Cardiorenal Medicine最新文献

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular disease (CVD). However, the risk of cardiovascular events is often underestimated and undertreated in daily clinical practice. In this review, we aim to answer ten brief but up-to-date questions on cardiovascular risk in CKD. Specifically, a group of ten expert nephrologists have summarized their evidence-based views on topics such as assessing the arterial tree, estimating CV risk, identifying biomarkers that can better stratify CV risk, and pharmacological and non-pharmacological interventions that have been shown to improve CV risk. They also discuss blood pressure goals, optimal dyslipidaemia management, and how CV risk should be managed in patients undergoing renal replacement therapy. Finally, we propose integrating all these strategies into clinical practice.

Introduction: Patients with chronic kidney disease have a high incidence of morbidity and mortality from cardiovascular causes. Among the most significant cardiovascular risk factors is undoubtedly hypercholesterolemia, especially elevated cholesterol-LDL levels. The first-line therapy for the management of hypercholesterolemia, including in patients with chronic kidney disease, is represented by statins even in combination with ezetimibe. In patients with chronic kidney disease, statin therapy is often poorly tolerated with high incidence of rhabdomyolysis. An alternative treatment is represented by siRNA Inclisiran, which has been shown to be effective in double yearly administration.

Methods: Thirty-two patients (19 male and 13 female) with a mean age of 60.2 years, basal total cholesterol values of 225 mg/dl and LDL cholesterol values of 138 mg/dl were enrolled in our observational study. The mean eGFR value at baseline was 36.93 ml/min/m2. All patients had a diagnosis of chronic ischemic heart disease (CAD), and 4 patients also had type 2 diabetes mellitus. The patients received therapy with Inclisiran 284 mg at time zero, then repeated at 3 months and then at 6 months.

Results: After 12 months of treatment, there was almost 50% reduction in both total and LDL cholesterol values with no significant change in eGFR values. Only one patient presented with an episode of myocardial infarction 11 months after treatment was started, and no drug-related side effects were reported.

Conclusion: Inclisiran should be considered as a viable therapeutic alternative for the management of pure hypercholesterolemia in patients with chronic kidney disease who are intolerant to statin treatment because it achieves the optimal LDL-cholesterol targets required by actual guidelines without side effects.

Background: The risk for contrast-induced acute kidney injury (CI-AKI) following cardiac procedures involving contrast administration is particularly high among chronic kidney disease (CKD) patients. Neutrophil gelatinase-associated lipocain (NGAL) has been widely studied as an early marker for renal injury. However, CKD could impact NGAL levels and alter their predictive performance. This study aimed to evaluate a novel baseline "indexed NGAL" (I-NGAL), calculated by adjusting NGAL to the estimated glomerular filtration rate (eGFR), for the prediction of CI-AKI in CKD patients undergoing elective transcatheter aortic valve replacement (TAVR).

Methods: A total of 134 CKD patients undergoing elective TAVR were included. Serum NGAL levels were drawn at hospital admission. Patients were followed for the occurrence of CI-AKI. Receiver-operator characteristic (ROC) methods were used to identify optimal sensitivity and specificity for I-NGAL. Univariate and multivariate binary logistic regression models were used to assess I-NGAL predictive performance.

Results: Overall 35/134 patients (26%) developed CI-AKI following TAVR both NGAL and I-NGAL were significantly higher among patients having CI-AKI. I-NGAL results had a higher predictive ability than unindexed NGAL results (AUC of 0.83 vs. 0.78, p<0.001). The optimal I-NGAL cutoff for prediction of CI-AKI was 4, with sensitivity of 71%, specificity of 77%, and a negative predictive value (NPV) of 88%. In a multivariate logistic regression model, I-NGAL was independently associated with CI-AKI (OR 1.22, 95% CI: 1.05-1.41; p = 0.007). I-NGAL level>4 was also independently associated with CI-AKI (OR 8.13, 95% CI 3-21.8, p<0.001).

Conclusion: Among CKD patients undergoing elective TAVR, adjusting baseline NGAL values according to eGFR yields an indexed NGAL that serves as an improved tool for predicting and ruling out CI-AKI, regardless of baseline renal function.

Introduction: Chronic kidney disease (CKD) is a major risk factor for cardiovascular morbidity and mortality, particularly in patients with acute myocardial infarction (AMI). Dual antiplatelet therapy (DAPT) is essential for secondary prevention in AMI, but the optimal P2Y12 inhibitor in CKD patients remains unclear. While ticagrelor has demonstrated superior cardiovascular outcomes compared to clopidogrel in the general population, its safety and efficacy in advanced CKD are not well established.

Methods: This retrospective cohort study analyzed data from the Chang Gung Research Database (CGRD) to compare ticagrelor and clopidogrel in CKD stage III-V patients hospitalized with AMI between 2001 and 2020. Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics. Clinical outcomes, including recurrent AMI, ischemic stroke, cardiovascular death, major bleeding events, and all-cause mortality, were evaluated using Cox proportional hazards models and competing risk analysis.

Results: Among 3,461 patients (ticagrelor: 704, clopidogrel: 2,757), ticagrelor was associated with a significantly lower risk of all-cause mortality (HR 0.694, 95% CI 0.539-0.894, p = 0.047), with no significant differences in recurrent AMI, ischemic stroke, cardiovascular death, or major bleeding events.

Conclusions: In CKD patients with AMI, ticagrelor was associated with reduced all-cause mortality compared to clopidogrel, without an increased risk of major bleeding. These findings highlight the need for further prospective studies to confirm ticagrelor's benefits and inform optimal antiplatelet strategies in this high-risk population.

Introduction: Renal risk stratification after transcatheter aortic valve implantation (TAVI) remains anchored to filtration metrics such as serum creatinine and estimated glomerular filtration rate (eGFR). These indices may not capture early tubular injury, which is clinically relevant in older TAVI populations. We therefore investigated whether four urinary biomarkers-N-acetyl-β-D-glucosaminidase (NAG), liver-type fatty acid-binding protein (L-FABP), β2-microglobulin, and α1-microglobulin-measured the day after TAVI, are associated with subsequent cardio-renal outcomes.

Methods: We enrolled 191 consecutive patients undergoing TAVI in a single-center cohort within the LAPLACE-TAVI registry (February 2016-December 2019). Spot urine collected 12-18 hours post-procedure was assayed for four urinary markers. The primary endpoint was a 24-month composite of all-cause death or first heart-failure hospitalization; a renal composite used contemporary surrogate criteria. Multivariable Cox models adjusted for clinical covariates including eGFR. Biomarkers were examined using cohort medians as prespecified cut points.

Results: Median follow-up was 1.8 years (interquartile range [IQR] 1.1-2.0); the primary endpoint occurred in 27/191 (14.1%). NAG showed no correlation with eGFR (r = -0.03, p = 0.68), whereas β2-microglobulin and α1-microglobulin correlated inversely with eGFR (r = -0.27, p = 0.002; r = -0.34, p < 0.001); L-FABP was not correlated (r = -0.09, p = 0.21). Patients above the cohort median for NAG (6.8 IU/L) experienced higher 2-year event rates, with early separation of Kaplan-Meier curves (log-rank p = 0.02). In adjusted models, both high NAG (hazard ratio [HR] 2.63, 95% confidence interval (CI) 1.17-6.46; p = 0.02) and high L-FABP (HR 2.48, 95% CI 1.08-6.16; p = 0.03) remained independently associated with the primary endpoint, whereas β2-microglobulin and α1-microglobulin were not. Creatinine and eGFR were comparable across NAG strata; renal composite events were higher in the high-NAG group but did not reach statistical significance.

Conclusion: A single urinary NAG and L-FABP measurement within 24 hours post TAVI identified increased 2-year risk of death or heart-failure hospitalization despite preserved filtration indices. Although limited by sample size and single-center design, these pilot data support external validation and the evaluation of biomarker-guided surveillance and reno-protective strategies following TAVI.

Background: Diabetic kidney disease (DKD) remains the leading cause of chronic kidney disease (CKD) and kidney failure worldwide. Over the past three decades, management has evolved from strict glycemic and blood pressure control to targeted therapies that modify disease progression.

Summary: The DCCT/EDIC (1993) confirmed the impact of intensive glycemic and multifactorial risk factor management. But the early 1990s established the foundation of nephroprotective therapy with the Captopril trial (1993) in type 1 diabetes and subsequent IRMA-1 (2001), IDNT (2001), and the RENAAL (2001) studies established renin-angiotensin-system (RAAS) blockade as the first disease-specific therapy. More than a decade later, sodium-glucose cotransporter-2 (SGLT2) inhibitors transformed care, with EMPA-REG OUTCOME (2015) and CANVAS (2017) studies first demonstrating kidney benefits as secondary outcomes, which were confirmed in subsequent dedicated kidney trials: CREDENCE (2019), DAPA-CKD (2020), and EMPA-KIDNEY (2022) studies, demonstrating consistent reductions in kidney failure and cardiovascular mortality. Finerenone further advanced outcomes in FIDELIO-DKD (2020) and FIGARO-DKD (2021), and combination therapy with SGLT2 inhibition showed additive benefit in the CONFIDENCE (2025) study. Most recently, the FLOW (2024) trial confirmed glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as promising fourth pillar of nephroprotective therapies.

Key messages: Together, these advances, termed the "Fantastic Four", have redefined standards of care in DKD. This review synthesizes pivotal clinical trials and highlights evolving strategies to guide individualized treatment and future research.

Introduction: Guidelines recommend oral hydration (OH) to prevent contrast-associated acute kidney injury (CA-AKI) after coronary angiography or intervention, but quantitative protocols are lacking, and practice varies. Shorter hospital stays limit opportunities for post-procedure creatinine monitoring, and real-world OH patterns and their early renal effects remain poorly described. This study aimed to characterize periprocedural weight-adjusted OH trajectories and to assess whether trajectory membership was associated with a change in serum creatinine within 24 h.

Methods: This single-center prospective cohort study enrolled 192 inpatients undergoing coronary angiography or intervention between November 2024 and May 2025. We recorded weight-adjusted oral intake in four windows: pre-12 h, post-0-6 h, 6-12 h, and 12-24 h. We computed partial-overlap dynamic time warping distances and clustered trajectories using partitioning around medoids. Group comparisons used nonparametric tests. The primary outcome was percent change in serum creatinine, and dose-response was assessed with generalized additive models (GAMs) adjusted for baseline creatinine, estimated glomerular filtration rate, comorbidities, procedural indication, contrast volume, and intravenous hydration.

Results: After excluding 18 patients for missing periprocedural oral intake or post-procedure creatinine, 174 patients were analyzed (median age 65.0 years, IQR 57.2 to 72.0; 71.8% male). Median weight-adjusted cumulative oral intake was 10.9, 18.6, 23.9, and 33.3 mL/kg for the pre-12 h, post-0-6 h, 0-12 h, and 0-24 h windows. Time-series clustering produced two stable groups (low-OH n = 85, high-OH n = 89; average silhouette = 0.393; bootstrap adjusted Rand index = 0.845). The largest between-group difference occurred in the 0-6 h window (median 4.12 vs. 2.00 mL/kg/h, p < 0.001). No patient met CA-AKI criteria. In adjusted GAMs, the 0-6 h OH rate was not a significant smooth term (edf = 3.79, p = 0.795), and cluster membership was not associated with creatinine change. However, the high-OH cluster had substantially greater 6-h urine output and a larger positive fluid balance (p < 0.001), while serum potassium was similar between clusters.

Conclusion: Periprocedural OH was generally ample and formed two reproducible patterns. Concentrating oral intake in the first 6 h increased early urine output and positive fluid balance but did not show a significant dose-response association with early serum creatinine change. This null result should be interpreted cautiously because the cohort was generally low-risk, follow-up was short, and the study had limited power. Future studies should validate whether early concentrated OH protects renal function using earlier sensitive biomarkers and by targeting high-risk patients.

Background: Stroke remains a leading cause of death and disability worldwide. Although individuals in cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 have not yet experienced overt clinical events such as stroke, mounting evidence suggests that these stages often involve subclinical metabolic and vascular injury. Insulin resistance (IR), a hallmark of CKM syndrome, contributes to cerebrovascular injury via mechanisms such as inflammation, oxidative stress, and endothelial dysfunction. The estimated glucose disposal rate (eGDR), a noninvasive index of IR, has shown cardiovascular prognostic value, yet its utility in predicting stroke across early CKM stages remains unclear.

Methods: This study analyzed 4,065 participants from the China Health and Retirement Longitudinal Study (CHARLS) classified as CKM stages 0-3. The eGDR was computed using waist circumference, HbA1c, and hypertension status. K-means clustering identified four longitudinal eGDR changes. Restricted cubic spline (RCS) models were used to determine stage-specific eGDR thresholds for stroke prediction. Cox regression assessed associations between baseline, cumulative, and dynamic eGDR with stroke incidence, while subgroup analyses also employed.

Results: During follow-up, 383 incident stroke cases were observed. Lower baseline and cumulative eGDR levels were independently associated with higher stroke risk. Participants with persistently low or sharply declining eGDR group exhibited more than double the stroke risk compared to those with stable high eGDR. The RCS analysis confirmed a linear inverse association between cumulative eGDR and stroke in CKM stages 2-3 and identified optimal thresholds that maximized sensitivity and specificity. Notably, stage 2 presented the lowest threshold (7.41), potentially reflecting a critical tipping point where metabolic burden exceeds vascular compensation.

Conclusion: eGDR is a clinically relevant predictor of stroke in asymptomatic individuals with CKM syndrome. The application of stage-specific thresholds enhances the precision of early risk stratification and highlights the need for tailored surveillance strategies. These findings suggest the potential value of eGDR monitoring as a practical tool for early risk stratification in metabolically at-risk populations.

Background: Systemic inflammation (SI) contributes to increased cardiovascular risk in patients with atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD). We assessed clinical perceptions toward SI and usage of high-sensitivity C-reactive protein (hsCRP) among nephrologists.

Methods: FLAME-ASCVD Nephro was an online survey of nephrologists from 10 countries who treat ≥20 patients with ASCVD and CKD a month and were practicing for ≥3 years. Results were analyzed using descriptive statistics.

Results: Of 513 nephrologists who responded, 300 completed and were included in the survey; the mean age was 46 years and the mean time in practice was 16 years. Hypertension (89%), overweight/obesity (81%), and CKD (80%) were the ASCVD risk factors most often discussed with patients (SI was ninth). The most common unmet needs (ranked 1-3) for patients with ASCVD and CKD were "lack of effective SI treatment options" (44%), "limited awareness of the role of SI in ASCVD" (35%), and "higher risk of CV events" (33%). Seventy-four percent of nephrologists wanted to learn more about the role of SI in ASCVD and 71% test for and use SI results when determining management approaches. Seventy percent of nephrologists considered hsCRP testing in patients with ASCVD and CKD (aided), and proven clinical efficacy of hsCRP was the top reason (37%); out-of-pocket cost (30%) was the most common reason for not considering hsCRP testing.

Conclusion: Lack of effective treatment options for SI remains the most common unmet need for patients with ASCVD and CKD. Further medical education is needed to raise awareness among nephrologists about the role of SI and hsCRP testing.