Determination of Continuous Ambulatory Peritoneal Dialysis and Automated Peritoneal Dialysis Prescriptions

Dialysis Adequacy for Patients Receiving Peritoneal Dialysis

A major goal of dialysis therapy is to restore patients to their previous quality of life. For most patients, the objective is to eliminate uremic symptoms, such as poor appetite and fatigue. This is accomplished by prescribing a dialysis treatment of sufficient intensity to remove uremic toxins. There are numerous solutes that accumulate in kidney failure; ascribing the uremic syndrome to specific solutes is very difficult.

Self-reported patient outcomes are one key component of adequate dialysis. Improvement in common uremic symptoms (nausea, poor appetite, and fatigue) is a major goal. Many patients choose peritoneal dialysis (PD) due to the flexibility provided by the therapy. PD may provide a better quality of life for patients who work or travel. For patients on PD, “adequate” dialysis entails a regimen without unacceptable interference in their lifestyle. For example, most patients on continuous cycling peritoneal dialysis (CCPD) will not accept 14 hours of cycler time daily, nor will most continuous ambulatory peritoneal dialysis (CAPD) patients want to perform five to six manual exchanges daily. Abdominal distention is undesirable for many patients; limiting day dwell volumes may be necessary.

Normalization of serum biochemical markers is also an important goal for PD. While hyperkalemia is rare for patients on PD, an adjustment in the prescription may be necessary in patients with elevated serum potassium. Metabolic acidosis can also be associated with adverse clinical outcomes, including muscle wasting, bone disease, and deterioration in residual kidney function (RKF). In order to improve metabolic acidosis, the dialysis prescription can be increased to obtain a normal serum bicarbonate value. Disorders in mineral metabolism also can be partially treated through dialysis. Elevated serum phosphate is associated with a higher risk of mortality. Since most phosphate is intracellular, dialytic removal of phosphate is time dependent. Therefore, prescriptions that utilize short dwell times may adversely affect phosphate removal.

The dialysis prescription can be tailored to achieve sufficient clearance of urea. Urea is a small, water-soluble molecule that quickly diffuses into dialysate. Urea itself does not appear to be overtly toxic. However, urea is easily measured, and the kinetics of urea removal is very well understood in both hemodialysis and PD. Urea removal with PD has also been examined in two randomized controlled trials (RCT) that compared different dialysis doses. While urea removal is a commonly used measure of dialysis dose, it should be emphasized that focusing solely on urea removal may lead to inattention to other measures of dialysis adequacy. Recognizing this, the most recent iteration of the International Society of Peritoneal Dialysis guidelines regarding quality of dialysis does not mandate a specific target for urea removal in a patient who is otherwise doing well clinically.

Dialytic removal of creatinine has also been used to measure the adequacy of the dose of PD. Similar to urea, creatinine is unlikely to mediate major components of the uremic syndrome. Creatinine diffuses into peritoneal dialysate more slowly than urea because creatinine is a larger molecule (113 vs. 60 Da). In addition, creatinine is secreted into the urine in the proximal tubule, in contrast to urea, which is absorbed from the urine in the terminal portion of the collecting duct. Due to those characteristics, small increases in RKF have a disproportionately greater effect to increase creatinine clearance rather than urea clearance. Increasing creatinine clearance was the target in the intervention arm of the ADEquacy of peritoneal dialysis in MEXICO (ADEMEX) trial, an RCT comparing two different dialysis doses; however, now it is used less often in clinical practice.

The minimum amount of solute clearance necessary has not been thoroughly tested in prospective clinical trials. Observational studies provide some guidance regarding solute clearance. Studies from North America and Europe have suggested that Kt/V urea values exceeding 1.7 may be associated with better clinical outcomes. Two RCTs have examined the effect of different dialysis doses on outcomes, including mortality. One trial, performed in Hong Kong, randomly assigned groups to three different treatment targets using the Kt/V urea: 1.5–1.7, 1.7 to 2.0, and greater than 2.0. There was no difference in mortality between the groups; however, patients in the low-dose group had increased hospitalizations. The second trial (ADEMEX) assigned patients receiving CAPD to two different regimens. One group received four exchanges of 2 L while the high-dose group received a therapy targeted to a creatinine clearance of 60 L/week. The low-dose group had a total Kt/V urea of 1.8, while the high-dose group achieved a total Kt/V urea of 2.27. There was no significant difference in mortality or any of the other clinical endpoints.

Targeting urea (or creatinine clearance) can be useful in clinical practice. However, it is likely that other molecules contribute significantly to uremia and morbidity in patients. Larger molecules, such as β2-microglobulin, have been associated with dialysis-related amyloidosis. Protein-bound toxins, such as indoxyl sulfate have been associated with adverse clinical effects. Dialytic removal of these molecules does not correlate well with urea clearance. It is important not to sacrifice dialytic removal of these other molecules with a myopic focus on urea. For example, in some patients, rapid dialytic exchanges can achieve good urea clearance but not good clearance of sequestered molecules, protein-bound solutes, and larger molecules, such as creatinine, phosphate, and β2-microglobulin.

The Importance of Residual Kidney Function

It has been long appreciated that RKF is associated with better outcomes. For example, in the CANUSA (Canada–USA) observational study, higher RKF was associated with better survival, whereas higher peritoneal solute clearance was not. To deliver comprehensive care to patients on PD, one should employ strategies that preserve RKF. This may include therapy with antagonists of the renin-angiotensin-aldosterone system and avoidance of known nephrotoxic agents, including nonsteroidal anti-inflammatory drugs. High ultrafiltration volumes may decrease RKF if associated with a significant decrease in blood pressure. An increased number of exchanges with CAPD does not appear to reduce RKF, nor does increased ultrafiltration with icodextrin. Dialysate fluids that have a neutral pH and contain low levels of glucose degradation products (GDPs) appear to be associated with improved maintenance of RKF; however, this may come at the expense of increased extracellular volume.

RKF provides multiple benefits to the patient. One clear benefit is continuous sodium and volume removal. Patients with large urine volumes do not require large ultrafiltration volumes and, generally, can use a lower dextrose concentration during treatments. Urine volume removal is also more continuous and less likely to be associated with adverse cardiac consequences seen with faster ultrafiltration. Observational studies have suggested that urine volume is an important prognostic factor. In these trials, urine volume itself, not glomerular filtration rate, has been associated with lower mortality.

In addition to the salutary effects on volume status, it is also likely that solute removal from RKF significantly differs from that of PD. For small molecules, such as urea, dialytic removal of the toxin greatly slows as the dialysate approaches saturation; however, native kidney function allows for a more constant rate of solute removal. Some other molecules that accumulate in kidney failure are mainly intracellular, such as phosphate. Dialytic removal of these molecules is generally slow but is significantly enhanced in patients with RKF. Clearance of larger molecules and protein-bound molecules is also higher in patients with RKF. It is unknown which specific uremic toxins mediate specific pathophysiologic events, but it is likely that RKF is beneficial by removing a large number of these molecules.