Key Advances in Nephrology

Chronic kidney disease is characterized by dyslipidaemia and lipid accumulation in the kidney. In this Review, the authors examine the evidence that links alterations in lipid metabolism to kidney injury and progression of kidney disease, and explore potential lipid-targeted therapeutic approaches.

This Review examines the contribution of innate and adaptive immune cells to the pathogenesis of lupus nephritis, including new insights into the molecular mechanisms that drive this disease, such as recognition of endogenous chromatin by endosomal and cytosolic nucleic acid sensors.

Complement proteins and receptors with intracellular activity — the complosome — have emerged as important regulators of physiological processes. In this Review, the authors examine evidence of complosome activity across a variety of cells and tissues, as well as their contributions to human disease and therapeutic potential.

This Review discusses the mTORC1 and AMPK nutrient sensing pathways, their downstream effects in kidney cells, their roles in the development of kidney disease and the therapeutic potential of approaches that target these pathways in various chronic kidney diseases.

This Review focuses on the potential applications of CRISPR to treat diseases that cannot be overcome by inducing frameshifts or premature stops in coding genes. The authors discuss Cas protein engineering and CRISPR systems beyond Cas9 that create a toolbox to engineer the human genome.

Clinical trials have demonstrated sodium–glucose co-transporter 2 (SGLT2) inhibitors to be safe and effective drugs that improve kidney outcomes in patients with and without diabetes. SGLT2 inhibitors also improve heart failure outcomes for patients with preserved or reduced ejection fraction. This Review summarizes findings from clinical trials of SGLT2 inhibitors, focusing on the effects of these agents in patients with chronic kidney disease and heart failure, and describes how potential mechanisms of action may translate into clinical benefit.

Here, the authors describe the determinants of ‘absolute’ and ‘relative’ glomerular hyperfiltration and discuss single-nephron haemodynamic changes as pathophysiological factors that might result in progressive kidney injury. They also explain how interventions that mitigate glomerular hyperfiltration might translate into long-term renoprotection.

Meaningful involvement of patients in clinical trial design could lead to improvements in participant recruitment and retention, the uptake of the tested intervention and the impact of the findings. Here, the authors discuss the involvement of patients at all stages of trial design.

Chronic kidney disease (CKD) is associated with an elevated risk of cardiovascular disease (CVD). Here, the authors examine CKD-associated risk factors for CVD and consider the prediction and management of CVD risk in patients with CKD, including research and implementation gaps.

This Review summarizes the current state of knowledge regarding immunological barriers to xenotransplantation and discusses the major approaches that are being used to overcome these barriers, including immunosuppression, genetic engineering of pigs and tolerance induction.