News & Views in 2015

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.

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.

Treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD) can be challenging. Now, data from the phase III C-SURFER study show that grazoprevir and elbasvir — a new all-oral combination therapy for HCV — is safe and effective in patients with stage 4–5 CKD.

Fluid therapy with saline is considered by some to confer a notable risk of acute kidney injury and mortality. However, data from the SPLIT trial — the first large, randomized controlled trial to compare saline to a 'balanced' solution — do not indicate any marked signal of harm in critically ill patients.

A new study reports that B7-1 is not expressed on the podocytes of patients or mice with diabetic nephropathy. In contrast to the findings of some previous studies, these data suggest that targeting B7-1 on podocytes using abatacept might not be an appropriate therapeutic strategy for diabetic renal disease.

A new study reports that addition of the nonsteroidal mineralocorticoid receptor antagonist finerenone to renin–angiotensin system (RAS) blockade resulted in a reduction in albuminuria in patients with diabetic nephropathy. Such a strategy might provide an opportunity to maximize the beneficial effects of RAS blockade without increasing the risk of hyperkalaemia.

Autosomal dominant polycystic kidney disease is a challenging disorder to diagnose and treat effectively. Promising research over the past decade has, however, provided novel interventions, modifications to clinical practice and new areas to investigate with the aim of identifying approaches to slow disease progression.

Although the first 50 years of renal transplantation were marked by great advances in immunosuppressive therapies, the past decade has been marked by an unprecedented increase in technology. This progress has spurred investigators to challenge old paradigms and investigate how best to utilize these technologies to further improve patient care.

The past decade has seen developments in several aspects of acute kidney injury (AKI), including the discovery of an array of biomarkers, assessment of the optimal dose intensity for renal replacement therapy, and the impact of fluid administration. Furthermore, AKI has emerged as an important risk factor for chronic kidney disease.

In the past decade, major advances have been made in defining the antigens and pathogenesis of immune complex diseases such as membranous nephropathy and IgA nephropathy. Probing of rare genetic diseases has revealed new pathways of injury in proteinuric conditions, including channel abnormalities in the podocyte and complement dysregulation underlying proliferative glomerular lesions.

Advances in genome sequencing and genetic manipulation techniques over the last decade have helped identify numerous single-gene causes of early-onset kidney diseases and risk alleles for complex, polygenic traits. Subsequent studies regarding the underlying disease mechanisms will help lead to personal genetic diagnoses and unique therapeutic interventions in the future.

A new meta-analysis shows that dual blockade of the renin–angiotensin system is the most effective approach to prevent end-stage renal disease in patients with diabetes and kidney disease. Combination therapy should therefore be reconsidered as the most powerful tool for nephroprotection, provided that treatment is individually tailored by careful dose-titration.

A randomized multicentre controlled study of 240 cardiac surgery patients at high risk of acute kidney injury (AKI) has demonstrated that remote ischaemic preconditioning can reduce the rate of AKI and requirement for renal replacement therapy. These findings suggest this procedure could be a promising therapeutic option for this high-risk patient group.

Elevated levels of fibrobast growth factor 23 (FGF-23) are associated with cardiovascular and all-cause mortality in patients with kidney disease. A secondary analysis of the EVOLVE trial reports that cinacalcet-induced reductions in FGF-23 were associated with a reduced risk of cardiovascular events in patients with secondary hyperparathyroidism on dialysis.

The constitutive uptake and degradation of filtered albumin by the proximal tubule has resulted in this process being relegated a passive player in albuminuria. Real-time intravital imaging of the rat kidney now describes a new paradigm in which the proximal tubule dynamically increases or decreases albumin uptake following changes in plasma albumin levels.

Maintaining steroid-free remission in children with idiopathic nephrotic syndrome is an important goal of therapy. A new trial provides evidence that mycophenolate mofetil can be added to the list of effective steroid-sparing agents. The majority of participants relapsed, however, highlighting an unmet need for more effective treatment modalities.

A new study reports that state-level policies have had little effect on rates of organ donation in the USA, highlighting the limited ability of scattered initiatives to have a national effect. Regardless of their impact on donation rate, a need exists for policies that make donation financially neutral for donors.

Chronic kidney disease is associated with an increased risk of cardiovascular disease that often exceeds risk of progression to end-stage renal disease. A meta-analysis has shown that the addition of glomerular filtration rate and albuminuria to traditional risk factors for cardiovascular outcomes improves the discrimination of cardiovascular risk prediction models.