Management of Cardio-Renal Syndrome and Diuretic Resistance

Abstract

Diuretic resistance in acute heart failure has emerged as a powerful predictor of adverse outcome, which is often independent of underlying glomerular filtration rate (GFR). Metrics of diuretic efficacy differ in their accuracy, convenience, and biological plausibility, which should be taken into account when interpreting their results. Loop diuretic efficacy depends on adequate delivery of both the pharmacological agent itself and its substrate (i.e., sodium chloride) to the loop diuretic site of action at the luminal side of the thick ascending limb of Henle's loop. This requires an adequate dosing strategy, with higher doses needed when GFR is low. Importantly, the kidneys are able only to regulate the effective circulatory volume. Thus, specific problems of intravascular volume depletion and poor cardiac output with impaired renal perfusion should be addressed. Addition of thiazide-type diuretics should be considered when a progressive decrease in loop diuretic efficacy is observed with prolonged use (i.e., the braking phenomenon). Furthermore, thiazide-type diuretics are a useful addition in patients with low GFR to maximally boost fractional sodium excretion when nephron perfusion is poor. However, thiazide-type diuretics limit free water excretion and should be withheld in cases of hypotonic hyponatremia. Mineralocorticoid receptor antagonists (MRA) and acetazolamide are interesting options to increase loop diuretic efficacy, but further study is needed to assess whether improved diuretic efficacy also translates into clinical outcome benefits. Finally, ultrafiltration should be considered in patients with refractory diuretic resistance as persistent volume overload after decongestive treatment is associated with worse outcomes. Whether more upfront use of individually tailored ultrafiltration is superior to pharmacological therapy remains to be shown by adequately powered randomized clinical trials.

Keywords: Acetazolamide; Cardio-renal syndrome; Cardiotonic agents; Diuresis; Glomerular filtration rate; Heart failure.