KIDNEY DISEASE:Improving Global Outcomes (KDIGO) has published the Clinical Practice Guidelines (CPG) on managing diabetes in CKD in 2022 and the CPG for managing blood pressure in CKD in 2020. KDIGO organized a guideline implementation summit targeting the Asia-Pacific region in Kuala Lumpur in 2024 with the aim to understand existing barriers and challenges in implementation of the two CPGs and to propose possible solutions, tailored to the country or region's income level to bridge existing gaps in guideline implementation. The implementation summit discussion covered 4 key themes: i) lifestyle intervention; ii) adoption of comprehensive team-based integrated care model; iii) achievement of various treatment targets albuminuria screening and monitoring of kidney disease; and iv) implementation of guideline-directed medical therapies. The Summit was attended by co-chairs of the KDIGO CPGs on diabetes and blood pressure management in CKD, with nephrologists, endocrinologists, primary care physicians, dietitians, a health economist, and patient partners from 13 Asia-Pacific countries or regions. This conference report summarizes the key challenges in the CPG implementation for diabetes, hypertension in people with CKD in Asia-Pacific region, and provides a strategic framework of actions to overcome these barriers.
C3 glomerulopathy-primary immune complex membranoproliferative glomerulonephritis (C3G/IC-MPGN) is an ultrarare disease spectrum associated with a significant health burden and for which there is a huge unmet need for safe and effective treatment. The underlying pathophysiology is dysregulation and overactivation of the alternative complement pathway. Two new therapeutic agents, iptacoplan and pegcetacoplan, that target proximal steps in the cascade, have demonstrated to be effective and have been approved for use in patients with C3G alone and with C3G/IC-MPGN, respectively. A key challenge to the nephrology community is how to incorporate these disease-modifying drugs into clinical practice in a timely and equitable manner. This report summarizes the deliberations and recommendations that emerged from the SEISMIC (Addressing access issues in diagnosis and treatment of C3G nephropathy and IC-MPGN) summit in July 2025. The meeting assembled a broad panel of experts and patients and addressed the following three aims: 1) define issues in proper and timely diagnosis of this complex disease spectrum, 2) assess management strategies in light of the availability of this new class of therapeutic agents, and 3) identify barriers to access to care and treatment with these new therapeutic agents and design strategies to surmount them.
The 15th International Podocyte Conference was held in Hamburg, Germany from June 10 to 13, 2025, marking the inaugural meeting of the International Society of Glomerular Disease (ISGD). The conference opened with a vibrant Pre-Meeting Day for Emerging Career Researchers, featuring early-career talks and exchanges on scientific and career development. The main program reflected the evolution of the field and underscored the rationale for a sustained focus on podocyte biology. Key insights included the need to shift from a disease-oriented model towards glomerular health, the complexity of glomerular cell types and interactions, and advances in identifying causal genes in kidney function through genetic studies. Unmet needs were also emphasized around patient experience, access to expert care, and trial design. Serving as a report from the 15th International Podocyte Conference, this review captures the evolving landscape of podocyte and glomerular disease research as discussed by the global scientific community.
Introduction A fundamental challenge in treating chronic kidney disease (CKD) is the lack of therapies to reverse established fibrosis. While systemic hypoxia sensors like erythrocyte sphingosine kinase 1 (eSPHK1) can initiate fibrotic signaling, the mechanisms driving self-perpetuating and progressive fibrosis remain unknown. Methods eSphk1 specific deficient mice underwent four-week angiotensin-II infusion, unilateral ureteral obstruction or ischemia reperfusion injury. Untargeted metabolomics profiled purified kidney macrophages, and [13C615N4]-arginine fluxomic tracked arginine-creatine metabolism in hypoxia treated macrophages. Multi-color immunofluorescent images of kidney tissues were scanned and scored. Preclinical studies by hypoxia inducible factor-1α (HIF-1α) inhibitor or knockdown macrophage creatine kinase B (Ckb) were performed. Clinical relevance was evaluated by measuring CKB mRNA level in peripheral blood mononuclear cells obtained from 131 patients with CKD and determining its correlation with disease severity. Results We identify a HIF-1α-CKB feedforward loop within profibrotic macrophages that functions as an autonomous engine of kidney fibrosis. This circuit, which can be triggered by established pathways such as eSphk1 dysfunction, is characterized by its capacity for self-renewal. Specifically, HIF-1α drives Ckb expression, reprogramming arginine metabolism toward creatine phosphate shunt (CPS) to generate an ATP surge that synergizes with an S1PR3-PKC signaling cascade to phosphorylate and stabilize HIF-1α, effectively bypassing the need for continued hypoxic input. This metabolic rewiring drives macrophage profibrotic polarization and leads to kidney fibrosis. Preclinically, pharmacologic HIF 1α inhibition or knockdown macrophage Ckb collapses this autonomous loop and halts fibrosis. Translationally, CKB mRNA in peripheral blood mononuclear cells rises in parallel with estimated glomerular filtration rate decline and histologic fibrosis score in patients with CKD. Conclusions Our work identifies a novel HIF-1α-CKB feedforward circuit in macrophages that sustains HIF-1α induction, channeling arginine metabolism toward CPS and thus promoting kidney fibrosis. These findings highlight that fibrosis is conceptualized from a passive end-stage outcome to an actively maintained process driven by the macrophage metabolic-polarization circuit, suggesting that breaking this malicious loop, in addition to initiating triggers, is critical to halt kidney fibrosis.
INTRODUCTION:Hematuria is a hallmark clinical manifestation of IgA nephropathy (IgAN) and largely reflects underlying glomerular inflammation. Despite this, current guidelines prioritize proteinuria and estimated glomerular filtration rate for risk assessment, and the association between urinary findings and underlying histologic lesions remains incompletely characterized. METHODS:Here, we conducted a multicenter retrospective cohort study of patients with biopsy-proven IgAN (July 2015-July 2025) with concurrent urinalysis. Associations between hemoglobinuria (dipstick), hematuria (microscopy), proteinuria and individual Oxford Classification MEST-C components, and composite inflammatory lesions (M1, E1, and/or C1/C2; and E1 and/or C1/C2) were evaluated using unadjusted cohort-specific logistic regression models. Pooled odds ratios (ORs) were estimated using random-effects meta-analysis. RESULTS:Among 441 patients, hemoglobinuria was associated with M1 lesions (pooled OR 1.77, 95% CI 1.25-2.51), E1 lesions (1.75, 1.44-2.11), and crescentic lesions (1.57, 1.20-2.07). Hematuria was also associated with M1 lesions (1.24, 1.14-1.35), E1 lesions (1.22, 1.13-1.31), and C1/C2 lesions (1.18, 1.09-1.28). For the composite outcome (M1, E1, and/or C1/C2), pooled ORs were 2.28 (1.76-2.97) for hemoglobinuria, 1.36 (1.22-1.51) for hematuria, and 1.20 (1.04-1.38) for proteinuria. Hemoglobinuria and hematuria were not associated with chronic lesions, whereas proteinuria was consistently associated with T1/T2 lesions (1.35, 1.20-1.52). CONCLUSIONS:Dipstick hemoglobinuria is associated with histologic markers of active disease in IgAN and may provide clinically relevant information to complement current assessment of disease activity in IgAN.
