Reviews & Analysis

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.

Several studies published in 2014 might facilitate improvements in the treatment and long-term care of renal transplant recipients. The potential risks of living kidney donation, the efficacy and safety of alemtuzumab-based induction therapy, and the treatment of chronic hepatitis E virus infection have been addressed.

Chronic kidney disease (CKD) is an established independent risk factor for increased cardiovascular events and cardiovascular mortality. During 2014, several research efforts focused on clarifying the complex pathophysiology, assessing the prognostic associations and improving the treatment of cardiovascular disease in patients with CKD.

New research suggests that rigorous blood pressure control is beneficial in early autosomal dominant polycystic kidney disease (ADPKD). Although a positive effect on the rate of decline of estimated glomerular filtration rate remains to be demonstrated, this study is likely to change current treatment strategies for young patients with ADPKD.

New data suggest that aortic stiffness results in the transmission of excessive flow pulsatility to the renal microcirculation. Further understanding of the mechanisms that regulate the relationship between large arteries and the renal microcirculation could lead to new strategies to protect the kidneys from increased blood pressure load owing to systemic hypertension.

In 2014, key studies in the field of diabetic nephropathy highlighted the importance of albuminuria as a predictor of cardiovascular risk and showed that the incidence of renal and cardiovascular complications is decreasing. Promising efficacy data were obtained with atrasentan, whereas a trial of bardoxolone methyl led to safety concerns.

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.

A new study demonstrates that knockdown of miR-193a in human parietal epithelial cells induces their differentiation into podocytes. Inhibition of miR-193a in a model of nephrotoxic nephritis resulted in reduced proteinuria and crescent formation. These data suggest that promoting differentiation of parietal progenitors into podocytes has potential therapeutic relevance.

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.

A new study shows that statin therapy before diagnosis of diabetes mellitus is not associated with an increased risk of microvascular disease and might even be beneficial for retinopathy and neuropathy. These data suggest a potential protective effect of statins in specific complications, which should be further investigated in randomized controlled trials.

A 6-year follow-up study of the ADVANCE trial participants reports that intensive glycaemic control is renoprotective—but does not reduce mortality—in patients with type 2 diabetes mellitus. By contrast, a post hoc analysis of the ACCORD trial suggests that intensive glycaemic control might increase mortality in patients with diabetic nephropathy.

It is now accepted that climate change is occurring as a result of human activity and that it will have potentially devastating effects on health. Nephrologists are likely to see a changing spectrum of disease as a consequence of climate change and are ideally placed to lead mitigating strategies in health-care provision.

Findings from the ARISE and TRISS trials indicate that protocolized therapy might be no better than contemporary management for patients in intensive care, and that in the absence of coronary disease a haemoglobin level of 70 g/l should be the new trigger for transfusion in patients with sepsis.

FDA approval of the first device to use novel biomarkers of kidney damage to assess risk of acute kidney injury (AKI) potentially brings forward diagnosis of moderate-to-severe AKI to a time frame that could enable early intervention. Although the device awaits greater scrutiny, its approval marks the beginning of a new era.

A new study has reported a molecular signature of T-cell-mediated rejection in human kidney transplant biopsy samples that is enriched for effector T cells, interferon-γ and macrophages. Inhibitors of T-cell activation, such as CTLA4 and PDL1, were also prominent, raising the possibility that these immunological constrains could be harnessed by therapies for treating rejection.