Baseline eGFR Research Articles

Abstract 4134949: Effect of anakinra in patients with ST-elevation myocardial infarction according to the renal function

Introduction: Interleukin(IL)-1 blockade with anakinra dampens the inflammatory response and prevents heart failure (HF) events in patients with ST-elevation myocardial infarction (STEMI). The efficacy of anakinra according to the baseline renal function in STEMI has not been addressed. Hypothesis: The efficacy of anakinra is independent of the baseline renal function. Aim: To determine the effect of anakinra according to the baseline renal function in patients with STEMI. Methods: We pooled patients with STEMI from 3 double-blind randomized clinical trials. Patients with estimated glomerular filtration rate (eGFR) <15 mL/min/1.73m2 were excluded. We divided the cohort based on the median baseline eGFR using the modified 2021 CKD-EPI equation (≥ or < 86 mL/min/1.73m2). We analyzed the area-under-the-curve for C-reactive protein (AUC-CRP) at 14 days, and the incidence of the composite outcome of all-cause death or new-onset HF at 1 year using the Log-rank test. We also evaluated the creatinine changes at 48-72 hours after percutaneous coronary intervention (PCI). Results: We analyzed 139 patients, 110 (79%) males, 52 (37%) Black or African-American, with a median age of 56 [49–63] years. The AUC-CRP at 14 days was significantly higher in patients receiving placebo vs. anakinra both in those with eGFR <86 mL/min/1.73m2 (250.5[131.4-512.0] vs. 66.4[42.3-126.5] mg●day/L, p<0.001) and those with eGFR ≥86 mL/min/1.73m2 (214.2[113.6-303.4] vs. 86.4[35.9-194.3] mg●day/L, p<0.01). Anakinra significantly reduced the composite outcome of all-cause death or new-onset HF in patients with baseline eGFR <86 mL/min/1.73m2 (4/41 [9.8%] vs. 9/27 [33.3%], Log-rank p=0.024) as well as in patients with baseline eGFR ≥86 mL/min/1.73m2 (3/43 [6.9%] vs. 7/28 [25%], Log-rank p=0.038)(p=0.97 for interaction)(Figure). No differences in creatinine changes 48-72 hours after PCI were observed (0.01 [-0.10 to 0.15] mg/dL in anakinra vs. 0.01[-0.08 to 0.14] mg/dL in placebo; p=0.80). Conclusion: In a cohort of patients with STEMI and mainly preserved or mildly reduced renal function, IL-1 blockade with anakinra blunts the acute inflammatory response and prevents all-cause death or new-onset HF at 1 year independent of baseline renal function.

Association of lower serum sclerostin levels with elevated risk for increased arterial stiffness: The JPOS Cohort Study.

Studies on the relationship between serum sclerostin, a Wnt/β-catenin pathway inhibitor, and atherosclerosis have yielded inconsistent results. We aim to longitudinally investigate the relationship between serum sclerostin levels and the risk of increased arterial stiffness in Japanese community-dwelling women. Of 1044 women aged ≥50 years whose brachial-ankle pulse wave velocity (baPWV) value was available in a baseline survey in 2011-2012, we excluded 374 whose baPWVs were ≥1800 cm/s, set as the cutoff for increased arterial stiffness, and eight with missing data. Of the remaining 662 women, we included in the analysis 556 followed in the 4- to 5-year follow-up study. The coefficient of variation of the sclerostin measurement was 3.45%. We obtained odds ratios (ORs) for sclerostin at baseline categorized by tertiles, with the high tertile as reference for increased arterial stiffness. Ninety-four women showed increased arterial stiffness during a mean follow-up of 4.0 years. The increased arterial stiffness rates in the low, medium, and high tertiles were 22.2%, 16.1%, and 12.4%, respectively (trend test p = 0.013). The ORs for the medium and low tertiles for increased arterial stiffness were 1.58 (p = 0.205) and 2.16 (p = 0.027), respectively, after adjusting for age and baseline baPWV. After further adjustment for baseline BMI, hypertension, hyperlipidemia, diabetes mellitus, eGFR, and BMC at whole body, the ORs for the medium and low tertiles were 1.65 (p = 0.181) and 2.50 (p = 0.014), respectively. Lower serum sclerostin levels were associated with elevated risks for increased arterial stiffness in Japanese community-dwelling women.

Abstract 4114406: Galectin-3 and Progression of Kidney Disease in Patients With Type 2 Diabetes Mellitus: Analyses From the DECLARE-TIMI 58 Trial

Background: Galectin-3 (Gal-3) is a circulating biomarker of fibrosis, with higher levels having been associated with an increased risk of progression of kidney disease. Patients with type 2 diabetes mellitus (T2DM) are at increased risk for kidney disease with fibrosis. Aims: To study the association of Gal-3 with chronic kidney disease progression, and the effect of the SGLT2-inhibitor dapagliflozin in pts with T2DM. Methods: DECLARE-TIMI 58 was a randomized, placebo-controlled trial of dapagliflozin in pts with T2DM with or at high risk for atherosclerotic cardiovascular (CV) disease and creatinine clearance ≥60ml/min. In a nested biomarker substudy, Gal-3 was measured at baseline (Alinity, Abbott Diagnostics) in the TIMI Clinical Trials Laboratory (Boston, MA). The prespecified kidney-specific composite endpoint (Kidney-EP) was a sustained ≥40% decrease in eGFR to <60 mL/min, initiation of renal replacement therapy or confirmed sustained eGFR <15 mL/min, or adjudicated renal death. Cox models were adjusted for baseline eGFR, urine albumin-creatinine ratio (UACR), patient characteristics, CV risk factors, NTproBNP and hs-cTnT. Results: Among 14,530 pts, median Gal-3 was 14.9 ng/mL [IQR, 11.9, 18.4]. Gal-3 was weakly associated with UACR (r = 0.098, p < 0.0001) and eGFR (r = -0.27, p<0.001) at baseline. Gal-3 was independently associated with the incidence of the Kidney-EP (adj-HR 1.15 [95% CI 1.03, 1.28] per 1-SD log(Gal-3), p = 0.013). Upon stratification by quartiles, there was a gradient of higher adjusted risk of the Kidney-EP with higher Gal-3 ( Fig., A ; p-trend <0.0001). There were 111 (1.5%) and 203 (2,8%) Kidney-EPs in the dapagliflozin and placebo groups, respectively. Dapagliflozin significantly and similarly reduced the relative risk of the Kidney-EP across quartiles of Gal-3 (overall HR 0.45 [95%CI 0.23, 0.85], p<0.0001; p-interaction = 0.97, Fig., B ). However, there was greater absolute benefit of dapagliflozin with higher Gal-3 (ARR Q4 1.9 [95% CI 0.6, 3.2] vs. Q1 0.6% [-0.1, 1.3], ARR p-trend 0.048). Conclusion: Plasma Gal-3 is associated with progression of kidney dysfunction in patients with T2DM independently of patient characteristics, including baseline kidney function. Moreover, Gal-3 identified an increasing gradient of absolute benefit of dapagliflozin for reducing kidney disease progression.

Chronic kidney disease in patients with psoriatic arthritis: a cohort study

ObjectivesChronic kidney disease (CKD) is a comorbidity in psoriatic arthritis (PsA). We aimed to define the prevalence of CKD in patients with PsA, describe their long-term renal outcomes and identify...

Acute kidney injury predicts the risk of adverse cardio renal events and all cause death in southeast Asian people with type 2 diabetes

Patients with diabetes are susceptible to acute kidney injury (AKI) as compared to counterparts without diabetes. However, data on the long-term clinical outcome of AKI specifically in people with diabetes are still scarce. We sought to study risk factors for and adverse cardio-renal outcomes of AKI in multi-ethnic Southeast Asian people with type 2 diabetes. 1684 participants with type 2 diabetes from a regional hospital were followed an average of 4.2 (SD 2.0) years. Risks for end stage kidney disease (ESKD), major adverse cardiovascular events (MACE) and all-cause death after AKI were assessed by survival analyses. 219 participants experienced at least one AKI episode. Age, cardiovascular disease history, minor ethnicity, diuretics usage, HbA1c, baseline eGFR and albuminuria independently predicted risk for AKI with good discrimination. Compared to those without AKI, participants with any AKI episode had a significantly high risk for ESKD, MACE and all-cause death after adjustment for multiple risk factors including baseline eGFR and albuminuria. Even AKI defined by a mild serum creatinine elevation (0.3 mg/dL) was independently associated with a significantly high risk for premature death. Therefore, individuals with diabetes and any episode of AKI deserve intensive surveillance for cardio-renal dysfunction.

Risk factors for occurrence and death of sepsis-associated acute kidney injury in children with sepsis

IntroductionThe 28th Acute Disease Quality Initiative (ADQI) Workgroup proposed the first international consensus on definition of SA-AKI in June 2023. The incidence and mortality of ADQI-defined SA-AKI in septic children is unknown, and the risk factors for the occurrence and death of SA-AKI is unexplored. MethodsWe conducted a retrospective study of septic children between January 1, 2018 and December 31, 2022. Logistic regression analysis was used to identify risk factors for SA-AKI. COX proportional hazards regression analysis was utilized for analyzing the risk factors for 30-day mortality in SA-AKI and septic children. Results221 children were included, of which 81 (36.7 %) developed SA-AKI, with 25.9 % developed into acute kidney disease. Older age, lower baseline eGFR and mechanical ventilation were independently associated with SA-AKI (P < 0.001, P < 0.01 and P < 0.05 respectively). Among the 81 SA-AKI children, 32.1 % died within 30 days from sepsis diagnosis, with higher mortality in children with late SA-AKI than early SA-AKI (72.2 % versus 20.6 %, P < 0.001). Septic shock was independently associated with 30-day death in SA-AKI children (P < 0.05). The overall 30-day mortality of septic children was 19.0 %, with mechanical ventilation, SA-AKI, and septic shock identified as independently associated with 30-day death (P < 0.001, P < 0.05 and P < 0.001 respectively). ConclusionsSA-AKI is of high incidence and mortality in septic children. Older age, lower baseline eGFR and mechanical ventilation were independent risk factors for SA-AKI. SA-AKI was independently associated with 30-day mortality in septic children.

Myocardial work assessment to improve baseline risk stratification in patients with transthyretin amyloidosis

BackgroundCardiac transthyretin (ATTR) amyloidosis is an often underdiagnosed and potentially fatal disorder associated with poor survival. The National Amyloidosis Centre (NAC) staging system, based on NT-proBNP level and eGFR value, discriminates patients according to survival rates. However, NAC stage II involves a heterogenous group of patients with variable prognosis. This retrospective single-center study was set up to explore the potential role of myocardial work (MW) analysis to enhance risk stratification of ATTR patients prior to therapy. Methods and Results37 patients diagnosed with ATTR between March 2021 and August 2023 were included. Baseline NT-proBNP and eGFR values were collected and LVEF, GLS and MW parameters were obtained from stored echocardiographic images. Patients were categorized per NAC stage (16 NAC I, 13 NAC II and 8 NAC III). Whereas the survival rate in NAC II and NAC III was significantly worse than in NAC I (p = 0.031 and p = 0.045 respectively), no significant difference was found between NAC II and III. In the ROC analysis, GCW proved to be the best survival predictor (AUC: 0.7) with optimal cut-off value 1294 mmHg%. Patients from NAC stage II were re-stratified according to GCW cut-off into HIGH RISK together with patients from NAC III or LOW RISK together with patients from NAC I. Patients in the HIGH RISK group exhibited a significantly worse prognosis with only 40 % survival at 2 years follow-up. ConclusionOur results demonstrate the advantages of incorporating MW analysis, particularly the use of a GCW cut-off, in the baseline risk stratification of ATTR patients.

The prognostic role of activation of the complement pathways in the progression of advanced IgA nephropathy to end-stage renal disease

IntroductionThe role of complement system in late stage of IgA nephropathy (IgAN) remains unknown. We therefore investigated the effects of complement system on worsening kidney function in advanced (stage 4 CKD) IgAN.MethodsRenal specimens of 69 IgAN patients who underwent renal biopsy during stage 4 CKD between 2010 and 2021, were stained using immunofluorescence (IF) and immunohistochemistry (IHC) for glomerular complement components. The primary outcome was progression to end-stage renal disease (ESRD). Associations of complement components with baseline clinicopathological characteristics and outcomes were assessed using multivariable Cox regression and Spearman analyses.ResultsDuring a median follow-up of 18.0 months, 26 (37.7%) patients progressed to ESRD and none died. C1q and C3 deposition were detected in 12 and 66 patients, respectively. Higher eGFR [hazards ratio (HR), 0.852, 95% confidence interval (CI), 0.756–0.959; P = 0.008], higher C3 intensity (HR, 2.955, 95%CI, 1.063–8.220; P = 0.038) and T1-2 score (HR, 2.576, 95%CI, 1.205–5.576, P = 0.015) were predictive of time to ESRD in CKD 4 stage IgAN. Significant expressions of C1q (P = 0.005), C4d (P < 0.001), factor B (P < 0.001), C3 (P = 0.042) and C5b-9 (P = 0.004) were identified in ESRD group than in non-ESRD group by IHC, while MBL expression was low. Although they were not associated with baseline 24 h-UP, higher factor B and C1q expressions were both correlated with a lower baseline eGFR (P < 0.001 and = 0.04, respectively) and the deterioration of kidney function during follow-up (P = 0.046 and 0.015, respectively).ConclusionComplement deposition in IgAN patients with stage 4 CKD portends a faster deterioration of kidney function. Activation of classical and alternative complement pathways plays a major role in this stage.

The safety of in-hospital initiation of SGLT2 inhibitor with MRA therapy in patients hospitalized for heart failure with a reduced left ventricular ejection fraction and chronic kidney disease

Abstract Deferring in-hospital initiation of guideline-recommended medications in HFrEF has a few chances they will be initiated ambulatory, especially in the case of coexisting HFrEF and chronic kidney disease (CKD). The aim was to investigate the safety of in-hospital initiation of SGLT2i with MRA therapy for patients hospitalized for HFrEF and CKD 3. Methods 88 patients with HFrEF (on top of standard therapy ACE-I/ARB, B-blockers) and CKD (baseline eGFR between 30 and 60 ml/min) were included in the study. The potassium (K), creatinine (C), uric acid (UA) levels were estimated at baseline and week 12. After biochemical evaluation, patients started on spironolactone (SP) treatment with a median dose of 20 mg daily (titrated) and dapagliflozin (D) with a dose of 10 mg daily (D+SP). Blood pressure (BP), K, and renal function (RF) were checked at weeks 1 (in-hospital), 2, 4, 6, 8, 12 (ambulatory), and more frequently as necessary. Results After the start of therapy D+SP mean eGFR decreased significantly at week 1 from 51.14±9.18 to 46.26±7.91 ml/min/1.73m2 (P&amp;lt;.0001) and at week 2 to 44.18±6.51 ml/min/1.73m2 (-2.08±1.2; P&amp;lt;.001). At week 4 mean eGFR decreased to 42.73±6.86 ml/min/1.73m2 (-1.45±1.1; P&amp;lt;.05). So, a significant decrease in eGFR was observed only during the first month with no significant decrease at 6 and 12 weeks after the start of therapy. Six patients (8%) experienced a significant decline in RF resulting in temporary withdrawal of SP. At week 2 mean K level increased significantly from 4.56±0.63 to 5.07±0.57 mmol/L (P&amp;lt;.001). At weeks 4, 6, 8 K levels remain stable. At week 12 mean K level decreased significantly compared with week 2 (to 4.92±0.57 mmol/L, P&amp;lt;.05). The incidences of severe hyperkalemia (HK) (K+≥6.0mmol/L) were in three patients &amp;lt; 2 %, and moderate HK (K 5.5–5.9 mmol/L) occurred in ten patients (11 %). Patients who experienced inpatient hyperkalemia had a significantly lower eGFR than patients without episodes of HK (38.70 vs. 55.21 mL/min/1.73 m2; P&amp;lt;.0001). Episodes of HK were predicted by baseline K≥5.0 mmol/L and eGFR≤40 ml/min/1.73m2. Additionally, there was a significant improvement in blood UA (-1,53±0.49 mg/dL, P&amp;lt;.01). By multivariate analysis older age, diabetes, low diastolic BP (&amp;lt;60 mm Hg), eGFR≤40 ml/min/1.73m2 at baseline were associated with decreased RF (0.378, P&amp;lt;.01; 0.632, P&amp;lt;.001; 0.771, P&amp;lt;.0001; 0.397, P&amp;lt;.01; respectively), whereas episodes of HK were predicted by baseline K≥5.0 mmol/L and eGFR≤40 ml/min/1.73m2 (0.785, P&amp;lt;.0001; 0.542, P&amp;lt;.001; respectively). Conclusion Initiation of SGLT2i with MRA in patients hospitalized for HFrEF and CKD 3 was mainly safe although it caused an early drop in eGFR. Importantly, a fall in eGFR was observed during the first month. Concern about the reduction in eGFR should be in older diabetic patients with eGFR≤40 and low diastolic blood pressure. Although hyperkalemia was common, the occurrence of it was predicted by baseline potassium level and eGFR.

Natriuretic peptides, kidney function and clinical outcomes in heart failure with mildly reduced or preserved ejection fraction: pooled data from the I-PRESERVE, TOPCAT, PARAGON and DELIVER trials

Abstract Background The prognostic utility of N-terminal pro-B-type (NT-proBNP) in patients with heart failure and chronic kidney disease (CKD) is incompletely understood since elevations in NT-proBNP could be related either to decreased clearance by the kidney or to increased severity of structural heart disease. Purpose We sought to assess the association of NT-proBNP with cardiovascular and mortality outcomes in patients with heart failure and mildly reduced or preserved ejection fraction, stratified by baseline kidney function. Methods We conducted a pooled analysis of individual participants with NT-proBNP and estimated glomerular filtration rate (eGFR) measured at baseline in the I-PRESERVE, TOPCAT (Americas region), PARAGON and DELIVER trials. We evaluated the relationship between NT-proBNP and kidney function using piecewise linear regression. Using multivariable Cox and Poisson regression models, we assessed the association of NT-proBNP with clinical outcomes across different levels of eGFR (≥60, 45-&amp;lt;60 and &amp;lt;45 mL/min/1.73m2). The primary outcome was hospitalisation for heart failure or cardiovascular death. Results Among 14,831 participants (mean age 72.1 years, 50.3% female, mean eGFR 63.3 mL/min/1.73m2 and median NT-proBNP 840 pg/mL) followed for a median 33.5 months, there were 3,092 primary outcomes, 2,184 heart failure hospitalisations, 1,465 cardiovascular and 1,049 non-cardiovascular deaths. Participants in lower eGFR categories were more likely to be older, female, and have atrial fibrillation and diabetes (all p&amp;lt;0.001). NT-proBNP levels increased by 9%, 8%, and 23% per 10 mL/min/1.73m2 lower eGFR in patients with baseline eGFR ≥60, 45-60, and &amp;lt;45 mL/min/1.73m2, respectively (P for non-linearity &amp;lt;0.001). For any given NT-proBNP concentration, participants with eGFR &amp;lt;45 mL/min/1.73m2 were at highest risk (Figure 1). Each doubling in NT-proBNP was associated with a 37% relative increase in the primary outcome (HR 1.37, 95% CI 1.34-1.41), consistent across different eGFR categories (P-interaction=0.42). Association between NT-proBNP and other clinical outcomes were also consistent across different levels of kidney function (all P-interaction&amp;gt;0.3; Figure 1). Equivalent risk for the primary outcome was apparent at NT-proBNP levels approximately 2.5- to 3.5-fold lower in patients eGFR &amp;lt;45 mL/min/1.73m2, compared to those with eGFR ≥60 mL/min/1.73m2. (Figure 2). Conclusion NTproBNP is a potent predictor of risk in patients with heart failure with mildly reduced or preserved ejection fraction across the spectrum of kidney function. However, in patients with reduced kidney function, lower NT-proBNP levels confer absolute risk of cardiovascular outcomes similar to substantially higher NT-proBNP levels in patients with normal kidney function. Accordingly, interpretation of NTproBNP levels should vary according to kidney function, particularly in those with eGFR &amp;lt;45 mL/min/1.73m2.

Mildly decreased egfr modifies the association between uric acid and risk of kidney function decline: a 5-year population-based cohort study

Abstract Background the role of uric acid (UA) in chronic kidney disease (CKD) remains controversial. In this study, the effects of UA levels on risk of kidney function (KF) decline in patients with normal or mildly decreased KF at baseline were investigated. Methods Data were extracted from the community-based Tongzhou Cohort Study. The cohort of 4246 patients was divided into the normal KF group (estimated glomerular filtration rate [eGFR] ≥ 90 mL/min/1.73 m2) or mildly decreased KF group (60 ≤ eGFR &amp;lt; 90 mL/min/1.73 m2). The primary endpoint was the risk of kidney function decline, which defined as a composite of a ≥ 30% decrease in eGFR from baseline or new onset of CKD diagnosed during the annual checkups. Results A total of 284 participants reached the primary endpoint during the 5-year follow-up period. There was a significant interaction between UA levels and baseline eGFR (p &amp;lt; 0.001). Restricted cubic spline analysis revealed a U-shaped association between baseline UA levels and the risk of decreased KF for participants with normal KF (cut-off value = 5.0 mg/dL; pnonlinear = 0.025) and a linear association for participants with mildly decreased KF (pnonlinear = 0.384). The odds ratio of an increase in UA levels by 1 mg/dL was 1.15 [95% confidence interval (CI) 1.02–1.31, p = 0.028] for the primary endpoint and 1.15 (95% CI = 1.01–1.31, p = 0.037) for new onset of CKD for participants with mildly decreased KF. Conclusion The association between uric acid and risk of KF decline was U-shaped in participants with normal KF while linear in participants with mildly decreased KF.

A larger reduction of spatial mean QRS-T angle during cardiac resynchronisation therapy is associated with a lower risk of mortality and heart failure hospitalisation

Abstract Background Predicting clinical outcome in heart failure patients undergoing cardiac resynchronization therapy (CRT) remains challenging, necessitating improved risk stratification for CRT recipients. Previous studies have shown an association between large spatial peak and mean QRS-T angles and cardiovascular disease. Little is known, however, about their relation to clinical outcome following CRT. Purpose To investigate the association between spatial peak and mean QRS-T angles and long-term clinical outcome following CRT initiation. Methods All patients with native LBBB receiving CRT at a large-volume tertiary care center between 2015 and 2020 were retrospectively evaluated. Spatial peak and mean QRS-T angles were derived from digital pre- and post-CRT 12-lead ECGs that were processed using Glasgow algorithm and Kors’ regression transformation. The QRS-T angles and their change after CRT were analyzed in relation to the primary composite endpoint of heart failure hospitalisation or all-cause mortality using Cox regression analysis adjusted for clinical covariates (age, gender, CRT-P or CRT-D, secondary ICD indication, ischemic etiology, NYHA class, LVEF, diabetes, atrial fibrillation, baseline QRS duration, NT-proBNP, and eGFR). Results The study group comprised 250 patients (a median age [Q1–Q3] of 72.2 years [64.5–76.3]; 22% female; 58% New York Heart Association (NYHA) class III-IV; LVEF 27% [22–30]) who were followed over a median follow-up time of 4.5 years [3.2–5.8] after CRT implantation. The median post-CRT spatial peak and mean QRS-angles were 142° [116–160] and 152° [127–166], and the median angle was decreased by 16° [-0.6–41] and 14° [-0.4–38], respectively. Both a larger post-CRT mean QRS-T angle (HR 1.20, 95%CI 1.08-1.33, p=&amp;lt;.001) and peak QRS-T angle (HR 1.08, 95%CI 1.01-1.17, p=0.046) were associated with the primary endpoint. A larger reduction of mean QRS-T angle, but not peak QRS-T angle, was associated with a risk reduction (HR 0.87, 95%CI 0.79-0.95, p&amp;lt;0.003). In Kaplan-Meier analysis, patients with a post-CRT mean QRS-T angle above median had a higher risk of reaching the endpoint (log-rank p=0.002, Figure 1). Conclusion Our results show that a larger magnitude of the post-CRT spatial peak and mean QRS-T angles, and a larger reduction of the latter, are associated with long-term heart failure hospitalisation and death. These findings suggest that spatial QRS-T angle may have a potential role in refined risk stratification of CRT patients.Figure 1.K-M curve spatial mean QRS-T

Systemic inflammation in patients with atherosclerotic cardiovascular and chronic kidney disease in Spain: a population-based study using electronic medical records from a primary care database

Abstract Background Systemic inflammation (SI) is recognized as a critical driver of atherosclerotic cardiovascular disease (ASCVD), and it is frequently observed in ASCVD patients with comorbid chronic kidney disease (CKD). Elevated C-reactive protein (CRP) levels, a common biomarker for SI, have been associated with poor prognosis in ASCVD and CKD patients, increased risk of major adverse cardiovascular events and renal disease progression, as well as greater mortality. Purpose To estimate the prevalence of SI in patients with ASCVD in Spain overall and by CKD status, and to describe patients’ clinical characteristics. Methods In this population-based observational study, data from THIN Spain, a database of electronic medical records from a large network of general practitioners, were used to identify adult patients with a diagnosis code of ASCVD (atherosclerotic coronary or cerebrovascular event, peripheral arterial disease, or other atherosclerotic vascular event) and ≥1 eligible CRP measurement between January 1st 2014 to July 31st 2023 (latest data available at time of data extraction).[Figure] SI was defined as CRP ≥ 2mg/L. Point prevalence of SI at the end of the study (among patients alive with ≥1 CRP in the prior 18 months) and the proportion of patients with evidence of SI during the study period (2014-2023) were estimated overall and by CKD status (defined as CKD stage 3+, or eGFR &amp;lt;60 mL/min/1.73m², or urinary albumin-to-creatinine ratio ≥30 mg/g). Patients’ comorbidities (defined using primary care diagnoses), and laboratory values were reported by SI status at first CRP measurement during the study period. Results Among 76,423 patients with ASCVD diagnosis, 15,798 patients (20.7%) were included in the study (mean age: 71.1 years; 43% females), of whom 5,111 (34%) had CKD at first eligible CRP (n=975 with unknown CKD status). Mean CRP in ASCVD patients with CKD was 24% higher than in those without CKD (4.36 vs 3.53 mg/L, p&amp;lt;0.001). The proportion of ASCVD patients with SI at first CRP measurement was 58% overall (65% among CKD patients; 55% among patients without CKD; p&amp;lt;0.001). The point prevalence of SI at the end of the study was 56% among ASCVD patients overall (62% among CKD patients; 52% among patients without CKD; p&amp;lt;0.001), while 64% of ASCVD patients had evidence of SI at any time during the study period (72% among CKD patients; 59% among patients without CKD; p&amp;lt;0.001). Compared to ASCVD patients without SI, higher proportion of SI patients were smokers and with comorbidities. Also, ASCVD patients with SI had lower baseline eGFR levels and higher levels of LDL-C and triglycerides than ASCVD patients without SI.[Table] Conclusions SI prevalence is high among patients with ASCVD in Spain, especially among patients with comorbid CKD. Strategies to target SI may have beneficial effects in prevention of cardiovascular events and mortality in ASCVD patients.

The very long-term risk of stroke after acute coronary syndrome and geographic differences. The ABC-10* study on heart disease

Abstract Background Little is known about the very long-term risk of stroke among acute coronary syndrome (ACS) survivors. Methods In this prospective study, we enrolled 535 ACS patients admitted to hospitals in three Italian provinces, discharged alive and followed for 24 years or death. The patient's residency was classified into three urban and three nearby rural areas. Results All patients completed the follow-up (6142 Perso-years). 85 (16%) patients suffered an acute stroke. Patients median age was 67 years, 70% were male, and 318 patients were residing in rural areas. Patients who had a stroke and those who had not shared most of the demographic and clinical characteristics. The incidence rate of overall stroke was 14/1000 person-year. Cox analyses showed older age (HR 3.13;95%CI 2.31-4.26), male gender (HR 1.88;95%CI 1.20-2.95), baseline diabetes (HR 2.25 95%CI 1.37-3.69), heart failure (HR 2.69;95%CI 1.71-4.24), and higher albumin/creatinine ratio (HR 1.75;95%CI 1.33-2.30) were all associated with an increased risk of stroke. while higher baseline eGFR, reperfusion, statin and beta-blockers treatment during follow-up were associated with a decreased risk; HR (0.55 (95%CI 0.42-0.72), 0.45(95%CI 0.29-0.71), 0.21(95%CI 0.13-0.34), and 0.37(95%CI 0.23-0.57), respectively). In the multivariate analysis, only older age (HR1.55;95%CI 1.08-2.21; p=0.02) was an independent predictor of stroke while statin treatment was independently associated with a lower risk (HR 0.35;95% CI 0.21-0.58; p&amp;lt;0.0001). However, all these variables did not predict the risk of stroke in competing risk regression analysis where death was treated as the competing event. A sub-analysis of the 43 patients who had a fatal stroke (FS) revealed 7/1000 person-year FS IR. The Cox regression and competing risk analyses of predictors of FS showed similar results. Interestingly, we observed an association between geographic areas of residence and the long-term FS risk as the risk increased going from rural to urban (HR 2.08;95%CI 1.14-3.80; p=0.02) areas and from north to middle and south provinces (HR 1.47;95%CI 1.00-2.15; p=0.04) in the univariate Cox regression analysis. Results kept true using multivariate Cox and Competing risk regression models. Conclusion This analysis reveals the significant urban-rural difference in the very long–term risk of fatal stroke among unselected ACS patients which highlights the importance of implementing a preventive policy based on area-specific knowledge.

Prediction of subsequent CKD according to eGFR decline slope varies by the presence of hypertension

Abstract Background We reported that a declining slope in eGFR evaluated from 3-year observation could predict subsequent CKD among the relatively healthy population, even adjusted for baseline eGFR. However, its certainty may vary depending on the presence of comorbidities such as diabetes and hypertension, which are also recognized as the risk factors of CKD. Methods Annual health check-up data from a Japanese company spanning from 2009 to 2022 was used. The analyses included participants having 4 times continuous eGFR measurements for 3 years, undergoing health checkups at least once during a follow-up period, with negative for urinary protein (UP), and non-diabetic. Individual ‘eGFR slopes’ were calculated by the regression line with 4 times eGFR measurements. Participants with slopes of &amp;lt; -5 per year were categorized as the “decreased” group and -5 or more were categorized as the “stable” group. The cases of positive UP or less than 45mL/min/1.73m2 in eGFR during a follow-up period were defined as CKD. Cox regression analyses adjusted for sex, age, and eGFR at baseline were performed to calculate the hazard ratios and 95% CIs for CKD in the decreased group (reference; stable), stratified by hypertension. Results Out of 5598 study participants(men 36%, mean age 48.2±10.1years, mean follow-up period 4.3 years), 260 CKD cases (4.6%) were observed. CKD cases accounted for 4.5% (235/5218) in the stable group and 6.6% (25/380) in the decreased group. Multivariate-adjusted hazard ratios [95%CIs] of CKD by eGFR decline was 1.50[0.99-2.27]. The eGFR decline increased the risk of CKD only in participants with hypertension (2.09[1.09-4.04]), but not in those without hypertension (1.25[0.73-2.13]). After excluding individuals with eGFR slopes exceeding 10 per year to consider for hyperfiltration of eGFR, the results were consistent. Conclusions The eGFR decline over a 3-year observation may predict subsequent CKD only in individuals with hypertension. Key messages • With a relatively short-term evaluation period of three years, eGFR decline can predict subsequent CKD only in hypertensive individuals. • In middle-aged hypertensive patients, it would be important for the prevention of CKD to pay attention not only to low eGFR but also to the progression of eGFR decline.

Association between change in serum uric acid and rapid decline in kidney function in China

While the elevation of serum uric acid (SUA) is acknowledged as a risk factor for chronic kidney disease, the independent extent to which variations in SUA levels are correlated with temporal changes in estimated glomerular filtration rate (eGFR) remains uncertain. In light of this uncertainty, our research endeavored to elucidate the temporal associations between change in SUA and rapid eGFR decline in China. In this longitudinal study of China’s middle-aged and elderly between 2011 and 2015, we analyzed 5421 individuals with complete SUA and eGFR data. Logistic regression was applied to evaluate the risk factors associated with a rapid eGFR decline (defined by a 5 mL/min/1.73 m2 decrease or falling to less than 15 mL/min/1.73 m2 by 2015), adjusted for age, gender, marital, residence, income, BMI, hypertension, diabetes, dyslipidemia, CRP, Hba1c, baseline eGFR and baseline SUA. Linear regression was used to evaluate the relationship between variations in SUA and changes in eGFR. After multivariable adjustments, the risk factors of a rapid eGFR decline included aging (OR per 1-year increase: 1.1, 95% CI 1.08–1.12, P < 0.001), being female, being single, having hypertension, a higher baseline eGFR, a higher baseline SUA (OR per-1 mg/dL increase: 1.68, 95% CI 1.48–1.90, P < 0.001), and increase in change in SUA (OR per-1 mg/ dL increase: 1.92,95% CI 1.71–2.16, P < 0.001). Pearson’s analysis showed a significant inverse correlation between SUA changes and eGFR decline, particularly pronounced in females, with correlation coefficients of − 0.349 for females and − 0.306 for males (95% CI − 0.347 to − 0.299, P < 0.001). A significant correlation was found between the change in SUA and the rapid decline in eGFR, with this association being particularly pronounced in females.

Risk of Postoperative Hypermagnesemia in Cardiopulmonary Bypass Assisted Cardiovascular Surgery.

Magnesium administration is a common practice in cardiovascular surgeries utilizing cardiopulmonary bypass (CPB). However, concerns persist regarding the risk of hypermagnesemia, particularly in patients with kidney dysfunction. This study aims to determine the incidence of postoperative hypermagnesemia in CPB-assisted cardiovascular surgeries and identify the associated risk factors. This was a retrospective cohort study conducted at a tertiary medical center. Data from adult patients undergoing open-heart surgery utilizing CPB between 2018 and 2020 were analyzed. Sociodemographic, perioperative, and clinical variables were collected from electronic medical records. Logistic regression was utilized to identify independent risk factors for hypermagnesemia. Of 278 patients analyzed, 53.2% developed postoperative hypermagnesemia (Mg ≥2.5 mg/dL). Mild hypermagnesemia (Mg 2.5-3.9 mg/dL) was most common, with no significant impact on clinical outcomes observed. Patients with hypermagnesemia were older, with higher comorbidity burdens and lower baseline estimated glomerular filtration rate (eGFR). Cardioplegic solutions with higher magnesium content and lower baseline eGFR were independently associated with hypermagnesemia (OR 64.3; 95% CI 12.9-501.1 and OR 1.3; 95% CI, 1.1-1.5 respectively). Notably, ultrafiltration on CPB was associated with low risk of hypermagnesemia (OR 0.4, 95% CI 0.1-1.0, P value 0.048). This study highlights the importance of mindful magnesium supplementation strategies in those with advanced kidney disease. Future large-scale prospective multicenter studies should validate these findings and explore the extended effects of hypermagnesemia on clinical outcomes in patients with advanced CKD undergoing CPB surgeries.

Risk Stratification for Chronic Kidney Disease After Liver Transplant for Metabolic Dysfunction-associated Steatohepatitis (MASH) Cirrhosis: Results From the NailMASH Consortium.

Chronic kidney disease (CKD) is a well-recognized complication in patients undergoing liver transplantation (LT), particularly those with metabolic dysfunction-associated steatohepatitis (MASH), a leading cause of cirrhosis in the modern era. This study sought to refine risk stratification for CKD events post-LT in cirrhosis patients with MASH by leveraging baseline renal function at transplant. A total of 717 MASH cirrhosis patients who had LT (1997-2017) at 7 US centers (NailMASH Consortium) were analyzed. Patients were categorized by estimated glomerular filtration rate (eGFR) at transplant: low (LGFR, eGFR ≤30 mL/min/1.73 m²), medium (MGFR, eGFR >30-≤60 mL/min/1.73 m²), and high (HGFR, eGFR >60 mL/min/1.73 m²). Time-related eGFR intercepts, slopes, and assessments of advanced-stage CKD (aCKD) events, defined as 2 eGFR levels <30 mL/min/1.73 m² separated by ≥90 d, were examined. Post-LT, LGFR group showed increased eGFR, whereas the HGFR group experienced a decline. The 3-mo mark was identified as a "reset point," signifying a new reference level, beyond which a different rate of decline was observed. After 3 mo, mean eGFRs of the LGFR group approached MGFRs, whereas the mean eGFR of the HGFR group continued to decrease but remained higher than other groups during a 60-mo follow-up. LGFR patients had significantly higher aCKD probability than MGFR and HGFR groups. Subanalysis at 3 mo post-LT revealed more aCKD events in the LGFR group compared with MGFR and HGFR groups (P < 0.0001). The study underscores renal impact of LT in MASH cirrhosis, indicating unique eGFR trajectories post-LT tied to baseline eGFR, with a reset point at 3 mo. Monitoring post-LT renal function, especially in those at aCKD risk, is crucial. Renal-sparing immunosuppression may help, regardless of baseline eGFR. Further studies are needed for interventions addressing renal dysfunction of patients with MASH post-LT.

Effective tricuspid regurgitation reduction is associated with renal improvement and reduced heart failure hospitalization.

Several studies have demonstrated an association between tricuspid regurgitation (TR) and organ dysfunction including hepatic and renal insufficiency. Improvement of liver function following transcatheter edge-to-edge repair (T-TEER) has already been linked to reduction of venous congestion due to TR reduction. This study analyzes whether TR-reduction using T-TEER is also associated with improved renal function. The TRIC-ULM registry includes 92 selected patients undergoing T-TEER between March 2017 and May 2023. Estimated glomerular filtration rate (eGFR) improvement was evident in 53 patients (57%) at 3-months follow-up (FU) and defined by FU eGFR > baseline eGFR. Median age was 80 [interquartile range 75-83] years, pre- and postinterventional TR grades were 4 [3-5] and 1 [1-2], baseline eGFR was 36 [30-53] ml/min and New Yeark Heart Association (NYHA) IV was evident in 15% of patients. Multiple logistic regression analysis revealed TR vena contracta reduction (Odds ratio (OR) 1.35 [95% CI: 1.12-1.64] per mm, p = 0.002) and reduced preinterventional tricuspid annular plane systolic excursion (TAPSE) [OR 0.89 (95% CI: 0.79-0.99) per mm, p = 0.033] to independently predict renal improvement at FU. An eGFR improvement threshold of >9 ml/min was associated with reduced 1-year heart failure hospitalization rates [adjusted hazard ratio 0.22 (95% CI: 0.07-0.62) p = 0.005]. Effective tricuspid edge-to-edge repair is associated with improved renal function and reduced heart failure hospitalization. In patients without renal improvement at 3-months follow-up, residual tricuspid regurgitation should be reevaluated for reintervention.

Renal Allograft Function and the Tacrolimus C/D Ratio: Insights from a Prospective Study on MeltDose Tacrolimus

Background: The tacrolimus concentration-to-dose (C/D) ratio is valuable for optimizing nephrotoxicity-related renal outcomes. Prospective data on the C/D ratio in kidney transplant recipients newly treated with MeltDose tacrolimus are limited. We analyzed the C/D ratio pattern of MeltDose tacrolimus and its effect on posttransplant renal function, comparing it with the literature data on immediate-release tacrolimus (IR-Tac). Methods: In total, 101 adult kidney transplant recipients on a standard immunosuppressive regimen including MeltDose tacrolimus were enrolled in this prospective, multicenter cohort study and followed for 12 months. The C/D ratio classified patients as fast, intermediate, or slow metabolizers. Renal function was assessed via the estimated glomerular filtration rate (eGFR). MeltDose tacrolimus data were compared with previous IR-Tac data by bootstrapping. Results: The cohort exhibited a right-skewed C/D ratio distribution with a mean of 2.12 ng/mL × 1/mg, which was significantly greater than the 1.29 mean for IR-Tac (p &lt; 0.001). Compared with fast metabolizers, slow metabolizers of MeltDose tacrolimus experienced greater eGFR gains at 6 months post-transplantation (median +7.9 vs. −3.6 mL/min; p = 0.005). A Bayesian linear mixed-effects model predicting the eGFR at month 12 identified the baseline eGFR, time from transplant, body mass index, and log-transformed C/D ratio as significant variables. A one-unit increase in the log-transformed C/D ratio corresponded to an approximate increase of 4.5 mL/min in the eGFR at month 12. Conclusions: Slow metabolizers of MeltDose tacrolimus had significantly better renal function outcomes than fast metabolizers. MeltDose tacrolimus is associated with slower metabolism than is IR-Tac, as evidenced by its higher C/D ratios.