Diuretic response and cardiorenal interaction in heart failure

The kidney plays a key role in patients with heart failure – poor function of either organ can negatively affect the other. This thesis examines the impact, measurement and modulation of kidney function in acute and chronic heart failure. One study confirmed the importance of kidney disease for predicting death in a meta-analysis of over 1 million heart failure patients. Other studies validated recent equations for estimating kidney function, and investigated the potential role novel biomarkers – substances that can be measured in blood or urine – may play in providing insights into (worsening) kidney function in heart failure patients.
The kidney is also a target for many heart failure therapies, including diuretics - drugs that improve symptoms of fluid retention by increasing urine production. Diuretic resistance – a condition where these drugs fail to work effectively – is a common problem in the treatment of heart failure, but remains poorly defined. We developed a measure to quantify diuretic response in acute heart failure to help improve understanding of this phenomenon. We found poor response to diuretics was more common in patients with more advanced heart failure, coronary heart disease, diabetes, anaemia and renal dysfunction. We also showed poor response was associated with death and rehospitalization, even after correcting for other risk factors. Multiple mechanisms are involved in diuretic resistance, including reduced drug availability and effects of hormonal activation on the kidney, representing potential avenues for addressing this problem. Further research will be required to identify which treatment strategies will best benefit diuretic resistant patients.