Showing papers in "CardioRenal Medicine in 2020"
TL;DR: The exaggerated cytokine release in response to viral infection, a condition known as cytokinerelease syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed anti-inflammatory therapeutic strategies could improve patients’ clinical outcomes and prognosis.
Abstract: Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis Summary: The pathophysiology of COVID-19 is far from being completely understood, and the lack of effective treatments leads to a sense of urgency to develop new therapeutic strategies based on pathophysiological assumptions The exaggerated cytokine release in response to viral infection, a condition known as cytokine release syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed anti-inflammatory therapeutic strategies could improve patients' clinical outcomes and prognosis Key Messages: The objective of this article is to explore and comment on the potential role of the promising immunomodulatory therapies using pharmacological and nonpharmacological approaches to overcome the dysregulated proinflammatory response in COVID-19
80 citations
TL;DR: SGLT2i are associated with significantly lower major adverse cardiovascular events, heart failure hospitalizations, and all-cause mortality, and the evidence is strongest in reducing heart failureospitalizations.
Abstract: Background: Previous meta-analyses demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) primarily on patients with established atherosclerotic cardiovascular disease (ASCVD), but with questionable efficacy on patients at risk of ASCVD. Additionally, evidence of beneficial cardiorenal outcomes in patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 with the CV outcomes trials remains unclear. Canagliflozin, one of the SGLT2i, has recently been studied in a large randomized controlled trial in diabetic patients with chronic kidney disease. Thus, there is a need to understand the combined outcomes on the population targeted for treatment with SGLT2i as a whole, regardless of ASCVD status. This meta-analysis will therefore assess the efficacy of SGLT2i in cardiovascular and renal outcomes in general, and in patients with eGFR under 60 mL/min/1.73 m2 in particular. Methods: We searched PubMed and Cochrane databases for randomized, placebo-controlled studies involving SGLT2i. We examined composite cardiovascular outcomes of death from cardiovascular causes, nonfatal myocardial infarctions, nonfatal stroke, and heart failure hospitalizations. Renal composite outcomes and progression of albuminuria were also analyzed. Pooled relative risks (RR) and their 95% confidence intervals (CI) were calculated using a fixed-effects model. Results: The search yielded a total of 252 articles. Four studies were ultimately included in the meta-analysis after exclusion of other irrelevant studies. The pooled RR (95% CI) for the composite cardiovascular outcome was 0.93 (0.87–0.99) with a number needed to treat (NNT) of 167 in the general study population and 0.89 (0.77–1.02) in patients with eGFR <60 mL/min/1.73 m2. The pooled RR for all-cause mortality was 0.9 (0.84–0.97) with NNT = 143. The pooled RR for death from cardiovascular causes alone was 0.89 (0.81–0.99) in the general population and 0.82 (0.62–1.07) in patients with eGFR <60 mL/min/1.73 m2. The pooled RR for heart failure hospitalizations was 0.71 (0.63–0.79) with NNT = 91. With respect to renal outcomes, the pooled RR for the composite renal outcome was 0.63 (0.56–0.71) with NNT = 67; this was true even in patients with eGFR <60 mL/min/1.73 m2 0.67 (0.59–0.76). Lastly, the pooled RR for progression of albuminuria was 0.80 (0.76–0.84). Conclusion: SGLT2i are associated with significantly lower major adverse cardiovascular events, heart failure hospitalizations, and all-cause mortality. The evidence is strongest in reducing heart failure hospitalizations. However, the evidence is weaker when it comes to the population subset with eGFR <60 mL/min/1.73 m2. SGLT2i are also associated with significantly lower adverse renal events, with these effects apparent even in the population with eGFR <60 mL/min/1.73 m2.
69 citations
TL;DR: A high burden of AKI is reported among underserved COVID-19 patients with multiple comorbidities, and those who had HA-AKI had worse clinical outcomes compared to those who with CA-AKi.
Abstract: INTRODUCTION: Emerging data have described poor clinical outcomes from infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) among African American patients and those from underserved socioeconomic groups We sought to describe the clinical characteristics and outcomes of acute kidney injury (AKI) in this special population METHODS: This is a retrospective study conducted in an underserved area with a predominance of African American patients with coronavirus disease 2019 (COVID-19) Descriptive statistics were used to characterize the sample population The onset of AKI and relation to clinical outcomes were determined Multivariate logistic regression was used to determine factors associated with AKI RESULTS: Nearly half (493%) of the patients with COVID-19 had AKI Patients with AKI had a significantly lower baseline estimated glomerular filtration rate (eGFR) and higher FiO2 requirement and D-dimer levels on admission More subnephrotic proteinuria and microhematuria was seen in these patients, and the majority had a pre-renal urine electrolyte profile Patients with hospital-acquired AKI (HA-AKI) as opposed to those with community-acquired AKI (CA-AKI) had higher rates of in-hospital death (52 vs 23%, p = 0005), need for vasopressors (42 vs 25%, p = 0024), and need for intubation (55 vs 25%, p = 0006) A history of heart failure was significantly associated with AKI after adjusting for baseline eGFR (OR 3382, 95% CI 1121-13231, p = 0032) CONCLUSION: We report a high burden of AKI among underserved COVID-19 patients with multiple comorbidities Those who had HA-AKI had worse clinical outcomes compared to those who with CA-AKI A history of heart failure is an independent predictor of AKI in patients with COVID-19
62 citations
TL;DR: In this paper, the authors evaluated whether MOTS-c, a novel mitochondria-related 16aa peptide, can reduce vitamin D3 and nicotine-induced VC in rats.
Abstract: Introduction Vascular calcification (VC) is a complex, regulated process involved in many disease entities. So far, there are no treatments to reverse it. Exploring novel strategies to prevent VC is important and necessary for VC-related disease intervention. Objective In this study, we evaluated whether MOTS-c, a novel mitochondria-related 16-aa peptide, can reduce vitamin D3 and nicotine-induced VC in rats. Methods Vitamin D3 plus nicotine-treated rats were injected with MOTS-c at a dose of 5 mg/kg once a day for 4 weeks. Blood pressure, heart rate, and body weight were measured, and echocardiography was performed. The expression of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and the angiotensin II type 1 (AT-1) and endothelin B (ET-B) receptors was determined by Western blot analysis. Results Our results showed that MOTS-c treatment significantly attenuated VC. Furthermore, we found that the level of phosphorylated AMPK was increased and the expression levels of the AT-1 and ET-B receptors were decreased after MOTS-c treatment. Conclusions Our findings provide evidence that MOTS-c may act as an inhibitor of VC by activating the AMPK signaling pathway and suppressing the expression of the AT-1 and ET-B receptors.
33 citations
TL;DR: A Tri-POCUS approach is suggested that represents concurrent bedside assessment of the lungs, heart, and the venous system that is likely to overcome the limitations of the individual methods and provide a more precise evaluation of the volume status in critically ill patients with COVID-19.
Abstract: As the coronavirus disease 2019 (COVID-19) continues to spread across the globe, the knowledge of its epidemiology, clinical features, and management is rapidly evolving. Nevertheless, the data on optimal fluid management strategies for those who develop critical illness remain sparse. Adding to the challenge, the fluid volume status of these patients has been found to be dynamic. Some present with several days of malaise, gastrointestinal symptoms, and consequent hypovolemia requiring aggressive fluid resuscitation, while a subset develop acute respiratory distress syndrome with renal dysfunction and lingering congestion necessitating restrictive fluid management. Accurate objective assessment of volume status allows physicians to tailor the fluid management goals throughout this wide spectrum of critical illness. Conventional point-of-care ultrasonography (POCUS) enables the reliable assessment of fluid status and reducing the staff exposure. However, due to specific characteristics of COVID-19 (e.g., rapidly expanding lung lesions), a single imaging method such as lung POCUS will have significant limitations. Herein, we suggest a Tri-POCUS approach that represents concurrent bedside assessment of the lungs, heart, and the venous system. This combinational approach is likely to overcome the limitations of the individual methods and provide a more precise evaluation of the volume status in critically ill patients with COVID-19.
23 citations
TL;DR: A decision-making pathway for the use of RAASi in the setting of acute HF that would help guide the cardiologist and nephrologist caring for patients with acute HF and cardiorenal syndrome is offered.
Abstract: Background The renin-angiotensin-aldosterone axis plays a pivotal role in the pathophysiology of acute and chronic heart failure (HF) and represents an important target for guideline-directed medical therapy. Summary The use of appropriate directed medical therapies for inhibition of the renin-angiotensin-aldosterone axis in chronic HF has been the subject of several landmark clinical trials, with high levels of adherence exhibited in the outpatient setting. However, less clarity exists with respect to the initiation, continuation, and cessation of renin-angiotensin-aldosterone system inhibitors (RAASi) in the setting of acute HF and exacerbation of HF necessitating hospitalization. In this review, we summarize relevant aspects of the physiology of the renin-angiotensin-aldosterone axis in acute HF and during decongestion. We also summarize the available evidence for the risks and benefits of initiating and continuing RAASi in acute HF. Key Message: We offer a decision-making pathway for the use of RAASi in the setting of acute HF that would help guide the cardiologist and nephrologist caring for patients with acute HF and cardiorenal syndrome.
20 citations
TL;DR: Addition of eplerenone to ACEI shows an added antialbuminuric effect without significant change of the serum K level compared with eplererenone or ACEI.
Abstract: INTRODUCTION Angiotensin-converting enzyme inhibitors (ACEI) combined with mineralocorticoid receptor antagonists were found to have a beneficial effect on patients with chronic kidney disease. OBJECTIVE The aim of our clinical trial was to compare the antialbuminuric effect of ramipril monotherapy, eplerenone monotherapy and eplerenone/ramipril combination therapy in patients with stage 1 hypertension and type 2 diabetes mellitus. METHODS In a single-blind, randomized clinical trial, 75 hypertensive patients (stage 1 hypertension) with type 2 diabetes mellitus and microalbuminuria were randomized in a 1:1:1 ratio to 1 of 3 groups: ramipril 10 mg monotherapy (25 patients), eplerenone 50 mg monotherapy (25 patients) and combination therapy of eplerenone/ramipril 50/10 mg (25 patients) through a randomized clinical trial. Blood pressure, urinary albumin/creatinine ratio (UACR), serum creatinine, estimated glomerular filtration rate (eGFR) and serum K level were measured before randomization and after 24 weeks. RESULTS Ramipril and eplerenone monotherapy showed a significant lowering of UACR compared with baseline levels (p ≤ 0.0001). The eplerenone/ramipril combination group showed a more significant reduction of UACR compared with the ramipril and eplerenone monotherapy groups (p = 0.0001). There was a more significant lowering of systolic blood pressure in the combination group (p < 0.0001). A nonsignificant change of serum potassium level, serum creatinine and eGFR was found among the 3 groups. CONCLUSION Addition of eplerenone to ACEI shows an added antialbuminuric effect without significant change of the serum K level compared with eplerenone or ACEI.
19 citations
TL;DR: Preliminary data suggests that kidney is a target for the virus and deterioration of renal function was associated with poor outcomes including in-hospital mortality, and acute kidney injury might help risk stratify critically ill patients on a fatal course of COVID-19.
Abstract: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting more than 200 countries and 180,000 cases in the United States. While the outbreak began in China, the number of cases outside of China exceeded those in China on March 15, 2020 and are currently rising at an exponential rate. The number of fatalities in the United States are expected to exceed more than Italy and China. The disease is characterized predominantly as an acute respiratory illness. However, preliminary data suggests that kidney is a target for the virus and deterioration of renal function was associated with poor outcomes including in-hospital mortality. We pre-sent a report of a patient with COVID-19 who presented with acute onset of symptoms and normal renal function at baseline but rapidly deteriorated resulting in death. The timing of decline in renal function correlated with his worsening clinical status. He was started on continuous veno-venous hemofiltration without signs of clinical benefit. We also present the possible mechanisms for acute kidney injury in these patients. We performed a review of the emerging literature by searching PubMed, Google Scholar, and EMBASE for studies and/or case series published on this topic. Acute kidney injury might help risk stratify critically ill patients on a fatal course of COVID-19.
17 citations
TL;DR: Treatment adherence and ultrafiltration amounts of patients increased with the use of RM-APD, as well as better blood pressure control with fewer antihypertensive drugs.
Abstract: Introduction Peritoneal dialysis (PD) provides a safe, home-based continuous renal replacement therapy for patients. The adherence of the patients to the prescribed dialysis fluids cannot always be monitored by physicians. Remote monitoring automated peritoneal dialysis (RM-APD) can affect patients' compliance with treatment and, thus, clinical outcomes. Objective We aimed to evaluate the clinical outcomes of patients with a remote access program. Methods This was an observational study. We analyzed the effect of RM-APD on treatment adherence, dialysis adequacy, and change in blood pressure control, sleep quality, and health-related quality of life during the 6 months of follow-up. Results A total of 15 patients were enrolled in this study. It was found that there was a significant decrease (99 ± 19 vs. 89 ± 11 mm Hg) in mean arterial blood pressure of patients, and a considerable increase in Kt/V was observed in the sixth month after the RM-APD switch (2.11 ± 0.4 vs. 2.25 ± 0.5). A significant increase was found when comparing the 3-month and 6-month ultrafiltration amounts before RM-APD and the ultrafiltration amount within 6 months after RM-APD (800 mL [500-1,000] and 752 mL [490-986] vs. 824 mL [537-1,183]). The daily antihypertensive pill need (4 [0-7] vs. 2 [0-6]) and alarms received from the device decreased (from 4 [3-8] to 2 [0-3]) at the sixth month of the switch. There was no significant change in sleep quality and health-related quality of life within 6 months. Conclusion This study showed that treatment adherence and ultrafiltration amounts of patients increased with the use of RM-APD, as well as better blood pressure control with fewer antihypertensive drugs.
16 citations
TL;DR: Insight is provided into the pathophysiology of AKI and may serve at developing preventing strategies for AKI targeting this pathway and outperformed the predictive value of the clinical model alone.
Abstract: Background/Aims: The pathophysiology of acute kidney injury (AKI) in ST-elevation myocardial infarction (STEMI) patients remains poorly explored. The involvement of the nitric oxide (NO) pathway has been demonstrated in experimental ischemic AKI. The aim of this study was to assess the predictive value of circulating biomarkers of the NO pathway for AKI in STEMI patients. Methods: Four hundred and twenty-seven STEMI patients treated with primary percutaneous coronary intervention were included. The primary end point was AKI. Biomarkers of the NO pathway (plasma superoxide dismutase [SOD], uric acid, nitrite/nitrate [NOx], neopterin) as well as cardiac biomarkers (B-type natriuretic peptide [BNP] and troponin) were sampled 12 h after admission. The predictive value of circulating biomarkers was evaluated in addition to the multivariate clinical model. Results: AKI developed in 8.9% of patients. The 3-month mortality was significantly higher in patients with AKI (34.2 vs. 4.1%; p = 45 mu mol/L was 8.0 (95% CI 3.1-20.6) for AKI. Conclusion: Biomarkers of the NO pathway are associated with the development of AKI in STEMI patients. These results provide insights into the pathophysiology of AKI and may serve at developing preventing strategies for AKI targeting this pathway.
12 citations
TL;DR: Rivaroxaban is identified as the DOAC having the best safety profile, based on the ADR RI, which was calculated using a previously described risk index in daily clinical practice in Italy.
Abstract: BACKGROUND The availability of direct oral anticoagulants (DOAC) in clinical practice has transformed the health care provided to patients for the prevention and treatment of thromboembolism. Safety and efficacy data guide clinicians in the choice of the drug used. To date, no evidence is available from head-to-head trials comparing different DOAC with regard to safety and efficacy; information is mainly derived from several meta-analyses and real-life studies. Conclusions from these studies are inconsistent and unsatisfactory. The evaluation of self-reported adverse drug reactions (ADR) available from databases of drug-regulatory agencies such as the Italian Medicines Agency (AIFA) pharmacovigilance database represents a novel aid to guide decision-making. OBJECTIVE To analyze potential suspected ADR of DOAC using a previously described risk index (RI) in daily clinical practice in Italy. METHODS The National Pharmacovigilance Network database (from the AIFA website) was searched in order to retrieve information on all ADR related to oral anticoagulants occurring from 2013 to 2018. The ADR RI for each drug was calculated, where an RI = 1 indicates a balance between the percentage of ADR share and the percentage of market share for each DOAC; and an RI <1 indicates a rate of ADR lower than the rate of market share (safer DOAC). The following DOAC molecules were considered: dabigatran, rivaroxaban, apixaban, and edoxaban. RESULTS The results showed that rivaroxaban is the DOAC with the lowest RI among the 4 molecules available today in Italy. CONCLUSIONS Based on the RI, we identified rivaroxaban as the DOAC having the best safety profile.
TL;DR: It was showed that intra-arterial modern contrast media administration may have a nephrotoxic effect in a population without pre-existing chronic kidney disease.
Abstract: INTRODUCTION The nephrotoxicity of modern contrast media remains controversial. Novel biomarkers of kidney damage may help in identifying a subclinical structural renal injury not revealed by widely used markers of kidney function. OBJECTIVE The aim of this study was to investigate clinical (contrast-induced acute kidney injury [CI-AKI]) and subclinical CI-AKI (SCI-AKI) after intra-arterial administration of Iodixanol and Iopamidol in patients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2. METHODS This is a prospective observational monocentric study. Urinary sample was collected at 4-8 h after contrast medium exposure to measure neutrophil gelatinase associated lipocalin (NGAL) and the product tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2] × [IGFBP7]), while blood samples were collected at 24 and 48 h after exposure to measure serum creatinine. RESULTS One hundred patients were enrolled, of whom 53 were exposed to Iodixanol and 47 to Iopamidol. Patients in Iodixanol and Iopamidol groups were comparable in terms of demographics, pre-procedural and procedural data. No patient developed CI-AKI according KDIGO criteria, while 13 patients reported SCI-AKI after exposure to iodine-based medium contrast (3 patients in Iodixanol group and 10 patients in Iopamidol group), defined by positive results of NGAL and/or [TIMP-2] × [IGFBP7]. A positive correlation was found between NGAL and [TIMP-2] × [IGFBP7] in the analysed population (Spearman's rho 0.49, p < 0.001). In logistic regression analysis, Iopamidol exposure showed higher risk for SCI-AKI compared to Iodixanol (OR 4.5 [95% CI 1.16-17.52], p = 0.030), even after controlling for eGFR and volume of contrast medium used. CONCLUSIONS This study showed that intra-arterial modern contrast media administration may have a nephrotoxic effect in a population without pre-existing chronic kidney disease. Further investigations on larger scale are warranted to confirm if Iopamidol exposed patients to increased risk of SCI-AKI compared to Iodixanol.
TL;DR: The occurrence of hyperkalemia is common among outpatients with HF and it is the main cause of MRA withdrawal, which is associated with a worse prognosis, in this setting, the possibility of managing hyperKalemia using new classes of drugs could allow continuation of M RA therapy.
Abstract: Background Hyperkalemia is one of the most frequent side effects related to renin-angiotensin-aldosterone system (RAAS) inhibition, and can influence optimization of heart failure (HF) therapy. Aim To evaluate the occurrence of hyperkalemia in a series of outpatients with chronic HF and its relationship with RAAS inhibitor therapy. Method We evaluated consecutive outpatients with HF and a reduced left ventricular ejection fraction. The incidence of hyperkalemia and consequent changes in RAAS inhibitor therapy were evaluated for each patient. Results A history of hyperkalemia or at least 1 episode of hyperkalemia during follow-up was observed in 104 of 351 patients. Hyperkalemia mainly influenced mineralocorticoid receptor antagonist (MRA) therapy and, among patients with hyperkalemia, not taking MRA was associated with a greater risk of death on univariate analysis (HR = 6.39; 95% CI 2.76-14.79, p 1,000 pg/mL. Conclusion The occurrence of hyperkalemia is common among outpatients with HF and it is the main cause of MRA withdrawal, which is associated with a worse prognosis. In this setting, the possibility of managing hyperkalemia using new classes of drugs could allow continuation of MRA therapy.
TL;DR: It is suggested that lower serum Klotho levels are independently associated with overall mortality and CVD events in nondiabetic predialysis CKD patients.
Abstract: Background Experimental studies indicate that Klotho deficiency is a pathogenic factor for CKD-related complications, including cardiovascular disease (CVD). However, the association between serum Klotho and clinical outcomes in nondiabetic CKD patients needs to be further clarified. We aimed to determine whether serum Klotho levels are associated with CVD events and mortality in predialysis CKD patients without diabetes. Methods A total of 336 CKD stage 2-5 predialysis patients without diabetes were recruited and followed from the end of 2014 to January 2019 for CVD events and overall mortality. Serum Klotho was detected by ELISA and divided into quartiles (lowest, middle, second highest, and highest quartiles) according to their serum Klotho category. Results After a median follow-up of 3.52 years (IQR 3.34-3.76), Kaplan-Meier analysis showed that, compared to participants with a Klotho level in the highest quartile (the reference category), those in the lowest Klotho quartile were associated with a higher all-cause mortality risk (HR = 7.05; 95% CI 1.59-31.25) and a higher CVD event risk (HR = 3.02; 95% CI 1.45-6.30). In addition, the middle Klotho quartile was also associated with CVD event risk (HR = 2.56; 95% CI 1.21-5.41). Moreover, in the multivariate-adjusted model, the lowest Klotho quartile remained significantly associated with all-cause mortality (HR = 5.17; 95% CI 1.07-24.96), and the middle Klotho quartile maintained a significant association with CVD event risk (HR = 2.32; 95% CI 1.03-5.21). Conclusion These results suggest that lower serum Klotho levels are independently associated with overall mortality and CVD events in nondiabetic predialysis CKD patients.
TL;DR: Hemodynamically effective BPA procedures improve renal function in patients with CTEPH with a minimal risk of CI-AKI in the course of treatment.
Abstract: Background: Balloon pulmonary angioplasty (BPA) is a novel treatment option for inoperable or persistent chronic thromboembolic pulmonary hypertension (CTEPH). Little is known about renal function in CTEPH patients undergoing BPA. Objectives: The aim of this study was to assess the frequency of contrast-induced acute kidney injury (CI-AKI) in patients with CTEPH undergoing BPA and to evaluate the relationship between hemodynamic and renal function. Methods: A total of 41 CTEPH patients were included and 250 consecutive BPA sessions were analyzed for frequency of CI-AKI. The serum creatinine (SC) concentration was measured and the glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease equation before and 72 h after each BPA procedure. CI-AKI was defined as an increase of 25% or 0.5 mg/dL in SC from the baseline value within 48–72 h of contrast administration. SC and GFR were assessed before and after 3–6 months of completing the BPA treatment and correlated with hemodynamic parameters. Results: The SC concentration and GFR did not change significantly within 72 h after BPA (+1%, p = 0.921, and +4%, p = 0.112, respectively). CI-AKI was noted in 2 cases (0.8%). Significant improvement was noted in GFR (75.4 ± 21.2 vs. 80.9 ± 22.4 mL/min/1.73 m2; p = 0.012) in addition to improvement in right atrial pressure (RAP; 9.1 ± 4.1 to 5.0 ± 2.2 mm Hg; p < 0.001), mean pulmonary artery pressure (49.1 ± 10.7 to 29.8 ± 8.3 mm Hg; p < 0.001), cardiac index (CI; 2.42 ± 0.6 to 2.70 ± 0.6 L/min/m2; p = 0.004), and pulmonary vascular resistance (9.42 ± 3.6 to 4.4 ± 2.3 Wood units; p < 0.001). In a subpopulation of 12 patients with impaired renal function at baseline, the relative increase in GFR was significantly correlated with relative improvement in CI (r = 0.060; p = 0.037), RAP (r = –0.587; p = 0.044), and mixed venous saturation (r = 0.069; p = 0.012). Conclusions: Hemodynamically effective BPA procedures improve renal function in patients with CTEPH with a minimal risk of CI-AKI in the course of treatment.
TL;DR: Systemic anticoagulation could prove to be essential in the treatment of COVID-19 and further studies are required to assess its role in improving long-term morbidity and mortality in these patients.
Abstract: Introduction Coronavirus disease 2019 (COVID-19) is a pandemic that has affected >188 countries, involved >24 million people, and caused >840,000 deaths. COVID-19, in its severe form, presents as acute respiratory distress syndrome (ARDS), shock, and multiorgan failure. Thrombotic microangiopathy of the lungs and kidneys has been observed in these patients. Elevated D-dimer levels have been observed in people with serious COVID-19 illness, and this could be helpful in guiding treatment with anticoagulation in these patients. Objective To analyze the role of anticoagulation as a treatment modality for COVID-19. Methods We present the unique case of a COVID-19 patient who developed sepsis, ARDS, acute kidney injury, and deep-vein thrombosis (DVT), who was deteriorating clinically. She was treated with anticoagulation. Results There was rapid recovery after treatment with systemic anticoagulation. Conclusions Systemic anticoagulation could prove to be essential in the treatment of CO-VID-19. Further studies are required to assess its role in improving long-term morbidity and mortality in these patients.
TL;DR: Echocardiographic indexes showed independent predictive power for mortality in ESRD patients and may constitute a promising prognostic tool in this population.
Abstract: Aim To derive an echocardiography-based prognostic score for a 3-year risk of mortality in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD). Methods 173 ESRD patients hospitalized in the second affiliated hospital of Soochow University from January 1, 2010, to July 31, 2016, were enrolled and followed up for 3 years. All subjects began to receive HD from recruitment. Baseline clinical and echocardiographic parameters were collected and screened for risk factors using univariate and multivariate analysis. The prognostic value of echocardiographic indexes was determined by concordance indexes and reclassification assay. Restricted cubic spline models (RCS) and forest plots were employed to visualize the association between risk factors and all-cause mortality. A multivariate nomogram including the identified factors was developed to estimate the prognosis. Results After multivariate adjustment for advanced age, hypertension, diabetes, and decreased hemoglobin (Hb), echocardiographic indexes including left atrial diameter index (LADI), cardiac valvular calcification, and moderate to severe cardiac valve regurgitation were independently associated with the risk of 3-year mortality in HD patients. RCS showed that age, Hb, and LADI were positively associated with the risk of mortality. Adding multiple echocardiographic indexes to a basic model containing age, hypertension, diabetes, and Hb increased the concordance index and improved reclassification. A multivariate Cox model-derived nomogram showed the association between each factor and mortality by the end of follow-up. Conclusions Echocardiographic indexes showed independent predictive power for mortality in ESRD patients and may constitute a promising prognostic tool in this population.
TL;DR: Elevated NGAL levels, suggesting renal tubular damage, are independently associated with AKI in STEMI patients undergoing primary PCI.
Abstract: Introduction and Objective: Neutrophil gelatinase-associated lipocalin (NGAL), a glycoprotein released by renal tubular cells, can be used as a marker of early tubular damage. We evaluated plasma NGAL level utilization for the identification of acute kidney injury (AKI) among ST-elevation myocardial infarction (STEMI) patients undergoing primary coronary intervention (PCI). Methods: 131 STEMI patients treated with PCI were prospectively included. Plasma NGAL levels were drawn prior to PCI (0 h) and 24 h afterwards. AKI was defined per KDIGO criteria of serum creatinine increase. Receiver-operating characteristic (ROC) methods were used to identify optimal sensitivity and specificity for the observed NGAL range. Results: Overall AKI incidence was 14%. NGAL levels were significantly higher for patients with AKI at both 0 h (164 ± 42 vs. 95 ± 30; p 120 ng/mL) predicted AKI with 80% sensitivity and specificity (AUC 0.881, 95%, CI 0.801–0.961, p < 0.001). In a multivariate logistic regression model, NGAL levels were independently associated with AKI at 0 h (OR 1.044, 95% CI 1.013–1.076; p = 0.005) and 24 h (OR 1.018, 95% CI 1.001–1.036; p = 0.04). Conclusions: Elevated NGAL levels, suggesting renal tubular damage, are independently associated with AKI in STEMI patients undergoing primary PCI.
TL;DR: Use of minimally invasive surgery and therapies mitigating PSPAP and intraoperative blood loss may offer protection against CSA-AKI.
Abstract: Introduction Cardiac surgery-associated acute kidney injury (CSA-AKI) is associated with increased morbidity and mortality Objectives We aimed to identify potentially modifiable risk factors for CSA-AKI Methods This was asingle-center retrospective cohort study of 495 adult patients undergoing cardiac surgery AKI was diagnosed and staged using full KDIGO criteria incorporating baseline serum creatinine (SC) levels and correction of postoperative SC levels for fluid balance We examined the association of routinely available clinical and laboratory data with AKI using multivariate logistic regression modeling Results A total of 103 (208%) patients developed AKI: 16 (155%) patients were diagnosed with AKI upon hospital admission, and 87 (845%) patients were diagnosed with CSA-AKI Correction of SC levels for fluid balance increased the number of AKI cases to 104 (210%), with 6 patients categorized to different AKI stages Univariate logistic regression analysis identified five preoperative (age, sex, diabetes mellitus, preoperative systolic pulmonary arterial pressure [PSPAP], acute decompensated heart failure) and five intraoperative predictors of AKI (age, sex, red blood cell [RBC] volume transfused, use of minimally invasive surgery, duration of cardiopulmonary bypass) When all preoperative and intraoperative variables were incorporated into one model, six predictors remained significant (age, sex, use of minimally invasive surgery, RBC volume transfused, PSPAP, duration of cardiopulmonary bypass) Model discrimination performance showed an area under the curve of 069 for the model including only preoperative variables, 076 for the model including only intraoperative variables, and 077 for the model including all preoperative and intraoperative variables Conclusions Use of minimally invasive surgery and therapies mitigating PSPAP and intraoperative blood loss may offer protection against CSA-AKI
TL;DR: Elevated BUN/Cr ratio is associated with poor prognosis in patients with AFH and is an independent predictor of all-cause mortality.
Abstract: Objective To further explore the relationship between the blood urea nitrogen to creatinine (BUN/Cr) ratio and the prognosis of patients with acute heart failure (AHF), a two-part study consisting of a prospective cohort study and meta-analysis were conducted. Methods A total of 509 hospitalized patients with AHF were enrolled and followed up. Cox proportional hazards regression was used to analyze the relationship between the BUN/Cr ratio and the long-term prognosis of patients with AHF. Meta-analysis was also conducted regarding the topic by searching PubMed and Embase for relevant studies published up to October 2019. Results During a median follow-up of 2.8 years, 197 (42.6%) deaths occurred. The cumulative survival rate of patients with a BUN/Cr ratio in the bottom quartile was significantly lower than in the other 3 groups (log-rank test: p = 0.003). In multivariate Cox regression models, the mortality rate of AHF patients with a BUN/Cr ratio in the bottom quartile was significantly higher than in the top quartile (adjusted HR 1.52; 95% CI 1.03-2.24). For the meta-analysis, we included 8 studies with 4,700 patients, consisting of 7 studies from the database and our cohort study. The pooled analysis showed that the highest BUN/Cr ratio category was associated with an 77% higher all-cause mortality than the lowest category (pooled HR 1.77; 95% CI 1.52-2.07). Conclusions Elevated BUN/Cr ratio is associated with poor prognosis in patients with AFH and is an independent predictor of all-cause mortality.
TL;DR: The predictive ability of all models was similar and only modest, derived mainly by identifying true-negative cases, and different combinations of the >35 independent variables used in the published models either by down- or by up-scaling did not result in significant improvement in predictive performance.
Abstract: Introduction Contrast-induced acute kidney injury (CI-AKI) is a frequent complication of percutaneous coronary interventions (PCI). Various groups have developed and validated risk scores for CI-AKI. Although the majority of these risk scores achieve an adequate accuracy, their usability in clinical practice is limited and greatly debated. Objective With the present study, we aimed to prospectively assess the diagnostic performance of recently published CI-AKI risk scores (up to 2018) in a cohort of patients undergoing PCI. Methods We enrolled 1,247 consecutive patients (80% men, mean age 62 ± 10 years) treated with elective or urgent PCI. For each patient, we calculated the individual CI-AKI risk score based on 17 different risk models. CI-AKI was defined as an increase of ≥25% (liberal) or ≥0.5 mg/dL (strict) in pre-PCI serum creatinine 48 h after PCI. Results CI-AKI definition and, therefore, CI-AKI incidence have a significant impact on risk model performance (median negative predictive value increased from 85 to 99%; median c-statistic increased from 0.516 to 0.603 using more strict definition criteria). All of the 17 published models were characterized by a weak-to-moderate discriminating ability mainly based on the identification of "true-negative" cases (median positive predictive value 19% with liberal criterion and 3% with strict criterion). In none of the models, c-statistic was >0.800 with either CI-AKI definition. Novel, different combinations of the >35 independent variables used in the published models either by down- or by up-scaling did not result in significant improvement in predictive performance. Conclusions The predictive ability of all models was similar and only modest, derived mainly by identifying true-negative cases. A new approach is probably needed by adding novel markers or periprocedural characteristics.
TL;DR: Estimated GFRs calculated with cysC predicted the prognosis more accurately in patients with AHF than the eGFRs from creatinine only equations.
Abstract: Background Renal function is closely related to cardiac function and an important prognostic marker in heart failure. Objective We aimed to test the prognostic value of cystatin C (cysC)-derived estimated glomerular filtration rates (eGFR) in comparison with eGFRs from creatinine solely based equations in patients with acute heart failure (AHF). Methods This study included 262 patients (65.8 ± 14.9 years old, 126 male) with AHF. Prognostic value of the eGFRs, from cysC-based equations chronic kidney disease epidemiology collaboration (CKD-EPI-cysC and CKD-EPI-creatinine [cr]-cysC equations) were compared with eGFRs calculated from serum creatinine levels only (Modification of Diet in Renal Disease [MDRD]-4 and CKD-EPI-cr equations). Prognosis was evaluated with the composite of all-cause mortality and hospitalization for heart failure within 1 year. Results During the follow-up period (mean follow-up period, 264.0 ± 136.1 days), 67 (25.6%) events occurred. Estimated GFR using CKD-EPI-cysC was the best for predicting 1-year outcome using receiver operating characteristic curve analysis (area under curve 0.585, 0.607, 0.669, and 0.652 for eGFRs from MDRD-4, CKD-EPI-cr, CKD-EPI-cysC, and CKD-EPI-cr-cysC respectively). The Kaplan-Meier survival curve analysis showed that only the eGFRs classification from the equations based on cysC significantly predicted 1-year outcome in patients with AHF. Conclusions Estimated GFRs calculated with cysC predicted the prognosis more accurately in patients with AHF than the eGFRs from creatinine only equations.
TL;DR: The complete clinical course of a renal transplant recipient with critical COVID-19 pneumonia, who exhibited extensive lung lesions and significant acute kidney and heart injuries, and fully recovered in 69 days is reported.
Abstract: With the global spread of SARS-Cov-2 infections, increasing numbers of COVID-19 cases have been reported in transplant recipients. However, reports are lacking concerning the treatment and prognosis of COVID-19 pneumonia in renal transplant recipients with acute cardiorenal syndrome. We report here the complete clinical course of a renal transplant recipient with critical COVID-19 pneumonia. In the early phase of SARS-Cov-2 infection, the patient exhibited extensive lung lesions and significant acute kidney and heart injuries, which required treatment in the ICU. After correcting the arrhythmia and heart failure, the patient recovered quickly from the acute kidney injury with a treatment of intensive diuresis and strict control of fluid intake. Without cessation of oral immunosuppressive agents, the patient presented a delayed and low antibody response against SARS-Cov-2 and reappeared positive for the virus twice after being discharged. Nevertheless, the patient's pneumonia continued to improve and he fully recovered in 69 days. This effectively treated case may be meaningful and referable for the treatment of COVID-19 pneumonia in other transplant recipients with acute cardiorenal syndrome.
TL;DR: Both AKI and WRF were found to be closely associated with the 12-month cardiovascular outcome irrespectively of statin choice and high-dose rosuvastatin started upon hospital admission led to similar rates of AKI, 30-day renal function changes, and 12- month death or MI in NSTE-ACS patients who underwent an early invasive strategy.
Abstract: Background/aims Both high-dose atorvastatin and rosuvastatin have been shown to reduce contrast-induced acute kidney injury (AKI) occurrence and improve clinical outcomes in high-risk coronary patients undergoing angiographic procedures. However, there is a lack of head-to-head comparative studies on the effects of atorvastatin or rosuvastatin administered upon hospital admission in statin-naive patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS). Methods In this open-label, noninferiority study, we compared changes in renal function in 709 NSTE-ACS patients randomized to atorvastatin (80 mg upon admission followed by 40 mg/day) or rosuvastatin (40 mg upon admission followed by 20 mg/day). The primary end point was AKI (increase in serum creatinine ≥0.5 mg/dL or ≥25% above baseline within 72 h). Worsening renal function (WRF) (decrease of ≥25% in the glomerular filtration rate from baseline to 30 days), 30-day major adverse cardiovascular events, and 12-month myocardial infarction (MI) or death were also evaluated. Results The AKI incidence was similar in the 2 groups (i.e., 8.2% with rosuvastatin and 7.6% with atorvastatin; absolute risk difference = 0.54; 90% CI -3.9 to 2.8), satisfying the noninferiority criteria. WRF occurred in 53 (7.5%) patients, 19 (34%) of whom had developed AKI. The rates of WRF and adverse events at 30 days and at 12 months did not differ significantly between the 2 groups. Both AKI and WRF were found to be closely associated with the 12-month cardiovascular outcome irrespectively of statin choice. Conclusions High-dose rosuvastatin or atorvastatin started upon hospital admission led to similar rates of AKI, 30-day renal function changes, and 12-month death or MI in NSTE-ACS patients who underwent an early invasive strategy (clinical trial registration: https://www.clinicaltrials.gov; unique identifier: NCT01870804).
TL;DR: DKK-1 seems to have a direct relation with CVC and CIMT in HD patients, and age is the strongest independent determinant of CVC.
Abstract: Background Cardiac valve calcification (CVC) is common in hemodialysis (HD) patients, and associated with cardiovascular and all-cause mortality. Once believed to be a passive process, it is now understood that the Wnt signaling pathway has a major role. The aim of the current study was to assess the relationship between circulating DKK-1, a negative regulator of the Wnt signaling pathway, and CVC, as well as carotid intimal-medial thickness (CIMT) in HD patients. Methods We enrolled 74 consecutive adults on maintenance HD. Echocardiographic calcification of the mitral valve (MV) and aortic valve (AV) were detected according to Wilkins score (range 0-4), and the study of Tenenbaum et al. [Int J Cardiol. 2004 Mar;94(1):7-13] (range 0-4), respectively. CVC severity was calculated by a supposed score (range 0-8) that represents the sum of calcification grade of MV and AV. CVC severity was classified into absent (CVC score = 0), mild (CVC score = 1-2), moderate (CVC score = 3-4), and severe (CVC score ≥5). Demographic and biochemical data were collected in addition to serum DKK-1 levels and CIMT. Results CVC was present in 67 patients (91.0%). There was a highly significant negative correlation between serum DKK-1 level and CVC score (r = -0.492; p ≤ 0.001), as well as CIMT (r = -0.611; p ≤ 0.001). Age and CIMT were independent determinants of CVC. Conclusions CVC is almost present in all HD patients. DKK-1 seems to have a direct relation with CVC and CIMT in HD patients. Age is the strongest independent determinant of CVC.
TL;DR: In patients with AHF and RD at presentation, early spot UNa was inversely related to 24-h diuretic efficiency, and Natremia and surrogates of congestion emerged as the main factors related to UNa.
Abstract: OBJECTIVE In acute heart failure (AHF), early assessment of spot urinary sodium (UNa) has emerged as a useful biomarker for risk stratification and monitoring. The objective of this study was to investigate (a) whether early spot UNa predicts 24-h diuretic efficiency and (b) the clinical factors associated with early spot UNa in patients with AHF and concomitant renal dysfunction (RD). METHODS This is a post hoc analysis of the IMPROVE-HF trial, in which 160 patients with AHF and RD (estimated glomerular filtrate rate [eGFR] <60 mL/min/1.73 m2) were included. Diuretic efficiency was calculated as the net fluid output produced per 40 mg of furosemide equivalents in 24 h. The association between early spot UNa and diuretic efficiency and clinical variables associated with UNa were evaluated using multivariate linear regression analysis. The contribution of the exposures in the predictability of the models was assessed with the coefficient of determination (R2). RESULTS The mean age of the study population was 78 ± 8 years. The median (interquartile range) diuretic efficiency, early spot UNa, aminoterminal pro-brain natriuretic peptide, and eGFR were 747 (490-1,167) mL, 90 mmol/L (65-111), 7,765 pg/mL (3,526-15,369), and 33.7 ± 11.3 mL/min/1.73 m2, respectively. In a multivariate setting, lower UNa was significantly and nonlinearly associated with lower diuretic efficiency (p = 0.001), explaining the 44.4% of the model predictability. Natremia and surrogates of congestion emerged as the main factors related to UNa. CONCLUSIONS In patients with AHF and RD at presentation, early spot UNa was inversely related to 24-h diuretic efficiency.
TL;DR: The obtained data suggest that high levels of circulating resistin acting upon cells with an upregulated CAP1 gene could contribute to the increased inflammation and accelerated atherosclerosis seen in CKD patients.
Abstract: BACKGROUND Human resistin is a proinflammatory cytokine with significant proatherogenic effects which acts through adenylyl cyclase-associated protein 1 (CAP1). Chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients have increased cardiovascular risk and resistin levels. Previous studies indicated resistin significance as a predictor of mortality in CKD. AIMS We sought to investigate plasma resistin levels, peripheral blood mononuclear cell (PBMC) resistin mRNA, and for the first time CAP1 mRNA levels in ESRD patients and healthy controls. We also sought to investigate the relation of resistin and CAP1 to carotid intima media thickness (CIMT), CD36 gene expression, and matrix metalloproteinase 9 (MMP-9) circulating levels in ESRD patients and healthy controls. METHODS This study included 33 patients with ESRD and 27 healthy controls. Resistin and MMP-9 levels were measured by ELISA. Resistin, CAP1, and CD36 PBMC mRNA were measured by quantitative PCR. RESULTS Our study showed that ESRD patients have significantly higher levels of circulatory resistin compared to healthy controls (p < 0.001), while there was no significant difference in resistin mRNA. A significant upregulation of CAP1 and CD36 was observed in the ESRD group (p < 0.001; p < 0.001). Resistin concentration correlated with CIMT in healthy controls (r = 0.512, p = 0.036), and with MMP-9 concentration in ESRD (r = 0.353, p = 0.044) and healthy controls (r = 0.463, p = 0.026). CAP1 correlated positively with CIMT (r = 0.464, p = 0.008) in ESRD, and with CD36 in healthy controls (r = 0.447, p = 0.022) and ESRD (r = 0.824, p < 0.001). CONCLUSION The obtained data suggest that high levels of circulating resistin acting upon cells with an upregulated CAP1 gene could contribute to the increased inflammation and accelerated atherosclerosis seen in CKD patients.
TL;DR: AKI following DCCV of AF is common, self-limited, and without the need for replacement therapies, and was independent of the success of the D CCV.
Abstract: Introduction Emerging data suggest that cardioversion for atrial fibrillation (AF) may be associated with acute kidney injury (AKI). However, limited data are available regarding the incidence and risk factors for AKI after direct current cardioversion (DCCV) of AF. Methods All patients undergoing DCCV at Mayo Clinic between 2001 and 2012 for AF were prospectively enrolled in a database. All patients with serum creatinine (SCR) values pre- and post-cardioversion were reviewed for AKI, defined as a ≥25% decline in eGFR (estimated glomerular filtration rate) from baseline value within 7 days of the DCCV. Results Of the 6,427 eligible patients, 1,256 (19.5%) patients had pre- and post-DCCV SCR available and formed the cohort under study. The mean age was 70.4 (SD 11.7) years, and 67.3% were male. During the study period, 131 (10.4%) patients suffered from AKI following DCCV. AKI was independently associated with inpatient status (OR 26.79; 95% CI 3.69-194.52), CHA2DS2-VASc score (OR 1.25; 95% CI 1.11-1.41), prior use of diuretics (OR 1.59; 95% CI 1.03-2.46), and absence of CKD (OR 1.61; 95% CI 1.04-2.49), and was independent of the success of the DCCV. None of the patients required acute dialysis during the study outcome period. Conclusion AKI following DCCV of AF is common, self-limited, and without the need for replacement therapies.
TL;DR: Based on limited data, CCTA appears to have comparable sensitivity but lower specificity relative to the non-kidney disease population.
Abstract: Introduction: Coronary computed tomography angiography (CCTA) is emerging as an important noninvasive testing modality for coronary angiography. The performance characteristic of CCTA in patients with advanced kidney disease is unknown. Methods: We performed a systematic review and meta-analysis of studies specifically investigating the sensitivity and specificity of CCTA compared to coronary angiogram as a reference standard in patients with advanced kidney disease, defined as dialysis dependence or nearing kidney transplantation. Two independent investigators assessed studies for inclusion/exclusion, quality, and characteristics, while a third investigator adjudicated. Results: We identified 4 studies including a total of 217 patients, of whom 159 were dialysis dependent. Three of the 4 studies had a high risk of bias in patient selection and study flow, while 1 study rated low in all areas of bias. The studies were heterogeneous in their patient selection and CCTA protocol but consistent in their definition of obstructive coronary artery disease. The pooled sensitivity and specificity for CCTA were 0.96 (0.87–0.99) and 0.66 (0.57–0.74), respectively. When we restricted the analysis to dialysis-dependent patients, the pooled sensitivity and specificity for CCTA were 0.99 (0.74–1.00) and 0.67 (0.49–0.82), respectively. Conclusions: Based on limited data, CCTA appears to have comparable sensitivity but lower specificity relative to the non-kidney disease population.
TL;DR: Plasma TWEAK is inversely associated with carotid IMT among patients undergoing HD and PD and its correlation with micro-inflammation and atherosclerosis in continuous ambulatory peritoneal dialysis patients is found to be significant.
Abstract: BACKGROUND/AIMS This study aimed to investigate the level of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and its correlation with micro-inflammation and atherosclerosis in continuous ambulatory peritoneal dialysis (PD) patients. METHODS This retrospective study involved 23 healthy subjects (control group), 23 hemodialysis (HD) patients (HD group) and 26 PD patients (PD group). Serum biochemical measurements and sTWEAK assessments were tested. The association between intima-media thickness (IMT) and sTWEAK concentrations was evaluated. RESULTS The TWEAK level was lower in PD (155.16 ± 3.69 pg/mL, p 161.9 pg/mL), patients who had a higher level of sTWEAK (>161.9 pg/mL) had a lower IMT (0.97 ± 0.04 vs. 0.84 ± 0.03 cm, p = 0.029). After adjusted for sex, age, hypertension, diabetes, duration of dialysis, triglyceride, total cholesterol, low-density lipoprotein, and serum glucose, sTWEAK (B = -0.002, r = 0.015) and CRP (B = 0.022, r = 0.015) were independent risk factors for the IMT of ESRD patients. CONCLUSION Plasma TWEAK is inversely associated with carotid IMT among patients undergoing HD and PD.