for the development of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This Review provides an overview of the role of complement activation in AAV, and discusses how targeting this pathway can provide opportunities for treatment.

T cells mediate injury in glomerulonephritis but mice devoid of T cells and B cells can also develop this disease. A new study shows that expression of the cytokine receptor common subunit γ and IL-15 in podocytes protects against crescentic glomerulonephritis, independent of B cells, T cells and natural killer cells.

A population of immature myeloid cells in the bone marrow can transfer proteinuric kidney disease from affected to unaffected mice. This new finding highlights a possible central role of bone marrow as the source of the circulating factor(s) that lead to recurrent focal segmental glomerulosclerosis and potentially other kidney diseases.

T cells are critical drivers of autoimmunity and related organ damage, by supporting B-cell differentiation and antibody production or by directly promoting inflammation and cytotoxicity. This Review discusses the immune features of autoimmune nephropathies, with a focus on systemic lupus erythematosus and the role of T cells.

Elimination of donor-specific antibodies against HLA has been used to enable transplantation of HLA-incompatible kidneys from living donors. In contrast to two previous US studies, a UK study now reports that desensitization does not offer a survival benefit over remaining on the waitlist for a compatible organ.

Several recent studies have provided insights into the genetic regulation of blood pressure. A new study extends these findings by coupling genome-wide association study data with functional validation approaches to identify and explore loci associated with blood pressure, and by generating a genetic risk score model to predict future cardiovascular risk.

Metabolomics has been instrumental for the identification of new biomarkers of chronic kidney disease (CKD). Here, the authors discuss metabolomics technologies and their application in renal disease, including the specificity and functional relevance of CKD-associated metabolic biomarkers.

An increasing body of evidence points toward a role for the complement system in the pathogenesis of diabetic nephropathy. Here, Allan Flyvbjerg describes the underlying experimental and clinical evidence and discusses how the association between complement activation and diabetic nephropathy might facilitate the identification of new biomarkers of disease progression and targets for therapeutic intervention.

Acute kidney injury (AKI) and chronic kidney disease are increasingly recognized as interconnected entities and the term acute kidney disease (AKD) has been proposed to define ongoing pathophysiologic processes following an episode of AKI. In this Consensus statement, the Acute Disease Quality Initiative 16 Workgroup propose definitions and staging criteria for AKD, and strategies for the management of affected patients. They also make recommendations for areas of future research with the aims of improving understanding of the underlying processes and improving outcomes.

Haemodialysis is associated with a high risk of cardiovascular events. Here, the authors discuss the mechanisms by which biomaterial-induced activation of the complement, contact and coagulation systems might contribute to the generation of arteriosclerosis and cardiovascular disease in patients on haemodialysis.

Crystals can trigger different types of renal injury according to their speed at which they form and their localization. Here, the authors discuss shared and specific mechanisms underlying crystal formation and renal injury, such as regulated cell death and inflammasome activation.

Non-alcoholic fatty liver disease (NAFLD) not only affects the liver, but can also increase the risk of developing extra-hepatic diseases, including type 2 diabetes mellitus, cardiovascular disease and chronic kidney disease (CKD). Here, Targher and Byrne discuss the epidemiologic and mechanistic evidence of a pathogenic link between NAFLD and CKD.

Acute kidney injury continues to challenge physicians, researchers and patients. To date, there is no efficient treatment for acute kidney injury and its occurrence in many critically ill patients seems inevitable. However, a new study might just change the way we approach this seemingly intractable problem.

New research supports the notion that pre-renal and intrinsic acute kidney injury are distinct molecular entities and hence different disease states despite similar increases in serum creatinine level. Pre-renal AKI induces protective molecular mechanisms whereas intrinsic AKI requires a 'second hit' that upregulates injury genes, and results in a persistent elevation of serum creatinine and kidney injury biomarkers.

Heparanase is an endoglycosidase that regulates numerous cell functions and is able to degrade the extracellular matrix component heparan sulfate, which has a key role in maintaining the integrity of the glomerular filtration barrier. In this Review, Rabelink and colleagues describe the biological regulation and functions of heparanase, including the role of this enzyme in the development of kidney disease.

Nicotinamide adenine dinucleotide (NAD⁺) depletion contributes to the pathogenesis of cardiac and renal diseases. Here, the authors review the roles of NAD⁺ in the heart and kidney and discuss the mechanisms by which NAD⁺supplementation might have therapeutic efficacy, with a focus on the role of mitochondrial sirtuins.

Regular physical activity is associated with reduced mortality in the general population and in patients with chronic kidney disease. Here, the authors discuss the importance of physical activity for patients with renal disease and patient-reported barriers and facilitators for physical activity.

Contrast agents can damage the kidney through several mechanisms. Here, the authors discuss current understanding of the incidence and pathophysiology of contrast-induced acute kidney injury and highlight the need to consider individual patient risk factors when considering prevention strategies.

Approaches to effectively prevent and manage organ dysfunction in critically ill patients remain elusive. Key studies in 2016 highlighted the challenges in finding effective treatments for renal failure in sepsis and assessed the optimal timing of renal replacement therapy initiation in critically ill patients with acute kidney injury.

Studies published in 2016 provide insights that bring us closer to achieving the goal of personalized therapy for primary glomerular diseases. Moreover, promising renal outcome data with new classes of glucose-lowering agents — SGLT2 inhibitors and GLP-1 agonists — offer new hope for patients with diabetic nephropathy.