The essential indicators for determining optimal dialysis. RRF , residual renal function
14.1.1 Adequate Solute Clearance
In dialysis patients, solute clearance is determined by clearance derived from both dialysis therapy and RRF. When we examined solute clearance of dialysis patients, we have to consider total solute clearance, the sum of clearance delivered by dialysis and RRF . In the early period of dialysis, most patients are likely to have sufficient RRF , which lead to significant contribution to total solute clearance. As dialysis duration is prolonged, RRF tends to decline. Therefore, patients may require more solute clearance via dialysis, and prescribing greater dose of dialysis may be necessary over time. Previous clinical studies and guidelines indicated a minimum or “adequate” solute clearance target. If this solute clearance target is achieved, further adjustment of dialysis dose may depend on various essential indicators for optimal dialysis.
188.8.131.52 Solute Clearance Derived from PD
For the estimation of solute clearance by PD, there are two commonly used methods: the weekly Kt/Vurea and the creatinine clearance normalized to body surface area (Chatoth et al. 1999). Using the Kt/Vurea is preferred more to the creatinine clearance , since it has been widely mentioned in the various clinical practice guidelines , including the 2006 Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines (Peritoneal Dialysis Adequacy Work Group 2006), the 2005 European Best Practices Guidelines (EBPG) (Dombros et al. 2005a), and the 2006 International Society for Peritoneal Dialysis (ISPD) guidelines/recommendations (Lo et al. 2006).
The Kt/Vurea is consisted of daily peritoneal urea clearance (Kt) and volume of distribution of urea (Vurea). The daily peritoneal urea clearance (Kt) is the value for the amount of 24-h drained dialysate multiplied by the ratio of the urea concentration in the drained dialysate to that in the plasma (dialysate/plasma urea, D/P urea). Compared with partial collection of dialysate or kinetic modeling programs, a 24-h collection of dialysate has been known to be more accurate (Burkart et al. 1993).
The volume of distribution of urea (Vurea) is approximately equal to body water and can be estimated by proposed equations. One should estimate V in adults by either the Watson or Hume equation in adults and by the Mellits-Cheek method in children (Table 14.1) (NKF-DOQI 1997; Peritoneal Dialysis Adequacy Work Group 2006).
Equations for estimating the volume of distribution (V)
V (L) = 2.447 + 0.3362*Wt (kg) + 0.1074*Ht (cm) – 0.09516*Age (y)
V (L) = −2.097 + 0.2466*Wt (kg) + 0.1069*Ht (cm)
V (L) = −14.012934 + 0.296785*Wt (kg) + 0.192786*Ht (cm)
V (L) = −35.270121 + 0.l83809*Wt (kg) + 0.344547*Ht (cm)
Mellits-Cheek method for children
V (L) = −1.927 + 0.465*Wt (kg) + 0.045*Ht (cm), when Ht is ≤132.7 cm
V (L) = −21.993 + 0.406*Wt (kg) + 0.209*Ht (cm), when Ht is >132.7 cm
V (L) = 0.076 + 0.507*Wt (kg) + 0.013*Ht (cm), when Ht is ≤110.8 cm
V (L) = −10.313 + 0.252*Wt (kg) + 0.154*Ht (cm), when Ht is >110.8 cm
Although actual body weight was recommended to use in 1997 K/DOQI guideline (NKF-DOQI 1997), the use of the patient’s ideal or standard (rather than actual) weight should be considered in the calculation of V in the subsequent guideline (Peritoneal Dialysis Adequacy Work Group 2006). The reason for using the ideal body weight (IBW) is that actual body weight results in underestimation of Kt/Vurea in large patients or overestimation of Kt/Vurea in malnourished or small patients (Tzamaloukas et al. 1993; Tzamaloukas et al. 1998). Although various equations for calculating IBW have been suggested, the results derived from those equations are similar; thus any one of them may be used to estimate IBW (Pai and Paloucek 2000).
The Devine formula in adults is as follows:
184.108.40.206 Solute Clearance Derived from RRF
If PD is initiated, there are many patients having still significant RRF, a urine volume of >100 mL/day (Peritoneal Dialysis Adequacy Work Group 2006). At first, they can be started with low-dose PD, and then the peritoneal Kt/V could be increased incrementally so the combined value of weekly peritoneal Kt/V and renal Kt/V (or total Kt/V) does not fall below the target level (NKF-DOQI 1997). With the incremental initiation approach, frequent measurement of RRF will be necessary to assure that total delivered solute removal does not drop below targets (NKF-DOQI 1997). Similar to calculation of peritoneal Kt/Vurea , the 24-h urine collection is necessary for calculation of renal Kt/Vurea and is usually performed at the same day of 24-h dialysate collection.
Although 24-h urine collection may be cumbersome in the everyday clinical practice, it should not be ignored. If we want the patient not to perform more dialysis than he or she actually requires, 24-h urine needs to be collected regularly until RRF disappears and solute clearance from RRF should be added up to peritoneal solute clearance when calculating total solute clearance. Thus, in the perspective of individualized care medicine, we suggest that PD dose should be changed and personalized according to RRF , volume status , uremic symptoms , and other factors in a specific PD patient.
220.127.116.11 Target of Total Solute Clearance
Continuous Ambulatory PD (CAPD)
In CAPD patients, the 2006 National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) guideline (Peritoneal Dialysis Adequacy Work Group 2006), the 2005 EBPG (Dombros et al. 2005a), and the 2006 ISPD guidelines/recommendations (Lo et al. 2006) suggest a total weekly Kt/Vurea ≥1.7 as the minimum target of solute clearance. Previous randomized study clearly demonstrated that patients with Kt/Vurea <1.7 were significantly associated with higher erythropoiesis-stimulating agent use and more uremic symptoms than those with Kt/Vurea of 1.7–2.0 and >2.0 (Lo et al. 2003). Furthermore , targeting a Kt/Vurea higher than 1.7 did not show additional improvement in other randomized controlled study (Lo et al. 2003; Paniagua et al. 2002), securing a total weekly Kt/Vurea ≥1.7 as the minimum target in CAPD patients. Detailed review of evidences would be described in “Chapter 5: Kinetic Modeling and Adequacy in Peritoneal Dialysis.”
Automated PD (APD)
In APD patients, the 2006 K/DOQI guideline recommended a total weekly Kt/Vurea ≥1.7 as the minimum target of solute clearance (Peritoneal Dialysis Adequacy Work Group 2006). However, this recommendation is actually based on the results of CAPD patients. Although some patients require midday exchange (“wet abdomen” in daytime), a number of APD patients performed only overnight exchange with “dry abdomen” in daytime and did not undergo dialysis during 24 h.
Example of Total Solute Clearance Calculation
A 66 kg male patient undergoes CAPD , and these are the results of 24-h peritoneal dialysate and urine collection to calculate total weekly Kt/Vurea . The steps for calculating total Kt/Vurea is as follows (Fig. 14.2):
24-h drained PD effluent
Dialysate urea nitrogen concentration
Plasma urea nitrogen concentration
Urine urea nitrogen concentration
Plasma urea nitrogen concentration
Calculation of total weekly Kt/Vurea
In this example, weekly peritoneal Kt/Vurea of 1.2 may be suboptimal, if this patient is anuric. However, because RRF provides renal Kt/Vurea of 0.5 in this patient, minimal target of solute clearance is considered to be achieved. Again, total weekly Kt/V is peritoneal Kt/V plus renal Kt/V ; we should adjust the PD prescription as RRF declines for achieving target minimum Kt/V of 1.7 (Fig. 14.3).
Contribution of renal solute clearance to achieve a total weekly Kt/V = 1.7 in patients with decreasing RRF. In this imaginary patient, if we assume the values of BUN, urine and dialysate urea nitrogen are not changed during the 3-year follow-up period, weekly renal Kt/V decreases according to the reduction in urine volume; solute clearance should be replenished by the increment of the dose of PD for achieving Kt/V of 1.7, and PD effluent volume should be increased from 5 L/day at the start of PD to 9.5 L/day at 3 years later. As a result, the patient who could achieve target Kt/V with 2 PD exchanges should increase the number of PD exchanges up to 4 times a day at 3 years later. Volume (V) of urea distribution is calculated by Watson formula. UN, urea nitrogen
14.1.2 Maintenance of Euvolemia
Volume overload is significantly implicated with adverse cardiovascular disease including congestive heart failure , left ventricular hypertrophy, and hypertension; therefore, it is important to monitor ultrafiltration volume , dry weight , sodium intake, and other clinical assessments of volume status (Peritoneal Dialysis Adequacy Work Group 2006). In addition, several studies have indicated that volume overload is closely implicated with mortality in PD patients, irrespective of symptom and signs of volume overload (Blake 1997). Although there was no published evidence, the EBPG committee suggested an arbitrary target ultrafiltration goal of 1.0 L/day to increase the awareness of the maintenance of a euvolemic state (Dombros et al. 2005a). Afterward, the work group for the clinical practice guidelines on PD adequacy of Canadian Society of Nephrology suggested the more detailed guidelines on the management of hypervolemia. They suggested that a low net daily peritoneal ultrafiltration volume (<750 mL in anuric patients or <250 mL in patients with RRF ) would be an indication for careful evaluation of volume status (looking for evidence of volume overload) and of dietary fluid and food intake (looking for evidence of insufficient intake or malnutrition) (Blake et al. 2011). In contrast, some experts did not suggest a minimum target of ultrafiltration volume, because aggressive ultrafiltration may facilitate RRF decline. In accordance with the 2006 NKF-K/DOQI guidelines (Peritoneal Dialysis Adequacy Work Group 2006), we propose that optimal amount of ultrafiltration should be tailored by individual volume status and blood pressure levels rather by arbitrary goal. In addition, we need to monitor the nutritional status such as the amount of food and water intake in patients without any sign of volume overload in spite of an ultrafiltration volume of <1.0 L/day.
14.1.3 Avoidance of Malnutrition
Nutrition is an important predictor of clinical outcomes in dialysis patients whether on HD or on PD. A large number of factors have been identified as the causes of malnutrition in dialysis patients, which include anorexia, uremia derived from insufficient dialysis, advanced age, chronic inflammation , metabolic acidosis , impaired anabolism, gastrointestinal or medical comorbidities, and socioeconomic problems (Blake et al. 2011). Notably, in PD, protein loss to dialysate may happen, resulting in increased risk of malnutrition. Estimated amount of protein and amino acid loss is reported to be up to 15 g and 2–4 g per day, respectively (Bergstrom et al. 1993). Therefore, assessment of nutritional status should be performed as a routine practice in PD patients. The EBPG recommended to use subjective global assessment (SGA), protein intake derived from the protein equivalent of nitrogen appearance (PNA) or dietary recall, and an assessment of protein nutrition in PD patients every 6 months (Dombros et al. 2005b). Multidisciplinary team including physician, nurse, dietician, social worker, and family members is necessary for comprehensive assessment and effective management of malnutrition . If malnutrition of the patients is likely to be associated with underdialysis, the adherence of the patients to the PD prescription and the delivered dose of PD should be reevaluated at the time and adjusted to a sufficient level.
14.1.4 Resolution of Uremia
Routine evaluation for uremia in PD patients is required for determining optimal dialysis. Patients may be asked if they have intractable anorexia , vomiting , or itching for the assessment of uremic symptoms . In addition to uremic symptoms , pericardial effusion, confusion suggestive of uremic encephalopathy, and gum or mucosal bleeding are also indications to deliver more dialysis dose even the minimum target Kt/Vurea of 1.7 is achieved.
14.1.5 Balance of Electrolyte, Acid-Base, and Mineral Metabolism
Prevention of hyperkalemia is crucial in dialysis patients. Because PD solution does not contain potassium and potassium is constantly removed by diffusion, hyperkalemia is less likely to occur in PD patients who maintain adequate dialysis. Therefore, PD patients with severe hyperkalemia should be evaluated whether they had drugs causing hyperkalemia including renin-angiotensin receptor blockers, nonsteroidal anti-inflammatory drugs, nutritional supplements, and herbal remedies or whether they skip PD exchanges. Metabolic acidosis has been regarded to induce harmful complications such as malnutrition , inflammation , and mineral bone disease (Kraut and Kurtz 2005). However, only 25% of CAPD patients achieve normal serum bicarbonate value by using a lactate solution (Feriani 1996). Although there is no consensus regarding the optimal serum bicarbonate levels in PD patients, individualizing PD solution using different buffers may be helpful to correct metabolic acidosis (Feriani et al. 1997; Feriani et al. 2004). To date, there is growing attention to mineral metabolism and patient outcome in PD patients (Noordzij et al. 2006). Standard solution containing 3.5 mEq/L calcium may be associated with hypercalcemia especially in patients with high-dose calcium-based phosphate binders. Even though optimal calcium concentrations of PD solution remain unclear, adjusting dialysis solution and phosphate binders is necessary in patients with hypo-/hypercalcemia .
14.1.6 Preservation of RRF
RRF is independently associated with clinical outcomes in dialysis patients. It is recognized that PD preserves RRF better than HD at the initiation of dialysis . RRF promotes urea or creatinine clearance , helping to achieve target Kt/Vurea . If a patient has a creatinine clearance of 1 mL/min and weekly creatinine clearance reaches 10 L/week, it is a very considerable value which we should do our best to preserve. RRF also increases fluid excretion, leading to mitigation of adverse effect derived from chronic volume overload (Bragg-Gresham et al. 2007). Furthermore, greater clearance of middle molecule such as β2-microglobulin and indoxyl sulfate (Bammens et al. 2003), better phosphate and anemia control (Penne et al. 2011), and increased dietary protein and calorie intake representing better nutritional status (Wang et al. 2001) were significantly associated with RRF. To preserve RRF, all PD patients are indicated to take renin-angiotensin receptor blockers, even they are not hypertensive. Two randomized controlled study demonstrated that angiotensin receptor blockers (ARB) or angiotensin-converting enzyme inhibitors (ACE inhibitor) preserved RRF in PD patients (Li et al. 2003; Suzuki et al. 2004). In addition, although blood pressure requires strict control, excessive ultrafiltration should be avoided due to harmful effect of volume depletion (Table 14.2).
Clinical advantages of RRF preservation and treatment strategies
Clinical advantages of RRF preservation
Acceleration of achieving euvolemia via renal clearance of solute and fluid
Better blood pressure control
Stabilization of left ventricular hypertrophy
Greater clearance of middle molecule including β2-microglobulin
Better phosphate control
Better anemia control
Improvement of nutritional status
Improvement of quality of life
Strategies to preserve RRF
Strict blood pressure control
Use of renin-angiotensin receptor blockers, irrespective of hypertension
Avoidance of nephrotoxic drugs
Avoidance of excessive ultrafiltration, resulting in volume depletion
14.1.7 Patient’s Adherence to the Dialysis Prescription
Since PD is a home-based therapy, it usually requires a daily performance of dialysis and clinical assessment of patient’s condition by a patient and/or a caregiver. Therefore, adherence to therapy is a critical issue in PD. However, according to a systematic review investigating nonadherence in PD patients, rates of missing PD exchanges or sessions were reported to be 2.5–53%, and shortening of cycles was reported in 4–15% of patients (Griva et al. 2014). Moreover, over half of the studies (13 of 20 studies, 65%) indicated the rates of nonadherence to PD regimen to be higher than 20%. Previous studies have demonstrated that non-compliance to dialysis therapy increased the risk of mortality and hospitalization in PD patients (Bernardini et al. 2000; Bernardini and Piraino 1998). In this regard, clinician should pay attention to patient’s adherence and adjust dialysis regimen.
14.2 Prescribing PD at the Start of Dialysis
Each of the patients starts PD for a wide variety of reasons. PD prescription should be tailored in consideration of these reasons and circumstances. However, in real world, it is impossible to fulfill all of the aforementioned indicators for optimal dialysis at the first prescription of PD. For practical application, we categorized patients into three groups according to the chronicity of kidney disease and planned start of dialysis, (1) acute PD in patients with acute kidney injury (AKI), (2) urgent start of PD in newly diagnosed chronic kidney disease (CKD) patients, and (3) planned start of PD in known CKD patients, and suggest empirical prescription of the first PD. Nevertheless, we should keep in mind that these empirical prescriptions may not be appropriate for all patients and prescription can be changed for individual goal of optimal dialysis.
14.2.1 Acute PD in Patients with AKI
In the management of AKI, there are few data comparing the effect on mortality between PD and extracorporeal blood purification therapies, such as intermittent HD and continuous renal replacement therapy. Recent systematic review showed that the mortality rate of acute PD is at least comparable with continuous or intermittent HDs (Chionh et al. 2013). Although the application of PD to AKI patients has been overlooked particularly in the developed countries, PD should be considered as a relevant option having several advantages in the management of AKI. First, due to continuous nature of modality, PD can be utilized in hemodynamically compromised patients. Continuous and slow removal of solutes and fluid permit large amounts of fluid removal without hemodynamic instability. PD enables gradual removal of uremic toxin and slow correction of acid-base and electrolyte imbalance. High-volume PD can attain at least 2 L of ultrafiltration during 24 h and stable value of serum urea , creatinine, bicarbonate, and potassium concentrations within 3–4 days in AKI patients (Gabriel et al. 2007; Ponce et al. 2012a). Technically, insertion of PD catheter can be easily performed even in the bedside and there is no need for temporary vascular access and the use of anticoagulants. Therefore, patients with bleeding diathesis or contraindicated to systemic anticoagulation, including trauma, operation, and internal bleeding might have benefit from PD. Furthermore, PD is widely accessible, which has less constraint such as dialysis machinery, water or power supply.
18.104.22.168 Patients Selection
There are few absolute indication and contraindication for PD in AKI , if patients require renal replacement therapy and there were no other modalities except PD. Patients should be carefully selected by considering the following relative indications and contraindications (Table 14.3).
Relative indication and contraindications for PD in AKI patients
Hemodynamically compromised patients
Patients with bleeding diathesis
Patients who have contraindications to systemic anticoagulation
Patients who do not have available vascular access
Patients with clinically significant hypothermia and hyperthermia
Refractory congestive heart failure
Recent abdominal and/or cardiothoracic surgery
Abdominal wall or peritoneal infection
Diaphragmatic peritoneal-pleural connections
Severe respiratory insufficiency
Life-threatening volume overload
Severe hypercatabolism or malnutrition
Although solutes and fluid are removed slowly in PD, PD can be an effective modality for the management of hyperkalemia and volume overload by adjusting dwell volume , time, number of exchanges, or dialysate tonicity (Cullis et al. 2014).
22.214.171.124 Peritoneal Access
For acute PD, the flexible Tenckhoff catheter is preferred to the rigid catheter. Rigid catheter is easily inserted at the bedside under local anesthesia, but several disadvantages such as high risk of infection , bowel perforation, and catheter dysfunction exist (Wong and Geary 1988; Chadha et al. 2000). Since the rigid acute PD catheter does not have cuff, it is associated with greater risk of bacterial migration and peritonitis and should be removed within 72 h (Wong and Geary 1988). For mechanical reasons, movement of patients is restricted and the risk of bowel perforation and catheter dysfunction increased unless colon evacuation persists well (Ash 2004). In contrast, the flexible Tenckhoff catheter is usually inserted in the operating room by a surgeon . However, recently, many nephrologists have inserted the Tenckhoff catheter at the bedside using fluoroscopy or peritoneoscope. This cuffed permanent catheter has several benefits over the rigid catheters (Wong and Geary 1988; Chadha et al. 2000). The risk of peritonitis and bowel perforation is lower and patients feel more comfortable. This catheter also assures a good immediate catheter function and high dialysate flow rate.
Similar to chronic PD, there are various techniques in acute PD according to the use of cycler and patterns of inflow and outflow (Chionh et al. 2009). Manual PD requires a lot of nursing effort, whereas the use of cyclers can decrease nursing labor. A cycler also makes the number of interruptions or breaks to be reduced, because setting of dialysate is usually preceded at the start of session. Patterns of inflow and outflow are determined by demand of fluid and solute removal.
Acute Intermittent PD (AIPD)
This technique is widely applied to AKI patients, which consists of frequent exchanges with short dwell time, an inflow volume of 1–3 L, and a dialysate flow rate of 2–6 L per hour (Ponce et al. 2012a; Cullis et al. 2014; Chionh et al. 2009; Passadakis and Oreopoulos 2003). Each session, which lasts 12–24 h, is intermittently (2–3 sessions a week) occurred. Because of its intermittent nature, AIPD may provide inadequate fluid and solute clearance. This technique can be performed manually or using an automated cycler.
Chronic Equilibrated PD (CEPD)
CEPD is similar to chronic ambulatory peritoneal dialysis (CAPD), which has 4 exchanges a day with inflow volumes of 2 L and dwell times of 4–6 h (Steiner 1989). In accordance with CAPD, this technique provides stable fluid and solute clearance , but adequacy may be insufficient. However, due to long dwell times, middle molecule clearance may be higher than other techniques with short dwells. Not only manual exchange but an automated cycler can be utilized in this technique.
Tidal PD (TPD)
The key features of TPD are “tidal” drain and fill volume . Initial inflow volume (2–3 L) infused to the peritoneal cavity; then, a constant tidal volume is drained (tidal drain volume, usually 10–50%, 0.3–1.5 L) and replaced with fresh dialysate (tidal fill volume). The peritoneal cavity always contains the reserved volume across the whole session (Agrawal and Nolph 2000). Since TPD requires rapid and multiple exchanges with large volume dialysate, it needs automated cycler often and relatively higher costs. Theoretically, TPD improves solute clearance that reserved dialysate and continues to increase solute and water removal during inflow and outflow time. But increased solute clearance has not consistently confirmed in chronic dialysis patients. In AKI patients, one randomized crossover study showed that urea clearance of TPD was significantly higher than that of CEPD with 2 L of tidal fill volume (Chitalia et al. 2002). Another advantage of TPD is the relief of drainage problems including inflow/outflow pain and slow drainage, because PD catheter does not irritate the peritoneal membrane directly (Dombros et al. 2005c). When prescribing TPD, tidal volume, flow rate, and expected ultrafiltration should be considered.
High-Volume PD (HVPD)
HVPD employs very frequent exchanges with a large volume of dialysate, and this is usually delivered by an automated cycler. HVPD involves 18–22 exchanges (30–60 min of dwell time) with 2 L of dialysate, resulting in a total of 36–44 L of total dialysate volume per day (Gabriel et al. 2007; Ponce et al. 2012a). HVPD can provide the greatest small solute and fluid clearance than any other acute PD techniques, and one study showed that urea clearance of HVPD with 36–44 L of dialysate per day was comparable to that of daily HD (Gabriel et al. 2007). However, it needs very large volume of dialysate; consequently, it is highly expensive. Moreover, due to rapid exchanges and reduced contact time between dialysate and peritoneum , middle and larger molecule clearance may be reduced compared to technique with slower exchanges (Cullis et al. 2014; Chionh et al. 2010).
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