Review Articles in 2019

Applying single-cell RNA sequencing (scRNA-seq) to human tissues can reveal the phenotypic diversity of resident and infiltrating cells at high resolution. In this Review, the authors examine important design considerations for applying this technology to kidney cells and discuss current findings from scRNA-seq studies of lupus nephritis.

In this Review, Stewart and colleagues describe how single-cell technologies, in particular single-cell RNA sequencing, can be used to map the complex immune landscape within organs, and how such technologies might provide insights into the role of the immune system in kidney health and disease pathogenesis.

Hepatorenal syndrome type 1 (HRS-1) is a specific type of acute kidney injury (AKI) that is largely considered a functional derangement that ultimately affects renal vasculature tone. This Review describes new insights that suggest that non-haemodynamic tubulo-toxic factors, such as endotoxins and bile acids, might mediate parenchymal renal injury in patients with cirrhosis, suggesting that concurrent mechanisms might contribute to the development of AKI in patients with cirrhosis.

The field of nephrology has conducted fewer trials than other medical specialties. Here, the authors discuss how innovations in trial design and conduct could help achieve the goal of conducting a greater number of larger renal trials.

Here, the authors discuss evidence for a role of NAD⁺ imbalance in the pathogenesis of acute kidney injury (AKI) and chronic kidney disease (CKD). They suggest that disruption of NAD⁺ metabolism may contribute to mechanistic links among AKI, CKD and ageing.

Greater understanding of podocyte biology has improved our understanding of the mechanisms that contribute to the development of nephrotic syndrome. Here, Saleem outlines how our understanding of disease mechanisms that contribute to nephrotic syndrome could transform the classification and treatment of this disease.

Oncometabolites — conventional metabolites that, when aberrantly accumulated, have pro-oncogenic capabilities — have been implicated in renal cell carcinoma (RCC). Here, the authors review the role of oncometabolites in RCC, their origins and downstream effects and their potential applications as novel therapeutic targets and biomarkers.

Iron is essential for life but must be strictly regulated to avoid harmful effects. The authors discuss new insights into systemic and cellular iron handling with respect to renal physiology and pathology, current treatment practices and novel therapies for kidney disease.

Fibroblast growth factor 23 (FGF23) is crucial to phosphate and calcium homeostasis. In this Review, the authors discuss how levels of biologically active FGF23 are controlled by balanced FGF23 transcription and protein cleavage, and how serum iron levels, inflammation and erythropoietin affect that balance.

In this Review, the authors examine current efforts to develop a precision medicine approach that informs the diagnosis and treatment of patients with sepsis. Prognostic and predictive enrichment strategies in sepsis might also provide insight into the mechanisms that drive sepsis-associated acute kidney injury, a common complication of sepsis.

Therapeutic modulation of hypoxia-inducible factors, which transduce adaptive transcriptional responses to hypoxia, is an emerging theme in kidney disease. This Review summarizes the hypoxia signalling mechanisms underpinning these novel treatments and highlights key remaining questions relevant to their clinical use.

Increasing evidence suggests that dysregulation of cellular metabolism has a role in the pathophysiology of autosomal dominant polycystic kidney disease. Here the authors discuss the underlying pathways and review efforts to use pharmacological interventions and lifestyle modifications to slow disease progression.

Immunological ageing has profound effects on the immune system and its ability to protect the host against infection, cancer and autoimmunity. In this Review, the authors discuss how the processes of immunosenescence and inflammageing drive these age-related changes, and their effects on the ageing kidney.

Intravascular haemolysis and the subsequent release of proinflammatory haemoglobin and haem into the circulation are characteristic of several diseases. This Review discusses the major pathophysiological mechanisms and consequences of intravascular haemolysis with a focus on the kidney, and highlights emerging therapeutic strategies to target haemolysis-related kidney injury.

Acute kidney injury (AKI) is diagnosed by the serum concentration of creatinine (SCr), an insensitive marker of kidney function. The authors of this Review discuss the properties of ideal biomarkers of tubular damage and how they can be combined with SCr-based AKI definitions to provide greater insights into the processes underlying acute tubular injury.

Staphylococcus infection-associated glomerulonephritis (SAGN) and acute post-streptococcal glomerulonephritis (APSGN) are the two main types of bacterial infection-associated glomerulonephritis. In this Review, the authors discuss the epidemiology of these diseases, common histopathology findings and the complexities of clinical diagnosis, as well as patient management and renal outcomes.

Kidney organoids have the potential to advance the field of nephrology. Here, the author discusses progress in the development of kidney organoids and describes remaining challenges to the use of these cultures for the study of kidney physiology and disease.

The microbiome is increasingly recognized as an element that contributes to health and disease. Here, the authors take an ecological approach to describe the impact of factors related to chronic kidney disease on the fitness of different physiological systems and the effects of these changes on microbiota composition.

Sodium has a crucial role in osmoregulation and fluid balance. In this Review, the authors discuss how sodium is also an important functional modulator of innate and adaptive immune cells and how it might be linked to chronic inflammatory conditions.

Various cell types release extracellular DNA traps that protect the host against microbial infections. In this Review, the authors discuss how DNA traps not only participate in pathogen clearance but can also promote vascular disease and autoimmunity.