Clinical Utility of a Biomarker to Detect Contrast-Induced Acute Kidney Injury during Percutaneous Cardiovascular Procedures

<b><i>Introduction:</i></b> Contrast-induced acute kidney injury (CI-AKI) is a major clinical complication of percutaneous cardiovascular procedures requiring iodinated contrast. Despite its relative frequency, practicing physicians are unlikely to identify or treat this condition. <b><i>Methods:</i></b> In a 2-round clinical trial of simulated patients, we examined the clinical utility of a urine-based assay that measures liver-type fatty acid-binding protein (L-FABP), a novel marker of CI-AKI. We sought to determine if interventional cardiologists’ ability to diagnose and treat potential CI-AKI improved using the biomarker assay for 3 different patient types: pre-procedure, peri-procedure, and post-procedure patients. <b><i>Results:</i></b> 154 participating cardiologists were randomly divided into either control or intervention. At baseline, we found no difference in the demographics or how they identified and treated potential complications of AKI, with both groups providing less than half the necessary care to their patients (46.4% for control vs. 47.6% for intervention, <i>p</i> = 0.250). The introduction of L-FABP into patient care resulted in a statistically significant improvement of 4.6% (<i>p</i> = 0.001). Compared to controls, physicians receiving L-FABP results were 2.9 times more likely to correctly identify their patients’ risk for AKI (95% CI 2.1–4.0) and were more than twice as likely to treat for AKI by providing volume expansion and withholding nephrotoxic medications. We found the greatest clinical utility in the pre-procedure and peri-procedure settings but limited value in the post-procedure setting. <b><i>Conclusion:</i></b> This study suggests L-FABP as a clinical marker for assessing the risk of potential CI-AKI, has clinical utility, and can lead to more accurate diagnosis and treatment.

Association of trimethylamine-N-oxide levels with risk of cardiovascular disease and mortality among elderly subjects: a systematic review and meta-analysis

Background: Trimethylamine-N-Oxide (TMAO) is a microbiome-related metabolite that has been linked to cardiovascular and renal function. This study has reviewed and analyzed the relationship between TMAO and all-cause mortality and adverse cardiovascular events in the elderly subjects. Methods: We determined whether this association was modified in the presence of CKD, heart failure and diabetes. Based on the criteria, systematic review and meta-analysis were conducted and performed. Results: A total of 27 prospective cohort studies were retrieved finally to examine the associations. The high TMAO was positively associated with all-cause mortality [HR: 1.38 (95% CI: 1.306 to 1.460)] as well as adverse cardiovascular events. [HR: 1.032 (95% CI: 1.014 to 1.051)]. The association remained upon subgroup analysis for patients with CKD and heart failure but no association for patients with diabetes [HR: 1.15 (95% CI, 0.81–1.64)]. Conclusions: The findings of this review revealed that the TMAO level is associated with all-cause mortality and adverse cardiovascular events.

When Heart Failure Collides with Diabetes and Chronic Kidney Disease: Challenges and Opportunities

Background: Heart failure (HF), diabetes mellitus (DM), and chronic kidney disease (CKD) are commonly occurring and interlinked conditions. Approximately 25% to 40% of patients with HF have DM, and approximately 40% to 50% of patients with HF have CKD. Both DM and CKD are associated with increased risk of incident HF. Further, 40% of people with DM develop CKD, making DM the leading cause of kidney failure globally. Importantly, 16% of patients with HF have both comorbid DM and CKD, and the combination of these 3 comorbidities is associated with substantially increased risk for hospitalization and mortality. Mechanisms that underlie the relationships between HF, DM, and CKD are complex but likely relate to shared cardiovascular and metabolic risk factors, as well as downstream effects on inflammation, oxidative stress, and neurohormonal pathways. Summary: This review outlines the epidemiology and links between HF, DM, and CKD, as well as current clinical evidence for the treatment of individuals with a combination of these comorbidities. A case study of a patient with concomitant HF, DM, and CKD is discussed to explore potential treatment approaches for patients in whom all 3 comorbidities exist. Key Messages: Treatment plans for patients with a combination of these 3 comorbidities should consider the available clinical evidence.

Patterns of Use and Clinical Outcomes with Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Acute Heart Failure and Changes in Kidney Function: An Analysis of the Veterans’ Health Administrative Database

<b><i>Objective:</i></b> The aim of the study was to determine patterns and predictors of utilization of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs) in patients with acute heart failure (AHF) and changes in kidney function at admission, hospitalization, and discharge in relation to clinical outcomes. <b><i>Methods:</i></b> This retrospective analysis of the Veterans’ Health Administration data (2016) included patients with heart failure (HF) with reduced ejection fraction who were hospitalized. Patients with an estimated glomerular filtration &#x3c;15 cm³/min/1.73 m² and those on dialysis were excluded. Patients were categorized based on the use of ACEI/ARB as continued, initiated, discontinued, or no therapy. Multivariable logistic regression evaluated predictors of being discharged home on an ACEI/ARB. Cox regression analysis evaluated outcomes (30 and 180-day mortality/HF readmissions). <b><i>Results:</i></b> 3,652 patients were included, of which 37% of patients hospitalized for AHF had ACEI/ARB discontinued on admission, or not initiated. After adjusting for age, blood pressure, and serum potassium, a per-unit increase in admission serum creatinine (SCr) was independently associated with lower rates of continuation or initiation of ACEI/ARB odds ratio 0.51 95% confidence interval (CI) (0.46–0.57). Discharge on ACEI/ARB was independently associated with lower odds of 30- and 180-day mortality hazard ratio (HR) 0.36 95% CI (0.25–0.52), and HR 0.23 95% CI (0.19–0.27), respectively. <b><i>Conclusion:</i></b> Higher SCr at admission is an important determinant of ACEI/ARB being discontinued or withheld in patients admitted with AHF. ACEI/ARB at discharge was associated with lower mortality in patients with AHF.

The Role of Cell-Free Plasma DNA in Patients with Cardiorenal Syndrome Type 1

<b><i>Background:</i></b> Recent research highlighted the potential role of circulating cell-free DNA (cfDNA), resulted by apoptosis or cell necrosis, as a prognostic marker in the setting of different clinical conditions. Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Apoptosis of renal epithelial cells is proposed as a mechanism involved in CRS type 1. In this study, we investigated cfDNA levels in patients with acute heart failure (AHF) and CRS type 1 and the possible correlation between cfDNA levels and inflammatory and apoptotic parameters. <b><i>Methods:</i></b> We enrolled 17 AHF patients and 15 CRS type 1 who exhibited AKI at the time of admission (caused by AHF) or developed AKI during the first 48 h from admission. cfDNA was extracted from plasma and quantified by real-time polymerase chain reaction. Plasma levels of NGAL, tumor necrosis factor-α, interleukin (IL)-6, IL-18, and caspase-3 were measured. <b><i>Results:</i></b> We observed significantly higher levels of cfDNA in patients with CRS type 1 than patients with AHF. Caspase-3, IL-6, IL-18, and NGAL levels resulted significantly increased in patients with CRS type 1. Moreover, a positive correlation between cfDNA levels and caspase-3 levels was found, as well as between cfDNA levels and IL-6 and renal parameters. <b><i>Conclusion:</i></b> Our study explores the premise of cfDNA as a marker for apoptosis and inflammation in CRS type 1 patients. cfDNA could potentially serve as an index for noninvasive monitoring of tissue damage and apoptosis in patients with AKI induced by AHF.

The Association of Pre-Kidney Transplant Dialysis Modality with de novo Posttransplant Heart Failure

<b><i>Background:</i></b> Heart failure (HF) after kidney transplantation is a significant but understudied problem. Pretransplant dialysis modality could influence incident HF risk through differing cardiac stressors. However, whether pretransplant dialysis modality is associated with the development of posttransplant HF is unknown. <b><i>Methods:</i></b> We used the US Renal Data System to assemble a cohort of 27,701 patients who underwent their first kidney transplant in the USA between the years 2005 and 2012 and who had Medicare fee-for-service coverage for &#x3e;6 months preceding their transplant date. Patients with any HF diagnosis prior to transplant were excluded. Detailed baseline patient characteristics and comorbidities were abstracted. The outcome of interest was de novo posttransplant HF. Pretransplant dialysis modality was defined as the dialysis modality used at the time of transplant. We conducted time-to-event analyses using Cox regression. Death was treated as a competing risk in the study’s primary analysis. Graft failure was included as a time-varying covariate. <b><i>Results:</i></b> Among eligible patients, 81% were treated with hemodialysis prior to transplant, and hemodialysis patients were more likely to be male, had a shorter dialysis vintage, and had more diabetes and vascular disease diagnoses. When adjusted for all available demographic and clinical data, pretransplant treatment with hemodialysis (vs. peritoneal dialysis) was associated with a 19% increased risk in de novo posttransplant HF, with sub-distribution HR 1.19 (95% CI: 1.09–1.29). <b><i>Conclusions:</i></b> Our results suggest that choice of pretransplant dialysis modality may impact the development of posttransplant HF.

Major Adverse Renal and Cardiovascular Events following Intra-Arterial Contrast Media Administration in Hospitalized Patients with Comorbid Conditions

<b><i>Introduction:</i></b> Several clinical studies and meta-analyses have demonstrated lower incidence of adverse renal and cardiovascular outcomes associated with the use of iso-osmolar contrast media (IOCM) than low-osmolar contrast media (LOCM) in patients with variable risk profiles undergoing intra-arterial interventional procedures. However, the association of contrast-type and major adverse renal and cardiovascular events (MARCE) has not been studied via comprehensive and robust real-world data analyses in patients with comorbid conditions considered at risk for post-procedural acute kidney injury (AKI). The objective of this study was therefore to retrospectively assess the MARCE rates comparing IOCM with LOCM in at-risk patients receiving iodinated intra-arterial contrast media using a real-world inpatient data source. <b><i>Methods:</i></b> Patients who underwent a diagnostic or treatment procedure with intra-arterial IOCM or LOCM administration were identified using the Premier Healthcare Database. Patient subgroups including those with diabetes, heart failure, chronic kidney disease (CKD) stages 1–4, CKD 3–4, or diagnosis of chronic total occlusion (CTO) were formed. Subgroups with combinations of diabetes and CKD 3–4 with and without CTO were also investigated. We compared the primary endpoint of MARCE (composite of AKI, AKI requiring dialysis, acute myocardial infarction, stroke/transient ischemic attack, stent occlusion/thrombosis, or death) after IOCM versus LOCM administration via adjusted multivariable regression analyses. <b><i>Results:</i></b> A total of 536,013 inpatient visits met the primary inclusion and exclusion criteria (IOCM = 133,192; LOCM = 402,821). After multivariable modeling, the use of IOCM was associated with a significantly lower incidence of MARCE than LOCM in patients with CKD 1–4, CKD 3–4, diabetes, or heart failure, with greatest absolute risk reduction (ARR) of 2.4% (<i>p</i> &#x3c; 0.0001) in CKD 3–4 patients (relative risk reduction [RRR] = 13.8%, number needed to treat [NNT] = 43). Additionally, ARR associated with IOCM increased to 3.5% (<i>p</i> &#x3c; 0.0001) in patients with combined comorbidities of diabetes and CKD 3–4 (RRR = 19.1%, NNT = 29). Statistically significant risk reduction was also found for the use of IOCM among patients who underwent revascularization for CTO (ARR = 1.6% [<i>p</i> &#x3c; 0.0001], RRR = 22.3%, NNT = 62). <b><i>Conclusion:</i></b> Intra-arterial administration using IOCM in at-risk patients is associated with lower rates of MARCE than the use of LOCM. This difference is especially apparent in patients with a combination of CKD 3–4 and diabetes and in patients with CTO, providing real-world data validation with meaningful NNT in favor of IOCM.

The Contribution of Known Familial Cardiovascular Disease Genes to Sudden Cardiac Death in Patients Undergoing Hemodialysis

<b><i>Introduction:</i></b> Patients with chronic kidney disease experience high rates of cardiovascular mortality and morbidity. When kidney disease progresses to the need for dialysis, sudden cardiac death (SCD) accounts for 25–35% of all cardiovascular deaths. The objective was to determine if rare genetic variants known to be associated with cardiovascular death in the general population are associated with SCD in patients undergoing hemodialysis. <b><i>Methods:</i></b> We performed a case-control study comparing 126 (37 African American [AfAn] and 89 European ancestry [EA]) SCD subjects and 107 controls (34 AfAn and 73 EA), matched for age, sex, self-reported race, dialysis duration (&#x3c;2, 2–5 and &#x3e;5 years), and the presence or absence of diabetes mellitus. To target the coding regions of genes previously reported to be associated with 15 inherited cardiac conditions (ICCs), we used the TruSight Cardio Kit (Illumina, San Diego, CA, USA) to capture the genetic regions of interest. In all, the kit targets 572-kb regions that include the protein-coding regions and 40-bp 5′ and 3′ end-flanking regions of 174 genes associated with the 15 ICCs. Using the sequence data, burden tests were conducted to identify genes with an increased number of variants among SCD cases compared to matched controls. <b><i>Results:</i></b> Eleven genes were associated with SCD, but after correction for multiple testing, none of the 174 genes were identified as having more variants in the SCD cases than the matched controls, including previously identified genes. Secondary burden tests grouping variants based on diseases and gene function did not produce statistically significant associations. <b><i>Discussion/Conclusions:</i></b> We found no associations between genes known to be associated with ICCs and SCD in our sample of patients undergoing hemodialysis. This suggests that genetic causes are unlikely to be a major pathogenic factor in SCD in hemodialysis patients, although our sample size limits definitive conclusions.

Valvular Calcific Deposits and Mortality in Peritoneal Dialysis Patients: A Propensity Score-Matched Cohort Analysis

<b><i>Objective:</i></b> This study aimed to compare mortality between peritoneal dialysis (PD) patients with and without cardiac valve calcification (CVC). <b><i>Methods:</i></b> Patients undergoing PD at the dialysis center of the Second Affiliated Hospital of Soochow University from January 1, 2009, to June 31, 2016, were included and followed through December 31, 2018. The inclusion criteria were (1) age ≥18 years and (2) PD vintage ≥1 month. The exclusion criteria were (1) a history of hemodialysis or renal transplantation before PD; (2) diagnosed congenital heart disease, rheumatic heart disease, or hyperthyroid heart disease; and (3) loss to follow-up. Differences in mortality rates were compared using a Fine-Gray proportional hazards model. <b><i>Results:</i></b> A total of 310 patient cases were included in this study, including 237 cases without CVC (non-CVC group). The CVC group included 59 cases with aortic valve calcification (AVC), 6 cases with mitral valve calcification (MVC), and 8 cases of AVC associated with MVC. After propensity score matching, 68 pairs were selected. The multivariate competing risk regression analysis revealed that age (hazard ratio [HR]: 1.06, 95% confidence interval [95% CI]: 1.03–1.10, <i>p</i> &#x3c; 0.001) and CVC group (HR: 1.83, 95% CI: 1.04–3.20, <i>p</i> &#x3c; 0.05) were independent risk factors associated with mortality. No significant difference was observed in technique survival between the 2 groups. <b><i>Conclusion:</i></b> CVC is an independent risk factor for mortality in PD patients.