KDOQI (Kidney Disease Outcomes Quality Initiative)
NKF KDOQI GUIDELINES

Executive Summaries | Anemia | Hemodialysis | Peritoneal Dialysis |
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Updates 2006

Clinical Practice Guidelines and Clinical Practice Recommendations
2006 Updates
Hemodialysis Adequacy
Peritoneal Dialysis Adequacy
Vascular Access


I. CLINICAL PRACTICE GUIDELINES FOR PERITONEAL DIALYSIS ADEQUACY

GUIDELINE 4. MAINTENANCE OF EUVOLEMIA

Volume overload is associated with CHF, left ventricular hypertrophy (LVH), and hypertension; therefore, it is important to monitor ultrafiltration volume, dry weight, sodium intake, and other clinical assessments of volume status.

4.1 Each facility should implement a program that monitors and reviews peritoneal dialysate drain volume, RKF, and patient blood pressure on a monthly basis. (B)

4.2 Some of the therapies one should consider to optimize extracellular water and blood volume include, but are not limited to, restricting dietary sodium and water intake, use of diuretics in patients with RKF, and optimization of peritoneal ultrafiltration volume and sodium removal. (B)

BACKGROUND
There is a high prevalence of coronary artery disease, LVH, and CHF in patients with CKD stage 5, including those on PD therapy.112 Cardiovascular disease (CVD) is the largest cause of death in this population.112 In the general population without kidney failure, hypertension is a major risk factor for all these conditions.113 In patients with kidney failure, the literature is less clear, but volume overload is widely believed to be the major contributor to hypertension.114 Therefore, interventions to optimize volume status (and hence blood pressure) are considered central to the management of these patients.

RATIONALE
There are no RCTs addressing the effect on survival of interventions to improve blood pressure and volume control in PD patients, but there is broad consensus, based on the general cardiovascular literature, that normalization of blood pressure and volume status in these patients is desirable.

There is circumstantial evidence from observational studies suggesting that better volume control may improve outcomes. This evidence includes the finding in a number of studies that low transport status according to PET is associated with improved outcome in CAPD patients; this may reflect the beneficial effect of low transport status on peritoneal ultrafiltration and thus on clinical outcome.36,81 Greater fluid removal (peritoneal plus kidney) also was found to be a favorable predictor of outcomes in observational studies of both CAPD and APD patients; again, interpretation of this finding remains controversial because it is unclear whether greater fluid removal indicates better or worse control of volume status or it is just a marker of fluid intake.48,71,115 The relationship between blood pressure and survival in patients with CKD stage 5 is confounded by the high prevalence of cardiac failure, which is associated with both hypotension and greater mortality.116 However, 1 study found that hypertension is associated with a greater likelihood of de novo cardiac failure in patients with CKD stage 5 treated with HD.117

Each facility should implement a program that, each month, assesses patients' blood pressure and volume status and evaluates their drain volume, RKF, and dietary salt and water intake. To ensure good control of blood pressure and volume status in PD patients, clinical examination of the patient needs to be carried out on a monthly basis. Less frequent examination may be acceptable. An approach to the volume overloaded patient has been developed by the International Society for Peritoneal Dialysis and was published elsewhere.218 In particular, this should involve reevaluation of the patient's target weight. Clinical examination will need to be done more frequently in the initial weeks of PD therapy when target weight is being established for the first time. In stable well-established PD patients with well-controlled blood pressure, less frequent examination may be acceptable.

Key determinants of volume status in PD patients are salt and water intake, RKF, and net peritoneal fluid removal; these also should be reviewed on a monthly basis. Salt and water intake is not routinely restricted in PD patients, but should be evaluated if there is persistent volume overload and hypertension. This can be done by a dietitian or indirectly by measuring salt and water removal by RKF and PD.

Salt and water removal are evaluated by measuring daily urinary volume and sodium content and measuring the difference between the volume and sodium content over 1 day of the dialysate effluent and infused dialysis solution. In this calculation, it is important to remember that PD solution bags routinely are overfilled to allow for flushing of the tubing before infusion of fluid into the peritoneal cavity.118 Total sodium and water removal by peritoneal and urinary routes can be considered a reasonable indicator of sodium and water intake, provided the patient is clinically stable and sodium and water losses by other routes are taken into account.

Particular attention should be given to the net peritoneal fluid absorption that frequently occurs with long duration dwells, such as the nocturnal dwell in CAPD and diurnal dwell in APD, because this can be avoided by altering the PD prescription.

Some of the therapies one should consider implementing to optimize extracellular water and blood volume include, but are not limited to, restricting dietary sodium and water intake, use of diuretics in patients with RKF, and optimization of peritoneal ultrafiltration volume and sodium removal. As discussed, dietary advice can be given to reduce sodium and water intake in the event of a persistent problem with hypertension and/or fluid overload. In patients with RKF, a small RCT showed that urinary sodium and water removal can be enhanced, or at least maintained for longer, on PD therapy and that volume status can be improved with the use of high-dose loop diuretics.119 Other RCTs also showed urinary volume and clearance to be maintained better in patients treated with ACE inhibitors and also those treated with ARBs.99,100

Peritoneal fluid removal can be increased by using a more hypertonic glucose solution or an alternative osmotic agent, such as icodextrin. Consistent use of hypertonic glucose solutions raises concerns about damage to the peritoneal membrane and the adverse effects of increased systemic absorption of glucose. Concerns about the role of glucose in membrane deterioration, in particular, have been supported by recent studies.120,121 A preferred approach is to avoid long-duration dwells that often are associated with ineffective fluid removal or even net fluid resorption. In patients on APD therapy, this can be done by either shortening the day dwell and leaving the patient “dry” for a portion of the day or draining out the day dwell and replacing it with fresh dialysis solution partway through the day. In CAPD patients, it can be dealt with by switching to APD without a long day dwell or using a night-exchange device to divide the nocturnal dwell into 2 shorter dwells. An alternative strategy is to use icodextrin solution for the long nocturnal dwell in CAPD patients and the long day dwell in APD patients. This was shown in RCTs to both increase peritoneal ultrafiltration and decrease ECF volume.122,123 With icodextrin in place, there is no need to drain a day dwell early to optimize ultrafiltration. However, some patients may still request a shorter duration day dwell (6 to 8 hours) to allow for a period of day dry time, which some find more comfortable.

LIMITATIONS
While individual strategies—such as loop diuretics, ACE inhibitors, ARBs, and icodextrin—have been shown to increase fluid removal and decrease ECF volume in small RCTs, there have been no trials of sufficient size to examine whether these interventions impact on key patient outcomes, such as patient survival, technique survival, cardiovascular events, hospitalization, and QOL. The likelihood of such studies being done is compromised by the large numbers of patients that would be required to achieve statistical power to answer these questions and by the already widespread acceptance and use of the strategies concerned.

With regard to studies that have been done, use of fluid removal as an end point should be questioned because it is possible that greater fluid removal may simply lead to greater fluid intake without a change in ECF volume status or blood pressure. More weight therefore should be given to studies that use direct and indirect measures of volume status as end points, such as echocardiographic indices, blood pressure, body composition, and body compartment volume estimates.

The whole approach of “optimizing” blood pressure and volume status as a means of improving patient outcome also has not been validated in randomized trials and is justified only by reference to the beneficial effect of decreasing blood pressure that is evident from multiple studies of patients without kidney failure. Again, this strategy is so widely accepted and practiced that it is unlikely to be tested in the PD or CKD stage 5 population in a randomized trial. However, there is a case to be made for carrying out RCTs comparing more- and less-aggressive approaches to decreasing blood pressure because there is no consensus about what appropriate blood pressure targets are in the PD population. There also is little evidence about which antihypertensives are best to use to optimize blood pressure after volume status has been normalized, although benefits shown for high-dose loop diuretics, ACE inhibitors, and ARBs support a primary role for these agents.99,100,119

The question of whether greater use of hypertonic glucose damages the peritoneal membrane has been controversial for many years. Recent clinical studies have strengthened the evidence for this hypothesis, but it is not conclusively proven because studies are not randomized and potentially are confounded by such factors as RKF and inflammation.120,121 The question of whether more use of hypertonic glucose causes greater systemic harm to the patient with more hyperglycemia, hyperlipidemia, hyperinsulinemia, obesity, and consequent cardiovascular effects has been more difficult to answer, although it might appear intuitively logical that this is the case. In this situation, an appropriate response would be to give the patient the benefit of the doubt and minimize hypertonic glucose exposure while at the same time ensuring that this is not at the expense of volume overload and hypertension. Such a compromise would involve judicious use of salt and water restriction, loop diuretics, and nonglucose PD solutions.

Some cautions have been voiced concerning sodium and water removal in patients on APD. In some patients who are performing multiple short overnight dwells (>4 exchanges over 8 hours) the sodium sieving effect of short-duration APD cycles, as well as the tendency for salt and water resorption during the long day dwells may compromise BP and volume control with this modality.124,125 One study suggested superior SBP control with CAPD compared with APD therapy.125 However, this was not a randomized study and previous studies, including a randomized study, did not show worse outcomes on APD therapy.126 Also, although blood pressure likely is an important surrogate or intermediate outcome, it is not clear that salt and water removal is.115 It is important to note that blood pressure control is multifactorial. Control of blood pressure and euvolemia can be obtained in patients on APD if the prescription is individualized with attention to the UF profile on the long dwell and minimization of sodium sieving during overnight dwells. Possible maneuvers to minimize this problem include: using less than four overnight exchanges during 8 hours (average in the United States is currently less than 4 exchanges/night time); shortening the day dwell by draining and either doing an additional midday exchange or having a “dry time” with no dialysate present; or by substituting icodextrin for glucose solutions. At present, there is insufficient evidence to justify recommending one PD modality over another, but it would be reasonable to pay close attention to volume status and blood pressure in APD patients.

IMPLEMENTATION ISSUES
Implementation of these guidelines requires patients to have regular clinic visits and physical examinations. These generally should be monthly after the patient is established on PD therapy, but should be more frequent during and in the first weeks after initial training. Less frequent visits may be acceptable if the patient is stable on PD therapy with good blood pressure and volume status.

Access to dietitian assistance will be required to assess and advise patients about sodium and fluid intake. Use of icodextrin requires access to this solution, which is not available in some jurisdictions and which is limited by cost considerations in others.