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.