Volume 12 Issue 3, March 2016

The SPRINT data suggest a cardiovascular benefit of intensive blood pressure (BP) lowering in high-risk individuals. The BP measurement protocol, however, likely resulted in lower BP values than would normally be obtained in the clinic. Intensive BP targets might not be as safe if routine BP measurements are used.

The effects of SGLT2 inhibitors on lowering blood pressure are well characterized, but data now demonstrate their enhanced blood pressure-lowering capacity when combined with dual antihypertensive therapy. Specifically, blood pressure was markedly reduced when dapagliflozin was administered to patients receiving a renin–angiotensin system blocker plus a calcium antagonist or β-blocker.

Blockade of the renin–angiotensin–aldosterone system (RAAS) slows the progression of many forms of kidney disease, but whether this therapy is beneficial in kidney transplant recipients is unclear. A new randomized controlled trial suggests that RAAS blockade is not beneficial in the transplant setting, but the underpowered nature of this study limits its conclusions.

Genetic studies over the past few years have led to the discovery that a monogenic cause of disease can be detected in ∼20% of individuals with early-onset chronic kidney disease (CKD). In this Review, Vivante and Hildebrandt discuss some of the known single-gene causes of early-onset CKD and the implication of next-generation sequencing for genetic diagnosis. They describe how the discovery of novel causative genes has led to opportunities for delineating the pathomechanisms of disease and potential treatment approaches.

A relationship between IgA nephropathy (IgAN) and the mucosa has long been recognized with evidence from clinical observations and genetic studies suggesting that abnormalities in the IgA mucosal immune system could be a key element in the pathogenesis of IgAN. In this Review, Jürgen Floege and John Feehally describe current evidence that links the mucosa, in particular the gastrointestinal mucosa, and IgA produced in the bone marrow with IgAN.

Renal anaemia, resulting from impaired renal production of erythropoietin, is a common occurrence in patients with chronic kidney disease. Conventional erythropoiesis stimulating agents can be used to treat the condition, but small-molecule inhibitors of prolyl hydroxylase domain-containing (PHD) enzymes might provide a more efficient and tolerable approach to anaemia management. Here, Maxwell and Eckardt describe the rationale for targeting PHD enzymes to increase erythropoietin production. They also discuss other potential on-target consequences of HIF activation and possible off-target effects on enzymes that are structurally similar to PHD enzymes.

A close relationship has been described between cardiometabolic disorders (CMDs) and the gut microbiota. In this Review, Judith Aron-Wisnewsky and Karine Clément outline the evidence supporting a link between the composition of the gut microbiota with cardiovascular and chronic kidney disease. They outline the methods used to study the microbiome, the effect of dietary intake patterns on microbiota composition and its derived metabolites, and possible areas for intervention to prevent or treat CMDs.

In this Viewpoint, six leading researchers reflect on progress made in their specialist field of paediatric kidney disease. They provide their insight as to the direction research will take in future years, and comment on areas in which additional research or initiatives are required to improve renal outcomes and patient care for the paediatric and neonatal population.