Renal dysfunction and heart failure: things are seldom what they seem.

Heart failure (HF) is a risk factor for the development of chronic kidney disease (CKD) and vice versa, while the two conditions quite often co-exist. About one-third of HF patients suffer from at least mild to moderate CKD and about a quarter of them develop worsening renal function (WRF) during their hospitalization for HF. –4 Renal dysfunction is an independent predictor of adverse prognosis in HF, but the significance of transient WRF during hospitalization for HF has not been fully investigated. The potential pathogenetic pathways linking HF with renal dysfunction are outlined in Figure 1. In their comprehensive meta-analysis of studies on the association between renal dysfunction and HF outcomes, Damman et al. provide updated evidence covering the wide spectrum of HF in its acute and chronic setting. Pooled data from . 1 million HF patients showed that CKD was present in 32% of cases and conferred a double risk of all-cause mortality. In an additional pooled analysis of nearly 50 000 HF patients, WRF occurred in 23% of cases during their hospitalization, and was also associated with a 1.5-fold higher risk of all-cause mortality. Furthermore, baseline CKD, diabetes, hypertension, and use of diuretics were shown to be predictors of WRF. Although the association between HF and renal dysfunction is undoubtedly important, there are several issues that deserve further consideration. First, although the definition of CKD is well established and generally accepted, the same does not apply to WRF. There are many definitions for WRF that use different absolute or relative increases in serum creatinine (Table 1). The glomerular filtration rate (GFR), which is used in the case of CKD and provides more objective evidence of renal function, cannot be easily used and evaluated in the acute setting. In addition, the baseline renal function is obviously crucial. It is known that baseline CKD is a risk factor for WRF, but studies have not generally addressed the differential outcome of WRF in patients with and without CKD. A particular increase in serum creatinine has a different significance for patients with baseline CKD compared with for those without. To complicate things further, notonly theextentbut also the timing and the duration of decline of renal function are important components that are not usually taken into consideration. For example, data from the DOSE trial suggest that an early and transient WRF during hospitalization for acute HF may not have any prognostic significance, while a subanalysis of the ESCAPE trial showed that HF patients with WRF during hospitalization had an even better outcome than those without, as WRF was an indicator of effective management of congestion. Moreover, in the EVEREST trial, haemoconcentration, a marker of decongestion, has been found to be associated with decreased mortality and HF re-hospitalization despite in-hospital WRF. Thus, to be clinically meaningful, the definition of WRF should differentiate between a transient derangement that results from intensive therapy, is followed by favourable response of symptoms and signs of congestion to treatment, and thus lacks negative prognostic significance, and a more profound and persistent dysfunction that is associated with resistant congestion and is followed by an adverse outcome (Figure 2). Thus, besides the extent, timing, and duration of renal dysfunction and the monitoring of cardiac and renal haemodynamicparameters, theevaluationof symptomsand signsof congestion and their response to the applied therapy may help in differentiating the two forms of WRF. This consideration of WRF would further allow clinicians to enhance their therapeutic approach. The emerging renal biomarkers that provide earlier and/or more sensitive identification of kidney dysfunction may prove useful in this respect. However, we still require clinical trials to evaluate their use in the context of structured diagnostic and management strategies (Figure 2). Therapy is the second important issue concerning the association of HF with renal dysfunction. Although the latter is generally believed to be an important contributor to the progression of the HF syndrome, it has rarely been used as a therapeutic target in HF. The limited number of trials that have followed such an approach have failed to provide any encouraging data either with drugs or with