Reviews & Analysis

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.

HLA sensitization greatly increases the risk of transplant rejection and failure. An IgG endopeptidase derived from Streptococcus pyogenes (IdeS) may be an attractive new therapy for desensitization. Recent data indicate that IdeS effectively depletes anti-HLA IgG, creating a therapeutic window for successful renal transplantation in sensitized recipients.

Aspirin therapy for the prevention of pre-eclampsia in unselected women is minimally effective. New data suggest that use of a screening strategy based on clinical, biochemical and biophysical factors to identify those at high risk of pre-term pre-eclampsia could improve the efficacy of preventive aspirin therapy.

Pre-eclampsia is a common disorder of pregnancy for which the underlying mechanism is poorly understood. A genome-wide association study has now identified a pre-eclampsia susceptibility locus located near the FLT1 gene. This study brings us a step closer to dissecting the underlying causes of pre-eclampsia.

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.

Management of mineral and bone disorders in patients with chronic kidney disease (CKD–MBD) requires an understanding of the complex interactions among ions, hormones and their target organs. Since publication of the KDIGO CKD–MBD guideline in 2009, our understanding of disease pathophysiology has improved; however, a paucity of high-quality clinical evidence to support specific interventions remains. Using available data, KDIGO has now updated diagnostic and therapeutic recommendations for patients with CKD–MBD.

During injury, mitogenic signals from apoptotic cells may compensate for cell loss by promoting organ homeostasis and regeneration. A distinct type of early apoptotic extracellular vesicle with specific mitogenic activity has been identified. The detection of these vesicles in damaged mouse glomeruli highlights their possible role in response to renal injury.

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.

Inhibitors of renal sodium/glucose cotransporter 2 (SGLT2) are new anti-hyperglycaemic drugs that reduce proximal tubular glucose and sodium reabsorption. The Canagliflozin Cardiovascular Assessment Study (CANVAS) Program is the second major trial to demonstrate beneficial effects of SGLT2 inhibitors on the kidney and cardiovascular system in patients with type 2 diabetes mellitus.

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.

Debate exists regarding the safety of metformin and the risk of metformin-associated lactic acidosis, particularly in the setting of kidney dysfunction. Data from two studies examining the interplay between metformin, acute kidney injury, and complications including lactic acidosis suggest that metformin should be used conservatively in patients with kidney dysfunction.

New findings demonstrate a link between mutations in DZIP1L and an autosomal recessive polycystic kidney disease (ARPKD)-like phenotype. Rather than focus on DZIP1L as a second genetic locus for ARPKD, we suggest these data identify the ciliary transition zone as a functional domain central to the pathogenesis of ARPKD.

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.

Immunomodulatory treatment with mesenchymal stromal cells represents a novel therapeutic modality for immune-mediated kidney injury, including in the settings of renal transplantation and glomerulonephritis. A new study illustrates the complexity of aligning clinical trial design, manufacturing and availability of biomarkers in order to turn this promising concept into a therapeutic reality.

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.

The FOURIER trial shows that evolocumab, an injectable monoclonal antibody against PCSK9, decreased the risk of cardiovascular events in high-risk patients receiving statin therapy. The beneficial effects of this drug were consistent with an absolute reduction in LDL cholesterol levels, although studies with a longer follow-up period are needed.

Membranous nephropathy is an immune-mediated disease and is the leading cause of nephrotic syndrome in adults. Here, the authors discuss the role of B cell-depleting regimens in the treatment of this disease and the potential use of rescue therapy with agents that target plasma cells, which might prevent antigen–antibody interactions and immune complex-mediated complement activation.