Review Articles in 2013

As current treatment strategies for diabetic nephropathy, namely intensive control of glucose levels and blood pressure, cannot fully prevent the development and progression of the disease, new therapeutic approaches are urgently needed. Here, Muskiet and colleagues discuss the status of currently available incretin-based agents—agonists of glucagon-like peptide 1 and inhibitors of dipeptidyl peptidase 4—and their potential renoprotective effects in patients with type 2 diabetes mellitus.

Management of chronic kidney disease in elderly patients is challenging and complex. In this Review, the authors discuss the dilemmas that are associated with the planning and maintenance of a preferred vascular access for haemodialysis in elderly patients, including the ethical issues that might influence therapeutic decision making.

In diabetic nephropathy, excessive activation of the renin–angiotensin–aldosterone system (RAAS) results in progressive renal damage. Here, the authors discuss the efficacy of RAAS blockade for the prevention of disease progression and the mechanisms of renal protection. They also highlight new strategies aimed at optimizing RAAS blockade and improving outcomes in patients with diabetic nephropathy.

Cardiorenal syndrome comprises a heterogeneous group of acute and chronic conditions, which affect patients with combined cardiac and renal dysfunction. Although cardiorenal syndrome is widely recognized, research in this field is hampered by the lack of a universally accepted definition and limited understanding of the hierarchy of factors involved in pathogenesis of the disease. Here, the authors discuss the current understanding of cardiorenal syndrome and suggest a roadmap for future research.

Fluid therapy is essential to maintain renal oxygen delivery and glomerular filtration in patients who are at risk of acute kidney injury (AKI). However, patients with AKI are also at risk of fluid overload. This Review discusses the optimal fluid management strategy for patients with AKI, and the need to balance adequate shock resuscitation with the harmful effects of fluid overload.

Orthostatic hypertension—a condition characterized by a hyper-reactive pressor response to orthostatic stress—is an emerging new risk factor for the development of hypertension, hypertensive target-organ damage and subsequent cardiovascular events. In this Review, Kazuomi Kario describes the diagnosis, epidemiology and pathophysiology of orthostatic hypertension and discusses its clinical implications.

After a period of ischaemia, organs can be further damaged by inflammatory responses and oxidative stress induced by restoring circulation. However, prior application of a non-lethal ischaemic episode can protect the organ before a larger ischaemic event, known as conditioning. This Review discusses the role of ischaemic conditioning in nephrology, to both protect the kidney and improve cardiovascular outcomes in chronic kidney disease.

Antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides are characterized by inflammation of blood vessels, which can lead to severe organ and tissue damage. Previously considered life-threatening, they are now treated using remission induction and maintenance therapies. This article outlines the current treatment regimens, reviews clinical trial data, and discusses new developments in the treatment of ANCA-associated vasculitides.

Changes in bone quality and quantity are associated with an increased risk of fracture in patients with chronic kidney disease–mineral and bone disorder (CKD–MBD). Here, methods used to assess bone quality abnormalities across different hierarchical levels are outlined, as well as the results, such as abnormalities in structural parameters and bone material or mechanical properties, which are linked to an increased risk of fracture. Such assessment will improve our understanding of CKD–MBD and aid therapeutic development.

Co-inhibitory and co-stimulatory signals that are expressed upon T-cell-activation influence both autoreactive and alloreactive T-cell responses. Here, the authors describe the functional importance of T-cell co-stimulatory molecules in transplantation, tolerance and autoimmunity, and how therapeutic blockade of these pathways might be harnessed to manipulate the immune response to prevent or attenuate pathological immune responses.

Patients with chronic kidney disease (CKD) have a high risk of bone fracture and low bone mineral density, which resembles osteoporosis. However, the mineral and bone disorder associated with CKD (CKD–MBD) is more complex than osteoporosis and the same treatments might not be appropriate in these patients. In this Review, Susan Ott discusses therapies for osteoporosis, and the evidence for their use in patients with CKD–MBD.

The glomerular endothelium is the first part of the glomerular filtration barrier that provides a barrier to albumin. In this Review, Simon Satchell describes the evidence for a role of the glomerular endothelium, and particularly the endothelial surface layer, in albumin handling. He also discusses the roles of podocytes and glomerular endothelial cells in glomerular homeostasis, and the therapeutic potential of targeting the endothelial surface layer in glomerular and vascular diseases.

Cardiovascular mortality is very high in young patients with chronic kidney disease (CKD), and it has been suggested that patients with CKD exhibit a 'premature ageing' phenotype. This Review discusses data showing that uraemic toxins can drive vascular smooth muscle cell damage and phenotypic changes that promote vascular calcification. It also describes emerging data indicating that uraemic toxins may also promote DNA damage, which drives cellular ageing.

This article highlights the evolution in understanding of the podocyte slit diaphragm. Now appreciated as far more than a simple intercellular connection, the slit diaphragm controls the structure and function of the glomerular filtration barrier. However, several slit diaphragm properties remain unclear: its role in filtration, exact molecular structure, and the complex pathways initiated by this dynamic signalling hub.

Cardiac disease and renal disease are frequently accompanied by nonthyroidal illness, which can result in deterioration of cardiovascular and renal function via several pathways. In this Review, the authors discuss the hypothesis that nonthyroidal illness is a cardiorenal connector in the genesis and maintenance of the cardiorenal syndrome, and describe data from studies that have investigated the efficacy of thyroid hormone replacement therapy in patients with renal or cardiac disease.

Amyloid formation and deposition results in a progressive disturbance of organ function. The kidneys are frequently involved in systemic amyloidosis and, without treatment, the disease is usually fatal. In this Review, the authors discuss amyloid pathophysiology, diagnosis, and current and future therapeutic strategies for the various systemic amyloidosis syndromes.

In Africa, the burden of treating the more common and widespread communicable diseases such as HIV/AIDS and tuberculosis has meant that treatment of kidney disease has been a low priority. In this Review, the authors describe the epidemiology of acute kidney injury and chronic kidney disease in Africa. They discuss the unique problems faced across this continent and the programmes that have been put in place to attempt to tackle these problems.

Obesity-related metabolic syndrome is a growing health concern. The heart and kidneys are physiologically interdependent, and the pathological effects of obesity can lead to cardiorenal syndrome and, ultimately, kidney and heart failure. In this Review, the authors describe the complex interactions by which obesity might affect physiological cardiorenal interactions. They also discuss the potential roles of surgically induced weight loss and enhanced metabolic activity in the treatment of obesity-related cardiorenal syndrome.

Sporadic and hereditary forms of renal cell carcinoma, von Hippel–Lindau (VHL) disease and the familial paraganglioma syndromes are closely related in terms of their clinical and molecular genetic aspects. In this Review, the authors discuss pathogenesis, treatment and preventive strategies for VHL disease, VHL-disease-specific renal lesions, and familial paraganglioma syndromes.

In this Review, Zhi-Hong Liu describes the current status of nephrology in China, with particular reference to chronic kidney disease, acute kidney injury and kidney transplantation. She also discusses the potential of Chinese health-care reforms to increase the prevalence of dialysis and improve long-term outcomes for patients with chronic kidney disease.