**3. Peritoneal ultrafiltration (pUF)**

tions are a major concern among these patients, their families, and their health service provid‐ ers. CHF causes the highest rehospitalization rate among all chronic diseases, reaching up to 27% [5]. Patients with CHF have a poor prognosis, with a 1-year survival rate that is compara‐ ble or worse than that for common neoplasms such as prostatic or breast malignancies. Stewart et al. showed that the median survival time for patients with CHF was 16 months with 25% 5 year survival rate [6, 7]. Despite all advances in the management of CHF, it is still the leading cause of mortality among cardiac diseases [8, 9]. Fluid overload and lung congestion are the most recurrent cause of admissions in these patients [10]. Almost 50% of them are discharged with residual congestion, and most rehospitalizations occur in patients who are diuretic resistant [11]. Diuretic resistance, in which patients with CHF have reduced diuresis and natriuresis in response to diuretics, causes higher mortality and rehospitalizations [10, 12, 13]. CHF is also associated with cardiorenal syndrome (CRS), a condition in which renal function worsens and is challenging to manage [14]. Conventional diuretic therapy of both CRS and diuretic resist‐ ance has shown limited efficacy with no robust data on efficacy in terms of well-designed randomized clinical controlled trials [15, 16]. However, hemodiafiltration (HDF), isotonic fluid replacement through positive hydrostatic pressure, has recently emerged as an alternative or last resort for these complex patients. The aim of this physiological approach is to decrease neurohumoral activation, which in turn curbs the vicious cycle leading to cardiac and renal insult [17, 18]. Some promising results have been reported in initial studies, but the data conflict and are inconclusive. As a result, no clinical guidelines to date have adopted HDF as an alternative

No specified definition is available for diuretic resistance, as it is the outcome of treatment and not a pathological condition in itself. The efficacy of loop diuretics can be evaluated as a measure of urine output, change in weight, and balance in net fluid [23]. Patients unable to meet their needs for decongestion despite high doses of loop diuretics are generally labeled as diuretic resistant. Some current studies have reported the efficacy of diuretics in terms of clinical outcomes in patients with CHF [24–31]. Although these studies used different methods and metrics, the outcomes were similar in all: patients with diuretic resistance showed poor outcomes compared with those without diuretic resistance. Even after correcting for glomer‐ ular filtration rate (GFR), a strong correlation between worse clinical results and diuretic resistance was observed, showing that the efficacy of diuretics and the GFR each have a different impact on clinical outcomes. GFR is a good indicator of the kidney's clearance ability. When this rate is normal, the renal tubules are able to maintain homeostasis of electrolytes and euvolemia. Even if the GFR is reduced to up to 20 mL/min, usually 28.8 L of fluid is filtered, and sodium excretion is about 4000 mEq. The metrics used in current studies for diuretic efficacy are indirectly related to the effectiveness of loop diuretics for sodium excretion. Consequently, these metrics indicate a better prognosis than does the GFR in terms of the

to diuretic therapy [10, 19–22].

60 Advances in Hemodiafiltration

kidneys achieving euvolemia.

**2. Diuretic resistance and CRS syndrome**

In advanced stages of CHF, a decline in renal function can often be seen, consistent with type 2 CRS (CRS-2). Several therapies have been evaluated for this group of patients; however, the optimal therapy for "chronic" CRS remains elusive. It is believed that peritoneal ultrafiltration (pUF) may lead to improvement in the clinical function of these patients, with a reduction in the number of hospitalizations.

A study performed on patients without end-stage renal disease evaluated the efficacy of pUF in the treatment of chronic refractory heart failure (HF) [41]. For this evaluation, 39 consecutive patients with end-stage CHF and stable CRS-2 were given ambulatory pUF and prospectively followed for 1 year. The primary end point was all-cause hospitalization. Mortality, treatment changes, and weight changes with New York Heart Association (NYHA) functional class and quality of life were considered as the secondary end points. Compared with the control group, who received standard treatment, in the pUF group, there was a reduction in the number of 1-year hospitalization days (*p* = 0.07). However, the 1-year mortality was found to be 33% in the pUF group and 23% in the control cohort, although this result was not statistically significant. In comparison to standard medical treatment, pUF was found to significantly improve volume overload (*p* < 0.05), the NYHA functional class (*p* < 0.001), and mental health (*p* < 0.05) of the patients. Furthermore, in the pUF group, the hospitalization days for all causes, including cardiovascular incidents, were significantly reduced during the interim periods (*p* < 0.05 and *p* < 0.001, respectively).

Another study evaluated pUF in patients with severe HF that was refractory to aggressive drug therapy [42]. Treatment with pUF was considered in these patients, as they had been hospitalized at least three times in the preceding year for ADHF that had required extracor‐ poreal UF. This study comprised 48 patients; of those, 30 received one nocturnal icodextrin exchange, 5 received two daily exchanges, and the remaining 13 received two to four sessions per week of automated peritoneal dialysis (PD). In the first year of therapy, renal function remained stable with a decline in pulmonary artery systolic pressure to 40 ± 6.09 mmHg from 45.5 ± 9.18 mmHg (*p* = 0.03). At the same time, significant improvement was noted in the NYHA functional status. Furthermore, patient hospitalizations decreased to 11 ± 17 days/patient-year from 43 ± 33 days/patient-year seen in the preceding year, which was before the onset of PUF treatment (*p* < 0.001). Thus, this study confirms the efficacy of PUF treatment in elderly patients with chronic HF.

Recently, a systematic review conducted to evaluate the efficacy of PD in patients with refractory CHF identified 21 studies from 13 countries [43]. This review comprised 673 patients and suggested that in patients with refractory CHF, PD can be an effective and safe treatment option, leading to improved heart function and weight control. It also reported that PD can reduce patient hospitalization days without any progressive worsening of renal function. The rates of PD complications such as peritonitis were also found to be acceptable.
