Rapid podocyte loss activates adjacent parietal epithelial cells, triggering aberrant proliferation and migration, leading to crescents or pseudocrescents and eventual glomerulosclerosis. In this issue, Lazareth, Lenoir, and colleagues demonstrate that genetic and pharmacologic mineralocorticoid receptor inhibition in activated parietal epithelial cells blunts albuminuria, aberrant parietal epithelial cell activation and migration, extracapillary proliferation, and eventual glomerulosclerosis, thereby highlighting the potential use of mineralocorticoid receptor antagonists in the therapeutic strategy for glomerulonephritis and focal segmental glomerulosclerosis with parietal epithelial cell activation.

Chronic kidney disease is a major noncommunicable disease that affects approximately 850 million people worldwide and is associated with a high burden of morbidity and mortality, especially in low- and middle-income countries. The recent resolution on kidney health at the 78th World Health Assembly creates an unprecedented opportunity for concerted action on kidney disease to accelerate global progress on noncommunicable disease prevention and control. We illustrate these opportunities using a case-study format with 3 selected countries-Guatemala, Thailand, and Somalia-which together demonstrate how the unique challenges associated with chronic kidney disease can be effectively addressed by targeted action at the country level. From these early efforts at implementing the resolution's commitments, 3 key lessons emerge for other countries to consider. First, developing a dedicated national strategy for kidney health is an essential step, which should be pursued together with integrating kidney health into other national policies for noncommunicable disease prevention and control. Second, strengthening capacity for the early detection and timely management of chronic kidney disease in primary care is arguably the highest kidney-related priority for all countries. Third, strengthening health data systems and surveillance infrastructure is critical for priority setting, resource allocation, addressing inequalities, assessing return on investment, and ensuring continuous quality improvement. In parallel with actions at the country level, the World Health Organization and other stakeholders, such as the International Society of Nephrology, can provide Member States with technical assistance and knowledge exchange related to essential medicines, key diagnostics, and kidney replacement. The International Society of Nephrology has commenced a multiyear strategy that will assist countries in implementing the resolution's commitments; the first phase will culminate in an implementation summit at the 2027 World Congress of Nephrology in Dubai. These actions will help to translate the commitments of the 78th World Health Assembly resolution into action, improving kidney health and health equity worldwide.

Women worldwide face barriers to kidney transplantation. A qualitative study of 40 women transplant recipients from 16 countries identified key concerns: health system limitations, gender-related stigma, parenthood struggles, and social vulnerability. The study illuminated key insights not previously recognized by providers, but did not include those unable to access transplantation, potentially missing the most substantial obstacles. Addressing these multilevel barriers to transplant equity requires recognizing systemic sexism and listening to the perspectives of women patients.

Key events and a trajectory spanning more than 3 decades that led to the adoption of the World Health Organization resolution on kidney health, a historic milestone for public health, are described, highlighting the pioneering contributions of leaders from Latin America. Milestones include defining the concept of kidney health, framing chronic kidney disease within social determinants, pioneering programs, strategic alliances, and regional policies. Key events are contextualized, including the Puerto Rico Declaration, the Antigua Guatemala Summit, the El Salvador meeting on Mesoamerican endemic nephropathy, and the inclusion of chronic kidney disease medicines into the Pan American Health Organization Strategic Fund. The history of the World Health Organization resolution on kidney health shows how Latin America transformed an overlooked issue into a global political priority, demonstrating how science, cooperation, and a vision of equity have elevated a regional concern into a worldwide commitment. Today, the challenge is to implement this resolution to realize kidney health for all.

This commentary highlights the innovative use of the g-formula in the European QUALity (EQUAL) study to untangle the causal relationship between chronic kidney disease-mineral and bone disorder biomarkers and kidney disease progression. By addressing time-varying confounding, informative censoring, and competing risks, this approach moves beyond traditional association studies. However, as an observational study, it remains limited by the data collected. The next step is to demonstrate that lowering serum phosphate can effectively slow chronic kidney disease progression.

Proliferative glomerulonephritis with monoclonal Ig deposits was originally defined by glomerular immunostaining with single Ig heavy and light chain subclasses; however, its true monoclonality has been challenged because of low detection of monoclonal paraproteins. Using highly sensitive and specific methods, investigators now provide strong evidence against monoclonality in most proliferative glomerulonephritis with monoclonal Ig deposits cases, findings that challenge inclusion of this disorder as a monoclonal gammopathy of renal significance and have potentially important therapeutic implications.

Glomerular deposition of IgA, IgG, and C3 has been a continued focus of the study of IgA nephropathy (formerly Berger disease) and IgA vasculitis. Until recently, direct immunofluorescence with standard optical microscopy was the preferred method for the study of these phenomena. Through the use of high-resolution confocal immunofluorescent microscopy for colocalization of these immune markers, new insights have emerged concerning the participation of these proteins in inflammatory injury in IgA nephropathy and IgA vasculitis.

Chronic kidney disease (CKD) is a substantial global health problem with devastating impacts on patients' morbidity and mortality. Kidney fibrosis, specifically tubulointerstitial fibrosis, is considered the final common pathway in the progression of virtually all forms of CKD. Peritubular capillary rarefaction, which refers to a decrease in peritubular capillary density leading to hypoxic and ischemic conditions, has long been recognized as a hallmark pathologic feature of tubulointerstitial fibrosis and a pivotal biological alteration leading to CKD progression. Conversely, recent literature has challenged this paradigm by proposing that tubulointerstitial fibrosis and CKD progression are closely associated with the upregulation of pro-angiogenic pathways. As such, peritubular capillary rarefaction may be a consequence rather than a cause of tubulointerstitial fibrosis. Furthermore, a growing body of evidence suggests that the microenvironment of the kidney vasculature, which may be referred to as the 'vascular niche', is a dynamic entity that regulates vascular homeostasis, key molecular signaling pathways and inflammation. In this review, we detail how the vascular niche may modify the course of various kidney diseases by influencing cell differentiation and the immune response. Understanding the complex interplay between the cellular and molecular components of the vascular niche may eventually lead to the identification of novel therapeutic targets to limit tubulointerstitial fibrosis and halt CKD progression. This could potentially involve modulating the secretion of angiocrine factors, regulating immune cell activity within the vascular niche, or interfering with the transformation of endothelial cells and pericytes into myofibroblasts, which are key players in kidney fibrogenesis.

Malignant hypertension with acute kidney injury or acute kidney disease is a life-threatening condition requiring urgent antihypertensive treatment and that carries a serious risk of kidney function loss. The presence of thrombotic microangiopathy (microangiopathic hemolytic anemia, thrombocytopenia) further challenges the diagnosis and treatment of these patients. As shown by recent studies, a high proportion of patients with complement-mediated thrombotic microangiopathy present with severe and malignant hypertension; however, extreme elevation of blood pressure by itself, can induce vascular lesions of thrombotic microangiopathy. To resolve this conundrum, it is essential to rapidly investigate and exclude forms of secondary hypertension (in which hematologic features are rare) and secondary thrombotic microangiopathies, both of which require treatment of the specific underlying etiology. Definitive differentiation of essential hypertension and complement-mediated thrombotic microangiopathy requires complement genetic testing, the results of which usually take weeks to months. In this review, we analyze the clinical and histological data that would support the diagnosis of complement-mediated thrombotic microangiopathy before the results of genetic tests, prompting the rapid initiation of complement blockers. However, there are numerous unmet gaps in the pathogenesis, diagnosis, and treatment of this disorder that require further research.

Accumulating evidence indicates that kidney tubular injury is central to the pathogenesis of diabetic kidney disease (DKD). Mitophagy plays a pivotal role in maintaining mitochondrial homeostasis, particularly in kidney tubular cells since they are enriched with mitochondria. However, the molecular mechanisms regulating mitophagy in DKD remain poorly understood. Here, we investigated the role of translocase of outer mitochondrial membrane 7 (TOMM7), a key regulator of protein kinase/ubiquitin ligase PINK1/Parkin-mediated mitophagy, in the progression of DKD.

Life participation is of critical importance to children and adolescents with chronic kidney disease (CKD), their caregivers and health professionals. However, life participation is assessed and reported inconsistently and uncommonly in trials involving children with CKD. The consensus workshops aimed to describe the perspectives of patients, caregivers and health professionals on developing a core outcome measure for life participation in children with CKD. Four consensus workshops (one in-person [English language], three online [two English language and one Spanish language]) were held to discuss the relevance of content, appropriateness, and feasibility of a proposed patient-reported core outcome measure. Transcripts were analyzed thematically. 171 participants, including 79 patients and caregivers, and 92 health professionals from 16 countries attended. Four themes were identified. Allowing individual interpretation and valuation of life participation included encapsulating key domains of life participation, recognizing varying degrees of achieving participation in different domains, reflecting personal context and values, emphasizing meaningful participation in activities, acknowledging changes over time, and attributing responses to the intervention. Respecting developmental needs entailed developing age-specific measures, considering literacy, utilizing relevant and clear language, using engaging formats, and establishing an appropriate recall period. Capturing broad perspectives included ensuring universal applicability across settings and allowing for proxy completion. Establishing widespread implementation by reducing the completion burden, validating for all stages and diagnoses of CKD, and enabling comparisons across CKD stages were suggested. A core outcome measure for life participation in children with CKD should be widely applicable, developmentally appropriate, allow patients to interpret life participation in their own context, be psychometrically robust and feasible to implement. The proposed measure will be revised and validated to be included in all clinical trials in children with CKD. Measuring life participation in a consistent and meaningful way across trials can better support patient-centered decision making, disease management and outcomes in children with CKD.

The co-occurrence of lupus nephritis (LN) and chronic kidney disease (CKD) is associated with an excess risk of infection. However, it remains unknown whether the infection risk differs between LN with moderate and advanced CKD (LN-CKD) and other CKD etiologies.