Efficacy and safety of guselkumab in patients with active lupus nephritis: results from a Phase 2, randomized, placebo-controlled study.

Objective: Evaluate the efficacy and safety of guselkumab, an interleukin (IL)-23 inhibitor, in a Phase 2, multicentre, randomized, double-blind, placebo-controlled study of patients with active lupus nephritis (LN).

Methods: Adults (18-75 years) with active LN (Class III-IV proliferative nephritis [kidney biopsy] and urine protein-to-creatinine ratio [UPCR)] of ≥ 1 mg/mg despite standard-of-care therapy) were randomized (1:1; planned sample = 60) to receive intravenous infusions of guselkumab 400 mg or placebo at Weeks 0, 4, and 8, then subcutaneous injections (guselkumab 200 mg or placebo) at Week12 and every 4 weeks through Week48 in addition to their background therapy. The primary end point was achievement of ≥ 50% decrease in proteinuria from baseline at Week24.

Congenital Anomalies of the Kidney and Urinary Tract: A Continuum of Care.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of kidney failure in children and adolescents. CAKUT describes a wide spectrum of structural disorders with a prenatal origin. The etiology of CAKUT is multifactorial, including environmental, nongenetic, and genetic causes that impact kidney development as well as upper and lower urinary tract development.

Lupus nephritis-related chronic kidney disease.

Lupus nephritis is a common complication of systemic lupus erythematosus (SLE) and a determinant of overall morbidity and mortality, as lupus nephritis-related chronic kidney disease (CKD) drives cardiovascular disease and secondary immunodeficiency. Two lines of action are required to prevent the progression of lupus nephritis-related CKD: suppression of autoimmune SLE activity, which is a risk factor for immunopathology-related irreversible kidney injury, and management of non-immune risk factors that contribute to CKD progression. As each episode or relapse of active lupus nephritis implicates CKD progression, preventing flares of lupus nephritis is a key treatment target.

Beyond CAR T cells: exploring alternative cell sources for CAR-like cellular therapies.

Chimeric antigen receptor (CAR)-T cell therapy has led to remarkable clinical outcomes in the treatment of hematological malignancies. However, challenges remain, such as limited infiltration into solid tumors, inadequate persistence, systemic toxicities, and manufacturing insufficiencies. The use of alternative cell sources for CAR-based therapies, such as natural killer cells (NK), macrophages (MΦ), invariant Natural Killer T (iNKT) cells, γδT cells, neutrophils, and induced pluripotent stem cells (iPSC), has emerged as a promising avenue.

Gasdermin D drives focal crystalline thrombotic microangiopathy by accelerating immunothrombosis and necroinflammation.

Thrombotic microangiopathy (TMA) is characterized by immunothrombosis and life-threatening organ failure but the precise underlying mechanism driving its pathogenesis remains elusive. In this study, we hypothesized that gasdermin D (GSDMD), a pore-forming protein that serves as the final downstream effector of the pyroptosis/interleukin-1β (IL-1β) pathway, contributes to TMA and its consequences by amplifying neutrophil maturation and subsequent necrosis. Using a murine model of focal crystalline TMA, we found that Gsdmd deficiency ameliorated immunothrombosis, acute tissue injury, and failure.

Erythrocytosis and CKD: A Review.

Erythrocytosis or polycythemia is defined as an increase in red blood cell concentration above the age- and sex-specific normal levels. Unlike anemia, which is very common in patients with chronic kidney disease (CKD), erythrocytosis is less frequent but requires specific understanding by health care professionals in order to provide the best care. Erythrocytosis, especially when undiagnosed and untreated, can lead to serious thrombotic events and higher mortality.

GDF-15 Suppresses Puromycin Aminonucleoside-Induced Podocyte Injury by Reducing Endoplasmic Reticulum Stress and Glomerular Inflammation.

GDF15, also known as MIC1, is a member of the TGF-beta superfamily. Previous studies reported elevated serum levels of GDF15 in patients with kidney disorder, and its association with kidney disease progression, while other studies identified GDF15 to have protective effects. To investigate the potential protective role of GDF15 on podocytes, we first performed in vitro studies using a -deficient podocyte cell line.

A new era in the science and care of kidney diseases.

Notable progress in basic, translational and clinical nephrology research has been made over the past five decades. Nonetheless, many challenges remain, including obstacles to the early detection of kidney disease, disparities in access to care and variability in responses to existing and emerging therapies. Innovations in drug development, research technologies, tissue engineering and regenerative medicine have the potential to improve patient outcomes.

Balancing efficacy and safety of complement inhibitors.

Complement inhibitors have been approved for several immune-mediated diseases and they are considered the next paradigm-shifting approach in the treatment of glomerulonephritis. The hierarchical organization of the complement system offers numerous molecular targets for therapeutic intervention. However, complement is an integral element of host defense and therefore complement inhibition can be associated with serious infectious complications.

Regulators of necroinflammation in acute kidney injury.

Interleukin (IL)-22 is unique among the ILs as it elicits direct effects on kidney epithelia and regulates cell survival in a context-dependent manner. Studies published in Kidney International and other journals demonstrate opposing roles of IL-22 (e.g.

Incidence and prognosis of acute kidney injury versus acute kidney disease among 71 041 inpatients.

Background: Acute kidney disease (AKD) defines patients with acute kidney injury (AKI) or subacute loss of kidney function lasting for >7 days. Little is known about the prognosis of AKD in hospitalized patients. The aim of this study was to investigate the risk factors and prognosis of AKD and to compare different types of acute/subacute renal impairment among Chinese inpatients.

Voclosporin: Unique Chemistry, Pharmacology and Toxicity Profile, and Possible Options for Implementation into the Management of Lupus Nephritis.

Calcineurin inhibitors (CNI) can suppress allo- and autoimmunity by suppressing T cell function but also have anti-proteinuric effects by stabilizing the cellular components of the kidney's filtration barrier. Therefore, CNI are used in autoimmune kidney diseases with proteinuria. However, the traditional CNI, cyclosporine A and tacrolimus, have a narrow therapeutic range, need monitoring of drug levels, and their use is associated with nephrotoxicity and metabolic alterations.

Macrophages and fibrosis: how resident and infiltrating mononuclear phagocytes account for organ injury, regeneration or atrophy.

Mononuclear phagocytes (MP), i.e., monocytes, macrophages, and dendritic cells (DCs), are essential for immune homeostasis via their capacities to clear pathogens, pathogen components, and non-infectious particles.

No NLRP3 inflammasome activity in kidney epithelial cells, not even when the NLRP3-A350V Muckle-Wells variant is expressed in podocytes of diabetic mice.

Background: The NLRP3 inflammasome integrates several danger signals into the activation of innate immunity and inflammation by secreting IL-1β and IL-18. Most published data relate to the NLRP3 inflammasome in immune cells, but some reports claim similar roles in parenchymal, namely epithelial, cells. For example, podocytes, epithelial cells critical for the maintenance of kidney filtration, have been reported to express NLRP3 and to release IL-β in diabetic kidney disease, contributing to filtration barrier dysfunction and kidney injury.