Review Articles in 2015

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.

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 close relationship has been described between cardiometabolic disorders (CMDs) and the gut microbiota. In this Review, Judith Aron-Wisnewsky and Karine Clément outline the evidence supporting a link between the composition of the gut microbiota with cardiovascular and chronic kidney disease. They outline the methods used to study the microbiome, the effect of dietary intake patterns on microbiota composition and its derived metabolites, and possible areas for intervention to prevent or treat CMDs.

In the past decade considerable advances have been made in understanding the physiology and pathophysiology of coagulation proteases, their regulators and receptors in renal disease. In this Review, Berend Isermann and colleagues discuss the haemostatic and non-haemostatic functions of coagulation regulators and receptors in the kidney, the roles of coagulation proteases in acute kidney injury, chronic kidney disease and renal transplantation, and the potential for translating these insights into targeted therapies.

Hypertension is an important risk factor for cardiovascular and renal disease; however, despite the availability of several antihypertensive drug classes only about half of patients with treated hypertension achieve appropriate blood pressure control. This Review describes the potential of pharmacogenomics and other 'omics' approaches to identify genetic signals to predict an individual's response to a particular drug and enable a more personalized, or precision approach to antihypertensive treatment strategies.

Pattern recognition receptors and danger-associated molecular patterns of the innate immune system contribute to the initiation of an inflammatory response in diabetes mellitus and diabetic nephropathy. In this Review, Jun Wada and Hirofumi Makino discuss how these components of the innate immune system can lead to insulin resistance, diabetes mellitus, and renal failure and describe signalling mediators and pathways that could be targeted for treatment.

Renal involvement in primary Sjögren syndrome (pSS) is a rare complication, but regular screening is required for early detection and prevention of progression to chronic kidney disease. In this Review, Hélène François and Xavier Mariette discuss the most frequent renal complications that can occur in pSS, namely tubulointerstitial nephritis and membranoproliferative glomerular nephritis. They outline the pathophysiology of these complications, the differential diagnoses, and current treatment options.

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.

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.

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.

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.

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.

Human adult stem or progenitor cell organoid cultures have been established for multiple organs and have proved valuable in the basic study of pathophysiology as well as in clinical applications. Such an organoid culture system has not yet, however, been developed for the kidney. Here the authors describe the development and application of the available adult stem or progenitor cell organoid cultures, the challenges and feasibility of developing such a system for the kidney, and the potential kidney-specific applications of organoids.