Reviews & Analysis

Blood pressure (BP) goals and the management of BP in patients with chronic kidney disease (CKD) remain controversial topics. Key articles in the past year have addressed BP goals in CKD, the use of new agents to slow CKD progression and the effects of visit-to-visit variability in systolic BP on cardiovascular events and renal progression in patients with CKD.

As IgA nephropathy (IgAN) is considered to result in part from autoimmune processes, B-cell depletion using rituximab might be a plausible therapy. However, a small randomized, controlled trial in patients at risk of progressive IgAN reports that this therapy failed to reduce proteinuria over 1 year and was associated with more adverse events per patient.

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.

New data suggest that provision of high-protein, high-calorie intradialytic meals in combination with phosphate binder therapy could be an easy and effective strategy to reduce the risk of malnutrition in patients on haemodialysis. These findings highlight the importance of avoiding excessive dietary restrictions in these patients.

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.

In a recent trial, levosimendan therapy failed to ameliorate sepsis-induced organ dysfunction or improve the survival of patients with septic shock. The failure of levosimendan and many other potential therapies for sepsis, together with the findings of histopathologic studies, raise questions regarding the pathophysiologic basis of the disorder.

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.

Noradrenaline is the currently recommended first-line vasopressor agent for patients with refractory septic shock. Although vasopressin adjunct therapy might be beneficial, new data from the VANISH trial do not support use of vasopressin as a first-line agent in these patients.

Three large-scale association studies provide insights into the genetic architecture of blood pressure regulation, identifying new common variants of modest effect and providing insights into the impact of rare and low-frequency variants. The findings suggest that newly identified variants act through indirect disease pathways and suggest targeting of causal networks might improve outcomes in patients with hypertension.

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.

Minimal change disease and idiopathic focal segmental glomerulosclerosis are often described as separate disease entities. Here, the authors propose that they are in fact different manifestations of the same disease process and review the evidence that led to this hypothesis.

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.