News & Views in 2017

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

New data highlight the increasing global burden of cardiovascular disease, end-stage renal disease and disability adjusted life years that can be attributed to reduced glomerular filtration rate (GFR). These findings underline the need to evaluate whether screening for chronic kidney disease is effective and if early interventions can reduce the incidence of GFR-attributable adverse events.

A new study reports that a heart–brain–kidney network involving renal and cardiac macrophages is required for the adaptive response to cardiac stress. As well as highlighting the importance of inter-organ communication in complex pathological syndromes, the findings raise important questions with implications for the treatment of heart failure.

A new study of mortality of children on renal replacement therapy in 32 European countries demonstrates that 67% of the variance between countries can be explained by disparities in public health expenditure. Investment in health care is critical and has demonstrable benefits for the most vulnerable populations.