Evolving Treatment Strategies for Management of Cardiorenal Syndrome

Abstract

The treatment of acute decompensated heart failure in the presence of progressive renal dysfunction is a commonly encountered dilemma in clinical practice. Also known as cardiorenal syndrome, this complex disease state has forced researchers and clinicians to develop new treatment strategies to relieve the symptomatic congestion of heart failure while preserving renal function. Loop diuretics remain the standard of pharmacologic treatment of acute heart failure, but their effects on renal function have been called into question. The DOSE trial set out to determine optimal diuretic dosing strategies but no clear regimen was firmly established. Initial studies with vasopressin antagonists showed promise in their ability to increase urine output, provide short-term symptom relief, and correct hyponatremia while maintaining renal function. Unfortunately, the EVEREST trial did not demonstrate any benefit on long-term clinical outcomes. Adenosine antagonists also appeared to be an emerging therapeutic option, but the recently completed PROTECT trial failed to establish their role in the treatment of cardiorenal syndrome. Both nesiritide and low-dose dopamine have endured years of trials with mixed results. Most recently, findings from the ASCEND-HF trial showed that nesiritide was safe with no adverse effects on renal function or mortality and was associated with a modest improvement in dyspnea. The ongoing ROSE study, sponsored by the National Institutes of Health Heart Failure Research Network, will attempt to confirm the safety and efficacy profiles of low-dose nesiritide and dopamine, as well as clarify their roles within acute heart failure management. Despite its inherent complexities, ultrafiltration has demonstrated potential benefit in several clinical outcomes compared to traditional pharmacotherapy. The results of the CARRESS-HF trial will reveal how the use of ultrafiltration specifically applies to patients with cardiorenal syndrome. The most exciting aspects about our evolving understanding of the cardiorenal system are the innovative treatments that have emerged as a result. The creation of chimeric natriuretic peptides, targeted intra-renal pharmacotherapy, the novel use of phosphodiesterase inhibitors, and combination treatment strategies demonstrate that despite our varied success in treating cardiorenal syndrome in the past, there are highly encouraging translational therapies rapidly developing in the pipeline.