Can the difference in serum concentration of urea and cystatin C be used in diagnosis and prognosis of heart failure?

Abstract

Changes in renal function are an important diagnostic and prognostic indicator in patients with heart failure (HF). They are caused by decreased renal perfusion and consequently decreased glomerular filtration rate (GFR), or by the effect of increased neurohormonal activity (sympathetic nervous system [SNS], rennin-angiotensin-aldosterone system [RAAS] and arginine vasopressin [AVP]). However, the increase of serum concentration of urea, creatinine and other metabolites is not specific for HF. Therefore, it is not possible to distinguish HF from renal diseases solely based on the increase of their concentration, since the increase of their concentration caused by the decrease of GFR cannot be differentiated from the increase due to neurohormonal activity. Urea and cystatin C (Cys C) have different mechanisms of renal elimination, so it can be assumed that in HF their concentrations will not be increased proportionally, what can be used for diagnostic and prognostic purposes. After glomerular filtration Cy C undergoes proximal tubular reabsorption and breakdown, without returning to the blood flow. Since it is not secreted, its serum concentration depends only on GFR. In contrast to Cys C, urea is filtered in glomerulus and subsequently reabsorbed in proximal tubules and collecting duct. Reabsorption of urea is modified by effects of SNS, RAAS and AVP. Therefore its serum concentration depends upon GFR and neurohormonal effect on the tubular function. Since the increase of serum concentration of Cys C is caused only by the effect of the decreased renal perfusion on GFR, while the increase of urea is a result from both decreased GFR and tubular effects of increased neurohormonal activity, the paper hypothesis is that in HF the increase of urea will be significantly higher than the increase of serum Cys C, while in the patients with renal diseases their increase would be mostly proportional. It can be assumed that the disproportion between the increase of Cys C and urea would indicate an increased neurohormonal activity in patients with HF and correlate with its activity. If this hypothesis is proved correct, this parameter could be used in HF diagnosis and risk stratification of such patients.