A common observation in diabetic kidney disease is lipid accumulation, but the mechanism(s) underlying this pathology is unknown. Inhibition of Vascular endothelial growth factor B (VEGF-B) signaling was shown to prevent glomerular lipid accumulation and ameliorated diabetic kidney disease in experimental models. Here, we examined kidney biopsies from patients with Type 2 (84 %) and Type 1 diabetes

Kidney organoids represent a tangible in vitro system in which to model disease, identify novel therapeutics, and investigate cellular and physiological mechanisms. However, their relative immaturity and insufficient endowment of critical cell types limits their translational efficacy. Addressing a number of these shortcomings, Maggiore et al. present a novel genetically inducible vascularized kidney

Sympathetic overactivation contributes to hypertension. Renal denervation can reduce blood pressure. In the deoxycorticosterone acetate (DOCA)-salt model of hypertension, salt consumption contributes to high blood pressure. A report in Kidney International finds selective ablation of renal sensory afferent nerves diminishes self-directed saline intake in the DOCA-salt rat. This suggests that these

Two coding variants of APOL1 account for much of the excess risk of focal segmental glomerulosclerosis in people of recent West African ancestry. There is an unmet need of treatment for apolipoprotein L1 kidney disease. In this issue, Sula Karreci et al. reported that lisinopril reduced proteinuria and glomerulosclerosis in a mouse model of apolipoprotein L1-induced focal segmental glomerulosclerosis

Chronic kidney disease (CKD) is associated with an increased risk of cognitive impairment. Patients with CKD display an increased permeability of the blood-brain barrier. Zimmermann et al. highlighted the implication of potassium efflux in the microglia and its activation, the activation of the interleukin-1b/interleukin-1R pathway, linked to blood-brain barrier permeability and cognitive impairment

Recent reports have described acute kidney injury in otherwise healthy individuals after exposure to hair-straightening products. In this issue, Robert et al. help elucidate the underlying mechanisms in a murine model that replicates the human pathology. Cutaneous absorption of glyoxylic acid from hair-straightening products and its subsequent conversion to oxalate are identified as crucial steps in

Onset, progression and cardiovascular outcome of chronic kidney disease (CKD) are influenced by the concomitant sterile inflammation. The pro-inflammatory cytokine family interleukin (IL)-1 is crucial in CKD with the key alarmin IL-1α playing an additional role as an adhesion molecule that facilitates immune cell tissue infiltration and consequently inflammation. Here, we investigate calcium ion and

Glomeruli filter blood through the coordination of podocytes, mesangial cells, fenestrated endothelial cells, and the glomerular basement membrane. Cellular changes, such as podocyte loss, are associated with pathologies like diabetic kidney disease. However, little is known regarding the in situ molecular profiles of specific cell types and how these profiles change with disease. Matrix-assisted laser

Human pluripotent stem cell–derived kidney organoids hold promise for future applications in regenerative medicine. However, significant biological hurdles need to be overcome to enable their use as a transplantable stem cell–derived therapeutic graft. Current kidney organoid protocols do not recapitulate a complete integrated developing kidney, but embryonic kidney transplantations have provided clues

Idiopathic nephrotic syndrome, the most common glomerular disorder in children, has long been considered an immune-mediated disease based on the efficacy of glucocorticoids at inducing remission. Nevertheless, the immune processes leading to podocytopathy have largely remained elusive. The success of B-cell depletion with rituximab, descriptions of B-cell dysregulation during active disease, and the

Podocytes can undergo PANoptosis (apoptosis, pyroptosis, and necroptosis). Diabetic kidney disease (DKD) is the leading cause of kidney failure, and podocyte loss is a major event leading to the progression of DKD. Here, we compared single cell RNA sequencing (scRNA-seq) data between three normal and three DKD human kidney samples and found a significant increase of TNFSF10 and TNFRSF10B expression

Can direct activation of soluble guanylyl cyclase (sGC) provide kidney-protection? To answer this, we tested the kidney-protective effects of a sGC activator, which functions independent of nitric oxide and with oxidized sGC, in an acute kidney injury (AKI) model with transition to chronic kidney disease (CKD). We hypothesize this treatment would provide protection of kidney microvasculature, kidney

Endoplasmic reticulum (ER) stress is a condition in which the ER is overwhelmed and unable to manage its protein load properly. The precise activation mechanisms and role of ER stress in kidney disease remain unclear. To study this, we performed unbiased transcriptomics analysis to demonstrate ER stress in kidneys of patients with chronic kidney disease and in mouse models of acute and chronic kidney

Based on the hypothesis that hyperuricemia is a modifiable risk factor for chronic kidney disease (CKD) progression, there is an expectation that urate-lowering therapy (ULT) could delay the progression of CKD. Here, we investigated changes in kidney function and the association of the serum uric acid (sUA) level and kidney function during ULT in patients with gout. To do this we conducted post-hoc

Dialysis vascular access thrombosis poses a substantial challenge for individuals undergoing hemodialysis. The efficacy and safety of apixaban, a direct oral coagulation factor Xa inhibitor, in preventing recurrent access thrombosis have yet to be explored. Here, a multicenter randomized control study (NCT04489849) enrolled hemodialysis patients to evaluate this who underwent successful endovascular

The course of proliferative lupus nephritis is characterized by flares of activity alternating with periods of quiescence against a background of chronic immune dysregulation. An accurate assessment of disease activity is of unassailable importance to tailor therapy. In the present communication, we discuss the available clinical, serologic, and histologic tools to evaluate disease activity and how

Extracellular vesicles, small membrane-bound packages secreted by virtually all cells of the body, have become a focus of interest in nephrology over the recent years. After the first characterization of their proteomic and transcriptomic content, scientific attention shifted toward their potential as biomarkers for kidney diseases both as diagnostic and monitoring tools. More recently, researchers

Patients with glomerular disease are at high risk of cardiovascular disease but the contribution of immunosuppression to this risk is unclear. In this retrospective cohort study of 1912 patients (comprised of 759 with IgA nephropathy, 540 with focal segmental glomerulosclerosis, 387 with membranous nephropathy and 226 with minimal change disease) from British Columbia, Canada, we evaluated the association

Kidney physiology shows diurnal variation, and a disrupted circadian rhythm is associated with kidney disease. However, it remains largely unknown whether glomeruli, the filtering units in the kidney, are under circadian control. Here, we investigated core circadian clock components in glomeruli, together with their rhythmic targets and modes of regulation. With clock gene reporter mice, cell-autonomous

While epidemiological and experimental studies have demonstrated kidney-protective effects of estrogen and female sex in adulthood, some epidemiological data showed deterioration of kidney function during puberty when estrogen production increases. However, molecular mechanisms explaining these conflicting phenomena remain unknown. Here, we showed that the pubertal sex hormone surge in female mice

Amoxicillin crystalluria (AC) refers to the precipitation of amoxicillin in the urine as amoxicillin trihydrate crystals. Amoxicillin-induced crystal nephropathy (AICN) refers to the obstruction of kidney tubules by amoxicillin trihydrate crystals, resulting in acute kidney injury. Usually considered rare and not serious, AC and AICN would be more frequent in patients receiving high-dose i.v. amoxicillin

The MTOR inhibitors have demonstrated antiviral properties, and prior non-randomized studies have suggested they may have a suppressive effect on BKPyV replication. Here, in this randomized, multicenter, controlled trial (BKEVER study), we sought to evaluate the impact of everolimus (EVR) in facilitating the clearance of BKPyV compared to simply reducing immunosuppression among kidney transplant recipients

In recent years, advances in genetic sequencing techniques and in the analysis of sequencing data have significantly improved our ability to diagnose genetic kidney diseases. Identification of the disease-causing genetic variant(s) is crucial not only for prognostication and personalized management, but also for providing genetic counseling and guiding family planning decisions. It is particularly

Sex is a key variable in the regulation of human physiology and pathology. Many diseases disproportionately affect one sex: autoimmune diseases, such as systemic lupus erythematosus, are more common in women but more severe in men, whereas the incidence of other disorders such as gouty arthritis and malignant cancers is higher in men. Besides the pathophysiology, sex may also influence the efficacy

Cardiac arrythmias are common in patients undergoing maintenance hemodialysis. In this issue, Charytan et al. showed that in patients with hyperkalemia (serum potassium concentration 5.1–6.5 mEq/l) on hemodialysis, a dialysate concentration of 3 mEq/l combined with sodium zirconium cyclosilicate on dialysis-free days is associated with a low frequency of atrial fibrillation compared with a dialysate

The optimal approach towards managing serum potassium and hemodialysate potassium concentrations is uncertain. To study this, adults receiving hemodialysis for three months or more with hyperkalemia (pre-dialysis serum potassium (sK+) 5.1–6.5 mEq/l) had cardiac monitors implanted and were randomized to either eight weeks of 2.0 potassium/2.5 calcium mEq/l dialysate without sodium zirconium cyclosilicate

Hypotension is a common cause of acute kidney injury (AKI), with strong associations between the duration and magnitude of hypotension seen across a range of situations including major surgery. However, it is less clear whether targeting higher intraoperative MAP results in lower rates of AKI. In a prespecified analysis of the Perioperative Ischemic Evaluation-3 (POISE-3) randomized controlled trial

In this pre-specified sub-study of the POISE-3 trial, we examined the effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of postoperative acute kidney injury (AKI). Altogether, 7307 patients were included from 110 hospitals in 22 countries. Patients were 45 years and older, had or were at risk of atherosclerotic disease, took at least one antihypertensive

Pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter 2a and 2c are rare causes of phosphate wasting. Since data on presentation and outcomes are scarce, we collected clinical, biochemical and genetic data via an online questionnaire and the support of European professional organizations. One hundred thirteen patients (86% children) from 90 families and 17 countries with

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer and are now the backbone of therapy for several malignancies. However, ICIs can cause a spectrum of renal immune-related adverse events including acute kidney injury (AKI), most commonly manifesting as acute interstitial nephritis (AIN), although glomerular disease and electrolyte disturbances have also been reported. In

Persons with end-stage kidney disease treated with dialysis experience distressing reductions in quality of life and increased mortality. Few large, randomized trials in nephrology have reported on health-related quality of life. Rose et al. report beneficial effects of high-volume hemodiafiltration versus high-flux hemodialysis on secondary end points of health-related quality of life in the CONVINCE

Clinical risk prediction models are being generated at an increasing rate. One important component is the identification of groups for whom such models might require recalibration to retain their desired performance. To this end, an update of the postbiopsy International IgA Nephropathy Prediction Tool for children has been published in this issue of Kidney International. We review the methods used

Cholesterol crystal embolism (CCE) is a complication of atherosclerosis and can cause microvascular obstruction in multiple organs. Because the consequences may be fatal, and there is no specific treatment, it is crucial to understand the mechanisms and identify treatment strategies. In this issue, Zhao et al., using a mouse model of kidney CCE, demonstrated that inhibition of C5a/C5aR prevented and

This study investigated in-hospital outcomes and related factors in patients diagnosed with postearthquake crush syndrome after the earthquakes in Kahramanmaraş, Türkiye. One thousand twenty-four adult patients diagnosed with crush syndrome were analyzed. Data on demographic characteristics, clinical presentation, laboratory values, treatments, and outcomes were collected. A total of 9.8% of patients

The efficacy and safety of rituximab in childhood steroid-resistant nephrotic syndrome (SRNS) remains unclear. Therefore, we conducted a retrospective cohort study at 28 pediatric nephrology centers from 19 countries in Asia, Europe, North America and Oceania to evaluate this. Children with SRNS treated with rituximab were analyzed according to the duration of calcineurin inhibitors (CNIs) treatment

Hemolytic uremic syndromes (HUSs) are a heterogeneous group of conditions, only some of which are mediated by complement (complement-mediated HUS). We report the outcome of the 2023 International Society of Nephrology HUS International Forum where a global panel of experts considered the current state of the art, identified areas of uncertainty, and proposed optimal solutions. Areas of uncertainty

Chronic kidney disease (CKD) is an increasingly prevalent disorder that poses a significant global health and socioeconomic burden. East Asian countries such as China, Taiwan, Japan, and South Korea have a higher incidence and prevalence of kidney failure when compared to Western nations, and the reasons for this discrepancy remain unclear. Aldehyde dehydrogenase 2 (ALDH2) is an essential detoxifying