Cardiorenal syndrome: new developments in the understanding and pharmacologic management

Abstract

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.

Figure 1.

Dual hemodynamic pathways for acute cardiorenal syndrome. In this schematic, impaired forward flow and decreased effective circulating volume, as would be seen in severe systolic heart failure or cardiogenic shock, leads to arterial underfilling and activation of neurohormonal and inflammatory pathways. Autoregulation of GFR fails and kidney function declines, leading to worsening fluid retention, preload, and afterload. In a separate process, venous congestion and high right-sided pressure predominate, as would be seen in heart failure with preserved ejection fraction or isolated right heart failure. This also leads to decreased kidney function, worsening of fluid retention, and increased preload and afterload. These pathways are not mutually exclusive and often coexist in the same patient to varying degrees. AV, arteriovenous; IAP, intra-abdominal pressure; RAAS, renin-angiotensin-aldosterone system; RBF, renal blood flow; RPF, renal plasma flow; SNS, sympathetic nervous system.

Figure 2.

Changes in renal function over time. (A) For intermittent furosemide injection every 12 hours (blue line) versus continuous furosemide infusion (red line). (B) For high-dose furosemide (blue line) versus low-dose furosemide (green line). Modified from reference , with permission. P>0.05 for all timepoints.

Figure 3.

Loss of calculated GFR (GFR_c) for groups treated with placebo (open circle; n=104) or captopril (closed circle; n=121) versus baseline GFR_c (day 0) over the first year after myocardial infarction. Values are expressed in mean ± SEM. Reproduced from reference , with permission.