Worse Renal Function Research Articles

Role of renal function in patients with advanced heart failure: insights from the help-hf registry

Abstract Background Chronic kidney disease (CKD) and heart failure (HF) strongly interact in determining patients prognosis. However, the prevalence and impact of CKD in advanced HF is still poorly characterized. Objective To determine the prevalence and prognostic impact of CKD and how estimated glomerular filtration rate (eGFR) might limit the use of guideline directed medical therapy in a large cohort of HF patients with at least one high-risk I NEED HELP marker. Methods 1120 patients enrolled in the HELP-HF registry were included in the analysis; eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration formula. Patients were stratified according to eGFR into three categories (> 60 ml/min, 30-60 ml/min, <30 ml/min). The primary endpoint was a composite of all-cause death and HF-hospitalization. Secondary endpoints were all-cause death, HF-hospitalization and cardiovascular death. Results 291 patients (25.98%) had an eGFR>60 ml/min, whereas 497 (44.37%) had eGFR between 30 and 60 ml/min and 332 (29.64%) had <30 ml/min. The risk of the primary endpoint was increased in patients with worse renal function (eGFR 30-60, HR 1.34, 95%CI 1.05-1.71, p = 0.017; eGFR<30, HR 1.88, 95%CI 1.47-2.42, p<0.001), whereas only patients with eGFR<30 ml/min demonstrated higher risk of all-cause death (HR = 2.36, 95%CI 1.68-3.31, p<0.001) and CV death (HR = 3.08, 95%CI 2.00-4.75, p<0.001). No difference in HF hospitalizations was seen with respect to patients with eGFR>60 ml/min. Once analyzed as a continuous variable, eGFR was significantly associated with each outcome. The impact of CKD was also confirmed in patients fulfilling the 2018 ESC-HFA definition of advanced HF. Logistic regression showed that patients with lower eGFR and with HF with reduced (HFrEF) and mildly reduced ejection fraction (HFmrEF) were less frequently discharged on maximal tolerated dose of mineral corticoid receptor antagonists (p= 0.001 for HrEF, p= 0.013 for HFmrEF), while lower eGFR was associated with less frequent use of maximal tolerated dose of a renin-angiotensin inhibitors (including angiotensin receptor-neprilysin inhibitors) only among patients with HFmrEF (p = 0.018). Conclusions Chronic kidney disease is highly prevalent among patients with advanced HF and impacts on patients’ prognosis and survival. The use of GDMT was significantly limited in patients with lower eGFR only in patients with HFrEF and HFmrEF.

Non-progressors to cardiac resynchronization therapy show long-term mortality benefit compared to progressors

Abstract Introduction Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in selected patients with symptomatic heart failure with reduced ejection fraction (HFrEF) and prolonged QRS. However, approximately one-third of the implanted patients fail to show clinical improvement or reverse remodeling. The criteria by response have been recently changed, those patients with a minimal improvement in left ventricular ejection fraction (LVEF) are defined as "non-progressors" rather than as "non-responders", selecting from those patients in whom the progression could not be modified. Data are scarce regarding the long-term outcome of this patient population. Purpose We aimed to evaluate the long-term outcome of CRT patients by their response, comparing non-progressors with responders and progressors. Methods Altogether 1019 patients undergoing CRT implantation between 2000-2020 in our center were registered and analyzed retrospectively. Patients were divided into 4 groups according to their response status, which was defined on the basis of LVEF change in 12 months after CRT implantation as follows: super-responders ≥20% (n=113), responders 6-19% (n=448), non-progressors 0-5% (n=244), and progressors <0% (n=214). The primary endpoint was the composite of all-cause mortality, heart transplantation, or left ventricular assist device implantation. Results During the median follow-up time of 4.7 years 547 (54%) patients died, 35 (31%) super-responder, 223 (50%) responder, 133 (55%) non-progressor, and 156 (73%) progressor. The mean change in LVEF occurred as follows: super-responders 24.5% ± 4.1%, responders 11.5% ± 3.8%, non-progressors 2.8% ± 1.8%, and progressors -6.6% ± 4.5% (p<0.0001). Non-progressors were more commonly male, had worse NYHA functional status, worse renal function, higher baseline LVEF and serum creatinine levels, and more frequently had an ischemic etiology. Univariate Cox regression analysis revealed that non-progressors had similar outcome to responders (HR 1.17; 95%CI 0.94-1.45; p=0.15) and superior outcome to progressors (HR 0.60; 95%CI 0.48-0.76; p<0.0001), which was also confirmed by multivariate analysis after adjustment for age, gender, ischemic etiology, LVEF, and serum creatinine levels: nonprogressors vs. responders (HR 1.25; 95%CI 0.98-1.58; p=0.07) and nonprogressors vs. progressors (HR 0.62; 95%CI 0.47-0.80; p<0.0001). Conclusions In our current study, non-progressors to CRT had a similar long-term outcome to responders and superior outcome to progressors. These findings suggest that non-progressor patients would have continued to adversely remodel without CRT and CRT is beneficial for these patients by moderating the remodeling process rather than improving it. Our results support the fact that categorizing patients as "responders" or "non-responders" is inappropriate and patients could be grouped as super-responders, responders, non-progressors, and progressors.Probability of survival by CRT responseMultivariate analysis by response status

ACUTE HF score predicts in-hospital mortality in patients with acute heart failure

Abstract Background ACUTE HF is a multiparametric score combining clinical, biochemical and echocardiographic indexes, which was developed and validated in different studies as prognostic tool in acute heart failure (HF) patients for the prediction of 30-days, 6-months and 5-years mortality after discharge. However, in these critical patients the prediction of in-hospital mortality may be fundamental to guide therapeutic management during hospital stay. Objective The aim of our study was to assess the prognostic value of ACUTE HF score for in-hospital mortality in an external cohort of patients hospitalized for acute HF. Methods Consecutive patients hospitalized for acute HF between 2020 and 2021 in our University Hospital were retrospectively enrolled. Patients with unclear diagnosis of de-novo, decompensated HF or HF reacutization were excluded. Clinical, biohumoral and echocardiographic data were collected. ACUTE HF score was calculated as : 1.4*[serum creatinine>2mg/dl]+0.8*[ejection fraction<30]+ 0.7*[age>76]+0.7*[prior hospitalization for AHF]+0.9*[prior stroke/transient ischemic attack]+0.5*[more than moderate mitral regurgitation]+0.8*[use of non-invasive ventilation]. Then, it was used to divide the population into three risk groups (low risk: ACUTE HF ≤1.5; intermediate risk: 1.5 Results Overall, 1291 patients were included in the present study (age=77±13 years, mean ejection fraction = 41 ± 13%). Median in-hospital follow up was 9 [6;15] days, during which 115 patients died. Patients who died during hospitalization were older, had worse renal function and higher mitral regurgitation severity, and more frequently had arterial hypertension, diabetes mellitus, chronic obstructive pulmonary disease and history of stroke. With ROC curves, it showed to be a good predictor of in-hospital mortality, with an AUC=0.66, which was even higher in patients with preserved ejection fraction (AUC=0.76, Fig.1). With multivariate analysis, ACUTE HF score showed to be a predictor of in-hospital mortality independent from arterial hypertension, diabetes mellitus, chronic kidney disease (OR = 1.5 [C.I. 1.22 – 1.81 each point increase]. Kaplan Meier analysis showed a good risk stratification of study cohort divided into 3 risk groups according to ACUTE HF (Fig.2) Conclusions ACUTE HF score is an independent and reliable predictor of in-hospital mortality in patients hospitalized for acute HF. After multiple external validation, considering its rapid and easy calculation, we suggest its use in the management algorithms of acute HF patients in daily clinical practice.Fig.1Fig.2

Prognostic implications of angiopoietin-2 in heart failure and the influence of empagliflozin: the EMPEROR program

Abstract Background Heart failure (HF) development and progression is associated with endothelial dysfunction, oxidative stress, and inflammation. The mechanisms involved in endothelial repair in HF are not fully understood. Emerging evidence suggests that angiopoietin-2 (Angpt2), a vascular destabilizing factor, may be related to outcome in HF. Aim To assess the association between Angpt2 and clinical outcomes in a pooled analysis of the EMPEROR-Reduced and EMPEROR-Preserved trials, and to evaluate if the response to empagliflozin therapy in HF is modulated by Angpt2 levels. Methods and results Angpt2 levels (ng/ml) were measured in serum samples from 1131 EMPEROR study participants by using Roche Cobas Elecsys assay, within biomarker research agreement between Boehringer Ingelheim and Roche Diagnostics International Ltd, at baseline, week 12 and week 52. Patients were divided into tertiles of baseline Angpt2 levels (<2.58 ng/mL; ≥2.58 ng/mL <4.71 ng/mL and ≥4.71 ng/mL). Patients in the highest tertile were more frequently white people, had a higher prevalence of New York Heart Association class III-IV symptoms, HF hospitalization within 12 months, obesity, diabetes, atrial fibrillation, elevated natriuretic peptides, worse renal function, and lower prevalence of coronary disease, compared to the lowest tertile (p<0.05 for all). Higher tertile at baseline was associated with increased risk for adverse HF and kidney events (Table 1). Empagliflozin treatment was associated with reduction of the serum Angpt2 versus placebo at week 12 (adjusted gMean 0.872 [0.828-0.917], p<0.0001) but not at week 52 (adjusted gMean ratio 0.946, [0.879-1.019], p=0.145). Empagliflozin significantly reduced the risk of hospitalization for HF and cardiovascular death particularly for patients with highest baseline Angpt2 levels (lowest tertile HR 1.21 [0.63-2.31]; middle tertile HR 0.65 [0.37-1.16]; highest tertile HR 0.64 [0.42-0.97], P-trend=0.139). Conclusion Higher Angpt2 levels at baseline were associated with more advanced HF and worse prognosis. Treatment with empagliflozin was associated with reduction of Angpt2 level at week 12. The benefit of empagliflozin on major HF events was consistent across baseline Angpt2 levels.Table 1

J-shaped association between serum uric acid levels and chronic kidney disease: a cross-sectional study using large health examination data

Abstract Introduction Hyperuricemia has been recognized as a risk for cardiovascular disease based on the results of many observational studies. On the other hand, a J-shaped association has been reported in which people with very low serum uric acid levels also have increased cardiovascular risk. Although renal dysfunction is closely associated with cardiovascular disease, there are no reports on whether serum uric acid levels and renal function show a J-shaped association. Hypouricemia, defined as a serum uric acid level of 2.0 mg/dL or less, is relatively common among Japanese, but the absence of symptoms and low prevalence (0.2% in men and 0.4% in women) have made epidemiological studies difficult. Therefore, we used the large-sized data from Japanese population that underwent health examinations and evaluated the association between serum uric acid levels and chronic kidney disease. Methods Data from 227,672 individuals (104,854 men and 122,818 women) who underwent health examinations between 2001 and 2018 were included. All analyses were performed separately for men and women because of sex differences in serum uric acid levels. Participants were classified according to serum uric acid (SUA) quartiles, with hypouricemia SUA below 2.0 mg/dL being classified as a separate category, resulting in five groups (men: ≤2.0, 2.1-5.1, 5.2-5.9, 6.0-6.8, ≥6.9 mg/dL; women: ≤2.0, 2.1-3.7, 3.8-4.4, 4.5-5.1, ≥5.2 mg/dL) to describe the characteristics. We defined chronic kidney disease (CKD) as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 and examined the association between SUA category and CKD by univariable and multivariable logistic regression analysis, which included age, BMI, alcohol intake, presence of hypertension, dyslipidemia, and diabetes as covariates. Results The characteristics of the population were as follows. Men: age 56 ± 15 years, SUA 5.9 ± 1.3 mg/dL, eGFR 80 ± 17 mL/min/1.73 m2, CKD 9.4%; women: age 57 ± 15 years, SUA 4.5 ± 1.1 mg/dL, eGFR 81 ± 18 mL/min/1.73m2, CKD 9.4%. The results of univariable and multivariable analyses of the association between SUA categories and CKD by gender are shown in Table. Compared to the reference group (men, SUA 2.1-5.1 mg/dL; women, SUA 2.1-3.7 mg/dL), CKD risk was increased not only in the higher uric acid groups but also in the hypouricemia group with SUA 2.0 mg/dL or less. Conclusion For both men and women, serum uric acid levels and CKD prevalence showed a J-shaped association. Uric acid is itself an important antioxidant in vivo, and its absence may have induced a worsening of renal function due to increased oxidative stress.

Abstract 12153: Prevalence and Prognostic Implications of Worsening Renal Function After Acute Myocardial Infarction

Introduction: Limited data exist on the association between longitudinal changes in renal function and long-term clinical outcomes in patients who survive acute myocardial infarction (AMI) events. Hypothesis: We sought to investigate the relationship between worsening renal function (WRF) at one-year follow-up and clinical outcomes at three years after AMI. Methods: We analyzed data from 13,104 patients enrolled in the national AMI registry from November 2011 to December 2015. Patients with all-cause death, recurrent myocardial infarction (re-MI), and re-hospitalization for heart failure (rHHF) at one-year follow-up after AMI were excluded. A total of 6,235 patients were extracted and divided into WRF and non-WRF groups. WRF was defined as a ≥25% decrease in estimated glomerular filtration rate (eGFR) from baseline to one-year follow-up. The primary outcome was three-year major adverse cardiac events (MACE), a composite of all-cause death, re-MI, and rHHF. Results: On average, a -1.5 ml/min/1.73 m 2 /year rate of decline in eGFR was exhibited, and 575 (9.2%) patients exhibited WRF at one-year follow-up. After multiple adjustments, WRF at one-year follow-up was independently associated with increased risks of MACEs (adjusted hazard ratio: 1.498, 95% confidence interval: 1.113-2.016, P =0.01), all-cause death, and re-MI at three-year follow-up (Figure 1). Older age, female, diabetes, hypertension, non-ST segment elevation AMI, anterior AMI, anemia, left ventricular ejection fraction <35%, and baseline eGFR <30 ml/min/1.73 m 2 were identified as independent predictors of WRF after AMI. Conclusions: WRF at one-year follow-up after AMI intuitively seems like a risk marker indicating multiple comorbidities. Monitoring serum creatinine in patients at one-year follow-up after AMI may help to identify those who are at the highest risk and guide effective long-term therapeutics.

Abstract 18202: Sex Differences in Transthyretin Amyloid Cardiomyopathy

Introduction: Transthyretin amyloid cardiomyopathy (ATTR-CM) predominantly affects men. It is unknown if women are underdiagnosed or if female sex is protective. We investigated sex differences in clinical presentation and disease outcomes in ATTR-CM. Methods: Patients seen with ATTR-CM at our institution were included for analysis. Chi-squared or Fisher’s exact tests, and Wilcoxon tests were used to assess associations between clinical variables and sex in the overall cohort as well as by genotype (wtATTR and V122I). Hazard ratios with 95% confidence intervals were used to assess outcomes. Results: Of 293 subjects, 235 (80%) were men and 58 (20%) were women. Women vs men were more likely Black in the entire cohort (65% v 39%) and in the wtATTR group (70% v 8.7%, p<0.05). Women were significantly older in wtATTR (84 [6.6] v 79 [7.2] yrs) and V122I (75 [6] v 71 [8.3] yrs), had higher HR (83 v 75 bpm), lower eGFR (54 v 62 mL/min/1.73 m2), and thinner intraventricular septum diameter (1.54 [0.3] v 1.71 [0.3] cm) than men at time of diagnosis (p<0.05). Women with wtATTR had significantly higher mean RAP (14.8 [6.9] v 8.69 [4.8] v mmHg, p<0.05) and a trend toward higher PASP (55.5 [17.0] v 42.9 [12.8] and PCWP (22.5 [6.7] v 17.3 [6.4] mmHg, p=0.06) vs men. There was no difference in HF hospitalization or death at 5 years (HR 0.93 [0.59-1.45], p=0.70) and no significant increase in proportion of women diagnosed over disease eras (pre-2013, 2013-2018, and 2019-2023). Conclusions: In a well characterized cohort with ATTR-CM, women were diagnosed less frequently and at an older age with markers of more advanced disease including higher HR, worse renal function, and higher filling pressures compared to men. Disease recognition in women did not increase over time. While this may be due to the nature of the disease, the characteristics we identified at diagnosis support that women with ATTR-CM are under detected. Future sex-based screening studies are needed to increase detection of ATTR-CM in women.

Abstract 17725: Prognostic Implications and the Impact of Empagliflozin on Bone Morphogenetic Protein-10 in Heart Failure: Results from the EMPEROR Program

Background: Bone morphogenetic protein (BMP)-10 is upregulated in response to cardiac injury and exerts a protective role via activating transforming growth factor β/Smad and STAT3-pathways preserving normal cardiac function by inhibiting cell death and fibrosis. Aim: To assess association of baseline characteristics and prognostic significance of BMP-10 in patients with heart failure (HF) with reduced or preserved ejection fraction, and the effect of empagliflozin on BMP-10 level. Methods: Serum BMP-10 (Elecsys®, Roche Diagnostics) was assessed in 1127 patients from the EMPEROR-Reduced and Preserved trials, categorized by tertiles of baseline BMP-10 (<2.35; ≥2.35-<3.11; ≥3.11 ng/mL). Results: Median baseline BMP-10 was 2.71 ng/mL. Patients in higher tertiles tended to be older, women, NYHA class III-IV, with obesity, atrial fibrillation, and worse renal function (all P<0.05). Baseline BMP-10 level correlated with N-terminal pro B-type natriuretic peptides and high-sensitivity troponin T levels (Spearman rho=0.41, 0.26 respectively). Higher baseline BMP-10 was associated with increased risk for adverse outcomes ( Table 1 ). For each 2-fold increase in BMP-10, the adjusted hazard ratio (HR) for cardiovascular death (CV) or HF hospitalization was 2.85 (95% CI 1.99, 4.09, P<0.0001). Empagliflozin treatment was associated with reduction in BMP-10 at week 12 (adjusted gMean ratio 0.94 [0.91-0.97], P<0.001) but not week 52 (1.00 [0.96-1.04], P=0.86). Empagliflozin reduced the risk of CV death or HF hospitalization, particularly for patients at highest baseline BMP-10 level (<1 st tertile HR 1.03 [0.56-1.88]; ≥1 st and <2 nd tertile HR 0.74 [0.40-1.35]; ≥2 nd tertile HR 0.61 [0.40-0.92], P-trend=0.15). Conclusion: BMP-10 levels were associated with worse disease severity and outcomes in patients with HF. Empagliflozin was associated with reduction of BMP-10 at week 12. The benefit of empagliflozin on outcomes was more pronounced with higher BMP-10 levels.

Assessment of bone marrow fat by 3-Tesla magnetic resonance spectroscopy in patients with chronic kidney disease.

Proton magnetic resonance spectroscopy (1H MRS) is an imaging method for quantification of bone marrow fat. It has been used for evaluation of bone marrow changes in patients with chronic disorders, such as chronic kidney disease (CKD). In these patients, there is a high turnover state, with an excessive amount of non-mineralized component of bone, leading to skeletal fragility and subsequent increased fracture risk. Thirty CKD patients underwent magnetic resonance spectroscopy (MRS) and quantitative computed tomography (QCT), and eight healthy controls underwent MRS at lumbar spine. Proton density fat fraction (PDFF) and volumetric bone mineral density (vBMD) of L1-L3 were determined from MRS and QCT respectively. CKD patients were divided into three groups according to glomerular filtration rate (GFR); for each patient, blood levels of parathyroid hormone (PTH) were also reported. Paired t-tests, Pearson's correlation coefficients and analysis of variance were applied. The mean age of patients was 59.6±11.5 years, mean GFR value was 21.5±8.8 mL/min and mean PTH value was 149.2±53.1 pg/mL. PDFF at L1-L3 levels was significantly higher in CKD patients compared to controls (71.4±8.7 vs. 55.5±7.6; P<0.001) and showed an inverse correlation with vBMD (r=-0.71; P<0.001). PDFF significantly increased from CKD group 1 to CKD group 3 (P=0.002) and was inversely correlated with GFR (r=-0.53; P=0.003). There was no significant association between PDFF and PTH values (P>0.05). In CKD patients, PDFF assessed by MRS at lumbar spine is higher than in healthy population, correlates with bone loss assessed by QCT and significantly increases with the worsening of renal function. MRS is a reliable and highly repeatable tool for PDFF quantification in CKD patients.

Use of loop diuretics in patients with chronic heart failure: an observational overview

IntroductionThis study aimed to evaluate the use and dose of loop diuretics (LDs) across the entire ejection fraction (EF) spectrum in a large, ‘real-world’ cohort of chronic heart failure (HF)...

Glycemic control and prescription profiles in internal medicine inpatients: The role of frailty

AimThis work aims to characterize the clinical profile of individuals with frailty syndrome, diabetes mellitus (DM), and hyperglycemia during hospitalization in regard to glycemic control and treatment regimen. MethodsThis cross-sectional multicentric study included patients with DM or hyperglycemia at admission. Demographic data, blood glucose values, treatment administered during hospitalization, and treatment indicated at discharge were analyzed. The sample was divided into three groups according to score on a frailty questionnaire. Generalized additive models were used to describe the relationship between either glycemic variability (GV) or minimum capillary blood glucose and hypoglycemia. Models were adjusted for age, comorbidity, and sarcopenia. ResultsA total of 1,137 patients were analyzed. Patients with frailty syndrome had more comorbidity and sarcopenia, worse renal function, and lower albumin and lymphocyte levels. A GV between 21% and 60% was related to a higher probability of hypoglycemia, especially in patients with frailty. Regarding minimum capillary blood glucose, patients with frailty had the highest probability of hypoglycemia. This probability remained significant even in the group with frailty in which, with a reference value of 200 mg/dl, the adjusted odds ratio of a minimum capillary blood glucose of 151 mg/dL was 1.08 (95% confidence interval (1.12–1.05)). Baseline treatments showed a significant predominance of insulin use in the frailest groups. ConclusionsPatients with frailty had more sarcopenia and undernourishment. These patients were managed in a similar manner during hospitalization to patients without frailty, despite their higher risk of hypoglycemia according to GV or minimum capillary blood glucose levels.

Safety of continuing mineralocorticoid receptor antagonist treatment in patients with heart failure with reduced ejection fraction and severe kidney disease: Data from Swedish Heart Failure Registry.

Mineralocorticoid receptor antagonists (MRAs) improve outcomes in heart failure with reduced ejection fraction (HFrEF) but remain underused and are often discontinued especially in patients with chronic kidney disease (CKD) due to concerns on renal safety. Therefore, in a real-world HFrEF population we investigated the safety of MRA use, in terms of risk of renal events, any mortality and any hospitalization, across the estimated glomerular filtration rate (eGFR) spectrum including severe CKD. We analysed patients with HFrEF (ejection fraction <40%), not on dialysis, from the Swedish Heart Failure Registry. We performed multivariable logistic regression models to investigate patient characteristics independently associated with MRA use, and univariable and multivariable Cox regression models to assess the associations between MRA use and outcomes. Of 33 942 patients, 17 489 (51%) received MRA, 32%, 45%, 54%, 54% with eGFR <30, 30-44, 45-59 or ≥60 ml/min/1.73 m2 , respectively. An eGFR ≥60 ml/min/1.73 m2 and patient characteristics linked with more severe HF were independently associated with more likely MRA use. In multivariable analyses, MRA use was consistently not associated with a higher risk of renal events (i.e. composite of dialysis/renal death/hospitalization for renal failure or hyperkalaemia) (hazard ratio [HR] 1.04, 95% confidence interval [CI] 0.98-1.10), all-cause death (HR 1.02, 95% CI 0.97-1.08) as well as of all-cause hospitalization (HR 0.99, 95% CI 0.95-1.02) across the eGFR spectrum including also severe CKD. The use of MRAs in patients with HFrEF decreased with worse renal function; however their safety profile was demonstrated to be consistent across the entire eGFR spectrum.

Multicompartmental Trauma Induces Persistent Inflammation and Organ Injury

IntroductionPrevious preclinical models of multicompartmental injury have investigated its effects for durations of less than 72 h and the long-term effects have not been defined. We hypothesized that a model of multicompartmental injury would result in systemic inflammation and multiorgan dysfunction that persists at 1 wk. MethodsMale and proestrus female Sprague-Dawley rats (n = 16/group) underwent polytrauma (PT) (unilateral right lung contusion, hemorrhagic shock, cecectomy, bifemoral pseudofractures) and were compared to naive controls. Weight, hemoglobin, plasma neutrophil gelatinase-associated lipocalin, and plasma toll-like receptor 4 were evaluated on days two and seven. Bilateral lungs were sectioned, stained and assessed for injury at day seven. Comparisons were performed in Graphpad with significance defined as ∗P <0.05. ResultsRats who underwent PT had significant weight loss and anemia at day 2 (P = 0.001) compared to naïve rats which persisted at day 7 (P = 0.001). PT rats had elevated plasma neutrophil gelatinase-associated lipocalin at day 2 compared to naïve (P <0.0001) which remained elevated at day 7 (P <0.0001). Plasma toll-like receptor 4 was elevated in PT compared to naïve at day 2 (P = 0.03) and day 7 (P = 0.01). Bilateral lungs showed significant injury in PT cohorts at day 7 compared to naïve (P <0.0004). PT males had worse renal function at day seven compared to females (P = 0.02). ConclusionsMulticompartmental trauma induces systemic inflammation and multiorgan dysfunction without recovery by day seven. However, females demonstrate improved renal recovery compared to males. Long-term assessment of preclinical PT models are crucial to better understand and evaluate future therapeutic immunomodulatory and anti-inflammatory treatments.

Potassium level changes in chronic kidney disease patients following balanced crystalloid administration in the emergency department.

One common reason why clinicians are often hesitate to administer balanced crystalloids in the emergency department is the potential occurrence of unexpected hyperkalemia in patients with chronic kidney disease (CKD). In order to investigate the changes in potassium levels resulting from the administration of balanced crystalloids, specially Plasma Solution A (a generic version of Plasma-Lyte), to emergency department patients with CKD, we conducted an evaluation. A retrospective cohort study was conducted at a single academic hospital. Our study included patients with CKD who received intravenous Plasma Solution A and underwent electrolyte follow-up testing within 24 hours of administration. In total, there were 745 patients included in this study, of whom 87 had CKD. Through a 1:1 propensity score matching procedure for factors other than the estimated glomerular filtration rate, we matched 87 patients with normal kidney function to 87 CKD patients. For patients with CKD, the mean standard deviation SD administered volume of Plasma Solution A was 28.7 (21.0) mL/kg, and the mean SD administration duration was 13.2 (4.5) hours. The mean SD potassium level decreased from 4.3 (0.6) mmol/L to 4.1 (0.6) mmol/L (P = .029). Our study findings suggest that there may be no significant harmful increase in potassium levels or worsening of renal function within 24 hours after the intravenous administration of approximately 2 L of Plasma Solution A to patients with CKD.

Pickering Syndrome: An Overlooked Renovascular Cause of Recurrent Heart Failure.

ABSTRACTRecurring and rapidly developing (flash) pulmonary edema is the hallmark of Pickering syndrome, affecting patients with hypertension and atherosclerotic renal artery stenosis (either bilateral or unilateral) in a solitary functioning kidney, and impaired renal function. We herein report on a series of consecutive patients with recurrent hospital admissions for pulmonary edema, impaired renal function (chronic kidney disease class 4-5), and atherosclerotic bilateral renal artery stenosis, in whom Pickering syndrome had been long neglected. We also describe a streamlined diagnostic strategy entailing little or no need for contrast medium, thus carrying no risks of further worsening of renal function. This allowed us to make the correct diagnosis and opened the way to revascularization by percutaneous transluminal renal angioplasty with stent, which provided swift recovery of kidney function with resolution of pulmonary congestion and long-term pulmonary edema- and dialysis-free survival in all cases. In summary, these findings support the following key messages: (1) considering the diagnosis of Pickering syndrome, followed by searching atherosclerotic renal artery stenosis, is an essential step toward a life-saving revascularization that avoids dialysis and an otherwise poor outcome; and (2) a simplified strategy entailing little or no need for contrast medium, carrying no associated risks of deteriorating renal function, permits the diagnosis of Pickering syndrome.

Use of rasburicase to improve kidney function in children with hyperuricemia and acute kidney injury

BackgroundHyperuricemia contributes to decrease in kidney function and induces additional renal damage in children with acute kidney injury (AKI). Rasburicase oxidizes uric acid (UA), decreasing its serum quantities in less than 24 h.MethodsThis is a retrospective study involving hospitalized patients under 18 years of age with underlying pathology diagnosed with AKI and severe hyperuricemia treated with rasburicase over a 4-year period.ResultsWe describe 15 patients from 4 days of life to 18 years (median: 4.4 years). Seventy-three percent had known underlying pathologies. All presented worsening of basal renal function or AKI data. All received the usual medical treatment for AKI without response. Twenty percent received an extrarenal depuration technique. All had hyperuricemia with a mean (± SD) of 13.1 (± 2.19) mg/dl. After rasburicase administration UA levels fell to a mean (± SD) of 0.76 (± 0.62) mg/dl (p < 0.001) in less than 24 h. In parallel, a decrease in the mean plasma creatinine was observed (2.92 mg/dl to 1.93 mg/dl (p = 0.057)) together with a significant improvement of the mean glomerular filtration rate (16.3 ml/min/1.73 m2 to 78.6 ml/min/1.73 m2) (p = 0.001)). No side effects were recorded. Kidney function normalized in all cases or returned to baseline levels.ConclusionsAlthough the use of rasburicase is not routinely approved in pediatric patients with severe hyperuricemia and AKI, it has been used successfully without complications, and helped prevent progressive kidney damage. This study could serve as a basis for suggesting the off-label use of rasburicase for the management of complex pediatric patients in whom UA plays an important role in the development of AKI.

Bio-Humoral and Non-Invasive Haemodynamic Correlates of Renal Venous Flow Patterns across the Heart Failure Spectrum.

Background: We evaluated the bio-humoral and non-invasive haemodynamic correlates of renal congestion evaluated by Doppler renal venous flow (RVF) across the heart failure (HF) spectrum, from asymptomatic subjects with cardiovascular risk factors (Stage A) and structural heart disease (Stage B) to patients with clinically overt HF (Stage C). Methods: Ultrasound evaluation, including echocardiography, lung ultrasound and RVF, along with blood and urine sampling, was performed in 304 patients. Results: Continuous RVF was observed in 230 patients (76%), while discontinuous RVF (dRVF) was observed in 74 (24%): 39 patients had pulsatile RVF, 18 had biphasic RVF and 17 had monophasic RVF. Stage C HF was significantly more common among patients with dRVF. Monophasic RVF was associated with worse renal function and a higher urinary albumin-to-creatinine ratio (uACR). After adjusting for hypertension, diabetes mellitus, the presence of Stage C HF and serum creatinine levels, worsening RVF patterns were associated with higher NT-proBNP levels, worse right ventricular-arterial coupling, larger inferior vena cava and higher echo-derived pulmonary artery wedge pressure. This trend was confirmed when only patients with HF Stage C were analysed after adjusting for the left ventricle ejection fraction (LVEF). Conclusion: Abnormal RVF is common across the HF spectrum. Worsening RVF patterns are independently associated with increased congestion, worse non-invasive haemodynamics and impaired RV-arterial coupling. RVF evaluation could refine prognostic stratification across the HF spectrum, irrespective of LVEF.

Worsening Renal Function and Adverse Outcomes in Patients with HFpEF with or without Atrial Fibrillation.

Since worsening renal function (WRF) and atrial fibrillation (AF) often coexist in preserved ejection fraction (HFpEF), we aimed to investigate the effect of WRF on the prognosis of HFpEF patients with and without AF. The study population of this study (n = 1763) was based on the subset of the Americas in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT). We found that the cumulative probabilities of the primary composite outcome and cardiovascular death were significantly higher in AF patients post-WRF when compared to non-AF patients. In the time-dependent Cox proportional hazard model, WRF was significantly associated with higher risks of adverse outcomes (primary composite outcome: HR = 1.58 (95% CI, 1.19-2.11); all-cause death: HR = 1.50 (95% CI, 1.10-2.06); cardiovascular death: HR, 2.00 (95% CI, 1.34-3.00)) after adjustments for confounding factors at baseline in HFpEF patients with AF, whereas in HFpEF patients without AF, WRF was not significantly associated with any adverse outcome. p for interactions for the primary composite outcome, cardiovascular death, and AF were significant. In conclusion, these findings highlight that WRF was associated with a greater risk of the primary composite outcome, all-cause death, and cardiovascular death in HFpEF patients with AF.

Intrarenal Venous Flow Pattern Changes Do Relate With Renal Function Alterations in Acute Heart Failure

BackgroundThere is scarce evidence supporting the clinical utility of congestive intrarenal venous flow (IRVF) patterns in patients with acute heart failure. ObjectivesThis study aims to: 1) investigate the association between IRVF patterns and the odds of worsening renal function (WRF); 2) track the longitudinal changes of serum creatinine (sCr) across IRVF at predetermined points and its association with decongestion; and 3) explore the relationship between IRVF/WRF categories and patient outcomes. MethodsIRVF was assessed at baseline (pre–decongestive therapy), 72 hours, and 30 and 90 days postdischarge. Changes in sCr trajectories across dynamic IRVF variations and parameters of decongestion were assessed using linear mixed effect models. The association between IRVF/WRF categories and outcomes was evaluated using univariable/multivariable models. ResultsIn this prospective, multicenter study with 188 participants, discontinuous IRVF patterns indicated higher odds of WRF (OR: 3.90 [95% CI: 1.24-12.20]; P = 0.020 at 72 hours; and OR: 5.76 [95% CI: 1.67-19.86]; P = 0.006 at 30 days) and an increase in sCr (Δ-72 hours 0.14 mg/dL [95% CI: 0.06-0.22]; P = 0.001; Δ-discharge 0.13 mg/dL [95% CI: 0.03-0.23]; P = 0.007). However, the diuretic response and decongestion significantly influenced the magnitude of these changes. Patients exhibiting both WRF and discontinuous IRVF at 30 days experienced an increased hazard of adverse events (HR: 5.96 [95% CI: 2.63-13.52]; P < 0.001). ConclusionsDiscontinuous IRVF identifies patients with higher odds of WRF during admission and postdischarge periods. Nonetheless, adequate diuretic response and decongestion could modify this association. Patients showing both WRF and discontinuous IRVF at 30 days had increased rates of adverse events.

Cardiopulmonary bypass management and risk of new-onset atrial fibrillation after cardiac surgery.

Cardiopulmonary bypass (CPB) management may potentially play a role in the development of new-onset atrial fibrillation (AF) after cardiac surgery. The aim of this study was to explore this potential association. Patients who underwent coronary artery bypass grafting and/or valvular surgery during 2016-2020 were included in an observational single-centre study. Data collected from the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry and a local CPB database were merged. Associations between individual CPB variables (CPB and aortic clamp times, arterial and central venous pressure, mixed venous oxygen saturation, blood flow index, bladder temperature and haematocrit) and new-onset AF were analysed using multivariable logistic regression models adjusted for patient characteristics, comorbidities and surgical procedure. Out of 1999 patients, 758 (37.9%) developed new-onset AF. Patients with new-onset postoperative AF were older, had a higher incidence of previous stroke, worse renal function and higher EuroSCORE II and CHA2DS2-VASc scores and more often underwent valve surgery. Longer CPB time [adjusted odds ratio 1.05 per 10 min (95% confidence interval 1.01-1.08); P = 0.008] and higher flow index [adjusted odds ratio 1.21 per 0.2 l/m2 (95% confidence interval 1.02-1.42); P = 0.026] were associated with an increased risk for new-onset AF, while the other variables were not. A sensitivity analysis only including patients with isolated coronary artery bypass grafting supported the primary analyses. CPB management following current guideline recommendations appears to have minor or no influence on the risk of developing new-onset AF after cardiac surgery.