Vaughan, Lisa E.

ABSTRACT Background Membranous nephropathy (MN) associated with phospholipase A2 receptor (PLA2R) antibodies is the most common cause of nephrotic syndrome in non-diabetic adult patients. This study investigated the relationship between clinical phenotypes and renal outcomes in this population, emphasizing the potential for phenotype-based treatment stratification. Methods We conducted a retrospective, multi-center cohort study of PLA2R-positive MN. Unsupervised cluster analysis grouped patients based on clinicopathological characteristics. Primary outcomes included complete or partial remission within 2 years of biopsy and end-stage kidney disease (ESKD) or death during follow-up. Results Among 178 patients, three distinct clusters emerged (n = 89, 70, and 19). Within 2 years of biopsy, 102 patients (57%) achieved complete or partial remission. Cluster 1, characterized by the mildest disease markers, including the lowest body mass index, serum anti-PLA2R titer, serum creatinine, proteinuria, and triglycerides, had the highest remission rate of 72%, compared with 50% in cluster 2 and 54% in cluster 3. Cluster 2 had significantly lower remission compared to cluster 1 (HR 0.64, 95% CI 0.42–0.96, P = .03); results were similar in cluster 3, albeit not statistically significant (HR 0.50, 95% CI 0.23–1.09, P = .08). Elevated anti-PLA2R levels (>100 U/ml) and proteinuria (>8 g/24-hour) predicted reduced remission (HR 0.56, 95% CI 0.36–0.88, P = .01; HR 0.43, 95% CI 0.26–0.73, P = .002, respectively), while high high-density lipoprotein levels were protective (HR 1.01, 95% CI 1.00–1.02, P = .048). Overall, 21 patients (12%) developed ESKD or died. ESKD-free survival differed significantly across clusters (log-rank test P = .04). Conclusions Unsupervised clustering identified distinct clinical phenotypes in PLA2R-positive MN, each associated with different renal prognoses. Phenotype-based risk stratification could enhance treatment precision, improve patient outcomes, and potentially reduce treatment-related adverse effects.

Objective: Over 3 million Americans have heart failure with preserved ejection fraction (HFpEF). Effective guideline directed medical treatments (GDMT) are increasingly available but patients with HFpEF are likely under-detected (particularly women) and not receiving GDMT. Limited data are available informing the extent of HFpEF under-detection in the community. Hypothesis: Among patients with undifferentiated dyspnea and a high risk for unrecognized HFpEF, fewer than 50% will receive a HFpEF diagnosis during two years of follow-up; underrecognition will be greater among women. Methods: We identified 22,134 patients aged ≥30 in the Rochester Epidemiology Project (a medical records linkage system comprising a 27-county region of southeastern Minnesota and western Wisconsin) with evidence of unexplained dyspnea (≥2 ICD codes for dyspnea separated by >1 day) without prior documented etiology including HF or lung disease, during the time period 2018-2022. We calculated the recently validated HFpEF-Age-BMI-Atrial Fibrillation (HFpEF-ABA) score to estimate the probability of underlying HFpEF. Cox proportional hazards models regressed risk for incident HFpEF diagnosis on HFpEF-ABA score (dichotomized as ≥80% vs. <80%) with multivariable adjustment for sex, race and ethnicity. HRs(95%CIs) are presented. Results: Patients were 59±16 yrs, 50.8% women, 88.6% white, 3.1% Black, 3.7% other race, 4.6% Hispanic. Atrial fibrillation prevalence was 9.4% and mean BMI=31.4±7.8. Prevalence of HFpEF-ABA≥80% was 22.4%(n=4,958): 22.7% among women and 22.1% among men. The cumulative incidence of clinically-recognized HFpEF diagnosis at two years follow-up was 9.7% among women and 12.8% among men (log-rank p<0.01). HFpEF incidence was elevated with high HFpEF-ABA scores(≥80%): HR(95%CI) among women=3.72 (3.35, 4.14), and men=3.42 (3.11, 3.76). Among those with clinically diagnosed HFpEF during follow-up, mean time from date of first dyspnea ICD code to HFpEF diagnosis was 1.26 years overall: 1.31 and 1.21 years in women and men, respectively (p=0.05). Conclusions: One in five patients with undifferentiated dyspnea have probable undiagnosed HFpEF, and of that group, only 30% receive a clinical diagnosis, requiring an average of over 1 year to be recognized. The rate of diagnosis is even lower among women than men. Further study is warranted to implement evidence-based algorithms supporting detection of undiagnosed HFpEF in the community, especially in women.

Key Points Patient-centered care in an interdisciplinary CKD clinic addresses complex needs and supports comprehensive CKD management. Implementation of an interdisciplinary CKD clinic reduced hospital admissions by 26%, emergency department visits by 30%, and increased nephrology consultations. Comprehensive care models with integrated registries enhance tailored interventions, leading to improved CKD management outcomes. Background CKD is a significant public health issue globally. Its progressive nature calls for innovative care models to mitigate disease progression and enhance patient outcomes. An interdisciplinary clinic model may offer comprehensive care tailored to the needs of patients with CKD. The aim of this study was to evaluate the effect of an interdisciplinary CKD clinic on disease progression, health care utilization, and social determinants of health (SDOH). Methods We conducted a retrospective cohort study at the Mayo Clinic in Rochester, Minnesota. The study included 534 patients enrolled in the CKD clinic between March 5, 2021, and May 31, 2022, excluding those who opted out of research. The intervention involved a clinical registry and an interdisciplinary team delivering evidence-based care pathways, patient education, shared decision making, and care coordination. The primary outcomes assessed were CKD progression and health care utilization, while secondary outcomes examined the effect of SDOH. Results At entry, the median age was 73 (interquartile range, 64–79) years, with 60% at stage 4 or lower. Clinic implementation correlated with a 26% decrease in hospital admissions (incidence rate ratio [IRR], 0.74; 95% confidence interval [CI], 0.60 to 0.91; P = 0.004) and a 30% reduction in emergency visits (IRR, 0.70; 95% CI, 0.57 to 0.87; P = 0.001). Nephrology consultations increased by 46% (IRR, 1.46; 95% CI, 1.34 to 1.60; P < 0.001), reflecting enhanced specialized care. Lower exercise frequency and unemployment were linked to increased CKD progression and health care usage. Conclusions An interdisciplinary CKD clinic supported by a registry can potentially reduce health care utilization among patients with CKD, with SDOH playing a critical role in disease management.

ABSTRACT Background and Hypothesis Teclistamab, a novel bispecific monoclonal antibody targeting CD3 and B cell maturation antigen (BCMA), and chimeric antigen receptor T cell (CAR-T) therapy are promising options for treating relapsed/refractory multiple myeloma (MM). However, the rates of acute kidney injury (AKI) associated with teclistamab remain inadequately characterized. This study aims to compare the incidence, severity, and outcomes of AKI between patients receiving teclistamab and CAR-T therapy. Methods This was a retrospective study involving 64 patients with relapsed/refractory MM treated with either teclistamab or CAR-T therapy. All patients had previously received at least four lines of chemotherapy before being treated with either teclistamab or CAR-T. The primary outcome was the incidence of AKI, and secondary outcomes included AKI severity, kidney recovery rates, and mortality. Kaplan–Meier estimates for AKI-free survival were calculated, and hazard ratios (HRs) for AKI risk were determined using Cox proportional hazards models. Results Sixty-four patients met inclusion criteria for this study (30 received CAR-T and 34 received teclistamab therapy). Among these patients, 14 AKI events occurred in total (22%), with 10 events (29%) in the teclistamab group and four events (13%) in the CAR-T group. AKI-free survival estimates at 180 days after treatment initiation were 68% [95% confidence interval (CI): 53%–87%] for teclistamab patients and 90% (95% CI: 79%–100%) for CAR-T patients. While patients receiving teclistamab were found to have an increased risk of an AKI event compared to those receiving CAR-T therapy, the results were not statistically significant [HR (95% CI): 3.38 (0.93–12.31), P = .065]. Conclusions This study suggests that patients treated with teclistamab may experience a higher incidence of AKI compared to those receiving CAR-T therapy. However, further research is required to determine whether this increased risk is attributable to disease progression or teclistamab itself. These results highlight the need for close kidney function monitoring in patients receiving teclistamab.

Background Multimorbidity is common in patients with atrial fibrillation (AF), yet comorbidity patterns are not well documented. Methods The prevalence of 18 chronic conditions (6 cardiometabolic, 7 other somatic, 5 mental health) was obtained in patients with new-onset AF from 2013-2017 from a 27-county region and controls matched 1:1 on age, sex, and county of residence. For AF patients and controls separately, clustering of conditions and co-occurrence beyond chance was estimated (using the asymmetric Somers’ D statistic), overall and for ages <65, 65-74, 75-84, and ≥85 years. Results Among 16,509 patients with AF (median age 76 years, 57% men), few (4%) did not have any of the 18 chronic conditions, whereas nearly one-quarter of controls (23%) did not have any chronic conditions. Clustering of cardiometabolic conditions was common in both AF patients and controls, but clustering of other somatic conditions was more common in AF. Although the prevalence of most condition pairs was higher in AF patients, controls had a larger number of condition pairs occurring together beyond chance. In persons aged <65 years, AF patients more frequently exhibited concordance of condition pairs that included either pairs of somatic conditions or a combination of conditions from different condition groups. In persons aged 65-74 years, AF patients more frequently had pairs of other somatic conditions. Conclusion Patterns of co-existing conditions differed between patients with AF and controls, particularly in younger ages. A better understanding of the clinical consequences of multimorbidity in AF patients, including those diagnosed at younger ages, is needed.