Reviews & Analysis

Dysfunction of endolysosomal pathways can lead to generalized dysfunction of the proximal tubule. Here, De Matteis and colleagues describe the role of the inositol polyphosphate 5-phosphatase, OCRL, in the endolysosomal pathway and how mutations in the encoding gene lead to the clinical manifestations of Lowe syndrome and Dent disease 2.

Current treatment recommendations for lupus nephritis are largely guided by the 2003 International Society of Nephrology/Renal Pathology Society classification system. Here, the authors discuss potential approaches by which this classification system could be improved through consideration of underlying disease processes characterized by the presence of glomerular crescents, podocyte injury, tubulointerstitial lesions and vascular injury.

New data highlight the increasing global burden of cardiovascular disease, end-stage renal disease and disability adjusted life years that can be attributed to reduced glomerular filtration rate (GFR). These findings underline the need to evaluate whether screening for chronic kidney disease is effective and if early interventions can reduce the incidence of GFR-attributable adverse events.

Epigenetic factors control gene expression and activity in response to environmental perturbation and regulate ageing processes throughout the life course. Here, the authors discuss the epigenetic regulation of signalling pathways that modulate ageing and their impact on the kidney.

A new study reports that a heart–brain–kidney network involving renal and cardiac macrophages is required for the adaptive response to cardiac stress. As well as highlighting the importance of inter-organ communication in complex pathological syndromes, the findings raise important questions with implications for the treatment of heart failure.

A new study of mortality of children on renal replacement therapy in 32 European countries demonstrates that 67% of the variance between countries can be explained by disparities in public health expenditure. Investment in health care is critical and has demonstrable benefits for the most vulnerable populations.

The treatment of chronic kidney disease (CKD) and end-stage renal disease (ESRD) is associated with immense societal costs, with particularly high expenditure for renal replacement therapy. This Review addresses the economic aspects of CKD and ESRD with a focus on approaches to prevent the conditions that contribute to CKD and its progression.

Encouraging preliminary data from the NEFIGAN trial suggest that a novel oral formulation of budesonide might reduce disease progression in IgA nephropathy. This formulation releases corticosteroid in the distal small intestine and colon, so is thought to directly target the mucosal element of the pathogenesis of the disease.

The Oxford Classification of IgA nephropathy (IgAN) is the most widely accepted system for assessing histologic findings in IgAN. A new publication refines this classification by adding a crescent score, reassessing the segmental sclerosis score, and contextualizing the clinical relevance of the histologic lesions.

Mechanistic studies have implicated the alternative complement pathway, specifically C5a receptor activation, in the pathogenesis of anti-neutrophil cytoplasmic antibody-associated vasculitis. Results from a phase 2 trial suggest that C5a receptor blockade could enable the reduced use or complete withdrawal of steroids from induction protocols.

Alkaline phosphatase (ALP) drives skeletal mineralization and has a role in vascular calcification and resulting cardiovascular disease in patients with CKD. Here, the authors describe the mechanisms of ALP-mediated vascular calcification and discuss the therapeutic potential of targeting ALP to improve cardiovascular outcomes in these patients.

A recent study reports that coronary artery calcification (CAC) predicts the risk of heart failure, myocardial infarction and stroke in patients with moderate chronic kidney disease (CKD). This finding suggests that even in CKD, CAC is a marker of cardiovascular risk rather than a benign indicator of vessel healing and stability.

New findings challenge the dogma that high salt intake leads to increased thirst, water intake and diuresis. Titze and colleagues show that salt loading activates an adaptive regulatory network in the kidney, muscle and liver, which enables the reprioritization of energy metabolism to conserve plasma water in the setting of high salt intake.

Clear cell renal cell carcinoma is associated with reprogramming of metabolic pathways including glucose and fatty acid metabolism and the tricarboxylic acid cycle. Here, the authors discuss these reprogrammed pathways and the opportunities they provide for new therapies, imaging modalities and biomarkers.

Chronic kidney disease (CKD) affects numerous organs and systems, which in turn have effects on kidney function. This Review provides an overview of CKD as a systemic disease and discusses the multidirectional links between the kidney, bone, nervous and immune systems, and metabolism.

Hypertension in pregnancy is a known risk factor for increased cardiovascular risk for both the mother and her offspring. New findings suggest the offspring of normotensive pregnancies should also be considered at risk of high blood pressure if their mother has had hypertension in other pregnancies.

Chronic kidney disease accelerates atherosclerosis via augmentation of inflammation, perturbation of lipid metabolism, and other mechanisms. Here, the authors describe the role of the immune system in the initiation and progression of atherosclerosis and discuss potential opportunities for therapy.

Achieving optimal blood pressure with antihypertensive agents in hypertensive patients can be particularly challenging. A major factor in this challenge is poor implementation of and compliance with multidrug regimens. However, a recent study shows encouraging results with a new single pill product that contains ultra-low doses of four antihypertensive agents.

To ensure suitability for living kidney donation, donor candidates must be thoroughly evaluated. This Review describes current approaches to the assessment of renal function, haematuria, and cardiac risk in living kidney donor candidates as well as strategies to improve efficiency in the evaluation process, focusing on additional investigations that are commonly ordered by transplant centres rather than the minimum initial screening requirements.

Iodinated contrast media are essential for diagnostic and interventional radiological and cardiological procedures, but may cause kidney damage. Intravenous hydration is the current cornerstone for prevention of contrast-induced acute kidney injury; however, new data from the AMACING trial suggest that this approach might not be beneficial in low-risk patients.