As noted above, total Kt/V urea and CrCl are largely dependent on RRF, while urine volume is maintained. It can contribute approximately up to 50% of total clearance during the initial period of dialysis. Accordingly, physicians should be alert on decline of RRF and consider increasing peritoneal clearance targeted to Kt/V of at least >1.7 when patients become anuric (Fig. 15.4 and Fig. 15.5). The importance of RRF has recently been highlighted in many aspects. It has been well demonstrated that RRF is more important than small solute clearance in determining clinical outcomes in dialysis patients. Therefore, much effort should be made to preserve RRF. This is discussed in detail in Sect. 15.5.

Body size can also affect total clearance because Kt and CrCl are normalized to volume of distribution of urea, which is equal to total body water, and BSA, respectively. Theoretically, patients with extremely large body size may not adequately maintain PD in terms of small solute clearance. If a patient undergoes four exchanges of 2.0 L PD solutions per day to meet the target of Kt/V of >1.7 and net ultrafiltration is 1.0 L, then V = D/P urea ratio × (7 days × 9.0 L)/1.7. Assuming a D/P urea ratio of 0.9, then V is 40.6 L, which approximately fits to a man with a standard body size, 170 cm in height, and 70 kg in weight. Thus, obese patients have extremely high V, it is difficult to achieve a Kt/V urea target of >1.7 when typical peritoneal dialysis prescription is given. Conversely, Kt/V can be interpreted with caution in patients with very low V. Because these patients are more likely malnourished and deprived of muscle, it is not fair to say they do well on dialysis even though Kt/V is >1.7.

Peritoneal membrane transport types can be determined by peritoneal equilibration test. It is important to define membrane transport status in dialysis prescription. As seen in Fig. 15.2, equilibration of creatinine or larger molecules is slower and lower than that of urea. This can raise a problem regarding dialysis adequacy in patients on APD. These patients use a cycler and typically do 4–5 exchanges during 8–10 h. This inevitably requires short and frequent exchanges, resulting in lack of enough time for larger molecules to equilibrate. Urea clearance is acceptable because urea rapidly equilibrates within several hours. However, larger molecules than urea are not adequately removed due to the slower diffusion. This becomes more pronounced in slow transporters (previously known as low transport). These patients exhibit much slower equilibration of solutes than fast transporters. For this reason, dialysis prescription can be tailored depending on transport types. In general, high-volume exchanges and long-duration dwells are recommended in slow transporters, whereas short-duration dwell is more effective in fast transporters.

In typical patients on CAPD with average peritoneal transport types, increasing frequency from four to five exchanges per day accompanied by shortened dwell time does not hamper urea equilibration, which remains at 85–90% as long as patients ensure adequate dwell time of at least 4 h. In slow transporters, increasing clearance can be achieved by increasing dwell duration because creatinine equilibration still rises 4 h after the initiation of the dwell. On the other hand, in fast transporters, osmotic gradient is dissipated soon after the dwell, thus increasing frequency of daily exchanges can be an option to increase peritoneal clearance in these patients. However, one more exchange can be burdensome and limit daily activities in patients who have active lifestyle. They do not want to be tied up with PD exchange procedure. In this regard, increasing dwell volume is more effective and preferred to enhance clearance.

In patients on APD, this strategy of adjusting dwell time and frequency of exchanges can be also applied in clinical practice. These patients use a cycler during nighttime, thus problems of increasing frequency of exchanges can be resolved by the aid of the machine, which is particularly helpful in fast transporters. However, as aforementioned, shortened dwell time caused by frequent exchanges may result in insufficient solute clearance. Loss of RRF can worsen this problem. Moreover, middle molecule clearance is time dependent. Therefore, in this case, many patients require one or more exchanges of daytime dwell to increase clearance. Another way to increase clearance is to increase dwell volume as in CAPD. APD patients are unlikely to complain of abdominal discomfort because intra-abdominal pressure is not increased in supine position. How to prescribe dialysis in APD is described in detail in Chap. 4.

Because ultrafiltration is mainly derived from osmotic gradient, the use of high concentration glucose solution can increase ultrafiltration volume by inducing higher osmotic gradient. Accordingly, peritoneal clearance can increase as total drained volume is a determinant of Kt. However, there is much concern about glucose toxicity to the peritoneal membrane damage. In addition, glucose can be absorbed via peritoneal capillary beds, leading to systemic harmful effects such as hyperglycemia, hypertriglyceridemia, weight gain, inflammation, etc. For this reason, it is generally recommended to limit the use of high concentration glucose solutions unless volume overload should be controlled. Moreover, glucose-sparing strategies have recently prevailed to preserve peritoneal membrane and to prevent glucose toxicity-associated complication.

There have been a number of studies to explain mechanisms responsible for the improved survival conferred by RRF. As seen in Fig. 15.6, RRF plays an important role in the regulation of a variety of disturbances in dialysis patients. Fluid overload is a significant determinant of adverse outcomes and is highly associated with increased blood pressure, cardiac hypertrophy, and congestive heart failure in these patients. Ates et al. evaluated the effects of fluid and sodium removal on mortality in 125 PD patients (Ates et al. 2001). They observed an increased patient survival rate in proportion to the amount of sodium and fluid removal. In particular, a 3-year patient survival rate was highest in patients with fluid removal >2035 mL/24 h/1.73 m², whereas it was lowest in those with fluid removal <1265 mL/24 h/1.73 m². Their findings highlight the harmful effects of fluid retention on patient survival. Not surprisingly, fluid overload can be more easily controlled in patients with RRF than in anuric patients. In a cross-sectional study by Konings et al. (2003a, b), extracellular water content was significantly and inversely correlated with residual GFR. In addition, patients with residual GFR < 2 mL/min had higher extracellular water than those with residual GFR > 2 mL/min. This finding suggests that presence of RRF is advantageous for fluid management. Accordingly, blood pressure can be more controlled by maintaining fluid balance in patients with preserved RRF. Menon et al. performed a retrospective observational study to identify factors associated with uncontrolled blood pressure in 207 PD patients (Menon et al. 2001). In their study, declining RRF was significantly associated with high blood pressure. Moreover, fluid overload can contribute to the development of left ventricular hypertrophy. The prevalence of left ventricular hypertrophy is remarkably high, up to 75–90% in patients who initiate dialysis (Wang et al. 2002a, b, 2004a, b, c). It is well known that it is an independent predictor of cardiovascular events and death in dialysis patients (Silberberg et al. 1989). In a cross-sectional study by Wang et al., left ventricular hypertrophy index was significantly lower in patients with preserved RRF than anuric patients. However, this association was not observed for peritoneal clearance. Interestingly, sodium and fluid removal differ between the kidney and the peritoneum depending on presence or absence of RRF in patients undergoing PD. Cheng et al. evaluated fluid status by using bioimpedance analysis in 195 CAPD patients and found that sodium and fluid removal was greater by the kidney than by the peritoneum in patients with urine volume > 400 mL per day (Cheng et al. 2006). Conversely, peritoneal clearance in sodium and fluid removal became more important as RRF declined. Taken together, all these findings suggest that in the absence of RRF, patients are more likely to have fluid overload, high blood pressure, and cardiac dilatation, which ultimately result in the increased cardiovascular morbidity and mortality.

Middle molecule clearance has recently emerged as an important therapeutic target in dialysis patients. Among many middle molecules, β2-microglobulin (β2MG) has widely been investigated. Many studies have consistently shown that β2MG is a strong and independent predictor of mortality in ESRD patients. RRF is also associated with removal of middle molecules. Bammens et al. conducted a longitudinal observational study to evaluate relative contribution of the peritoneum and the kidney to the clearance of small solutes and β2MG (Bammens et al. 2005). Renal clearance of urea and creatinine declined over time, while peritoneal clearance of these molecules increased. Interestingly, there was also a decline in renal clearance of β2MG, but its peritoneal clearance remained stable throughout the study period. These findings suggest that, for small solutes, peritoneal clearance can increase in compensation for loss of RRF. However, the elimination of middle molecule, β2MG, is less likely to be counterbalanced by the peritoneum.