Search

This study analyzed the association of romosozumab, a human monoclonal antibody with bone-forming and bone resorption-inhibiting effects, and bisphosphonates with the development of cardiovascular disease among patients with osteoporosis. A new-user design was employed to address selection bias, and instrumental variable analysis was used to address confounding by indication. Japanese patients aged ≥40 years, diagnosed with osteoporosis or experienced a fragility fracture, were admitted to medical facilities covered by a commercial administrative claims database, and newly prescribed romosozumab or bisphosphonates after the commercialization of romosozumab in Japan (March 4, 2019) were included based on verification of a 180-day washout period. Cardiovascular disease (myocardial infarction or stroke) was identified based on information regarding diagnosis, medical procedures, and drug codes. Facility-level prescription preference for romosozumab was used as an instrumental variable, defined as the proportion of romosozumab prescribed at the patient's facility within 90 days prior to the index date. Of the 59 694 included prescriptions, 8808 were for romosozumab and 50 886 were for bisphosphonates. The mean age in the romosozumab group was higher than that in the bisphosphonates group (80.5 vs. 78.2 years, respectively), and most patients were females (85.3 vs. 80.2%, respectively). The incidence of cardiovascular disease within 1 year of prescription was 12.3 per 100 person-years for romosozumab versus 11.4 for bisphosphonates (unadjusted incidence rate ratio: 1.08, 95% confidence interval: 1.00-1.18). An instrumental variable analysis using the two-stage residual inclusion method yielded a hazard ratio of 1.30 (95% confidence interval: 0.88-1.90) for romosozumab compared with bisphosphonates over 1 year. Although possibly underpowered, this study showed that no definitive evidence of increased cardiovascular risk associated with romosozumab use compared with bisphosphonates was observed in patients with osteoporosis. These findings should be further validated by larger pharmacoepidemiological studies to alleviate clinicians' concerns about romosozumab's safety., (© The Author(s) 2025. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Rationale & Objective: Prolonged end-stage kidney disease (ESKD) is a risk factor for frailty, and the number of patients in Japan receiving maintenance dialysis for more than 20 years is large and growing. This study characterized the association of dialysis vintage and frailty among patients receiving dialysis in Japan., Study Design: Cross-sectional study., Setting & Participants: Patients with ESKD aged over 50 years who received maintenance dialysis in 2018 as represented in the JSDT Renal Data Registry database (n = 227,136)., Exposure: Dialysis vintage categorized as: 0-<5 years, 5-<10 years, 10-<20 years, 20-<30 years, and over 30 years., Outcome: Frailty and bedridden status were defined as graded≥2 and graded 4, respectively, according to the Eastern Cooperative Oncology Group Performance Status scale., Analytical Approach: Poisson regression models with robust error variance adjusted for potential covariates were used to estimate the adjusted prevalence ratios (APRs) for frailty and bedridden status. Clinical characteristics of patients undergoing dialysis for≥30 years were also described., Results: Among the study cohort, 5,510 patients (2.4%) had been undergoing dialysis for 30 years or more. The prevalence of frailty in the group with over 30 years of dialysis history was 36.2%, and the rate of being bedridden was 6.4%. Compared with<5 years, dialysis vintages of 5-<10 years, 10-<20 years, 20-<30 years, and over 30 years were associated with frailty (APR, 1.06 [95% CI, 1.05-1.08], 1.10 [95% CI, 1.08-1.11], 1.14 [95% CI, 1.10-1.17], and 1.67 [95% CI, 1.60-1.73]), respectively. Compared with<5 years, dialysis vintages of 5-<10 years, 10-<20 years, 20-<30 years, and over 30 years were associated with being bedridden (APR, 1.17 [95% CI, 1.13-1.22], 1.26 [95% CI, 1.20-1.31], 1.17 [95% CI, 1.08-1.26], and 1.66 [95% CI, 1.49-1.86], respectively., Limitations: Patients receiving short-term dialysis may have more unmeasured comorbidities compared with patients receiving long-term dialysis., Conclusions: Long-term dialysis therapy, particularly exceeding 30 years, is associated with deterioration of physical function and frailty., Plain-Language Summary: End-stage kidney disease increases the risk of frailty. Understanding how long-term dialysis affects physical function may help patients and caregivers plan their lives better. Our research explores the relationship between duration of maintenance dialysis and frailty. We found that longer durations of maintenance dialysis, especially longer than 30 years, were associated with a higher risk of frailty and being bedridden among Japanese patients. The factors responsible for these associations should be the focus of future research., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Aims: The aim of this cohort study was to evaluate the association between urinary levels of C-megalin, a full-length form of megalin, and kidney dysfunction progression and its dependence on the urinary albumin-creatinine ratio (UACR) in individuals with diabetes., Methods: We enrolled 1,547 individuals with diabetes who visited the ambulatory clinic at Tenri Hospital, a regional tertiary-care hospital in Tenri City, Nara Prefecture, Japan, with an estimated glomerular filtration (eGFR) of ≥ 30 mL/min/1.73 m 2 . The hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox proportional hazard models to examine the association between urinary C-megalin levels and eGFR decline by ≥ 40% from baseline., Results: Urinary C-megalin level was not associated with ≥ 40% eGFR decline in an age-, sex-, eGFR-, systolic blood pressure-, hemoglobin-, and UACR-adjusted model in the 1,547 patients enrolled in the study. However, urinary C-megalin levels were associated with a ≥ 40% decline in eGFR when accounting for the relationship between urinary C-megalin levels and UACR in the model. This association was UACR-dependent., Conclusions: High urinary C-megalin levels were associated with progressive kidney dysfunction in individuals with diabetes, and this association was attenuated by high UACRs., (© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Background: Evidence on renin-angiotensin system inhibitors (RASis) effect in reducing urinary protein levels in patients with nephrotic syndrome is insufficient. We determined whether RASis can induce complete remission (CR) in patients on immunosuppressive therapy., Methods: This cohort study included 84 adults (median age, 65 years; males, 57%) with primary nephrotic syndrome (excluding minimal change disease) not receiving RASis during enrollment in the Japanese Nephrotic Syndrome Cohort Study from January 2009 to December 2010, and were followed up for 5 years. Exposure and outcome were RASi initiation and first CR, respectively. Marginal structural models and Poisson regression were used to account for time-varying covariates and estimate causal effects of RASis on CR., Results: Overall, 51 (61%), 73 (87%), and 55 (66%) patients had membranous nephropathy, were prescribed immunosuppressive agents at baseline (1-month post-renal biopsy and/or at start of immunosuppressive therapy), and were prescribed RASis during the study period, respectively. Sixty-five patients experienced first CR (incidence rate, 5.05/100 person-months). RASi use was associated with a higher (adjusted incidence rate ratio [aIRR] 2.27, 95% confidence interval [CI] 1.06-4.84), and lower (aIRR: 0.17, 95% CI 0.04-0.68) first CR in patients with membranous nephropathy and other pathologies, respectively., Conclusion: RASis are beneficial as adjuvant therapy for inducing remission in patients with membranous nephropathy., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Nephrology.)

Aims: Megalin is a multiligand receptor expressed in proximal tubular cells that reabsorbs filtered albumin and correlates cross-sectionally with albuminuria. We investigated the association between urinary C-megalin levels and the incidence of microalbuminuria in patients with diabetes mellitus., Methods: This cohort study included 752 patients with type 1 or 2 diabetes mellitus and a urinary albumin-to-creatinine (Cr) ratio (UACR) within the normoalbuminuric range (<30 mg/g Cr). The association between urinary C-megalin and persistent microalbuminuria, accounting for the possible interaction between baseline UACR and urinary C-megalin, was estimated using a Cox proportional hazards model., Results: During a median follow-up period of 1.99 years, 179 cases of persistent microalbuminuria were observed. The association between urinary C-megalin and persistent microalbuminuria was UACR-dependent (P for interaction < 0.001), with the highest association observed in the absence of UACR (per 100 fM/gCr of urinary C-megalin: adjusted hazard ratio, 1.13; 95% CI 1.07-1.19), gradually decreasing as UACR increased to 30 mg/g Cr. UACR dependence was confirmed by sensitivity analyses according to low-normal (<10 mg/gCr) or high-normal (10-<30 mg/gCr) UACR., Conclusions: Urinary C-megalin is associated with progression to microalbuminuria, especially in those with low-normal UACR levels, and its usefulness to identify high risk patients requires further investigation., (Copyright © 2022 Elsevier B.V. All rights reserved.)