Reviews & Analysis

Blockade of the renin-angiotensin-aldosterone system (RAAS) is a standard treatment for patients with chronic kidney disease (CKD). Intensive strategies with single-agent or dual-agent RAAS blockade have been used to reduce proteinuria and blood pressure in these patients. This Review discusses strategies for improving the long-term outcomes of patients with CKD treated with RAAS blockade, focusing on the effects of combined low-dietary sodium intake and RAAS-blockade on the risk of renal and cardiovascular outcomes.

Heart failure and renal dysfunction frequently coexist. The term cardiorenal syndrome (CRS) is frequently used to describe this scenario, but the definition of CRS has been a matter of debate and has evolved over time. Here, the authors review the concept of CRS and its evolution and classification, and describe current and future targets for the clinical management of CRS. In addition, they propose a new classification system with seven distinct categories.

In the past few years, basic research and epidemiological studies have provided a wealth of new data on renal prognosis following acute kidney injury (AKI) and the potential association of AKI with incident chronic kidney disease (CKD), progression of CKD, and incident end-stage renal disease. The authors of this Review describe these findings and discuss the possible mechanisms by which AKI might lead to CKD or CKD progression.

The European Paediatric Dialysis Working Group has recently produced recommendations for the management of infants on dialysis. This document is timely because, despite the fact that such infants are increasingly being accepted onto renal replacement therapy programmes, most centres have very little experience in the care of this demanding group of patients.

Central venous catheters are currently the primary method of vascular haemodialysis access used by paediatric nephrologists in the USA. However, new data from Ma and colleagues suggest that in children who require chronic haemodialysis, arteriovenous fistulas might be a safer option.

Isakova et al. report that kidney transplant recipients on mammalian target of rapamycin (mTOR) inhibitors do not have a lower risk of allograft failure but do have a higher risk of death than those on calcineurin inhibitors. Careful consideration is, therefore, required before converting to mTOR inhibitors to preserve renal function.

A recent study reports that the combination of an angiotensin-receptor blocker (ARB) and a calcium-channel blocker (versus a high-dose ARB) is associated with improved blood pressure control and reduced cardiovascular, cerebrovascular and heart failure events in an elderly chronic kidney disease population. This finding raises the possibility of using fixed-dose drug combinations to improve efficacy and compliance of antihypertensive medications.

As granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) share histopathologic and clinical features, including the presence of antineutrophil cytoplasmic autoantibodies (ANCAs), patients with these syndromes are commonly labelled as having ANCA-associated vasculitis (AAV) and are subjected to similar treatments. A recent study suggests that dividing AAV into five classes based on disease phenotype provides better prognostic information than the classic division into GPA and MPA.

The development of blockers of the renin–angiotensin–aldosterone system (RAAS) has led to the identification of new RAAS components that might contribute to the effectiveness and/or adverse effects of these drugs. Here, the authors describe the roles of the prorenin receptor, type 2 angiotensin II receptors, angiotensin 1–7 and aldosterone–angiotensin II interactions and discuss the potential of modulators of these components to enhance RAAS blockade with potentially beneficial effects in patients with cardiovascular and renal diseases.

Alport syndrome is a rare disease caused by mutations in the genes encoding collagen type IV. The underlying disease mechanisms are unknown, but disrupted formation of glomerular basement membranes is thought to have a key role in pathogenesis. In this Review, the authors describe the diagnosis of Alport syndrome, current understanding of underlying pathogenetic mechanisms and treatment of this disease.

Hyponatraemia—the most common serum electrolyte disorder—is an important marker of the severity and prognosis of a number of diseases. In this Review, Schrier et al. discuss the effect of hyponatraemia in different patient groups, including those with pneumonia, heart failure, cirrhosis, and the elderly population. The authors discuss the need for prospective studies to examine whether correcting hyponatraemia can improve outcomes or whether hyponatraemia is just a marker of severe disease.

Chronic kidney disease (CKD) is an important public health issue that is strongly associated with adverse outcomes. Evaluation of existing therapies, development of new interventions, and timely patient counselling requires accurate prediction models that estimate individual-level risk. Here, Grams and Coresh outline the fundamentals of risk prediction, including considerations pertinent to CKD, common methodological shortcomings in risk prediction studies, and metrics often used to assess the performance of risk prediction models.

Resistant hypertension is defined as failure to reach goal blood pressure in patients who are compliant with maximal doses of three antihypertensive drugs, one of which is a diuretic. Despite improvements in controlling blood pressure in the past decade, studies show the prevalence of resistant hypertension is increasing. In this Review, the authors define resistant hypertension and discuss current data on its prevalence, associated comorbidities and prognostic implications.

Data from the ARISTOTLE trial showed that apixaban, compared with warfarin, reduced the rates of stroke, death and major bleeding in patients with atrial fibrillation, regardless of renal function. Is the problem of balancing the risks of thromboembolism and bleeding in patients with atrial fibrillation and chronic kidney disease finally solved?

Surprising new randomized trial data showed no clinically relevant decrease in bone mineral density at various skeletal sites 12 months after kidney transplantation in patients receiving baseline calcitriol and calcium therapy as well as ibandronate or placebo. These data raise important questions regarding strategies to prevent bone loss after renal transplantation.

A new multinational cohort study reports that patients receiving daily haemodialysis had a significantly higher mortality rate than those receiving conventional thrice-weekly treatments. Other studies have suggested that daily haemodialysis has beneficial effects. What are patients and nephrologists to make of these conflicting findings?

Flares of systemic lupus erythematosus are broadly defined as an increase in disease activity requiring an intensification of therapy. A renal flare is indicated by an increase in proteinuria and/or serum creatinine concentration, abnormal urine sediment or a reduction in creatinine clearance rate as a result of active disease. In this Review the authors examine current definitions of renal flares and describe developments in the diagnosis and treatment of renal flares.

As the world population continues to age, the number of elderly patients with chronic kidney disease who require a kidney transplant is increasing. In this Review, the effects of aging on the adaptive and innate immune systems are discussed, with a focus on the implications of age-related changes in the immune system on kidney transplantation and immunosuppression in elderly patients.

The appropriate use of lipid-lowering therapy in patients with chronic kidney disease (CKD) remains unclear. The results of two recent, robust systematic reviews and meta-analyses of lipid-lowering therapy in patients with CKD seem to support the use of lipid-lowering therapy. But is the story more complex?

Surprising new data from Sever and colleagues suggest that in patients who have hypertension and cardiovascular disease risk factors, increased plasma renin activity is associated with future renal impairment but not with cardiovascular events or all-cause mortality. These novel data are important but difficult to explain.