Reviews & Analysis

HDL exerts anti-inflammatory, antioxidative, and antithrombotic effects in healthy individuals. In this Review, Nosratola Vaziri outlines how HDL structure and function and reverse cholesterol transport is perturbed in patients with nephrotic syndrome, chronic kidney disease, and end-stage renal disease. The underlying mechanisms that contribute to HDL abnormalities and the consequences of these abnormalities, such as progression of cardiovascular complications, are discussed, as well as current treatment options.

Chronic kidney disease (CKD) is a common comorbidity in patients with type 2 diabetes mellitus (T2DM). In this Review, Paul Zimmet and colleagues discuss the changing epidemiology of T2DM and the effect of these changes on the prevalence of CKD. They indicate how the decreasing prevalence of cardiovascular disease in T2DM has resulted in an increased prevalence of CKD, outline differences in the prevalence and disease burden of T2DM and CKD in various populations worldwide, and describe the financial, societal, and clinical impact of these diseases.

The term 'hypertensive nephrosclerosis' is often used to define chronic kidney disease in non-diabetic patients with mild-to-moderate hypertension and low level or absent proteinuria; however, this terminology implies that the hypertension is causative of the kidney disease. Here, Barry Freedman and Arthur Cohen describe the differences between genetically mediated forms of glomerulosclerosis and arteriolar nephrosclerosis that is potentially related to hypertension and other vascular disease risk factors. They argue that the term 'hypertensive nephrosclerosis' should be replaced with terminology that better reflects the underlying disease aetiology, to improve diagnostic accuracy in this field.

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.

Albuminuria is used as a marker of kidney disease progression, but whether it has a role in the pathogenesis of kidney disease and the reasons for its association with cardiovascular disease are unclear. In this Review, Rabelink and de Zeeuw propose that degradation of the glycocalyx leads to albuminuria and that the filtered protein contributes to kidney disease pathogenesis. Furthermore, they discuss how systemic degradation of the gylcocalyx can lead to cardiovascular disease, providing an explanation for the association between these diseases and albuminuria.

Acute kidney injury (AKI) is highly prevalent in patients admitted to the intensive care unit, and many of these patients also develop concomitant respiratory complications. In this Review, Faubel and Edelstein discuss the traditional and non-traditional complications of AKI, focusing in particular on the pathologic mechanisms that underlie respiratory complications and the mediators of AKI-induced pulmonary inflammation.

In this Viewpoint, five members of theNature Reviews Nephrologyadvisory board reflect on the progress and frustrations of the past decade in basic and clinical nephrology research. They comment on areas where effort and money should be invested and the challenges that remain to be overcome, as well as give their predictions for progress in the next decade.

Dysregulated phosphate metabolism is a common consequence of kidney disease and renal transplantation. In this Review, Martin H. de Borst and colleagues outline the pathophysiology of dysregulated phosphate metabolism in renal transplant recipients and discuss the effect of this dysregulation on the cardiovascular system, bone, and the kidney graft. They also propose possible strategies to correct phosphate abnormalities in these patients.

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.

The development of effective desensitization strategies has enabled ABO incompatible (ABOi) kidney transplantation to become an established treatment option for patients with end-stage renal disease. Here, the authors review the mechanisms that underlie acceptance and rejection of ABOi grafts, recipient desensitization strategies, patient outcomes and novel treatment strategies that might promote graft acceptance and enable minimization of immunosuppression.

Congenital anomalies of the kidney and urinary tract (CAKUT) are a spectrum of renal disorders that commonly cause end-stage renal disease in children, but their genetic basis is largely unknown. In this Review, Nine Knoers et al. discuss the difficulties in identifying the genetic basis of CAKUT, the approaches used to detect genetic variants that confer risk of these anomalies, and the complex interplay between environmental factors, epigenetics, and genetic variants in contributing to the development of these syndromes.

The kidney and the brain exhibit extensive organ crosstalk due to similarities in their vasculature and shared humoral and non-humoral pathways. In this Review, Claudio Ronco et al. evaluate the effects of chronic kidney disease, end-stage renal disease, and acute kidney injury on cognitive and cerebrovascular function. The authors also highlight the risk factors for cognitive impairment in patients undergoing dialysis.

Vascular abnormalities, particularly those associated with rupture of intracranial aneurysms (IAs) or arterial dissections are among the most serious complications of autosomal dominant polycystic kidney disease (ADPKD). In this article, the authors discuss the pathophysiological mechanisms that might be involved in the development of vascular complications in patients with ADPKD and review strategies for screening, diagnosis and treatment of IAs in this population.

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.

Cell therapy holds promise to enable efficient repair of the adult human kidney, which could reverse damage caused by repeated renal injury. In this Review, Bussolati and Camussi consider the latest evidence for the existence and origin of functional renal progenitor cells in adult humans and the role of these cells in renal repair. They then discuss strategies for generating renal progenitor cells from pluripotent stem cells, human fetal cells and adult renal cells that could be used for cell therapy.

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.