Weiss JW, Hall R, Saeed F
… +3 more, Callahan MB, Shaban H, ASN Kidney Health Workgroup on Conservative Kidney Management
J Am Soc Nephrol
· 2026 Jun · PMID 41848792
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KEY POINTS: Conservative management is part of the standard of care for kidney failure management. Conservative management tailors kidney care to align with individual goals and values. Conservative management involves a...KEY POINTS: Conservative management is part of the standard of care for kidney failure management. Conservative management tailors kidney care to align with individual goals and values. Conservative management involves a multidisciplinary team to provide customized CKD care, symptom management, and navigation across care transitions. UNLABELLED: Conservative management is a holistic, whole-person model of care for people with kidney failure. A proactive, ethical treatment pathway, conservative management can help align personal goals and plan of care for people who prioritize quality of life and symptom management over potential life-prolonging therapies. The Kidney Health Guidance (KHG) on Conservative Management in People with Kidney Failure provides evidence-based clinical guidance supporting best practices in three components of the conservative management care pathway: customized CKD care to align with a person's values and goals, symptom management, and navigation of care transitions. The guidance also emphasizes the importance of shared decision-making in providing goal-concordant kidney care, engaging care partners and collaborating across disciplines. In this Executive Summary, a practical companion to the KHG, we highlight the key points of the KHG to facilitate implementation of conservative management into clinical practice. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3//www.asn-online.org/media/podcast/JASN/2026_03_18_KTS_March2026.mp3.
Usui T, Ishibashi S, Tanaka R
… +25 more, Morito N, Hamada M, Gogoleva N, Ning B, Kumaga E, Oki M, Tsunakawa Y, Murakami Y, Sadaki S, Fuseya S, Kanai M, Nishino T, Inoue Y, Sato Y, Gochi K, Shinohara M, Kuno A, Jeon H, Warabi E, Kudo T, Mizuno S, Muratani M, Levine MA, Yamagata K, Takahashi S
J Am Soc Nephrol
· 2026 Mar · PMID 41842942
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KEY POINTS: Multicentric carpotarsal osteolysis, a rare disorder, causes progressive osteolysis and kidney failure because of v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) gene mutations. A genome...KEY POINTS: Multicentric carpotarsal osteolysis, a rare disorder, causes progressive osteolysis and kidney failure because of v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) gene mutations. A genome-edited mouse model carrying the multicentric carpotarsal osteolysis mutation was used to obtain a deeper understanding of this rare disease. Targeting MAFB/IGF-1/PI3K/AKT signaling may provide new treatments for multicentric carpotarsal osteolysis-related nephropathy. BACKGROUND: Multicentric carpotarsal osteolysis (MCTO) is a rare condition characterized by progressive osteolysis and often kidney failure. It is caused by autosomal dominant mutations in the transcription factor v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B ( MAFB ). METHODS: Given the absence of efficacious therapeutic interventions for MCTO and the obscurity of its pathophysiologic mechanisms, we used mice with the MCTO mutation ( MafbMCTO/MCTO mice) to explore the role of MAFB. RESULTS: MafbMCTO/MCTO mice displayed FSGS, mirroring the manifestations seen in patients with MCTO. These mice showed that the MCTO mutation leads to the accumulation of MAFB protein. Heterozygous MafbMCTO/- mice, generated by crossbreeding to reduce MAFB levels, neither exhibited albuminuria nor showed any histologic abnormalities in the kidney, suggesting that excess MAFB was detrimental. We subsequently conducted RNA-seq on the glomeruli from MafbMCTO/MCTO mice and detected pronounced upregulation of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway through IGF-1. Given that receptor tyrosine kinases activate PI3K/AKT, we treated MafbMCTO/MCTO mice with the inhibitor imatinib. This led to a significant decline in urinary albumin levels compared with the control group. CONCLUSIONS: Our findings demonstrate that the MCTO mutation resulted in MAFB protein accumulation and led to the development of FSGS in mice.
Catanese B, Miller C, Wolf M
… +1 more, Edmonston D
J Am Soc Nephrol
· 2026 Mar · PMID 41817629
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KEY POINTS: Glucagon-like peptide-1 receptor agonists are increasingly used in patients with kidney failure despite trial exclusion. Initiation was associated with a 13% lower risk of cardiovascular events and 17% lower...KEY POINTS: Glucagon-like peptide-1 receptor agonists are increasingly used in patients with kidney failure despite trial exclusion. Initiation was associated with a 13% lower risk of cardiovascular events and 17% lower mortality versus dipeptidyl peptidase-4 inhibitors. Initiation was associated with a 10% lower risk of heart failure hospitalization versus dipeptidyl peptidase-4 inhibitors. BACKGROUND: Few therapies improve cardiovascular outcomes for people with kidney failure. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce cardiovascular risk in patients with non-dialysis-dependent CKD, but the cardiovascular benefits in patients with kidney failure remain uncertain. The objective of this study was to compare cardiovascular outcomes among patients with kidney failure and type 2 diabetes newly initiated on GLP-1 RA versus other antiglycemic agents. METHODS: We analyzed electronic health records, Medicare claims, and Part D data from the United States Renal Data System (2011-2021) to identify new users of GLP-1 RA ( n =3629), dipeptidyl peptidase-4 inhibitors (DPP4i; n =21,369), and sulfonylureas ( n =32,296) among patients with type 2 diabetes receiving maintenance dialysis. For the primary analysis, we performed 1:1 propensity score matching of GLP-1 RA to DPP4i initiators using 61 covariates. A prespecified secondary analysis compared propensity score-matched initiators of GLP-1 RA and sulfonylureas. The primary outcome was a modified major adverse cardiovascular event (MACE) composite of myocardial infarction, stroke, or all-cause mortality. Secondary outcomes included the individual components of the primary outcome and hospitalizations for heart failure. Cause-specific Cox models were used to estimate hazard ratios (HRs). RESULTS: Among 3284 matched pairs of GLP-1 RA and DPP4i initiators, GLP-1 RA use was associated with lower risks of MACE (HR, 0.87; 95% confidence interval [CI], 0.78 to 0.97), all-cause mortality (HR, 0.83; 95% CI, 0.74 to 0.94), and heart failure hospitalization (HR, 0.90; 95% CI, 0.83 to 0.99) over up to 2 years of follow-up. Among 2792 matched pairs, GLP-1 RA and sulfonylurea initiators, GLP-1 RA was associated with lower risks of MACE (HR, 0.83; 95% CI, 0.74 to 0.93) and all-cause mortality (HR, 0.80; 95% CI, 0.69 to 0.91). CONCLUSIONS: Among patients with type 2 diabetes receiving maintenance dialysis, GLP-1 RA initiation was associated with lower risk of cardiovascular events and all-cause mortality compared with other commonly prescribed antiglycemic agents.
Lam NN, Caliskan Y, Husain SA
… +1 more, Lentine KL
J Am Soc Nephrol
· 2026 May · PMID 41805749
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The evaluation of living kidney donor candidates is a complicated process to determine eligibility for donation and ensure that candidates are well-informed of postdonation risks, along with any uncertainty in risk estim...The evaluation of living kidney donor candidates is a complicated process to determine eligibility for donation and ensure that candidates are well-informed of postdonation risks, along with any uncertainty in risk estimations. The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Care of Living Kidney Donors provided recommendations to assist transplant programs in the evaluation and care of donors before, during, and after donation. In this review, we highlight new research that has changed the landscape of the evaluation and counseling of donor candidates. In 2021, a race-neutral equation for eGFR aimed to promote health equity; however, relying solely on this measure to assess kidney function may lead to more Black candidates being excluded from living kidney donation. The role of genetic testing in the evaluation of donor candidates continues to evolve as evidence accumulates about the higher risk of kidney failure among biologically related donors. Recent recommendations emphasize targeted evaluation for familial monogenic kidney diseases and suggest offering apolipoprotein L1 genotyping to living kidney donors of African ancestry, although the implications of apolipoprotein L1 results for donor eligibility is an area of ongoing research and debate. In 2025, North American guidelines revised the BP threshold for diagnosing and treating hypertension from ≥140/90 to ≥130/80 mm Hg. This will have implications in the assessment of donor candidates, who may be more likely to be declined for donation or put on hold until these new BP targets are reached. Finally, new evidence supports that male donor candidates should be informed of the higher risk of testicular-related complications postdonation compared with nondonors. Policy makers, guidance workgroups, and transplant programs will need to consider how these findings influence local practices related to the evaluation, counseling, and care of donor candidates.
Oh JI, Jeong K, Koh JH
… +14 more, Kwon JK, Cho S, Cho JM, Kim Y, Lee H, Kim HJ, Lee J, Lee JP, Park JI, Park JT, Kim K, Park S, Kim DK, KORNERSTONE investigators
J Am Soc Nephrol
· 2026 Mar · PMID 41779447
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KEY POINTS: Plasma proteome profiling identified distinct signatures across biopsy-proven primary glomerular disease subtypes. An elastic net model using 93 proteins classified primary glomerular disease subtypes and con...KEY POINTS: Plasma proteome profiling identified distinct signatures across biopsy-proven primary glomerular disease subtypes. An elastic net model using 93 proteins classified primary glomerular disease subtypes and controls, with external validation. Integrating proteomics with machine learning yields biologically interpretable insights in primary glomerular diseases. BACKGROUND: Primary GN is a heterogeneous group of kidney disorders where understanding of their pathophysiology remains incomplete. Despite the diagnostic potential of high-throughput proteomics, constrained proteomic depth and a reliance on binary comparisons have left the feasibility of using systemic signatures to differentiate multiple GN subtypes largely unexplored. METHODS: To identify protein signatures that noninvasively differentiate major primary glomerular disease subtypes and provide mechanistic insights, we performed large-scale systemic proteome profiling of 5416 plasma proteins via Olink Explore HT in a discovery cohort ( n =147) and an external validation cohort ( n =85) of Korean participants (mean age, 41±13 years; 46% female). The study population included patients with four GN subtypes-focal segmental glomerulosclerosis, IgA nephropathy, minimal change disease, and membranous nephropathy-alongside healthy controls. We developed a machine learning (ML) model using logistic regression with elastic net regularization to classify disease groups based on proteomic profiles and evaluated its performance in the independent validation cohort. RESULTS: Plasma proteome profiles were distinct among disease subtypes, emerging as a significant source of data variation independent of conventional markers such as eGFR or proteinuria levels. The ML model performed robustly in both the discovery and validation cohorts, achieving an area under the receiver operating characteristic curve >0.8 for differentiating minimal change disease, membranous nephropathy, and IgA nephropathy. The model, even without clinical information, correctly identified 93% of minimal change disease cases (14 of 15) and 63% of IgA nephropathy cases (20 of 32), but its performance was limited for focal segmental glomerulosclerosis, with only 21% of cases (three of 14) correctly classified. Functional analysis of key proteins highlighted distinct biologic pathways, such as hemostasis in minimal change disease. CONCLUSIONS: We identified distinct systemic proteome signatures for primary glomerular diseases, where disease subtype served as a major determinant of proteomic variance alongside conventional clinical markers. ML models demonstrated robust discriminatory performance for minimal change disease, membranous nephropathy, and IgA nephropathy, underscoring the potential for proteome-based classification.
Apoptotic bodies are membrane-bound vesicles generated during the terminal stages of programmed cell death and are traditionally viewed as inert cellular debris. Emerging evidence, however, positions apoptotic bodies as...Apoptotic bodies are membrane-bound vesicles generated during the terminal stages of programmed cell death and are traditionally viewed as inert cellular debris. Emerging evidence, however, positions apoptotic bodies as dynamic mediators of intercellular communication with critical roles in kidney physiology and pathology. In the healthy kidney, efficient efferocytosis of apoptotic bodies maintains tissue homeostasis by ensuring immunologically silent clearance of apoptotic remnants. In AKI, extensive tubular epithelial apoptosis generates a high burden of apoptotic bodies that can amplify inflammation, endothelial dysfunction, and adaptive immune activation when clearance is impaired, yet promote resolution and epithelial repair when efficiently removed. In CKD, persistent low-grade apoptosis combined with defective efferocytosis leads to progressive accumulation of apoptotic bodies in the interstitium, where their bioactive cargo-including damage-associated molecular patterns, cytokines, growth factors, and profibrotic microRNAs-drives fibroblast activation, extracellular matrix expansion, and fibrosis. In the vasculature, apoptotic bodies derived from vascular smooth muscle cells act as nucleation sites for calcium-phosphate crystal deposition, linking apoptosis to the development of medial vascular calcification in CKD. Together, these findings highlight apoptotic bodies as active regulators of injury, inflammation, fibrosis, regeneration, and vascular pathology. Understanding the determinants of their pathogenic versus reparative effects could yield new biomarkers and therapeutic strategies, including modulation of efferocytosis, targeting apoptotic body-derived signaling pathways, and engineering apoptotic bodies-based delivery systems.
Barrett N, Odera JO, Bethea K
… +9 more, Smith M, Sadeghpour A, Matthews L, Lucas A, Godbee RL, Dowdy O, Miles L, Olabisi OA, CARE Community Partners
J Am Soc Nephrol
· 2026 Mar · PMID 41774497
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KEY POINTS: Community engagement achieved high apolipoprotein L1 (APOL1)-mediated kidney disease screening rates but low yield of trial-eligible participants. Electronic health record and health care professional referra...KEY POINTS: Community engagement achieved high apolipoprotein L1 (APOL1)-mediated kidney disease screening rates but low yield of trial-eligible participants. Electronic health record and health care professional referrals identified more participants with APOL1 high-risk genotype and significant albuminuria. Hybrid community-electronic health record recruitment may improve equity and efficiency in APOL1-mediated kidney disease trial enrollment. BACKGROUND: Black individuals bear a disproportionate burden of kidney diseases, including genetically mediated risk related to apolipoprotein L1 ( APOL1 ) gene variants. Awareness of APOL1-mediated kidney disease (AMKD) and participation in therapeutic trials remain low. Whether different engagement strategies can raise awareness and identify trial-eligible individuals is uncertain. The Community APOL1 Research Engagement (CARE) study aimed to increase AMKD awareness through culturally tailored education and screening while building a clinical trial-eligible registry, CARE Registry, to support a phase 2 baricitinib trial for AMKD in the Janus kinase-Signal Transducers and Activators of Transcription Inhibition to Reduce APOL1-Associated Kidney Disease. METHODS: The CARE study was conducted from May 2022 to July 2025 across community and clinical settings in multiple US regions, in partnership with churches with predominantly Black attendees. Black adults aged 18-70 years without diabetes or dialysis dependence underwent APOL1 genotyping and kidney disease screening. Recruitment occurred via community events, electronic health record (EHR) queries, physician referrals, and self-referrals. The primary outcome was eligibility for the CARE Registry, defined by APOL1 high-risk genotype, urine albumin-to-creatinine ratio ≥300 mg/g, and eGFR ≥25 ml/min per 1.73 m 2 . RESULTS: Of 1052 individuals approached, 789 (75%) consented to screening. Overall, 128 (17%) carried APOL1 high-risk genotypes. Community events accounted for most enrollments (83%) but yielded low rates of registry-eligible albuminuria (1%). By contrast, EHR queries and physician referrals identified higher proportions of participants with APOL1 high-risk genotypes and urine albumin-to-creatinine ratio ≥300 mg/g. Twenty-four participants met CARE Registry criteria, and seven enrolled in the Janus kinase-Signal Transducers and Activators of Transcription Inhibition to Reduce APOL1-Associated Kidney Disease trial. Refusal was 4% and attrition was 2%. CONCLUSIONS: Community engagement achieved high participation and awareness but was less efficient for identifying trial-eligible individuals than EHR- and health care professional-based approaches. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ClinicalTrial.gov, NCT05237388 .