INTRODUCTION:Uremic toxins, including indoxyl sulfate (IS) and p-cresyl sulfate (PCS), contribue to cardiac fibrosis and maladaptive remodeling in chronic kidney disease (CKD). Although their roles in ventricular and vascular pathology are well established, their effects on sinus node cells and the associated molecular alterations remain poorly defined. Understanding how the uremic milieu affects sinus node cell homeostasis may provide insight into CKD-associated conduction abnormalities. METHODS:To investigate uremic toxin-induced stress responses, H9C2 cardiomyocytes were used as a comparative cardiac stress-model, whereas primary sinus node cells served as the principal pacemaker-relevant model. Both cell types were treated with IS and PCS. Profibrotic, pro-apoptotic, and stress-related signaling pathways were evaluated by protein and mRNA analyses, together p38 and ERK activation. In parallel, a CKD mouse model was generated by 2-week adenine feeding, and sinus node cells were isolated for molecular analysis. The effects of probenecid were examined in cultured cells and ex vivo using primary sinus node cells isolated from adenine-fed mice. Results IS and PCS induced profibrotic, pro-apoptotic, and remodeling-associated signaling in both H9C2 cardiomyocytes and primary sinus node cells, indicating activation of shared cardiac stress pathways. Conclusions regarding pacemaker-relevant molecular alterations were based primarily on primary sinus node cell findings, including cells isolated from 2-week adenine-fed mice., In primary sinus node cells, uremic toxin exposure increased fibronectin accumulation, altered the Bax/Bcl-2 balance, and activated p38 and ERK signaling, whereas TBX3 expression remained unchanged. changes occurred without overt loss of this pacemaker identity marker. These findings indicate apoptosis-associated, profibrotic, and stress-responsive molecular alterations rather than direct evidence of functional pacemaker impairment. Sinus node cells isolated from adenine-fed mice showed similar remodeling-associated molecular marker changes. Probenecid attenuated fibronectin accumulation, Bax/Bcl-2 imbalance, and stress kinase activation in primary sinus node cells, with similar effects observed ex vivo in cells isolated from adenine-fed mice. CONCLUSION:These findings suggest that uremic toxin-driven stress signaling is associated with molecular remodeling signatures in sinus node cells under CKD-related conditions. Although the functional consequences of these molecular alterations were not assessed, probenecid attenuated uremic toxin-associated profibrotic, pro-apoptotic, and stress kinase signaling, suggesting that targeting molecular stress pathways may help strategy sinus node cell homeostasis in CKD.
Cardiovascular and kidney diseases are tightly interconnected through a bidirectional cardio-renal axis and exhibit pronounced sex-specific differences, implicating estrogen-associated signaling networks as critical modulators of disease susceptibility and progression. Among these, G protein-coupled estrogen receptor 1 (GPER1,GPR30) has emerged as a rapid signaling hub integrating vascular function, inflammatory responses, oxidative stress, and tissue remodeling across the cardiac, renal, and vascular tissues. However, interpretation of the extensive phenotype literature-largely derived from studies using the prototypical agonist G-1-has become increasingly complex in light of recent advances in receptor structural biology and evolving physiological models. Accumulating evidence indicates that GPER1-associated signaling can attenuate maladaptive cardiac remodeling and inflammatory injury, modulate renal tubular transport and redox homeostasis, and preserve endothelial integrity through coordinated regulation of nitric oxide and endothelin pathways. Across organ systems, these effects converge on shared downstream signaling modules, including TGF-β/Smad, PI3K/Akt/eNOS, and NF-κB pathways. At the same time, emerging structural data, including identification of structurally supported agonists and alternative physiological activation mechanisms, challenge assumptions regarding direct ligand-receptor engagement. In this context, translational progress will require a more rigorous framework that integrates structure-guided pharmacology, standardized validation linking ligand binding to downstream signaling in matched experimental systems, and genetic epistasis approaches combining loss-of-function and rescue strategies. Rigorous mechanistic validation is essential to establish causal GPER1-associated signaling across the cardio-renal axis. Such approaches are required to determine whether GPER1 represents a tractable therapeutic target in combined cardiac and kidney disease.
Cardiovascular disease (CVD), the predominant cause of mortality among individuals with chronic kidney disease (CKD), is driven by chronic inflammation and oxidative stress, vascular calcification, accumulation of uremic toxins, ventricular remodeling, and microvascular dysfunction. Subclinical forms of CVD are highly prevalent in CKD and are often unrecognized until advanced stages, contributing to a substantial mortality gap due to delayed intervention. Therefore, screening for subclinical CVD among patients with CKD is important to potentially prevent CVD progression and mitigate downstream events. Advances in imaging-including echocardiography, coronary computed tomography angiography (CCTA), coronary artery calcium (CAC) scoring, and cardiac magnetic resonance imaging (CMR)-now offer sensitive, noninvasive detection of early cardiac and vascular abnormalities in CKD. Circulating and urinary biomarkers such as C-reactive protein (CRP), high-sensitivity troponin (hsT), N-terminal pro brain-type natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), fibroblast growth factor 23 (FGF-23), and urine albumin-to-creatinine ratio (UACR) provide valuable insight into underlying pathophysiological processes, risk stratification, and individualized management in the CKD population. This review summarizes recent progress in the identification of CVD in CKD, with an emphasis on novel imaging strategies, biomarker innovation, and the need for integrative approaches to closing the cardiovascular mortality gap in this vulnerable population.
BACKGROUND:Sodium-glucose cotransporter 2 (SGLT2) inhibitors have established long-term cardiorenal benefits in patients with type 2 diabetes mellitus. However, their short-term peri-procedural role in preventing contrast-induced acute kidney injury (CI-AKI) after coronary computed tomographic angiography (CCTA) remains uncertain, and their acute effects on renal oxygenation may be complex. METHODS:This prospective, randomized, double-blind, placebo-controlled single-center study screened 352 diabetic patients scheduled for CCTA. A total of 335 patients were randomized, and 322 patients with complete baseline and post-CCTA creatinine assessment were included in the modified intention-to-treat analysis. Participants received dapagliflozin 10 mg once daily or matched placebo beginning 3 days before CCTA and continuing through the 72-hour post-CCTA follow-up. CI-AKI was defined according to prespecified serum creatinine-based criteria within 72 hours after contrast exposure. Serial renal indices and exploratory biomarker variables were summarized at available time points, and logistic regression was restricted to a parsimonious covariate set because of the limited number of events. RESULTS:The modified intention-to-treat analysis included 322 patients, with 161 patients assigned to each group. CI-AKI occurred in 29 patients overall (9.0%), with a significantly lower incidence in the dapagliflozin group than in the placebo group (6/161 [3.7%] vs. 23/161 [14.3%]; odds ratio, 0.23; 95% confidence interval, 0.09-0.59; P = 0.001 by Fisher exact test). Baseline renal indices, including serum creatinine, estimated glomerular filtration rate, blood urea nitrogen, neutrophil gelatinase-associated lipocalin, and baseline eGFR category distribution, were comparable between groups. At 72 hours after CCTA, the dapagliflozin group had lower serum creatinine and higher eGFR than the placebo group. KDIGO creatinine-based AKI stage distribution did not differ significantly between groups (P = 0.064), and no patient required new dialysis or kidney replacement therapy during the 72-hour follow-up. Exploratory secondary biomarker analyses showed lower blood urea nitrogen and neutrophil gelatinase-associated lipocalin levels at 72 hours in the dapagliflozin group. CONCLUSION:In diabetic patients undergoing CCTA, short-term peri-procedural dapagliflozin was associated with a lower incidence of creatinine-defined CI-AKI and improved early post-contrast renal function profiles. By focusing on a noninvasive CCTA population, this study expands the potential application of SGLT2 inhibition from invasive coronary procedures to intravenous contrast-enhanced cardiac CT, suggesting a novel adjunctive approach for renal risk reduction in selected diabetic patients. Larger multicenter trials are needed to validate these findings and define the patients most likely to benefit.
Background Preserving lean body mass (LBM) is increasingly recognized as a critical determinant of survival and disease progression in individuals with cardiovascular-kidney-metabolic (CKM) syndrome. Sarcopenia is significantly associated with higher risk of all-cause, cardiovascular (CVD), and non-CVD mortality, as well as greater odds of advancing to later CKM stages. While incretin-based therapies, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/gastric inhibitory polypeptide (GIP) receptor agonists, are now cornerstones of CKM management, emerging evidence suggests a potential association with loss of LBM and skeletal muscle in vulnerable patients. The key gap in knowledge is that most trials and real-world evaluations prioritize weight and cardio-kidney-metabolic endpoints, while muscle mass, strength, functional trajectories, frailty progression, and patient-reported impacts are inconsistently measured, especially in high-risk CKM populations. This review synthesizes clinical trial and real-world evidence to characterize body composition changes with incretin-based therapies and proposes a conceptual, stepwise framework to maintain patient-centered muscle health. PubMed, Scopus, and Web of Science were searched for English-language peer-reviewed studies (January 2004-January 2026) evaluating incretin-based therapies and LBM outcomes; ClinicalTrials.gov and WHO ICTRP were also queried for trials with muscle-related endpoints. Summary Across incretin agents, weight loss is typically fat-predominant; however, available studies suggest approximately 25-39% of total weight loss may reflect LBM reduction over 36-72 weeks. Major evidence gaps include: (1) limited longitudinal data linking LBM loss to strength, mobility, frailty, falls, disability, and patient-reported function; (2) sparse head-to-head comparisons to clarify agent- and dose-specific muscle effects across the CKM continuum; (3) underrepresentation of high-risk CKM subgroups most vulnerable to protein-energy wasting, anabolic resistance, and polypharmacy; and (4) lack of scalable risk prediction and monitoring tools to detect early adverse body-composition trajectories. Key Messages Despite rapid expansion of incretin-based therapies across the CKM continuum, muscle health is rarely measured, yet it strongly shapes survival, frailty, and functional independence. Muscle preservation is a key consideration in benefit-risk assessment and merits explicit tracking in both clinical trials and routine practice. We outline a patient-centered, stepwise roadmap that pairs incretin prescribing with baseline muscle-risk characterization, serial tracking of body composition (e.g., DXA/BIA/BIS where feasible), simple functional measures, and early mitigation strategies (resistance training, nutrition optimization, and, when appropriate, adjunct anabolic/anti-catabolic approaches). Priorities to advance the field include pragmatic long-term studies in high-risk CKM populations and standardized capture of functional and patient-reported outcomes.
INTRODUCTION:Cardiovascular-kidney-metabolic (CKM) syndrome and depressive disorder represent major public health burdens. While associations between depression and individual components of CKM syndrome have been established, the relationship between depression and CKM syndrome as an integrated clinical construct remains poorly understood. METHODS:Data from the China Health and Retirement Longitudinal Study (CHARLS) were used, including 8,088 participants in cross-sectional analyses and 1,803 in longitudinal analyses. CKM syndrome was classified according to the American Heart Association (AHA) staging criteria, and depressive symptoms were assessed using the 10-item Center for Epidemiologic Studies Depression Scale (CES-D-10). The association between CKM stage and depressive symptoms was evaluated using ordinary least squares regression models with five levels of covariate adjustment. Subgroup analyses and interaction tests were conducted to investigate interaction effects across different populations. RESULTS:Higher CKM stages were significantly associated with increased depressive symptom severity. In the cross-sectional analysis (2011), mean CES-D-10 scores were 8.6 ± 6.4, 8.6 ± 6.3, 8.1 ± 6.2, and 10.7 ± 6.9 for the total population and CKM stages 0-1, 2-3, and 4, respectively. Scores in stage 4 exceeded the threshold for severe depressive symptoms and were significantly higher than those in other stages (p < 0.001). Subgroup analyses further confirmed the robustness of these findings. In longitudinal analyses, progression in CKM stage over a 4-year period was independently associated with an increase in CES-D-10 scores in the fully adjusted model (β = 0.31, 95% CI: 0.07-0.54). CONCLUSIONS:CKM syndrome is significantly associated with depressive symptoms, especially in stage 4. There is a positive relationship between CKM progression and depressive symptom severity, highlighting the need for integrated physical and mental health care for CKM patients.
INTRODUCTION:Patients with chronic kidney disease (CKD) are at a high risk of adverse outcomes after acute myocardial infarction (AMI); however, evidence on long-term outcomes after percutaneous coronary intervention (PCI) in this population remains limited. METHODS:This prospective cohort study, nested within the Kailuan Study, included patients with CKD who experienced AMI between 2006 and 2020. Participants were classified into PCI and non-PCI groups based on documented PCI receipt and were matched 1:2 on age and sex (452 PCI; 745 non-PCI). Follow-up began at the time of AMI diagnosis or PCI and continued until December 31, 2023. The primary outcome was all-cause mortality, with secondary outcomes being new-onset heart failure and CKD progression. Time-segmented Cox models were used for all-cause mortality, and standard Cox models were used for secondary outcomes. RESULTS:During follow-up, PCI receipt was associated with a lower risk of all-cause mortality compared with no PCI. The association was stronger during the first 5 years of follow-up (hazard ratio [HR], 0.34; 95% confidence interval [CI], 0.24-0.47) and was attenuated thereafter (HR, 0.73; 95% CI, 0.51-1.04). No significant associations were observed between PCI receipt and either new-onset heart failure (HR, 1.06; 95% CI, 0.72-1.57) or CKD progression (HR, 1.11; 95% CI, 0.72-1.71). CONCLUSION:In patients with CKD and AMI, PCI was associated with lower all-cause mortality during the first 5 years of follow-up, with no significant differences in new-onset heart failure or CKD progression.
Background: The European Kidney Function Consortium (EKFC) has introduced equations for estimating glomerular filtration rate (eGFR) using serum creatinine (Cr) and cystatin C (Cys). While their diagnostic accuracy is established, their comparative prognostic value for long-term mortality in the general population is not well-defined. This study compared the prognostic performance of three EKFC equations—creatinine-based (EKFC-eGFRcr), cystatin C-based (EKFC-eGFRcys), and the combined (EKFC-eGFRcrcys) model—for predicting all-cause and cardiovascular (CV) mortality. Method: We analyzed a population-based cohort of 4519 participants from the National Health and Nutrition Examination Survey (NHANES) 1999–2002. eGFR was calculated using all three EKFC variations (EKFC-eGFRcr, EKFC-eGFRcys, and EKFC-eGFRcrcys). The primary and secondary endpoints were all-cause and CV mortality, respectively, through December 31, 2019. Predictive improvements were evaluated using integrated discrimination improvement (IDI), net reclassification improvement (NRI), and number needed to measure (NNM). Result: The eGFR value calculated by the EKFC-eGFRcys, EKFC-eGFRcr, and EKFC-eGFRcrcys was 78.92±22.98, 84.45±23.21, and 81.68±22.13 ml/min/1.73m2, respectively. Over a median follow-up of 211 months, all three eGFR models were independent predictors of mortality (all P <0.001). Restricted cubic spline regression revealed significant non-linear, inverse associations between all eGFR measures and adjusted mortality risks (all P for non-linearity < 0.001). Compared to EKFC-eGFRcr, EKFC-eGFRcys significantly improved risk reclassification for all-cause mortality (categorical NRI = 15.9%; 95% CI: 14.1–17.8%; NNM = 7). The combined EKFC-eGFRcrcys also outperformed the creatinine-only model (NRI = 8.9%; NNM = 12). However, EKFC-eGFRcys demonstrated modestly better performance than the combined equation (NRI = 7.0%; NNM = 15), suggesting limited incremental value in adding creatinine to cystatin C. The superiority of EKFC-eGFRcys was primarily driven by improved classification of non-events. Conclusion: The EKFC-eGFRcys equation provides superior prognostic value for all-cause and CV mortality compared to both creatinine-based and combined EKFC equations. Notably, the combined model offered no prognostic advantage over cystatin C alone. These findings highlight the clinical importance of cystatin C-based eGFR for accurate risk stratification in the general population.
INTRODUCTION:This post hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial examined whether estimated plasma volume status (ePVS) modifies the association between estimated glomerular filtration rate (eGFR) and incident atrial fibrillation (AF) in patients with heart failure with preserved ejection fraction (HFpEF). METHODS:A total of 2,202 HFpEF patients without baseline AF were included. ePVS was calculated using the Duarte formula, and participants were stratified into low and high ePVS groups based on the cohort median. Multivariable Cox proportional hazards models were used to assess the association between eGFR and incident AF, with stratified analyses by spironolactone treatment. RESULTS:During follow-up, 4.9% of patients developed incident AF. No significant association between eGFR and AF was observed in the low ePVS group. In contrast, among patients with high ePVS, higher eGFR was associated with a reduced risk of incident AF after multivariable adjustment, with a significant nonlinear relationship (p for nonlinearity <0.001) and a statistically significant eGFR × ePVS interaction (p for interaction = 0.010). The association was consistent regardless of spironolactone use. CONCLUSION:This exploratory post hoc analysis suggested that ePVS may modify the association between eGFR and incident AF in HFpEF, with lower eGFR linked to higher AF risk primarily in patients with elevated ePVS. These hypothesis-generating findings should be interpreted cautiously given the limited number of events. Prospective studies are warranted to validate this potential interaction and its clinical implications.
INTRODUCTION:Acute kidney injury (AKI) and reduced glomerular filtration rate (GFR) are common complications following transcatheter aortic valve replacement (TAVR). Statins may exert renoprotective effects; however, the impact of statin intensity on renal outcomes remains uncertain. This study aimed to evaluate the association between preprocedural statin use and intensity with short-term renal outcomes after TAVR. METHODS:We conducted a retrospective longitudinal cohort study including 810 consecutive patients undergoing TAVR at Kaplan Medical Center between January 2014 and August 2024. Patients were stratified by statin use (users vs. non-users) and statin intensity (high-intensity statins [HISs] vs. low-to-moderate-intensity statins). The primary outcome was 30-day change in estimated GFR (eGFR), categorized as improved, stable, or deteriorated. The secondary outcome was 30-day incidence of AKI. Multinomial logistic regression and Cox proportional hazards models were used, adjusted for baseline and procedural confounders. RESULTS:Statin use was associated with an increased probability of GFR improvement (average marginal effect [AME], 20.7%; 95% CI, 12.3%-29.1%; p < 0.001) and a reduced risk of AKI (adjusted hazard ratio [HR], 0.53; 95% CI, 0.31-0.88; p = 0.015). In contrast, HIS therapy was associated with a higher risk of GFR deterioration (AME, 10.3%; 95% CI, 2.9%-17.8%; p = 0.006) and increased AKI incidence (adjusted HR, 2.85; 95% CI, 1.52-5.34; p = 0.001), particularly in the early postoperative period. CONCLUSION:Statin therapy is associated with improved short-term renal outcomes after TAVR. However, HISs may increase the risk of renal deterioration and AKI. These findings support individualized statin intensity strategies in the periprocedural period to balance cardiovascular benefit and renal safety.
BACKGROUND:Cardiovascular-kidney-metabolic (CKM) syndrome integrates the strong interrelationship among cardiovascular disease, chronic kidney disease (CKD), and metabolic risk factors such as obesity and diabetes. SUMMARY:Renal replacement therapy (RRT) is considered an essential component of management in advanced CKD. Kidney failure has unique therapeutic and prognostic challenges, particularly with the coexistence of heart failure, ischemic heart disease, and metabolic syndrome. In this review, we aim to evaluate challenges and therapeutic considerations in dialytic therapies and kidney transplantation in patients with CKM syndrome. KEY MESSAGES:Patients with CKM syndrome undergoing RRT represent a complex and vulnerable population requiring multidisciplinary and individualized management approaches. Optimization of cardiovascular and metabolic risk factors is essential to improve outcomes in dialysis and kidney transplantation settings.
INTRODUCTION:The goal of the current study was to evaluate the prognostic value of the potential cardiorenal biomarkers kidney injury molecule-1 (u-KIM-1), N-acteyl-ß-D-glucosaminidase (NAG) and urinary neutrophil gelatinase-associated lipocalin (u-NGAL) regarding mortality and major adverse cardiac events (MACEs) in patients presenting with acute chest pain in the emergency department. METHODS:The study cohort consisted of 294 patients who presented themselves with acute chest pain in the emergency department of the university hospital Regensburg. The urinary concentrations of NAG, KIM-1, and NGAL were measured alongside troponin I and NT-proBNP. The patients were followed for 60 months regarding the primary endpoints mortality of any cause and MACEs, consisting of mortality, stroke, congestive heart failure and acute coronary syndrome with the necessity of PCI was gathered (MACE). RESULTS:Fifty four patients died during the follow-up and 97 suffered from MACE. Regarding ROC-analysis NAG as well as u-KIM-1 showed promising predictive values (all-cause mortality: AUCNAG 0.821, AUCKIM-1 0.745, MACE: AUCNAG 0.778, AUCKIM-1 0.692). u-NGAL showed less promising AUCs regarding mortality (AUC 0.69) as well as MACE (AUC 0.66). According to the Kaplan-Meier analysis, patients with concentrations of urinary N-acetyl-β-D-glucosaminidase, u-KIM-1 or u-NGAL > median showed a significant worse outcome regarding MACE as well as all-cause mortality (each p < 0.05). Furthermore, Cox-regression analysis revealed NAG as independent predictor beside NT-proBNP and older age for mortality due to any cause and MACE (each p < 0.001), opposite to u-KIM-1, hypertension and diabetes (each p = n.s.). CONCLUSION:Urinary N-acetyl-ß-D-glucosaminidase and, to a lesser extent, kidney injury molecule-1 showed significant value in prediction MACEs and mortality due to any cause in patients with acute chest pain. But the clinical usability is still not certain and further studies are required.
Introduction: Fluid overload is a major determinant of morbidity and mortality in maintenance hemodialysis (MHD) patients. This exploratory study describes the integration of lung ultrasound (LUS), modified Venous Excess Ultrasound Score (mVExUS), and bioimpedance analysis (BIA) for non-invasive fluid status assessment in MHD. Additionally, this study aimed to correlate congestion with malnutrition using echographic parameters (nutritional ultrasound [NUS]) in congestive and non-congestive patients. Methods: In this single-center retrospective observational cohort study, 47 adult patients on MHD underwent pre-dialysis evaluation with LUS, mVExUS, NUS, and BIA. Patients were classified as congestive if they had an mVExUS score ≥2, LUS with ≥3 B-lines in ≥3 thoracic zones and BIA with the ratio of extracellular water to total body water ECW/TBW ≥0.39. NUS was used to assess the quadriceps rectus femoris (QRF) and preperitoneal visceral fat (PPVF), measuring Y-axis, Y-axis/height, cross-sectional muscle area rectus femoris (CS-MARF), and supramuscular fat (SMF). Demographic, biochemical, functional, and dialysis-related parameters were collected. Frailty, sarcopenia and nutritional status were evaluated. Congestive patients were reassessed after 5 weeks. Results: Eight patients (17%) met criteria for congestion. As expected by the predefined congestion criteria, patients classified as congestive showed higher mVExUS grades (p < 0.001), greater B-line burden (11.9 vs. 2.9), and higher ECW/TBW ratios (0.42 vs. 0.40; p = 0.004). After 5 weeks, congestive patients exhibited improvements in N-terminal pro-B-type natriuretic peptide (NT-proBNP), portal vein pulsatility index, and pulmonary congestion, without adverse hemodynamic events. The CS-MARF was 1.81 ± 0.11 cm2 in congestive versus 2.91 ± 0.78 cm2 in non-congestive (p = 0.0004). Conclusion: The integration of LUS, mVExUS, BIA and NUS provide a descriptive framework for multimodal assessment of fluid and nutritional status in MHD patients. These findings should be considered hypothesis-generating and require validation in prospective studies.
Introduction: This study aimed to estimate the impact of type II diabetes (DM-II) on kidney transplant outcomes and graft utility. Methods: A nationwide, registry-based study compares outcomes for all primary kidney transplantations performed between 2000 and 2022 in the Netherlands in DM-II patients (761 deceased and 364 living donor procedures) with nondiabetic controls. Results: Short-term (≤90 days) transplant outcomes for living donor procedures were similar for DM-II and nondiabetic controls. Deceased donor transplantations in DM-II patients were associated with an increased incidence of delayed graft function (p < 0.0002), and a doubling of 90-day mortality (HR: 2.19 [95% CI: 1.49–3.23], p < 0.0001). Evaluation of long-term graft survival, with death as competing risk, indicated an equal (sub-distribution hazard rate [sHR] 0.95 [0.74–1.23]), respectively, compromised (sHR 1.91 [1.37–2.65]; p < 0.001) survival for grafts from deceased or living donors. DM-II profoundly impacted recipient survival (HR for death, respectively, 1.63 [1.45–1.82] and 1.81 [1.51–2.17]; p < 0.001) for recipients of a deceased or living donor graft (nondiabetic recipient is reference), with cardiovascular event and infection as dominant causes of death. The compromised recipient survival profoundly impacted the utility of kidney transplantations (p < 0.001). Conclusions: Despite excellent graft survival, the efficacy of kidney transplantations in DM-II patients is compromised by reduced recipient survival. Cause of death distribution suggests a role for immunosuppressive regimens in the excess mortality observed. A shift in focus from optimized transplant to optimized patient survival is warranted for DM-II patients. Moreover, the conflict between increasing incidences of DM-II, a lower transplant utility, but persistent donor organ shortages, calls for development of novel organ allocation strategies.
Introduction: Predicting tolerance to fluid removal is particularly challenging in hospitalized, acutely ill patients. This study evaluated the association between the Venous Excess Ultrasound (VExUS) and IDHE in hospitalized patients. Methods: This single-center prospective cohort included hospitalized between 2022 and 2024 receiving hemodialysis. Ultrasound of the inferior vena cava (IVC), hepatic, portal, and femoral veins was performed. Patients were classified into four VExUS grades (0 to 3) based on IVC dimensions and venous Doppler waveforms. Follow-up at 3 months was conducted to evaluate outcomes across the different groups. Results: The cohort consisted of 93 patients. VExUS grading showed grade 0 in 52 patients (55.9%), grade 1 in 22 patients (23.7%), grade 2 in 11 patients (11.8%), and grade 3 in 8 patients (8.6%). The incidence of IDHE was tended to be higher in VExUS grade 0 (40.4%) and VExUS grade 3 (50.0%) patients compared with VExUS grade 1 (18.2%) or 2 (18.2%) (p = 0.145). The cumulative duration of hypotension (sBP <90 mm Hg) differed between VExUS groups (p = 0.03), with VExUS grade 3 patients experiencing longer median duration of hypotension compared to participants with a VExUS grade 1 (16.4 [0; 47.5] vs. 0 [0; 0] min, p = 0.04). Conclusion: Our findings showed a trend toward more frequent IDHE in both VExUS grade 0 and grade 3, with grade 3 patients experiencing a significantly longer cumulative duration of hypotension. High VExUS scores may identify patients at increased risk of hypotension due to impaired hemodynamic adaptability.
Introduction: This study evaluated the trajectory of the urine albumin-to-creatinine ratio (UACR) in patients hospitalized with acute heart failure (HF) from pre-admission (baseline), through hospital admission, discharge and 2 weeks post-discharge. We also assessed its association with congestion-related biomarkers, including N-terminal pro-B-type natriuretic peptide (NT-proBNP), CA 125, and the neutrophil-to-lymphocyte (N/L) ratio. Methods: Prospective, observational study including 99 consecutive patients admitted with acute HF. Blood and urine analyses were performed at admission, at discharge and 2 weeks post-discharge. Patients were stratified according to UACR at admission and the trajectories of UACR and biomarkers were evaluated. The clinical, analytical, and echocardiographic predictors of UACR were analysed. Results: Mean age was 70.8 ± 12.2 years, 57% were men. At admission, albuminuria was present in 65.7% of patients (45.5% microalbuminuria, 20.2% macroalbuminuria, respectively). A higher UACR at admission was associated with diabetes, lower eGFR, previous HF admission, higher clinical congestion score, mixed or right-sided congestive phenotype, higher NT-proBNP, and CA 125 levels. The UACR worsened from baseline to admission and improved at discharge, reflecting the congestion dynamics. NT-proBNP, CA 125, and N/L ratio showed similar patterns. Independent predictors of higher UACR at admission were diabetes, reduced renal function, higher aspartate aminotransferase (AST) and lower vitamin D levels. In the mixed linear regression analysis, lower eGFR, and higher AST levels remained independently associated with UACR trajectory. Admission UACR correlated with congestion score and predicted higher in-hospital mortality and early HF readmissions (<30 days). Conclusion: Albuminuria is common in acute HF and exhibits a dynamic change in relation to congestion. These findings suggest a potential role as a biomarker for congestion monitoring. However, given the study limitations, the results should be considered exploratory and warrant confirmation in larger prospective studies.
Introduction: Functional mitral regurgitation (FMR) is prevalent in CKD patients, but few studies have evaluated the effect of kidney transplant (KT) on FMR. This study aimed to clarify KT’s effect on FMR. Methods: This study included 115 living-donor KT recipients (2012–2023). Primary outcome was change in FMR severity (5 categories: none to severe) based on echocardiographic findings before and 1 year post-KT. Aortic regurgitation (AR) severity and changes in left atrial diameter (LAD), left ventricular end-diastolic dimension (LVDd), ANP, and BNP levels were also assessed. Change in FMR and AR severity was assessed using Wilcoxon signed-rank tests. Multivariable logistic regression models were used to identify factors associated with the worsening of FMR and AR. Results: At baseline, 76.5% had trivial FMR; 22.6% had mild/moderate/severe FMR. One year post-KT, moderate/severe FMR disappeared. Overall, FMR improved in 19.1%, remained unchanged in 73.1%, and worsened in 7.8%. FMR severity distribution significantly changed (p = 0.004). Reductions in LAD/LVDd aligned with decreased ANP/BNP. Multivariable analysis identified acute ABMR as an independent factor for worsening FMR (OR = 4.02, 95% CI: 1.81–8.91, p < 0.001). No significant AR improvement was observed (p = 0.377). A history of arrhythmia (OR = 2.68, 95% CI: 1.28–5.64, p = 0.009) and stroke (OR = 2.27, 95% CI: 1.12–4.59, p = 0.023) were identified as an independent factor for worsening AR. Conclusion: KT is associated with an improvement in FMR among patients with kidney failure. This is likely due to LA/LV reverse remodeling from reduced volume/pressure overload. However, this benefit may diminish with graft dysfunction (e.g., acute rejection). Conversely, KT is not associated with an improvement in AR. Our findings highlight another important cardioprotective benefit of successful KT. Further prospective studies are needed to better understand this association.
INTRODUCTION:Heart failure with reduced ejection fraction (HFrEF) commonly coexists with chronic kidney disease (CKD), conferring a markedly increased risk of adverse outcomes. Ivabradine and digoxin are both used for heart rate control in HFrEF, but their comparative effectiveness in patients with CKD remains uncertain. Therefore, this study aimed to compare the risk of major adverse cardiovascular events (MACE), including heart failure exacerbation (HFE) and all-cause mortality, between ivabradine and digoxin in patients with concomitant HFrEF and CKD. METHODS:Using the TriNetX global research network, we conducted a retrospective cohort study including adults with HFrEF and CKD between 2015 and 2025. Patients prescribed ivabradine were propensity score-matched 1:1 to those receiving digoxin based on demographic, clinical, laboratory, and medication variables. The primary outcome was MACE (composite of HFE or all-cause mortality). Secondary outcomes included each component separately. Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS:After matching, 3,140 patients were included (1,570 per group). Ivabradine use was associated with a significantly lower risk of MACE compared with digoxin (26.8% vs. 31.6%; HR: 0.79, 95% CI: 0.70-0.90; p < 0.001). Ivabradine also reduced the risk of HFE (HR: 0.83, 95% CI: 0.72-0.97; p = 0.015) and all-cause mortality (HR: 0.69, 95% CI: 0.56-0.85; p < 0.001). Subgroup and negative-control analyses yielded consistent results. CONCLUSIONS:In this large, real-world cohort of patients with HFrEF and CKD, ivabradine was associated with lower risks of MACE, HFE, and all-cause mortality compared with digoxin. Ivabradine may represent a safer and more effective heart rate-lowering option for this high-risk population.
INTRODUCTION:Sarcopenia has been proved to be associated with cardiovascular diseases (CVD), chronic kidney disease, and metabolic disorders, but the relationship between sarcopenia and all-cause and cardiovascular mortality risk among middle-aged and older adults across stages 0-3 of cardiovascular-kidney-metabolic (CKM) syndrome remains unclear. This study aimed to investigate the relationship between sarcopenia and all-cause and cardiovascular mortality risk among middle-aged and older adults across stages 0-3 of CKM syndrome based on Nutrition Examination Survey (NHANES) 2011-2018 and the China Health and Retirement Longitudinal Study (CHARLS) 2011-2020. METHODS:Multivariable Cox regression analysis was performed to analyze the association of sarcopenia with all-cause and CVD mortality. Restricted cubic spline (RCS) analysis was conducted to explore the non-linear relationship between body mass index (BMI)-adjusted muscle mass (appendicular skeletal muscle mass divided by BMI, ASMI) and all-cause and CVD mortality, and machine learning (ML) models were developed for mortality risk prediction. The CHARLS database was utilized as validation to enhance the stability of the results. RESULTS:Over an average follow-up of 5.11 years, NHANES recorded 85 all-cause deaths and 12 CVD deaths. After the full adjustment, sarcopenia was significantly associated with all-cause mortality (weighted hazard ratio [HR] = 3.428, 95% confidence interval [CI] 1.484-7.915, p = 0.004) and CVD mortality (weighted HR = 1.070, 95% CI 1.009-1.570, p = 0.049). RCS analysis revealed a nonlinear negative relationship between ASMI and CVD mortality (p for nonlinear = 0.009). ML models demonstrated better predictive performance, with random forest (area under the curve = 0.766) achieving the highest accuracy. In the CHARLS cohort, sarcopenia significantly increases all-cause mortality (HR = 2.519, 95% CI 1.402-4.527, p < 0.001), and subgroup analysis reported consistent results with the main analysis. CONCLUSION:Sarcopenia was significantly associated with all-cause mortality and with CVD mortality in fully adjusted models, though the latter association was modest, and exhibits good predictive performance for mortality among middle-aged and older individuals within CKM stages 0-3.
