Reviews & Analysis

Haemodialysis options for undocumented immigrants with end-stage renal disease range from standard of care thrice-weekly treatments to emergency-only haemodialysis. This latter approach is associated with poor patient outcomes and high costs. The time has come for the nephrology community to demand an end to the practice of emergency-only haemodialysis.

Immune mechanisms have important roles in the development of hypertension and end-organ damage. In this Review, David Mattson discusses these mechanisms with a focus on salt-sensitive hypertension and adaptive immunity.

This Review describes the reciprocal interactions between the immune system and the intestinal microbiota, focusing on components of the immune system that drive chronic diseases that involve the kidney. The authors also discuss limitations of current approaches to microbiota research and emphasize the need to move beyond studies of correlation to causation.

The PIVOTAL trial shows that proactive intravenous (i.v.) iron administration reduces cardiovascular events and deaths, transfusions and erythropoiesis-stimulating agent doses and does not increase infections in patients on haemodialysis. These findings upend the warnings of guidelines and experts about the dangers of i.v. iron and prove that maintaining low iron stores is harmful.

Pre-eclampsia is associated with substantial maternal and fetal morbidity and mortality worldwide. Here, the authors discuss the epidemiology, pathogenesis and current and future treatment of pre-eclampsia with a focus on the role of angiogenic imbalance.

A new study reports that human blood vessel organoids can be generated through the directed differentiation of human pluripotent stem cells. Use of these blood vessel organoids to model diabetic vasculopathy led to the identification of a new potential therapeutic target, suggesting that this system could have translational value for studies of diabetes complications.

A reduction in proteinuria and albuminuria has long been proposed as a surrogate biomarker for clinically validated end points for interventional trials in patients with kidney disease. Taken together, the findings of two recent landmark meta-analyses present a formidable argument favouring such surrogacy but some uncertainty remains.

This Review describes the main signalling pathways that are coordinated by primary cilia to control developmental processes, tissue plasticity and organ function and how defects in the output of ciliary signalling events are coupled to developmental disorders and disease progression.

The plasma accumulation of uraemic solutes seen in chronic kidney disease is associated with dysregulated homeostasis. In this Review, Nigam and Bush discuss uraemic syndrome in the context of the remote sensing and signalling hypothesis, which describes small-molecule-mediated communication between tissues and organs.

The analyses in the 2017 Global Burden of Disease Study demonstrate the growing burden of chronic kidney disease (CKD), mainly driven by population ageing; absolute levels for every CKD metric considered rose significantly, whereas age-standardized rates were fairly stable. The prevalence of key metabolic CKD risk factors, particularly obesity, also show a worrying increase.

Wilms tumour is the most common renal malignancy of childhood. Here, the authors review the genetic landscape of Wilms tumour and discuss how precision medicine guided by genomic information might lead to new therapeutic approaches and improve patient survival.

This Review presents our current understanding of C3 glomerulopathy. Smith et al. discuss the histopathological diagnosis and the crucial pathogenic role of complement dysregulation. Genetic and acquired drivers of C3 glomerulopathy, potential biomarkers and available treatments are highlighted.

Macrophages are versatile immune cells that protect the host against infection but can also promote chronic inflammation and fibrosis. In this Review, the authors discuss the diverse roles of macrophages in acute and chronic renal pathology as well as potential therapeutic targets.

New findings demonstrate that endothelial nitric oxide synthase regulates major metabolic pathways in the kidney proximal tubule, which confers protection against oxidative stress during acute kidney injury (AKI). These findings give new insights into AKI pathophysiology and nitric oxide biology, and identify new targets for the treatment of AKI.

Scientists have long wondered how maternal diabetes, malnutrition and placental dysfunction impair fetal nephrogenesis. A new study discovered a link between prenatal metabolic stress and nephron deficit via dysregulation of DNA methylation — an epigenetic mechanism that is essential for the renewal and differentiation of nephron progenitors.

Uraemic cardiomyopathy is the major phenotype of fatal cardiac disease in patients with end-stage renal disease. This Review focuses on the molecular mechanisms of uraemic cardiomyopathy, crosstalk between these mechanisms and implications for therapy

A growing body of evidence suggests that epigenetic regulation is involved in the process of acute kidney injury (AKI) and kidney repair. This Review provides a general overview of the main epigenetic mechanisms that have been linked to AKI and discusses the challenges and therapeutic implications of these findings.

Peritoneal dialysis has many advantages over haemodialysis in the treatment of acute kidney injury (AKI) in low-resource settings. One limitation, however, is the availability of commercial dialysis fluid. Following the International Society of Peritoneal Dialysis AKI guidelines, a frontline hospital in Cameroon now shows that locally prepared fluids are safe and effective.

The function of polycystin proteins and the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) are not well understood. Studies published in 2018 made important contributions to the understanding of genetic mechanisms, the structure of the polycystin complex and the roles of G-protein signalling and the immune system in ADPKD.

The kidney is a highly vascularized organ and contains a remarkable diversity of endothelial cell populations. Here, the authors describe unique features of the healthy renal endothelium and the pathological mechanisms that can lead to endothelial damage in renal disease.