Review Articles in 2014

Mutations in hepatocyte nuclear factor 1β (HNF1B) are the most common monogenic cause of developmental kidney disease. Affected patients commonly present with renal cysts; however, this condition is characterized by its diversity of renal and extra-renal phenotypes. Here, the authors analyse the clinical phenotypes, the spectrum of causative heterozygous HNF1B mutations, discuss the molecular pathways by which HNF1B might contribute to renal pathologies, and identify areas for future molecular, genetic and clinical research in HNF1B-associated disease.

Renal artery embolization (RAE) is becoming increasingly recognized as a beneficial adjunct in the treatment of numerous renal diseases. In this Review, the authors discuss the advantages and disadvantages of RAE in the management of conditions such as renal traumatisms, tumours, angiomyolipomas and aneurysms. The technical approaches are compared, and the benefits and complications associated with RAE are discussed.

Conventional diuretics target salt transporters in kidney tubules, but urea transporters have emerged as alternative targets for small-molecule salt-sparing diuretics. This Review summarizes the structure, expression and function of urea transporters and describes the evidence supporting the validity of using small-molecule inhibitors of urea transporters as salt-sparing diuretics.

Insights into the pathogenesis of membranoproliferative glomerulonephritis (MPGN) have transformed our understanding of the processes that can lead to the morphological appearance of this pattern of injury. It is now recognized that many cases of MPGN are characterized by the deposition of the complement component C3 in glomeruli without immunoglobulin deposition; this group of diseases is now referred to as C3 glomerulopathies. In this Review, Cook and Pickering discuss the morphological features of MPGN and their different associated pathological processes, in addition to the histological features of C3 glomerulopathies.

Focal segmental glomerulosclerosis is a heterogeneous disease characterized by primary podocyte injury or a lesion that occurs secondarily in any form of chronic kidney disease. In this Review, Agnes Fogo reviews the causes and pathogenesis of primary and non-immunologic adaptive secondary types of FSGS.

Lupus nephritis is a severe manifestation of systemic lupus erythematosus and a major cause of both acute kidney injury and end-stage renal disease. Preventing, or delaying progression of lupus nephritis is the primary objective of treatment. New treatments, or treatment regimens have substantially improved the overall prognosis of patients with lupus nephritis over the past 30 years. Here, Tak Mao Chan provides a detailed summary of the clinical efficacy of current treatment approaches, and the potential roles of emerging treatments for lupus nephritis.

Increasing evidence suggests that autophagy can modulate tissue responses during acute kidney injury, regulate podocyte homeostasis and protect against age-related renal disease. In this Review the authors describe the process of macroautophagy and its role in kidney health, ageing and disease. They also highlight the potential of autophagy as a target for renoprotective therapies.

The important roles of microRNAs (miRNAs) in kidney development, homeostasis and disease are becoming increasingly recognized. These small, non-coding RNA molecules are now understood to participate in the onset and progression of pathways involved in development of end-stage renal disease; they therefore represent potential new therapeutic targets for halting progression of chronic kidney diseases. This Review describes current research investigating the roles of miRNAs in normal kidney physiology and diseases with particular attention given to the TGF-β1 pathway and its regulation by miRNAs.

Dietary interventions that aim to delay progression of chronic kidney disease (CKD) and decrease disease-associated mortality have a pivotal role in the management of CKD. Here, the authors discuss key studies that have investigated the effects of dietary salt, protein, fruits and vegetables, water and alcohol consumption in patients with CKD, and describe appropriate evidence-based dietary strategies that could prevent, or delay the progression of CKD.

The immune system has a vital role in the renal response to acute kidney injury (AKI). In this Review, Hye Ryoun Jang and Hamid Rabb describe current understanding of the function of the innate and adaptive immune systems in the early and late injury phases of ischaemic and nephrotoxic AKI, and describe the influence of immune cells on recovery and long-term outcome following AKI.

Progression of kidney disease is characterized by the sustained release of proinflammatory and profibrotic cytokines and growth factors, leading to renal fibrosis. TGF-β is considered to be one of the main regulators of fibrosis, but preclinical studies have revealed important synergistic roles for other growth factors, including CTGF, EGF and PDGF, in this process. Here, the authors discuss the roles of these growth factors in kidney fibrosis, as well as the evidence supporting their qualification as additional targets for novel antifibrotic therapies.

Genetic studies have revealed a large number of gene mutations that can lead to the development of cystic kidney disease, but interpretation of genetic findings is complex and requires knowledge of differential diagnoses. This Review describes a clinical approach to the diagnosis of cystic kidney diseases on the basis of both kidney phenotype and extrarenal manifestations of the underlying disorder, in combination with genetic testing in selected patients.

Renal dendritic cells and macrophages are key factors in the initiation and propagation of renal disease and tissue regeneration. In this Review, the authors discuss the common and distinct characteristics of dendritic cells and macrophages as well as current understanding of the renal-specific functions of these important phagocytic, antigen-presenting cell types in potentiating or mitigating intrinsic kidney disease.

Numerous studies have identified associations between gene polymorphisms and altered drug pharmacokinetics, particularly of immunosuppressive drugs used in solid organ transplantation. In this Review, Teun van Gelder and colleagues examine data supporting the ability of pharmacogenetic information to predict the pharmacokinetics or pharmacodynamics of immunosuppressive drugs, and discuss the potential impact of these data on clinical practice, with a focus on studies performed in renal transplant patients.

Hyperkalaemia is common in patients with chronic kidney disease and is associated with adverse outcomes. Here, Csaba Kovesdy gives an overview of the mechanisms underlying hyperkalaemia and its clinical consequences in this patient population, and discusses current treatment regimens, as well as emerging therapies that might enable the more-liberal use of beneficial therapeutics in specific populations of patients at risk of hyperkalaemia.

Each year, over 70,000 organs are transplanted worldwide. The degree of risk of transmission of infection from transplanted organs to the recipient is largely unknown and is difficult to assess for specific organs. Here, Jay A. Fishman and Paolo A. Grossi describe the major risk factors for organ donor-derived transmission of infection and discuss opportunities to reduce the incidence of such events.

The cost and cost-effectiveness of dialysis therapy for patients with end-stage renal disease is a key consideration for health-care providers, particularly given the increasing prevalence of chronic kidney disease worldwide. Here, Klarenbach and colleagues discuss available data comparing the relative cost and cost-effectiveness of various dialysis modalities, including variations in the intrinsic costs of the different modalities and other factors, such as economic differences between high-income and low–middle-income nations.

In the past decade, rodent models have proven critical to study the molecular basis and natural history of polycystic kidney disease. Here, the authors provide an update on the models used to investigate the molecular pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) and test potential therapies. They also highlight progress that has been made in understanding the pathophysiology of ADPKD in humans.

Although vulnerable to infection, substantial numbers of kidney transplant recipients remain unvaccinated. This missed opportunity for protection can result in serious infection, graft loss and mortality. Here, Camille Kotton discusses the safety, efficacy, need for and timing of vaccination in adult transplant recipients, including discussion of specific vaccines and indications.

Nephritis is observed in around 30% of children with Henoch–Schönlein purpura (HSP). The treatment of these patients is complicated by similarity to IgA nephropathy. Here, the authors discuss advances in understanding of the pathophysiology, diagnosis and treatment of paediatric HSP nephritis. They suggest that current treatment guidelines based evidence obtained in adults with IgA nephropathy might be inappropriate for children with HSP nephritis.