Microvascular endothelial cells in the kidney have been a neglected cell type in sepsis-induced acute kidney injury (sepsis-AKI) research; yet, they offer tremendous potential as pharmacological targets. As endothelial cells in distinct cortical microvascular segments are highly heterogeneous, this Review focuses on endothelial cells in their anatomical niche. In animal models of sepsis-AKI, reduced

A new study reports that common mitochondrial DNA variants in specific haplogroups induce metabolic alterations that affect the onset of common age-related diseases. Unravelling the role of this subtle, long-lasting burden of mitochondrial DNA variants on kidney homeostasis could provide novel insights into the pathophysiology of chronic kidney disease.

Patients receiving dialysis are at high risk of contracting SARS-CoV-2 and developing severe COVID-19. Established SARS-CoV-2 vaccination schemes might lack efficacy in these patients and a personalized approach is therefore necessary. Importantly, given the enhanced infection risks associated with dialysis, current vaccines do not replace non-pharmacological measures to prevent infection.

Chronic pain is highly prevalent among adults treated with maintenance haemodialysis (HD) and has profound negative effects. Over four decades, research has demonstrated that 50–80% of adult patients treated with HD report having pain. Half of patients with HD-dependent kidney failure (HDKF) have chronic moderate-to-severe pain, which is similar to the burden of pain in patients with cancer. However

Dyslipidaemia is a hallmark of chronic kidney disease (CKD). The severity of dyslipidaemia not only correlates with CKD stage but is also associated with CKD-associated cardiovascular disease and mortality. Understanding how lipids are dysregulated in CKD is, however, challenging owing to the incredible diversity of lipid structures. CKD-associated dyslipidaemia occurs as a consequence of complex interactions

The lineage relationships of cells provide information about the origins of component cell types during development and repair as well as the source of aberrant cells during disease. Genetic approaches to lineage tracing applied in the mouse have revealed much about how the mammalian kidney forms, including the identification of key progenitors for the nephrons and stromal compartments. Inducible Cre

Evolutionary processes, including mutation, migration and natural selection, have influenced the prevalence and distribution of various disorders in humans. However, despite a few well-known examples, such as the APOL1 variants — which have undergone positive genetic selection for their ability to confer resistance to Trypanosoma brucei infection but confer a higher risk of chronic kidney disease —

Kidney transplant recipients receive therapeutic immunosuppression that impairs their immune responses to the COVID-19 mRNA vaccine. For this reason, this vulnerable patient population is insufficiently protected by the standard two-dose COVID-19 vaccination programme and requires a specific follow-up to guide personalization of an intensified vaccination approach.

The actions of immune cells within the kidney are of fundamental importance in kidney homeostasis and disease. In disease settings such as acute kidney injury, anti-neutrophil cytoplasmic antibody-associated vasculitis, lupus nephritis and renal transplant rejection, immune cells resident within the kidney and those recruited from the circulation propagate inflammatory responses with deleterious effects

Mesangial cells are stromal cells that are important for kidney glomerular homeostasis and the glomerular response to injury. A growing body of evidence demonstrates that mesenchymal stromal cells, such as stromal fibroblasts, pericytes and vascular smooth muscle cells, not only specify the architecture of tissues but also regulate developmental processes, vascularization and cell fate specification

Kidney involvement is common in patients with acute SARS-CoV-2 infection, and subclinical inflammation and injury may persist for many months, resulting in a progressive decline in kidney function that leads to chronic kidney disease. Continued research is imperative to understand these long-term sequelae and identify interventions to mitigate them.

To quote Nelson Mandela, “education is the most powerful weapon which you can use to change the world”. Education and training have changed the world of nephrology in Africa for many patients and their physicians, but most low- and middle-income countries still lack access to affordable therapies for kidney disease.

Unconventional T cells are a diverse and underappreciated group of relatively rare lymphocytes that are distinct from conventional CD4+ and CD8+ T cells, and that mainly recognize antigens in the absence of classical restriction through the major histocompatibility complex (MHC). These non-MHC-restricted T cells include mucosal-associated invariant T (MAIT) cells, natural killer T (NKT) cells, γδ T

An explosion in single-cell technologies has revealed a previously underappreciated heterogeneity of cell types and novel cell-state associations with sex, disease, development and other processes. Starting with transcriptome analyses, single-cell techniques have extended to multi-omics approaches and now enable the simultaneous measurement of data modalities and spatial cellular context. Data are

Chronic kidney disease (CKD) is a leading cause of global morbidity and mortality and is independently associated with cardiovascular disease. The mainstay of treatment for CKD is blockade of the renin–angiotensin–aldosterone system (RAAS), which reduces blood pressure and proteinuria and slows kidney function decline. Despite this treatment, many patients progress to kidney failure, which requires

Preparation for health-care transition from paediatric to adult-focused care must continue in young adulthood and requires coordination and an inter-disciplinary approach; however, the implementation of available tools and interventions remains challenging worldwide. Current practices fail to address issues related to patient safety, mental health, respect and equity, even in resource-rich societies

Building on previous cardiovascular outcome trials with glucagon-like peptide 1 receptor agonists, the AMPLITUDE-O trial reported significant improvements in major adverse cardiovascular and kidney outcomes with efpeglenatide in type 2 diabetes. A longer-term trial with dose-dependent analysis on kidney outcome components will better define the effects of efpeglenatide in the diabetic kidney.

Circular RNAs (circRNAs) are a class of endogenously expressed regulatory RNAs with a single-stranded circular structure. They are generated by back splicing and their expression can be tightly regulated by RNA binding proteins. Cytoplasmic circRNAs can function as molecular sponges that inhibit microRNA–target interactions and protein function or as templates for the efficient generation of peptides

Diabetic nephropathy has been traditionally diagnosed based on persistently high albuminuria and a subsequent decline in glomerular filtration rate (GFR), which is widely recognized as the classical phenotype of diabetic kidney disease (DKD). Several studies have emphasized that trajectories of kidney function in patients with diabetes (specifically, changes in GFR and albuminuria over time) can differ

Obesity, diabetes mellitus, hypertension and cardiovascular disease are risk factors for chronic kidney disease (CKD) and kidney failure. Chronic, low-grade inflammation is recognized as a major pathogenic mechanism that underlies the association between CKD and obesity, impaired glucose tolerance, insulin resistance and diabetes, through interaction between resident and/or circulating immune cells

Although respiratory failure and hypoxaemia are the main manifestations of COVID-19, kidney involvement is also common. Available evidence supports a number of potential pathophysiological pathways through which acute kidney injury (AKI) can develop in the context of SARS-CoV-2 infection. Histopathological findings have highlighted both similarities and differences between AKI in patients with COVID-19

The AURORA 1 study reports that low-dose voclosporin added to standard immunosuppressive treatment improved rate of remission in patients with lupus nephritis. Further studies are needed to investigate the long-term efficacy and tolerability of voclosporin and to compare the effects of this treatment with those of low doses of tacrolimus or ciclosporin.

Targeting the collecting duct water channel aquaporin 2 (AQP2) to the plasma membrane is essential for the maintenance of mammalian water homeostasis. The vasopressin V2 receptor (V2R), which is a GS protein-coupled receptor that increases intracellular cAMP levels, has a major role in this targeting process. Although a rise in cAMP levels and activation of protein kinase A are involved in facilitating

A huge array of data in nephrology is collected through patient registries, large epidemiological studies, electronic health records, administrative claims, clinical trial repositories, mobile health devices and molecular databases. Application of these big data, particularly using machine-learning algorithms, provides a unique opportunity to obtain novel insights into kidney diseases, facilitate personalized

In nephrology, differential diagnosis or assessment of disease activity largely relies on the analysis of glomerular filtration rate, urinary sediment, proteinuria and tissue obtained through invasive kidney biopsies. However, currently available non-invasive functional parameters, and most serum and urine biomarkers, cannot capture intrarenal molecular disease processes specifically. Moreover, although

The mammalian vascular system consists of two networks: the blood vascular system and the lymphatic vascular system. Throughout the body, the lymphatic system contributes to homeostatic mechanisms by draining extravasated interstitial fluid and facilitating the trafficking and activation of immune cells. In the kidney, lymphatic vessels exist mainly in the kidney cortex. In the medulla, the ascending

Proper glomerular basement membrane (GBM) structure and function are required for appropriate glomerular filtration and abnormalities in the α3α4α5 (α345) network of collagen IV — a GBM component — can lead to disease. New insights into the mechanisms underlying α345 hexamer assembly and function from genetic and structural data identify possible targets for therapeutic modulation.

Hypertension affects two-thirds of people aged >60 years and significantly increases the risk of both vascular cognitive impairment and Alzheimer’s disease. Hypertension compromises the structural and functional integrity of the cerebral microcirculation, promoting microvascular rarefaction, cerebromicrovascular endothelial dysfunction and neurovascular uncoupling, which impair cerebral blood supply

Interruptions to dialysis services in resource-limited settings, like India, amidst the COVID-19 pandemic has highlighted our ill-preparedness. We need alternative plans to safeguard the provision of this life-sustaining treatment and protect our vulnerable patients.

New data from the ILLUMINATE-A trial of lumasiran demonstrate the safety and efficacy of this RNA interference therapeutic in patients with primary hyperoxaluria type 1. Further studies are required to investigate the potential long-term benefits of this promising therapy.

The prevalence of cardiovascular and metabolic disease coupled with kidney dysfunction is increasing worldwide. This triad of disorders is associated with considerable morbidity and mortality as well as a substantial economic burden. Further understanding of the underlying pathophysiological mechanisms is important to develop novel preventive or therapeutic approaches. Among the proposed mechanisms

As witnesses to the health consequences of social discrimination, clinicians are uniquely positioned to build coalitions of stakeholders to address inequities and drive change. Such civic engagement is needed to ensure that all populations are given the opportunity to thrive.

In kidney transplantation, the use of minimally invasive damage biomarkers that are more sensitive and specific than plasma creatinine will be crucial to enable early, actionable detection or exclusion of structural kidney damage due to acute or chronic rejection. Donor-derived cell-free DNA (dd-cfDNA), which can be quantified, for example, through next-generation sequencing, droplet digital PCR and

Focal segmental glomerulosclerosis (FSGS) is not a specific disease entity but a lesion that primarily targets the podocyte. In a broad sense, the causes of the lesion can be divided into those triggered by a presumed circulating permeability factor, those that occur secondary to a process that might originate outside the kidneys, those caused by a genetic mutation in a podocyte or glomerular basement

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best

Chronic kidney disease (CKD) induces modifications in lipid and lipoprotein metabolism and homeostasis. These modifications can promote, modulate and/or accelerate CKD and secondary cardiovascular disease (CVD). Lipid and lipoprotein abnormalities — involving triglyceride-rich lipoproteins, LDL and/or HDL — not only involve changes in concentration but also changes in molecular structure, including

Key differences exist between clinical and research genomics. As genomic testing is adopted in nephrology clinical care, we propose focusing on clinical genomics approaches to obtain genetic diagnoses in order to ensure optimal use of resources and maximum patient benefit.

Studies of complement genetics have changed the landscape of thrombotic microangiopathies (TMAs), particularly atypical haemolytic uraemic syndrome (aHUS). Knowledge of complement genetics paved the way for the design of the first specific treatment for aHUS, eculizumab, and is increasingly being used to aid decisions regarding discontinuation of anti-complement treatment in this setting. Complement

Although overall donation and transplantation activity is higher in Europe than on other continents, differences between European countries in almost every aspect of transplantation activity (for example, in the number of transplantations, the number of people with a functioning graft, in rates of living versus deceased donation, and in the use of expanded criteria donors) suggest that there is ample