Articles in 2015

The year 2015 has seen great progress in the renal fibrosis field, as key studies began to build a consensus on the importance of epithelial-to-mesenchymal transition, cell cycle arrest, and defective metabolism in the pathogenesis of kidney fibrosis. New findings also point to a role of developmental signalling in renal fibrogenesis.

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.

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.

2015 saw the publication of several important studies in the renal stem cell and developmental biology fields. Key studies provided insights into the ageing of nephron progenitors and optimal conditions to stimulate the expansion of nephron progenitors, and reported the in vitro generation of kidney organoids.

Podocyte biologists can boast of some important advances in 2015. Some of the key developments include defining the transcriptional targets of the Wilms' tumour protein on a genome-wide scale, the identification of new mitochondria-centred pathways for maintaining podocyte homeostasis, and new insights into the regulation and pathogenic activation of TRPC6.

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.

Combination therapy with optimal doses of multiple antihypertensive drugs fails to achieve blood pressure (BP) control in up to 15% of hypertensive patients. Key studies in 2015 highlighted the risks of uncontrolled hypertension and evaluated new therapeutic modalities designed to achieve satisfactory BP control in patients with treatment-resistant hypertension.

Numerous studies in 2015 focused on therapeutic immune modulation and immunosuppression. Trials of budenoside in patients with IgA nephropathy who are unresponsive to supportive therapy, and of low-dose IL-2 to enforce regulatory T-cell-mediated immunosuppression in autoimmune disease all produced promising results.

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.

Renal transplantation can be successfully performed in patients of all ages, and the short-term and medium-term outcomes have improved over the past decades. In this Review, Christer Holmberg and Hannu Jalanko discuss the long-term effects of kidney transplantation on paediatric recipients. They outline the adverse effects that can occur with regard to growth, bone health, metabolic and cardiovascular complications, and malignancies, and highlight the challenges that remain in managing the care of paediatric renal transplant recipients.

A recent subanalysis of data from the PEGASUS-TIMI 54 trial indicates a favourable balance between the efficacy and safety of ticagrelor in patients with prior myocardial infarction (MI), irrespective of their renal function. These results support the long-term use of ticagrelor in patients with chronic kidney disease and prior MI.

Over the past decade remote ischaemic preconditioning (RIPC) has evolved as a promising strategy to reduce ischaemia in remote organs. Although previous studies using surrogate outcomes have encouraged further investigation, two recent randomized controlled trials — the ERICCA trial and the RIPHeart Study — were unable to detect a protective effect of RIPC.