Cardiorenal syndromes (CRSs) with bidirectional heart-kidney signaling are increasingly being recognized for their association with increased morbidity and mortality. In acute CRS, recognition of the importance of worsening kidney function complicating management of acute decompensated heart failure has led to the examination of this specific outcome in the context of acute heart failure clinical trials. In particular, the role of fluid overload and venous congestion has focused interest in the most effective use of diuretic therapy to relieve symptoms of heart failure while at the same time preserving kidney function. Additionally, many novel vasoactive therapies have been studied in recent years with the hopes of augmenting cardiac function, improving symptoms and patient outcomes, while maintaining or improving kidney function. Similarly, recent advances in our understanding of the pathophysiology of chronic CRS have led to reanalysis of kidney outcomes in pivotal trials in chronic congestive heart failure, and newer trials are including changes in kidney function as well as kidney injury biomarkers as prospectively monitored and adjudicated outcomes. This paper provides an overview of some new developments in the pharmacologic management of acute and chronic CRS, examines several reports that illustrate a key management principle for each subtype, and discusses opportunities for future research.
Abstract Introduction and Objectives The ImmuKnow assay measures cell‐mediated immunity by quantifying ATP release from CD 4+ T‐cells in peripheral blood. Herein, we hypothesized that this assay could predict complications associated with over‐/under‐immunosuppression in patients with kidney transplant ( KT ). Methods Sixty‐seven patients undergoing KT were recruited prospectively and had ATP levels measured preoperatively, and at specified intervals over two months. Clinicians were blinded to ATP levels. Clinical events including rejection and infection/cancer were documented with a median follow‐up of 21 months. Parameters including absolute ATP levels and changes in ATP patterns (slopes, delta) were analyzed. Association between ATP parameters and clinical outcomes was compared using the likelihood‐ratio test and Kaplan–Meier curves. Results Absolute ATP values postoperatively had poor predictive value with regard to rejection or infection/malignancy. As well, changes in ATP values were poorly associated with complications. Importantly, patients with pre‐transplant ATP values <300 ng/mL had significantly less rejection episodes vs. those with ATP values >300 ng/mL (p < 0.0001). Conclusions For the first time, we have evidence that a preoperative ImmuKnow level can stratify patients with KT into low/high risk groups for rejection. Future studies used to assess the utility of this assay to design individualized immunosuppressive regimens are required.
Biomarkers of carotid atherosclerosis range from those that are widely available and relatively simple to measure such as serum cholesterol levels, and B-mode Ultrasound measurement of intima media thickness (IMT) to those that are more complex and technologically demanding but perhaps potentially more sensitive and specific to disease such as total plaque volume and total plaque area measured from 3-dimensional ultrasound images. In this study we measured and compared intima media thickness (IMT), total plaque volume (TPV) and total plaque area (TPA) in two separate populations, both vulnerable to carotid atherosclerosis.In total, 88 subjects (mean age 72.8) with carotid stenosis of at least 60%, based on a peak Doppler flow, and 82 subjects (mean age 60.9) with diabetic nephropathy were assessed in a cross-sectional study. Conventional atherosclerotic risk factors were examined and the associations and correlations between these and carotid ultrasound phenotypes measured from B-mode and 3-dimensional ultrasound images were assessed.IMT and TPV were only modestly correlated in the two separate populations (r = .6, p < .01). ANOVA analyses indicated that both IMT and TPV were significantly associated with age (p < .001) and Framingham score (p < .05), but only TPV was associated with diabetes (p < .001) and presence of plaque ulcerations (p < .01)IMT and TPV were modestly correlated in a diabetic patient population and only TPV was associated with diabetes and the presence of plaque ulcerations in a diabetic population and carotid stenosis group. The 3-dimensional information provided by TPV can be critically important in unmasking association with risk factors not observed with less complex single-dimension assessments of carotid atherosclerosis such as those provided by IMT.
