Changyuan Yang

Key Points: EuroQol Five-Dimension, 36-Item Short Form Health Survey, and Kidney Disease Quality of Life-36 were the most common instruments measuring health-related quality of life in trials of disease-modifying pharmacologic therapies in nondialysis CKD. Health-related quality-of-life effects were instrument and domain specific, seen more often in physical and kidney-specific domains of Kidney Disease Quality of Life-36. Future CKD trials should use kidney-specific health-related quality-of-life measures, report all domains with multiple metrics, and discuss implications of design factors to aid interpretation. Background: Several novel pharmacologic therapies for CKD have been shown to reduce risks of disease progression, cardiovascular events, and mortality. However, their effects on health-related quality of life (HRQoL) remain scattered across trials and are difficult to interpret, owing to variability in instruments used and other design-related factors. Methods: PubMed and Web of Science were searched for randomized clinical trials of pharmacologic interventions aimed at slowing CKD progression in adults with nondialysis CKD, published between January 2000 and January 2026. Two authors independently screened and extracted data. Data on study characteristics, HRQoL instruments used, and intervention effects were synthesized descriptively, and key methodological considerations were reviewed. Results: Of 16,624 screened records, 13 trials collected HRQoL data. HRQoL was measured mainly using the EuroQol Five-Dimension questionnaire (EQ-5D) ( n =8), 36-Item Short Form Health Survey (SF-36) ( n =4), or Kidney Disease Quality of Life-36 (KDQOL-36) questionnaire ( n =5). Nine trials reported the effects of interventions on HRQoL. Three demonstrated statistically significant effects in at least one HRQoL domain, all involving interventions that also slowed CKD progression. Effects were generally greater for physical than for mental health domains and were detected more frequently using the disease-specific KDQOL-36 questionnaire, particularly in the symptoms and effects domains, than using the generic EQ-5D instrument. Observed population average intervention effects were generally below conventional minimal clinically important difference thresholds at the population level, although individual-level benefits were evident. Conclusions: The impact of disease-modifying therapies on HRQoL in nondialysis CKD was heterogeneous, instrument dependent, and domain specific.

Chronic kidney disease (CKD) management has evolved from supportive care with renin–angiotensin system inhibitors (RASi) alone to multi-target combination therapies. While RASi remain foundational, their limited efficacy in fully preventing disease progression (e.g. residual albuminuria) and safety concerns, such as hyperkalemia, have underscored the need for novel therapeutic agents. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA) and nonsteroidal mineralocorticoid receptor antagonists (nsMRA) demonstrate complementary nephroprotective effects by targeting metabolic, hemodynamic and inflammatory pathways within the cardiovascular–kidney–metabolic (CKM) syndrome framework. Evidence from large-scale studies demonstrates that combination four-pillar therapies are superior to monotherapy in reducing the risk of kidney failure in patients with diabetes and also exhibit complementary safety profiles that enhance tolerability and long-term patient adherence. For example, combining SGLT2i with RASi mitigates hyperkalemia risk and reduces RASi discontinuation, thereby enhancing treatment persistence. The KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD emphasizes patient-centered, team-based management integrating these therapies. Future directions include expanding evidence for non-diabetic CKD populations, more rapid implementation of these four-pillar therapies and new therapies such as aldosterone synthase inhibitors in this vulnerable group.

Background: Older adults with type 2 diabetes (T2DM) are less likely to receive sodium–glucose cotransporter‐2 (SGLT2) inhibitors, despite their proven cardio‐renal benefits and safety. Whether this age‐related gap is driven by frailty, sex, or other factors remains unclear. Methods: This observational study analysed data from adults registered in primary care during 2023, using the Groningen Initiative to Analyse Type 2 Diabetes Treatment (GIANTT) database. Eligibility for SGLT2 inhibitor treatment was determined based on the Dutch College of General Practitioners (NHG) guideline for T2DM. Prescription rates were assessed across demographics, comorbidities, and preceding medication use. Multivariable logistic regression models were used to assess the association of age and identify factors associated with SGLT2 inhibitor prescriptions. Results: Among 10 241 adults with T2DM, 41% ( n = 4223) were eligible for SGLT2 inhibitor prescription. The prescription rate in the overall population was 15.2% and among eligible people was 25.5%. In people eligible for SGLT2 inhibitors, prescription rates were markedly lower with increasing age, with 37.6% in those aged p _interaction = 0.01). Females had lower prescription rates than males across age groups and levels of frailty. Conclusions: SGLT2 inhibitor prescription rates among Dutch adults with T2DM were low, with persistent age‐ and sex‐related disparities independent of frailty, highlighting the need for equitable prescribing.

Cardiovascular disease (CVD), chronic kidney disease (CKD), diabetes, and obesity frequently coexist and share overlapping pathophysiological mechanisms, contributing to poor health outcomes and high mortality. Recognising this interaction, the cardiovascular-kidney-metabolic (CKM) syndrome has been proposed to advance and unify the concepts of cardiorenal syndrome and metabolic syndrome. CKM syndrome is staged from 0 to 4, reflecting disease progression tracking and risk stratification, and emphasizes life-course screening to detect early metabolic and kidney abnormalities. Early identification of albuminuria and reduced kidney function, even in youth with metabolic risk factors, may slow CKD progression and reduce long-term complications. Further development and validation of risk prediction tools for major cardiovascular and kidney failure events in patients with CKM will help to guide individual therapeutic intervention. For nephrologists, this paradigm offers an opportunity to be involved in the interdisciplinary care model. In the future CKM care model, it would be ideal to have dedicated CKM coordinators in place to enhance collaboration between primary care and all the other specialties involved to improve outcomes, and reduce the global burden of CKM syndrome.

Background: Body roundness index (BRI), an emerging anthropometric measure, has been shown to outperform body mass index (BMI) in predicting mortality risk in the general population. However, its prognostic value among patients with chronic kidney disease (CKD), where the obesity paradox may exist, remains unknown. Methods: This observational study utilized data from the National Health and Nutrition Examination Survey. BRI was calculated using waist circumference (WC) and height, whereas BMI was calculated using body weight and height. Restricted cubic splines (RCSs) were applied to determine optimal cut-off points of BRI for all-cause and cardiovascular mortality in patients with CKD. Associations were examined using Cox proportional hazards models adjusted for potential confounders. Results: Over a median follow-up of 6.6 years, 6240 patients with CKD (mean age 63 years, 43% men) were included, with 1922 all-cause and 715 cardiovascular deaths recorded. RCSs demonstrated J-shaped associations between BRI with mortality. A BRI >10 was associated with a significantly increased risk of all-cause {adjusted hazard ratio [aHR] 1.82 [95% confidence interval (CI) 1.34–2.47]} and cardiovascular mortality [aHR 2.15 (95% CI 1.27–3.62)] compared with the reference of 5.9–6.8 and 5.9–6.5, respectively, with dose-response trends (P for trend < .05). A BMI >30 was paradoxically associated with 44% and 40% lower risks of all-cause and cardiovascular mortality compared with the reference of 18.5–25, respectively. A WC >125 was associated with an increased risk of all-cause mortality [aHR 2.17 (95% CI 1.47–3.18)] but not with cardiovascular mortality [aHR 1.83 (95% CI 0.97–3.45)] compared with the reference of 95–105 cm. The associations between BRI >10 and mortality risks were particularly pronounced among younger adults <65 years of age or individuals with elevated albuminuria (P for interaction < .05). Conclusions: Higher BRI was independently associated with increased all-cause and cardiovascular mortality risk among patients with CKD, offering greater prognostic value for risk stratification than BMI or WC.