Key result
While many therapies for cardiorenal syndrome have failed to show survival benefits, recent trials involving relaxin and neprilysin inhibitors have demonstrated promising survival advantages.
This review highlights the pathophysiology and therapeutic challenges of cardiorenal syndrome, noting that while many interventions have failed to improve outcomes, novel therapies like neprilysin inhibitors and relaxin offer new hope.
May support further study of neprilysin inhibitors and relaxin in cardiorenal syndrome; leaves open need for confirmatory RCTs.
Kidneys have a pivotal role in maintaining our homeostasis. Kidneys and heart work in tandem to maintain volume homeostasis. Heart failure impacts renal function in many ways including renal hypo perfusion but also due to increased venous pressure along with stimulation of various neuro-humoral responses. Renal failure induces cardiac damage and dysfunction by causing volume overload, inflammation and cardiomyocyte fibrosis. Concomitant comorbidities like Hypertension and Diabetes also play important role resulting in Cardiorenal Syndrome (CRS). Acute Dialysis Quality Initiative, 2007 recognized the bidirectional nature and different manifestations of CRS in acute and chronic settings. Diuretics are the most common drugs to treat the most common symptoms of CRS i.e., peripheral edema and pulmonary congestion. Diuretics could nevertheless contribute to worsening renal function (WRF). Initially it was accepted that WRF during the course of treatment of acute decompensated heart failure (ADHF) uniformly resulted in worse prognosis. However, in view of a few recent studies, the significance of WRF early in response to treatment of ADHF is being debated. The optimal dose and method of delivery of diuretics is still undecided. Isolated ultrafiltration does not improve renal function in patients with CRS despite the early promise. A large, multicentre trial ruled out any survival benefits with Recombinant Brain Natriuretic Peptide (Nesiritide). Despite good physiological basis and early promise with smaller studies, many drugs like Dobutamine, Rolofylline and Tolvaptan failed to show survival benefit in larger studies. However, two recent studies involving Relaxin and Neprilysin have shown good survival advantage. There had been little progress in treatment of CRS until studies involving Relaxin and Neprilysin inhibitor combination with ARB were published. There may after all, be a glimmer of hope in the field of CRS bogged by multiple negative studies.
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Jagadish Jamboti (2015) conducted a review in Cardio Renal Syndrome. While many therapies for cardiorenal syndrome have failed to show survival benefits, recent trials involving relaxin and neprilysin inhibitors have demonstrated promising survival advantages.
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