Kidney Function, Albuminuria, and Risk of Incident Atrial Fibrillation
Lower eGFR and greater albuminuria were independently associated with increased risk of incident AF. CKD should be regarded as an independent risk factor for incident AF.
Summary
A Systematic Review and Meta-Analysis
[Posted 1/Mar/2024]
AUDIENCE: Nephrology, Internal Medicine
KEY FINDINGS: Lower eGFR and greater albuminuria were independently associated with increased risk of incident AF. CKD should be regarded as an independent risk factor for incident AF.
BACKGROUND: Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist. However, it is not known whether CKD is an independent risk factor for incident AF. Therefore, we evaluated the association between markers of CKD-estimated glomerular filtration rate (eGFR) and albuminuria-and incident AF.
DETAILS: Participants with measurement of eGFR and/or albuminuria who were not receiving dialysis.Selection Criteria for Studies: Cohort studies and randomized controlled trials were included that reported incident AF risk in adults according to eGFR and/or albuminuria. Age- or multivariate-adjusted risk ratios (RRs) for incident AF were extracted from cohort studies, and RRs for each trial were derived from event data. RRs for incident AF were pooled using random-effects models. 38 studies involving 28,470,249 participants with 530,041 incident AF cases were included. Adjusted risk of incident AF was greater among participants with lower eGFR than those with higher eGFR (eGFR <60 vs >=60 mL/min/1.73 m2: RR, 1.43; 95% CI, 1.30-1.57; and eGFR <90 vs >=90 mL/min/1.73 m2: RR, 1.42; 95% CI, 1.26-1.60). Adjusted incident AF risk was greater among participants with albuminuria (any albuminuria vs no albuminuria: RR, 1.43; 95% CI, 1.25-1.63; and moderately to severely increased albuminuria vs normal to mildly increased albuminuria: RR, 1.64; 95% CI, 1.31-2.06). Subgroup analyses showed an exposure-dependent association between CKD and incident AF, with the risk increasing progressively at lower eGFR and higher albuminuria
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Source: Ha, J. T., Freedman, S. B., Kelly, D. M., et al. (2024). Kidney Function, Albuminuria, and Risk of Incident Atrial Fibrillation: A Systematic Review and Meta-Analysis. American Journal of Kidney Diseases. Published: March, 2024. DOI: 10.1053/j.ajkd.2023.07.023.
NT-proBNP-Guided Screening Increases Uptake of Heart Failure Prevention Therapies in Type 2 Diabetes
A dose-response meta-analysis of 15 prospective studies involving 77,352 participants found that higher ferritin levels were associated with increased type 2 diabetes risk in both sexes. The association appeared stronger in women, with each 100-microgram-per-liter increase linked to a 53% higher risk compared with 21% in men. These findings highlight the potential value of investigating ferritin as a sex-specific marker of diabetes risk.
KEY FINDINGS: The STRONG-DM pilot demonstrates that integrating NT-proBNP screening with electronic clinical decision support and virtual CKM consultation is feasible in primary care and can substantially increase prescribing of therapies relevant to HF prevention. Biomarker screening also identified patients whose elevated risk was not captured by the clinical risk score alone.
The study evaluated prescribing behavior rather than reductions in incident HF, hospitalization, or mortality. Its findings therefore support the feasibility of this prevention strategy but do not establish that it improves clinical outcomes. Larger randomized trials are needed to determine whether the approach reduces the long-term burden of HF among adults with T2DM.
BACKGROUND: Adults with type 2 diabetes mellitus (T2DM) face an elevated risk of developing heart failure (HF), yet preventive cardiometabolic therapies remain underused. Identifying patients at increased risk before HF develops may provide an opportunity to initiate targeted treatment. The STRONG-DM pilot study evaluated a virtual cardio-kidney-metabolic (CKM) prevention strategy integrating clinical risk assessment, N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing, and specialist consultation to improve preventive prescribing.
DETAILS: The prospective intervention study included 545 adults with T2DM and no previous HF who received care from participating primary care physicians. The intervention combined physician education, electronic health record recommendations for NT-proBNP screening, and virtual CKM consultations for patients considered at high risk based on a WATCH-DM score of at least 12 or an NT-proBNP level of at least 125 pg/mL. New prescriptions for sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and finerenone were assessed over six months. Outcomes were compared with those of matched patients receiving usual care from nonparticipating physicians in the same practices.
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Primary care physicians ordered NT-proBNP testing in 93.4% of participants, and 36.9% were classified as being at high risk for HF. NT-proBNP testing identified an additional 16.7% of patients as high risk despite their low-risk classification using the WATCH-DM score.
Compared with matched controls, patients in the intervention group were more likely to receive new prescriptions for SGLT2 inhibitors (20.3% vs 5.8%; P < .001) and finerenone (4.1% vs 0.2%; P < .001). Initiation of GLP-1 RAs did not differ significantly between groups. Overall, the intervention was associated with a threefold higher rate of initiating any of the assessed CKM therapies (incidence rate ratio, 3.03; 95% CI, 2.18-4.31; P < .001). The increase was greater among patients classified as high risk (incidence rate ratio, 5.03; 95% CI, 3.06-8.77) than among those classified as low risk (1.82; 95% CI, 1.15-2.96; interaction P = .005).
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Source: Subramanian, V., Patel, K. V., Suh, J. M., et al. Screening and Treatment Using a Risk-Based Approach With NT-proBNP Guidance in Diabetes Mellitus: The STRONG-DM Pilot Study. JACC: Heart Failure. 2026; 14(10): 103153. Published: October 1, 2026. DOI: 10.1016/j.jchf.2026.103153.
Higher Ferritin Levels Associated With Increased Type 2 Diabetes Risk, Particularly in Women
A dose-response meta-analysis of 15 prospective studies involving 77,352 participants found that higher ferritin levels were associated with increased type 2 diabetes risk in both sexes. The association appeared stronger in women, with each 100-microgram-per-liter increase linked to a 53% higher risk compared with 21% in men. These findings highlight the potential value of investigating ferritin as a sex-specific marker of diabetes risk.
KEY FINDINGS: Higher circulating ferritin levels were associated with increased T2D risk in both men and women, with a stronger association observed in women in the primary sex-specific analysis after exclusion of a heterogeneous study. These findings suggest that ferritin may provide additional information for sex-specific diabetes risk assessment.
However, the meta-analysis establishes an association rather than causation. Differences in study populations, substantial between-study heterogeneity, and insufficient information on menopausal status limit interpretation. Further prospective research is needed to determine whether ferritin improves diabetes risk prediction beyond established clinical factors and whether the observed sex difference is consistent across diverse populations.
BACKGROUND: Iron metabolism has been implicated in glucose regulation and the development of type 2 diabetes (T2D). Ferritin, a marker of iron stores, has been associated with diabetes risk in observational studies, although findings have varied across populations. Because circulating ferritin concentrations differ between men and women, investigators conducted a dose-response meta-analysis to examine whether the association between ferritin levels and incident T2D varies by sex.
DETAILS: Researchers systematically searched PubMed, Web of Science, and EMBASE for prospective studies published through August 1, 2018. Fifteen studies involving 77,352 participants aged 20 to 80 years and 18,404 incident T2D cases were included. Follow-up ranged from approximately 3 to 17 years. The investigators assessed the relationship between circulating ferritin concentrations and T2D risk using pooled relative risk estimates and dose-response analyses. Sex-specific analyses were conducted to evaluate potential differences in the association between ferritin levels and diabetes development.
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Across all participants, each 100-microgram-per-liter increase in circulating ferritin was associated with a 22% higher risk of T2D (RR, 1.22; 95% CI, 1.14-1.31). In sex-specific analyses, after excluding a study contributing substantial heterogeneity, each 100-microgram-per-liter increase in ferritin was associated with a 53% higher T2D risk in women (RR, 1.53; 95% CI, 1.29-1.82), compared with a 21% increase in men (RR, 1.21; 95% CI, 1.15-1.27). The difference between sexes was statistically significant (P=0.020).
Nonlinear dose-response analyses also indicated that the association between ferritin and T2D risk was stronger in women than in men at comparable ferritin concentrations. The association remained evident after adjustment for several potential confounders, including inflammatory markers, body mass index, liver enzymes, and metabolic factors.
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Source: Jiang, L., Wang, K., Lo, K., et al. ex-Specific Association of Circulating Ferritin Level and Risk of Type 2 Diabetes: A Dose-Response Meta-Analysis of Prospective Studies. The Journal of Clinical Endocrinology & Metabolism. 2026; 104(10): 4539-4551. Published: August 22, 2026. DOI: 10.1210/jc.2019-00495.
Timing of Vascular Access Creation in Older Adults With ESKD
A prospective European cohort of older adults with ESKD found that only 32% of AVFs were created within the defined 6-month window before hemodialysis initiation, while 42% were created early and 26% late. The findings highlight the difficulty of predicting dialysis timing and the need for better tools to individualize vascular access planning.
KEY FINDINGS: In this European cohort of older adults with ESKD, vascular access creation frequently did not coincide with the timing of hemodialysis initiation. More than 4 in 10 AVFs were created early, while approximately 1 in 4 were created late, resulting in substantial use of CVCs at dialysis initiation. The findings highlight the difficulty of predicting dialysis initiation in older adults and support the development of clinical prediction tools to better individualize vascular access planning.
BACKGROUND: Planning vascular access for older adults with end-stage kidney disease (ESKD) is challenging because the timing of hemodialysis initiation is difficult to predict. Arteriovenous fistulas (AVFs) created too early may remain unused, whereas delayed creation can result in hemodialysis being initiated through a central venous catheter (CVC). This study evaluated the timing of vascular access creation relative to hemodialysis initiation in older patients across Europe.
DETAILS: This secondary analysis used data from the EQUAL cohort, a prospective observational study involving patients aged 65 years or older with stage 4 or 5 chronic kidney disease in six European countries. Patients were included when their estimated glomerular filtration rate fell below 15 mL/min/1.73 m², provided they received a vascular access and had at least 6 months of follow-up. AVF timing was categorized as early when hemodialysis did not begin within 6 months after AVF creation, on time when hemodialysis was initiated with an AVF within 6 months, and late when hemodialysis was initiated with a CVC before or within 6 months after AVF creation.
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A total of 332 patients were analyzed. An AVF was the first vascular access in 221 patients (67%), while 111 patients (33%) initially received a CVC. Among those initially receiving a CVC, 53 patients (48%) subsequently underwent AVF creation. At dialysis initiation, 158 patients (54%) were using an AVF and 136 (46%) were using a CVC. Among the 274 patients who underwent AVF creation, access was created on time in 88 patients (32%), early in 114 (42%), and late in 72 (26%). Despite the high proportion of early AVF creation, most fistulas were eventually used, with 90% of patients initiating hemodialysis within 3 years after AVF creation.
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Source: Heggen, B. D. C., Chesnaye, N. C., Dekker, F. W., et al. Vascular Access Surgery Timing: A Prospective European Cohort Study in Elderly Patients with ESKD. Kidney360. 2026; 7(9): 2066-2074. Published: September 22, 2026. DOI: 10.34067/KID.0000001180.
Palliative Extracorporeal Membrane Oxygenation Decannulation: An Ethical, Evidence-Based Approach
A structured approach to ECMO de-escalation and decannulation can reduce practice variability while incorporating patient and family preferences. Proactive symptom management may improve the patient and family experience, supporting a more comfortable and dignified end-of-life journey.
KEY FINDINGS: A structured, interprofessional approach to palliative ECMO de-escalation can reduce variability in end-of-life practice and support more consistent symptom management and communication. Incorporating patient and family preferences into the process, together with proactive symptom management and staff debriefing, was associated with a more comfortable and dignified end-of-life experience in this quality-improvement setting.
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an invasive, potentially lifesaving therapy associated with complications involving multiple organ systems. When ECMO is no longer considered beneficial, de-escalation or decannulation may be required as part of a transition to comfort-focused care and natural death. At a tertiary care facility with 64 beds using ECMO, variability was identified in ECMO initiation, communication with patients and families, determination of nonbeneficial therapy, and symptom management during de-escalation.
DETAILS: This quality-improvement project integrated palliative care, reviewed existing literature on best practices, and established an interprofessional task force focused on ECMO de-escalation. New clinical guidelines were developed to provide a consistent, evidence-based framework for communication, decision-making, symptom management, and de-escalation/decannulation. The initiative was designed to reduce practice variability while improving the experience of patients, families, and clinicians during transition to comfort-directed care.
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Implementation of the guidelines decreased practice variability and reduced patient and family stress and discomfort during ECMO de-escalation and decannulation. Team members reported decreases in symptoms of secondary trauma and moral distress associated with these situations. They also reported improved delivery of end-of-life care, including family education and support, patient advocacy, and symptom management. Family members valued greater attention to both patient and family well-being, while structured staff debriefings supported reflection and identification of opportunities for improvement.
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Source: Arbour, R., Abate, M., Garcia, O., et al. Palliative Extracorporeal Membrane Oxygenation Decannulation: An Ethical, Evidence-Based Approach. Critical Care Nurse. 2026; 46(4): 17-28. Published: August 1, 2026. DOI: 10.4037/ccn2026166.
Neovascular Glaucoma Associated With Increased Long-Term Mortality and Systemic Morbidity
A large TriNetX cohort study found that neovascular glaucoma was associated with increased long-term risks of mortality and systemic complications beyond underlying retinal vascular disease. At 10 years, NVG in patients with proliferative diabetic retinopathy was associated with higher mortality and end-stage renal disease, while NVG in patients with central retinal vein occlusion was associated with higher mortality and stroke risk. The findings highlight the potential value of coordinated ophthalmic and systemic care when NVG develops.
KEY FINDINGS: The development of NVG was associated with additional long-term systemic morbidity and mortality beyond the underlying PDR or CRVO in this large retrospective cohort. The strongest associations included mortality and ESRD among patients with PDR and mortality and stroke among those with CRVO. The findings suggest that development of NVG may identify patients with substantial systemic vascular risk and support closer coordination between ophthalmic and other medical specialties. Because the study was retrospective and based on electronic health records, the observed associations should not be interpreted as evidence that NVG itself directly causes these systemic outcomes.
BACKGROUND: Neovascular glaucoma (NVG) is a serious ocular complication of retinal vascular disease, including proliferative diabetic retinopathy (PDR) and central retinal vein occlusion (CRVO). Although NVG is primarily recognized for its effects on vision and intraocular pressure, less is known about whether its development is associated with additional long-term systemic health risks. This multicenter retrospective cohort study evaluated mortality and major systemic outcomes among adults with PDR or CRVO who did or did not subsequently develop NVG.
DETAILS: The investigators used the TriNetX Research Network, a deidentified electronic health record database containing information from more than 177 million patients across more than 150 healthcare organizations worldwide. Adults older than 40 years with PDR or CRVO were identified and compared according to whether NVG subsequently developed. Patients were propensity-score matched 1:1 based on demographic characteristics and comorbidities. Outcomes were assessed at 1, 5, and 10 years and included all-cause mortality, stroke, myocardial infarction (MI), end-stage renal disease (ESRD), and deep-vein thrombosis (DVT). A total of 1,278 patients with PDR and NVG were matched with 1,278 patients with PDR without NVG. The study also evaluated patients with CRVO and NVG compared with matched CRVO patients without NVG, as well as an NVG cohort compared with a cataract control cohort.
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Among patients with PDR, development of NVG was associated with higher 10-year mortality (HR, 1.34; 95% CI, 1.14-1.57) and ESRD (HR, 1.43; 95% CI, 1.23-1.67) compared with PDR without NVG. Ten-year survival was 60.4% in the PDR + NVG group compared with 68.4% in the PDR without NVG group. Among patients with CRVO, those who developed NVG had higher 10-year mortality (HR, 1.61; 95% CI, 1.17-2.20) and stroke risk (HR, 1.86; 95% CI, 1.19-2.90). Differences in MI and ESRD were not statistically significant in this comparison, and DVT risk was also not significantly different. When PDR + NVG was compared directly with CRVO + NVG, the PDR + NVG group had higher 10-year risks of mortality (HR, 1.56; 95% CI, 1.17-2.07), MI (HR, 1.94; 95% CI, 1.13-3.32), and ESRD (HR, 4.04; 95% CI, 2.43-6.73). Compared with the cataract control cohort, NVG was associated at 10 years with higher risks of mortality (HR, 2.66; 95% CI, 2.40-2.94), stroke (HR, 2.17; 95% CI, 1.85-2.54), MI (HR, 1.89; 95% CI, 1.60-2.23), and ESRD (HR, 3.34; 95% CI, 2.89-3.88).
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Source: Margolis, R., Vasu, P., and Dorairaj, S. K. Long-Term Risk of Mortality and Systemic Morbidity in Neovascular Glaucoma: A Multicenter Retrospective Cohort Study. Ophthalmology Glaucoma. 2026; 9(5): 517-526. Published: September-October, 2026. DOI: 10.1016/j.ogla.2026.01.017.
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