Review Articles in 2016

In many countries, patient outcomes with peritoneal dialysis are comparable or superior to those with haemodialysis. Here, the authors discuss the changing epidemiology of peritoneal dialysis worldwide, including the remaining country-specific challenges that must be overcome to improve utilization of this cost-effective therapy.

Senescent cells, which accumulate with ageing, are also involved in organ development and disease. Here, the authors examine the beneficial and detrimental effects of chronic and acute senescent cells in kidney formation, repair, disease and ageing and how these can be therapeutically modulated.

One of the first manifestations of cystinosis is a renal Fanconi syndrome, characterized by severe dysfunction of proximal tubule cells. This Review describes the pathogenesis of renal Fanconi syndrome in cystinosis, focusing on the importance of cystinosin in the maintenance of cellular homeostasis beyond its function in cystine transport.

Estimates of the prevalence of chronic kidney disease (CKD) vary widely, both within and between countries. Here, the authors discuss the origins of this variation, particularly issues relating to the use of estimated glomerular filtration rate, and present solutions for tackling the factors responsible.

The kidney has a key role in maintaining glucose homeostasis and is the site of action of SGLT2 inhibitors, which enhance glucose excretion to reduce plasma glucose levels. Here, Ralph DeFronzo and colleagues examine the role of the kidney in regulating glucose reabsorption and the effect of SGLT2 inhibition on renal function, glucose homeostasis, and cardiovascular disease.

Cellular plasticity facilitates organ repair after injury. Here, the authors discuss the modalities and mechanisms of cellular plasticity such as dedifferentiation and progenitor expansion in the kidney and their contribution to renal repair.

New data suggests that, in addition to mutations in tumour-suppressor genes, renal cancer is associated with epigenetic aberrations. Here, the authors discuss the mechanisms by which epigenetically silenced genes and mutations in genes that are involved in histone modification or chromatin remodelling dysregulate crucial cellular pathways in renal cancer.

Hyperphosphataemia is associated with poor clinical outcomes but strong evidence that targeting serum phosphate improves these outcomes is lacking. Here the authors discuss the role, regulation and management of serum phosphate in chronic kidney disease, including the efficacies of phosphate binder therapy and dietary interventions.

In this Review, the authors discuss spatial, temporal and molecular features of nephron formation through branching morphogenesis during kidney development. They also reflect on how genetic and environmental factors can alter these mechanisms and decrease nephron endowment in the adult kidney.

The use of nanoparticles has great potential for targeted delivery of therapeutics to specific cell types in the kidney. Here, the authors discuss the characteristics of nanoparticles and of renal physiology that must be considered when developing nanomedicines to treat kidney disease, as well as the remaining challenges in clinical translation of this technology.

Renal and vascular insulin resistance results in pathophysiological alterations including sodium retention, renal gluconeogenesis and podocyte dysfunction. Here, the authors discuss the mechanisms and effects of insulin resistance in the kidney and vasculature as well as therapeutic approaches to improve insulin sensitivity.

Epigenetic machinery and chromatin remodelling complexes are disrupted in >80% of clear cell renal cell carcinoma tumours. Here, the authors discuss the impact of genomics in identifying genes that affect susceptibility to renal cell carcinoma as well as the opportunities for a precision medicine approach to diagnosis and treatment.

The usefulness of total kidney volume (TKV) as a biomarker of disease progression in autosomal dominant polycystic kidney disease is disputed. Here, the authors propose that TKV can be used to monitor treatment efficacy and as a surrogate end point in clinical trials.

Scleroderma renal crisis is a rare, potentially life-threatening complication of systemic sclerosis. Here, the authors discuss advances made in the detection, management and prognosis of scleroderma renal crisis, which can limit the progression of affected patients to chronic kidney disease.

Human renal tissues can now be generated from human pluripotent stem cells in vitro. Here, Melissa Little and colleagues explore how improved understanding of renal development has guided differentiation protocols to generate kidney cellsin vitroand discuss the potential applications for these cells in nephrology.

Heart failure and kidney disease share a number of pathophysiological pathways. Here, Stefan Anker and colleagues discuss crosstalk between the heart and the kidneys, the epidemiology of heart failure and kidney dysfunction, and the treatment of cardio-renal syndromes.

Podocytes have a crucial role in maintaining the glomerular filtration barrier and their loss leads to glomerular disease. This Review discusses the role of podocyte actin dynamics in health and disease as well as the potential for personalized medicine approaches that target podocyte proteins.

The diagnosis and management of hypertension among patients on chronic dialysis represents a major challenge. In this Review, Georgianos and Agarwal discuss the epidemiology, diagnosis and treatment of hypertension in patients on dialysis on the basis of currently available evidence from randomized and observational studies.

Genome-wide association studies (GWAS) have shed light on the genetic basis of chronic kidney disease (CKD). Here, Matthias Wuttke and Anna Köttgen discuss the findings of GWAS of CKD-defining traits and of GWAS of specific CKD aetiologies and their follow-up experimental and epidemiological studies, as well as their implications for future study design.

The mTOR pathway has a role in the development of renal disease, kidney transplant rejection and malignancies. Here, the authors discuss the mechanisms by which mTOR complexes drive the pathogenesis of these diseases as well as the therapeutic potential of mTOR inhibitors.