Anemia Management Practices in Peritoneal Dialysis Patients Case Study of the Anemic Patient
Mary Ann MacCracken
The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) recommends a target hemoglobin (Hb) range of 11 to 12 g/dL (hematocrit [Hct] of 33% to 36%) for patients with end-stage renal disease (ESRD). This target range has been associated with improvements in: (a) survival, (b) hospitalization rates, (c) quality of life, (d) cardiac functioning (in the form of partial regression of left ventricular hypertrophy), and (e) exercise capacity (NKF, 2001).
While the recommended Hb/Hct target range is appropriate for all patients with ESRD, data from the United States Renal Data System indicate that peritoneal dialysis (PD) patients have significantly lower Hb/Hct levels then their hemodialysis (HD) counterparts. Figure 1 summarizes modality-specific data tracking the percentage of patients who achieved a Hb/Hct of at least 11 g/dL (33%) from 1990 through 1998. These data illustrate a steady improvement in the percentage of patients achieving this minimum standard, with only slight racial differences. In the early 1990s, the percentage of patients who achieved the minimum standard was comparable for HD and PD patients. Beginning around 1995, however, an ongoing trend began emerging in which comparatively fewer PD patients attained this goal (United States Renal Data System, 2000).
The reasons for this disparity remain unclear. While many aspects of anemia management are identical for PD and HD patients, the former present some unique challenges, including the following: (a) subcutaneous (SC) administration of Epoetin alfa, (b) management of supplemental iron regimens, and (c) prevention and management of peritonitis. This article provides an overview of these issues.
Administration and Dosing of Epoetin alfa
Administration of Epoetin alfa by the SC route is practical in peritoneal dialysis patients for several reasons. First, it allows self-administration or caregiver-assisted administration in the patient’s home. Second, it may allow less frequent dosing. Finally, it avoids unnecessary venipuncture, thereby preserving the integrity of veins for use if hemodialysis is necessary in the future (NKF, 2001).
Several principles should be considered when Epoetin alfa is administered to PD patients. First, patient-specific responses should be assessed to determine the optimum frequency of SC administration and an appropriate Epoetin alfa dose. A physiologic evaluation of SC Epoetin alfa dosing and administration conducted by the NKFK/DOQI Anemia Work Group showed that more frequent administration appears to be more efficacious than less frequent dosing. That is, administering Epoetin alfa two to three times a week is more efficacious than administering it once-a-week. However, despite the physiologic advantages of more frequent dosing, the guidelines also acknowledge that the once-weekly regimen will often be preferred, even if larger doses are sometimes required, because it is more convenient for patients (NKF, 2001).
Dialysis patients frequently progress from HD to PD–initiating renal replacement therapy on the former before switching to home-based therapy. No firm guidelines on how to convert a patient from intravenous (IV) to SC administration of Epoetin alfa have been developed. While some data indicate that administering Epoetin alfa by the SC route may be more efficient for some patients than IV administration (NKF, 2001), this is not universally true (Castro, et al., 1994; De Schoenmakere, et al., 1998; Goodkin, et al., 1999). Consequently, doses should be titrated based on individual response.
To avoid a potential decrease in Hb (Hct) when switching to SC administration a prudent dosing approach is to maintain the same weekly dose that the patient was receiving IV. For example, a patient receiving 5,000 Units IV three times a week should switch to 5,000 Units SC three times a week. If for some reason less frequent administration is desirable at the outset of therapy, the total weekly IV dose can be divided by the number of SC administrations. Following the conversion, the dose can be titrated upward or downward and the frequency of administration can be adjusted depending on individual response.
Dose changes should not occur more frequently than once very 4 weeks to allow adequate evaluation of the response (Amgen, 1999). Because patients on PD are not monitored as frequently, dose adjustments are conservative; for example, titrate the dose by only 10% upward or downward to avoid a precipitous change in Hb/Hct. After dosing changes or when there is a rise or fall in Hb/Hct, values are monitored at least every 2 weeks. Once patients are stable, trends are monitored monthly.
Iron Management in Peritoneal Dialysis Patients
Peritoneal dialysis patients do not have ongoing chronic blood loss related to the dialysis procedure, and iron deficiency occurs less frequently than in the hemodialysis population. Consequently, many peritoneal dialysis patients are able to maintain adequate iron stores (ferritin [is greater than or equal to] 100 ng/mL, transferrin saturation [is greater than or equal to] 20%) using only oral supplements ((NKF, 2001).
While oral iron is the preferred route of administration for PD patients, there are several barriers to its use, including inconvenient dosing (1 hour preprandial or 2 hours postprandial for optimal absorption), side effects (including gastric irritation, constipation, nausea, vomiting, or abdominal discomfort), and out-of-pocket costs (NKF, 2001). Proactive management of the known side effects of oral iron can often help improve tolerability and patient compliance (Table 1). (NKF, 2001; Warren Sims, Molzahn, & McGory, 1998).
Table 1: Tips for Increasing Compliance with Oral Iron Regimens
* Use an ionic iron salt (sulfate, fumarate, gluconate).
* Initiate therapy with small doses of elemental iron, administered frequently. Titrate upward as dictated by tolerability.
* Switch iron salts/preparations if tolerability is an issue.
* Take supplements at bedtime.
Oral iron supplements should provide a total adult dose of 200 mg of elemental iron a day, administered in two to three divided doses (pediatric patients require 2 to 3 mg/kg/day). Oral iron is best absorbed when it is ingested without medication or food–the former can decrease iron absorption or interfere with metabolism, while the latter can decrease absorption by up to one-half. For example, taking aluminum-based phosphate binders can lead to decreased iron absorption. Although some clinicians have advocated using concomitant ascorbic acid to increase the absorption of oral iron, an evaluation by the NKF-K/DOQI Anemia Work Group concluded that the data do not currently support this approach (NKF, 2001).
IV iron administration may be necessary to support Epoetin alfa-stimulated erythropoiesis in iron-deficient patients who cannot tolerate oral supplements, or those in whom oral agents are ineffective. However, as with other parenteral agents, IV iron should be avoided whenever possible in PD patients to ensure that veins are preserved in case HD is indicated in the future (NKF, 2001).
Peritonitis, Infection, and Hyporesponse to Epoetin alfa Therapy
PD patients are susceptible to most of the same conditions that can hinder erythropoiesis in patients who are receiving HD (Table 2). While iron deficiency is less commonly seen in this population, there is a greater risk of infections, primarily from peritonitis, soft tissue infections of the catheter exit site, and SC tunnel infections. This predisposition to infection results from factors such as: (a) a ready portal of entry for bacteria, and (b) dilution of host defenses by the large volume of dialysis solution routinely inserted into the peritoneum (Burrows & Prowant, 1998).
Table 2: Conditions That Can Decrease Red Blood Cell Levels in Peritoneal Dialysis Patients
* Occult blood loss
* Inadequate Epoetin alfa dosage/administration schedule
* Iron deficiency
* Vitamin deficiency
* Secondary hyperporathyroidism
Infections can aggravate anemia in patients with renal disease in different ways: (a) mediating the release of cytokines that hinder proliferation and maturation of erythroid precursors (Gunnell, Yeun, Depner, & Kaysen, 1999; Patruta & Horl, 1999; Remuzzi & Minetti, 2000),
(b) depleting the active iron pool through sequestration of cellular iron in macrophages, and (c) decreased production of transferrin receptors (Fishbane, 1999; Patruta & Horl, 1999).
Prevention, involving regular patient education on aseptic technique that can prevent the introduction of bacteria, is the most effective nursing strategy for managing peritonitis. Patients should be encouraged to report touch contamination and breaks in the closed system, and prophylactic antibiotics should be prescribed as appropriate. The seriousness of repeat episodes of peritonitis should also be stressed, including scarring of the peritoneal membrane and, ultimately, the need to switch dialysis modalities (Burrows & Prowant, 1998).
When patients present with peritonitis, the nurse should perform a careful assessment to determine the potential cause(s). If an obvious source (such as tears in the catheter or tubing) is not apparent, a careful patient history should be taken to identify the potential source of contamination. Aseptic technique should also be reviewed as soon as symptoms improve and the patient feels well enough to participate in an educational session. It is vital that patient-nurse interactions be conducted positively, without reproach or condemnation. A patient who feels reprimanded may delay reporting symptoms in the future, thereby postponing treatment and leading to more serious infections. Infections usually respond to antibiotic therapy, but, they can increase the cost of treatment and diagnosis and may result in deterioration in nutritional status, hospitalization, or, in extreme cases, a change in renal replacement therapy (Burrows & Prowant, 1998).
The following case studies illustrate the principles of anemia management in the PD population.
Case Study 1: Chronic Hyporesponse to Epoetin alfa
LT is a 59-year-old female PD patient whose Hb is consistently below the target range (it ranges from 8.1 to 10.2 g/dL). The Epoetin alfa dose was increased progressively from 15,000 (200 Units/kg) to 18,000 Units twice a week. Common causes of hyporesponse were progressively ruled out. The patient presented with some symptoms suggesting infection, however, no source could be detected and she failed to respond to antibiotics.
Ongoing assessment eventually resulted in a diagnosis of sarcoidosis, and a treatment regimen, including corticosteroid therapy, was initiated. Her Hb began to rise but stabilized below the target range. On the basis of the response, the Epoetin alfa regimen was changed to 10,000 Units three times a week, and Hb levels gradually began to rise, eventually reaching 11.5 g/dL. The patient then underwent open heart surgery, necessitating the administration of two units of packed red blood cells. Although the Epoetin alfa dose was continued, the Hb dropped to 9.8 g/dL and is still recovering.
Discussion: Sarcoidosis is a systemic granulomatous disease of unknown origin that can involve multiple systems, including the lungs, lymph nodes, skin, liver, spleen, eyes, and phalangeal bones. Patients may present with systemic symptoms that suggest malignant neoplasm or infection, and–as this case illustrates–chronic anemia manifesting as hyporesponse to Epoetin alfa therapy (Kelly & Neilson, 2000; Spraycar, 1995). These patients will often respond to therapy, although an increase in the Epoetin alfa dose may be required to achieve target Hb/Hct. This case also illustrates the fact that some patients may respond better to more frequent dosing.
Case Study 2: Acute Peritonitis
PS is a 63-year-old woman who has been on PD for 4 years. She receives 8,000 Units of Epoetin alfa twice a week and oral iron supplementation. Her Hb had been stable at 11.8 g/dL, with transferrin saturation at 31% and serum ferritin at 315 ng/mL. She presents to the PD clinic with a complaint of generalized myalgia and abdominal discomfort, which have been present for 2 days. Her husband reports the appearance of cloudy effluent in the last exchange. The Hb level is markedly decreased to 10 g/dL, with a transferrin saturation of 23% and a serum ferritin of 610 ng/mL. She is afebrile but uncomfortable.
Discussion: This case provides a classic presentation of an active peritoneal infection. Infection is known to blunt the response to Epoetin alfa by sequestering iron in the reticuloendothelial system. It is not uncommon for PD patients with active peritonitis to present with abdominal pain and generalized malaise. Elevations in the white blood cell count or the body temperature may or may not be present. It is critical that active peritonitis be treated with the appropriate antimicrobials. The Epoetin alfa dose should be maintained until the peritonitis resolves to decrease the effect on the Hb/Hct.
Case Study 3: Patient Monitoring and Compliance
RJ is a 35-year-old man who has been on PD for 6 months. He is receiving an Epoetin alfa dose of 13,000 Units once a week. Although side effects had initially hindered compliance with the oral iron regimen, this challenge was overcome by changing the preparation (from a sulfate to a fumarate salt) and starting with a smaller daily dose of elemental iron (150 mg/day) before incrementally increasing it. On this regimen, Hb increased from a baseline of 9.2 g/dL to 10.8 g/dL over about 3 months before stabilizing. Transferrin saturation was maintained at about 28% and serum ferritin at 425 ng/mL.
An increase in the Epoetin alfa dose to 16,000 Units a week caused no apparent change in Hb. None of the conditions known to commonly affect erythropoiesis were detected, and an assessment of the reticulocyte count revealed that the change in dose had no apparent effect. Persistent nursing discussions with the patient and repeat demonstration of administration technique revealed that he had inadvertently been administering 13,000 Units rather than the prescribed 16,000 Units. Once the technique was corrected, the Hb progressively began to increase and stabilized at 11.4 g/dL after about 5 weeks.
Discussion: This case illustrates the communication and monitoring challenges that may arise when managing anemia in PD patients. Although the change in dose had been discussed with the patient and written directions provided, he nevertheless forgot to administer the correct dose. Proactive and frequent patient correspondence, including phone calls or e-mails, can help nurses reinforce new concepts with PD patients and their caregivers, while keeping themselves apprised of the patient’s understanding of compliance with changes in the prescription.
Case Study 4: Epoetin alfa Dosing
TM is a 49-year-old woman who was switched from HD to PD. While she was on HD, she received 6,000 Units of Epoetin alfa three times a week, and her Hb was stable at about 11.7 g/dL. When she was switched to PD, oral iron was prescribed, and the Epoetin alfa dose was changed to 6,000 Units twice a week. The change in therapy resulted in a slow decrease in Hb, which fell to 10.4 g/dL. Iron parameters were within the facility’s target range, and she had no apparent conditions known to cause hyporesponse. The Epoetin alfa dose was slowly titrated upward over a period of several months, and the Hb eventually increased and stabilized at 11.6 g/dL (with a dose of 7,500 Units twice a week).
Discussion: In this case, the weekly dose of Epoetin alfa was initially decreased by one-third when the patient was switched from HD to PD, resulting in a gradual decrease in Hb. Through dose titration, the Hb eventually rebounded to previous levels at a dose that was slightly less than the previous IV dose. However, the patient’s Hb had decreased below the target range during this time, and several months and numerous dose adjustments were required to raise it. Hematologic parameters may have been more effectively maintained if the patient had initially received the same total weekly dose when she changed from IV to SC administration. This approach may increase the likelihood of maintaining a stable Hb/Hct level and allow clinicians to titrate the Epoetin alfa dose, if necessary, on the basis of individual response.
Anemia management in PD patients requires the application of many of the same techniques used with HD patients. Although tracking data indicate that Hb/Hct levels are consistently lower in PD patients, there is no physiologic basis for this difference. Nurses can help improve anemia-related outcomes in these patients through diligent monitoring of laboratory values, appropriate dosing and administration of Epoetin alfa and iron supplements, and proactive control of peritonitis and other conditions known to affect erythropoiesis.
Note: This article is supported by a financial grant from Amgen Inc. The manuscript has undergone an anonymous peer review. The information does not necessarily reflect the opinions of ANNA or the sponsor.
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Mary Ann MacCrachen, RN, CNN, is the Home Dialysis Coordinator at New York Dialysis Services, Inc. in Albany, New York.
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