PREVALENCE AND CONSEQUENCES OF NONADHERENCE TO HEMODIALYSIS REGIMENS. Renal Issues in Critical Care. 1.5 Hours

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1 Renal Issues in Critical Care PREVALENCE AND CONSEQUENCES OF NONADHERENCE TO HEMODIALYSIS REGIMENS By Kris Denhaerynck, RN, PhD, Dominique Manhaeve, MNS, Fabienne Dobbels, PhD, Daniela Garzoni, MD, Christa Nolte, RN, and Sabina De Geest, RN, PhD C E 1.5 Hours Abstract Adherence to fluid restrictions and dietary and medication guidelines as well as attendance at prescribed hemodialysis sessions of a hemodialysis regimen are essential for adequate management of end-stage renal disease. A literature review was conducted to determine the prevalence and consequences of nonadherence to the different aspects of a hemodialysis regimen and the methodological obstacles in research on nonadherence. Nonadherence to the prescribed regimen is a common problem in hemodialysis and is associated with increased morbidity and mortality. Research on nonadherence is associated with 2 major obstacles: inconsistencies in definitions and invalid measurement methods. Further research is needed to validate measurement methods and to establish clinically relevant operational definitions of nonadherence. (American Journal of Critical Care. 2007;16: ) Notice to CE enrollees: A closed-book, multiple-choice examination following this article tests your understanding of the following objectives: 1. Compare the differences between interdialytic weight gain and intradialytic weight loss. 2. Describe the consequences of nonadherence to hemodialysis regimens. 3. Identify nursing strategies to assist patients with compliance and adherence to hemodialysis regimens. To read this article and take the CE test online, visit and click CE Articles in This Issue. 222 AJCC AMERICAN JOURNAL OF CRITICAL CARE, May 2007, Volume 16, No. 3

2 According to registries in the United States and Europe, prevalence and incidence rates of end-stage renal disease are increasing. Currently, the prevalence is 479 to 1500 cases per million inhabitants and the incidence is 75 to 308 cases per million inhabitants, depending on the region studied. 1,2 These numbers are generally higher among minority groups (eg, African Americans). 2 During the past decade, the increase in the incidence rate has slowed in the United States, probably because of better management of the most important causes of renal failure: diabetes and hypertension. End-stage renal disease can be treated by renal replacement therapies, such as hemodialysis, transplantation, and peritoneal dialysis. Hemodialysis is the therapy used most often. Among patients with end-stage renal disease, 66% in the United States and 46% to 98% in Europe receive hemodialysis. 1,2 Although hemodialysis effectively contributes to long-term survival, morbidity and mortality of dialysis patients remains high, especially morbidity and mortality due to cardiovascular diseases. 3-7 Only 32% to 33% of patients on hemodialysis survive to the fifth year of treatment, whereas 70% of patients who have kidney transplants are alive after 5 years. 8 A hemodialysis regimen is based on 2 pillars: restriction of certain nutrients and removal of waste metabolites from the blood by regular dialysis. Central to effective management of patients with end-stage renal disease is adherence to this therapeutic regimen. Adherence refers to the extent to which a person s behavior taking medication, following a diet, and/or executing lifestyle changes corresponds [to] the agreed recommendations from a health care provider. 9 Successful hemodialysis depends on 4 factors: fluid restriction, dietary guidelines, medication prescriptions, and attendance at hemodialysis sessions. 10 Fluid restrictions can be as severe as a maximum 500 ml of fluid intake daily, depending on the residual diuresis. Patients receiving hemodialysis report a large preoccupation with About the Authors Kris Denhaerynck is a postdoctoral fellow and Sabina De Geest is a professor of nursing with the Institute of Nursing Science, University of Basel, Basel, Switzerland. Dominique Manhaeve is a clinical trial leader with Tibotec BVBA, Mechelen, Belgium. Fabienne Dobbels is a postdoctoral fellow at the Center for Health Services and Nursing Research, School of Public Health, Katholieke Universiteit Leuven, Leuven, Belgium. Daniela Garzoni and Christa Nolte are an attending physician and a study nurse from the Department of Transplant Immunology and Nephrology, University Hospital Basel, Basel, Switzerland. Corresponding author: Sabina De Geest, RN, PhD, Institute of Nursing Science, University of Basel, Bernoullistrasse 28, CH-4056 Basel, Switzerland ( sabina.degeest@ unibas.ch). thirst, rank fluid adherence as distressing, 11 and often embark on fluid and dietary binges. 12 Prescribed dietary restrictions limit sodium, potassium, and protein intake. The goals of the medication regimen are to treat or prevent cardiovascular comorbid conditions and keep a stable mineral blood balance, for instance by giving phosphate binders 13 ; this regimen consists of an average of 12 different drugs. 14 Attendance at the prescribed dialysis sessions implies both regular attendance (no skipping of sessions) and full completion of the sessions (no shortening of a session). Because of the demands of hemodialysis, many patients might not adhere to the prescribed regimen, thereby jeopardizing successful clinical outcomes. We provide an overview of the prevalence and consequences of nonadherence to the different aspects of hemodialysis and address a few methodological obstacles to research on adherence to hemodialysis. We used the following key words to search the research literature ( ) listed in the MED- LINE and CINAHL databases: nonadherence, adherence, compliance, noncompliance, end-stage renal disease, chronic renal failure, treatment failure, treatment adherence, hemodialysis, and renal replacement therapy. We also consulted reference lists and the Cochrane library for articles on adherence/compliance or nonadherence/noncompliance and hemodialysis. Prevalence of Nonadherence We limited our review to articles that provided basic data on design, sample, setting, and measurement of nonadherence and mentioned the prevalence of at least 1 of the 4 aspects of nonadherence in a general population. We excluded studies that did not provide basic information about the methods used, did not include the prevalence of nonadherence, 11,15,19-44 included children in the sample, 45 were based on a sample already reported in another About one third of hemodialysis patients survive 5 years, whereas 70% of transplant recipients are alive after 5 years. AJCC AMERICAN JOURNAL OF CRITICAL CARE, May 2007, Volume 16, No

3 Table 1 Prevalence of fluid nonadherence in hemodialysis patients Reference Sample and setting Measurement method Bame et al, Christensen et al, n = 1230, United States, 29 centers n = 57, United States, 2 centers Mean IWG of 3 monthly measurements Mean IWG of 12 consecutive dialysis sessions Lin and Liang, n = 86, Taiwan, 2 centers Mean IWG over 4 weeks (3 sessions per week) Leggat et al, Pang et al, Vlaminck et al, Lee and Molassiotis, Durose et al, Hecking et al, Kugler et al, n = 6251, United States, US Renal Data System n = 92, Hong Kong, 2 centers n = 564, Flanders, 10 centers n = 62, Hong Kong, 1 center Random sample, n = 71, United Kingdom, 1 center Random sample of units and patients France, 20 units, n = 672 Germany, 21 units, n = 571 Italy, 20 units, n = 600 Spain, 20 units, n = 576 United Kingdom, 20 units, n = 620 n = 916 Germany, 6 centers Belgium, 12 centers Self-reported adherence with fluid intake, from 1 (poor) to 6 (excellent) Collateral reported adherence with fluid intake, from 1 (poor) to 6 (excellent) Mean IWG, up to 6 consecutive monthly measurements Mean daily IWG 2 weeks before inclusion in the study Self-reported fluid adherence in past 14 days, from 0 (adherent) to 4 (nonadherent) Daily weight gain = IWG divided by the number of days between 2 sessions (2-3 sessions per week) Self-reported adherence with fluids, from 0 (poor) to 7 (excellent) Mean IWG during 1 month before enrollment in the study IWG before enrollment in study (3 sessions per week) Self-reported fluid adherence in past 14 days, from 0 (adherent) to 4 (nonadherent) Abbreviation: IWG, interdialytic weight gain. Patients who produce more urine can adhere to less stringent fluid restrictions than can those who are anuric. included research article, 46,47 had biased prevalences because only nonadherers were examined, 48,49 or included patients who received an adherence-enhancing intervention. 50 Our search yielded 17 articles on the prevalence of nonadherence. Fluid Nonadherence Nonadherence to fluid restrictions can lead to fluid overload and possibly complications such as pulmonary congestion. Fluid nonadherence can be assessed by measuring a patient s weight gain between 2 hemodialysis sessions, called interdialytic weight gain (IWG), or weight loss during a session, called intradialytic weight loss (IWL). Nonadherence with fluid restric- tions results in excess weight gain between 2 dialysis sessions (IWG), which is lost again during a dialysis session (IWL). Indirect measurement of nonadherence to fluid restriction is also possible by self-report. Table 1 presents an overview of the studies on fluid nonadherence and describes the different IWGand IWL-based operational definitions. In some studies, IWG was determined only once per patient. In other studies, the mean of several IWG or IWL results were determined for each patient; the percentage of time that IWG values exceeded a chosen threshold were calculated; or the IWG or IWL was compared with a patient s estimated dry body weight, commonly defined as the lowest weight a patient can tolerate without having signs and symptoms of hypotension. 61 Self-reported prevalences of nonadherence with fluid restrictions ranged from 30% to 74%. 53,56,57, AJCC AMERICAN JOURNAL OF CRITICAL CARE, May 2007, Volume 16, No. 3

4 Dichotomization adherent vs nonadherent Prevalence of nonadherence, % Percentage of patients with a mean daily weight gain 1 kg Percentage of patients with mean IWG 2.5 kg Excellent adherence: IWG kg Fair adherence: IWG kg Poor adherence: IWG >3.00 kg No cutoff score reported Mean IWG 2.84 kg, SD 1.12 Excellent adherence: 4.7 Fair adherence: 58.1 Poor adherence: No cutoff score reported 34 Percentage of patients with IWG >5.7% of dry weight 9.7 Percentage of patients with IWG >0.9 kg/d Percentage of patients admitting at least mild (score 1) nonadherence Percentage of patients with daily weight gain 0.7 kg (if dry weight <50 kg) or percentage with daily weight gain 1 kg (if dry weight 50 kg) Adherent if score > Mean daily weight gain 0.92 kg/d, SD Percentage of patients with weight gain 4% of dry body weight 22.5 Percentage of patients with IWG >5.7% of body weight France, 14.3 Germany, 5.6 Italy, 17.7 Spain, 7.5 United Kingdom, 3.4 Percentage of patients admitting at least mild (score 1) nonadherence 74 Nonadherence levels measured by calculating IWG had a similarly wide range, from 10% to 60% These wide ranges most likely are due to the heterogeneity of the samples (ie, patients from different countries, with different customs and healthcare systems) but also may be the consequence of the following biasing processes. Self-report measures are biased because patients consistently overestimate their adherence, even if nonadherence is assessed in a nonthreatening, nonaccusatory, open-ended, and information-intensive way. 62,63 IWG and IWL are biased because the values are influenced by many other variables. One possible bias is related to a patient s residual urine volume/residual kidney function. Patients who still produce large volumes of urine must adhere to less stringent fluid restrictions than must patients who are anuric. A second possible bias is related to IWG and IWL values that have not been corrected for a patient s body mass. 64 Body weight biases the amount of IWG and IWL tolerated. Compared with a lighter patient, a heavier patient will tolerate a certain IWG better. Adjustment for a patient s dry weight addresses this bias. 10 A third possible bias is related to characteristics of the dialysis, such as the duration of a dialysis session and the length of the interval between 2 sessions. Patients have different adherence depending on the length of the interdialysis period to be bridged. Differences in daily IWG and IWL exist between the longer weekend intervals and the shorter midweek intervals. 65 A fourth possible bias is the arbitrary cutoff values of IWG and IWL used to classify patients into adherent and nonadherent groups. In recent investigations, researchers used a cutoff defined by Leggat et al, 54 who AJCC AMERICAN JOURNAL OF CRITICAL CARE, May 2007, Volume 16, No

5 Table 2 Prevalence of dietary nonadherence in hemodialysis patients Reference Sample and setting Measurement method Bame et al, n = 1230, United States, 29 centers Mean of 3 consecutive monthly serum potassium levels Mean of 3 consecutive monthly serum urea nitrogen levels Mean of 3 consecutive monthly serum phosphate levels Lin and Liang, n = 86, Taiwan, 2 centers Mean of 4 monthly baseline serum potassium levels Self-reported adherence with diet, from 1 (poor) to 6 (excellent) Mean of 4 monthly baseline serum phosphate levels Leggat et al, Vlaminck et al, Kutner et al, Lee and Molassiotis, Durose et al, Hecking et al, n = 6251, United States, US Renal Data System n = 564, Flanders, 10 centers n = 119, United States, 26 centers n = 62, Hong Kong, 1 center Random sample, n = 71, United Kingdom, 1 center Stratified random sample of units, and random sample of patients within units France, 20 units, n = 672 Germany, 21 units, n = 571 Italy, 20 units, n = 600 Spain, 20 units, n = 576 United Kingdom, 20 units, n = 620 Baseline serum phosphate level Self-reported dietary nonadherence in past 14 days, from 0 (adherent) to 4 (nonadherent) Mean of 3 months serum phosphate levels (2 months before and 1 month after enrollment in the study) Baseline serum potassium level (mean over 3 months) Baseline serum phosphate level (mean over 3 months) Self-reported adherence with diet, from 0 (poor) to 7 (excellent) Mean of 3 bimonthly serum potassium levels Mean of 3 bimonthly serum phosphate levels Baseline serum phosphate level Baseline serum potassium level Kugler et al, n = 916 Germany, 6 centers Belgium, 12 centers Self-reported dietary nonadherence in past 14 days, from 0 (adherent) to 4 (nonadherent) defined a patient as nonadherent with fluid restrictions when the patient s IWG exceeded 5.7% of the patient s dry weight (for a patient of 70 kg, 5.7% is >4 kg). The precise clinical relevance of this cutoff value remains controversial. A high cutoff prevents confusion between good nutritional status and nonadherent to fluid restriction guidelines. 27,65-68 Having a good nutritional status, a protective factor for survival, is also reflected by somewhat higher IWG and IWL values. 27 Dietary Nonadherence Dietary nonadherence has been assessed by using indirect measures such as patients self-reports and direct measures such as predialysis serum levels of 226 AJCC AMERICAN JOURNAL OF CRITICAL CARE, May 2007, Volume 16, No. 3

6 Dichotomization adherent vs nonadherent Prevalence of nonadherence, % Percentage of patients with serum potassium 6.5 mmol/l Percentage of patients with serum urea nitrogen 35.7 mmol/l ( 100 mg/dl) Percentage of patients with serum phosphate 1.94 mmol/l ( 6.0 mg/dl) Adherence classified as excellent, serum potassium mmol/l; fair, mmol/l; and poor >6.5 mmol/l No cutoff score reported Percentage nonadherent: high, 1.2; fair, 27.9; low, Adherence classified as excellent, serum phosphate mmol/l ( mg/dl); fair, mmol/l ( mg/dl); and poor >1.94 mmol/l (>6.0 mg/dl) Percentage of patients with serum phosphate >2.42 mmol/l (>7.5 mg/dl) Percentage of patients admitting at least mild (score 1) nonadherence Percentage of patients with phosphate levels >2.42.mmol/L (>7.5 mg/dl) Percentage of patients with serum potassium 5.5 mmol/l Percentage of patients with serum phosphate 2.0 mmol/l Classified as adherent if score >4 Percentage nonadherent: high, 25.6; fair, 34.9; low, Percentage of patients with serum potassium 3.5 to 6.5 mmol/l Percentage of patients with serum phosphate 2.0 mmol/l Percentage of patients with serum phosphate >2.42 mmol/l (>7.5 mg/dl) Percentage of patients with serum phosphate >2.10 mmol/l (>6.5 mg/dl) Percentage of patients with serum potassium >6.0 mmol/l Percentage of patients admitting at least mild (score 1) nonadherence France, 9.4 Germany, 22 Italy, 3.8 Spain, 12.2 United Kingdom, 11.6 France, 21.3 Germany, 38.5 Italy, 15.5 Spain, 22.6 United Kingdom, 21.9 France, 10.9 Germany, 15.4 Italy, 28.0 Spain, 27.3 United Kingdom, potassium, phosphate, urea nitrogen, and creatinine as well as predialysis normalized protein catabolic rate. Nonadherence with sodium intake guidelines is measured by determining IWG or IWL, because excessive sodium intake causes thirst and leads to fluid nonadherence. 69 Table 2 gives an overview of the prevalence of dietary noncompliance in dialysis patients on the basis of the main measurement methods used: self-reports and laboratory reports (ie, predialysis serum levels of potassium, phosphate, and urea nitrogen). Estimates of nonadherence ranged from 2% to 39% for potassium intake and from 19% to 57% for phosphorus intake. 51,53,54,57-59,70 Bame et al 51 measured AJCC AMERICAN JOURNAL OF CRITICAL CARE, May 2007, Volume 16, No

7 Table 3 Prevalence of medication nonadherence in hemodialysis patients Reference Sample and setting Measurement method Lin and Liang, Curtin et al, n = 86, Taiwan, 2 centers n = 135, United States, 11 centers Self-reported adherence with medication intake, from 1 (poor) to 6 (excellent) Collateral reported adherence with medication intake, from 1 (poor) to 6 (excellent) Electronically monitored adherence (6 weeks) with antihypertensives (n = 81) or phosphate binders (n = 92) Adherence with antihypertensives (n = 69) or phosphate binders (n = 74) measured by self-report (in week 4) Adherence with antihypertensives (n = 69) or phosphate binders (n = 74) measured by patient-reported pill count Fluid nonadherence can provoke shortness of breath, muscle cramping, dizziness, anxiety, panic, lung edema, and hypertension. serum urea nitrogen and found that 9% of the patients were nonadherent when a cutoff of 35.7 mmol/l (100 mg/dl) was used. Self-reported estimates ranged from 24% to 81%. 53,56,57,60 The wide range of these estimates is due to several factors; potassium and phosphate values reflect not only food intake 27,68 but residual renal function, dialysis adequacy, time at which blood was obtained for the analysis between dialysis, acid-base and hormonal status, and adherence with medication. 28,51,53,71,72 Moreover, the large diversity in estimates is due in part to the lack of generally accepted clinically validated cutoff values (ie, what level of nonadherence is related to an increased risk for poor clinical outcomes). This problem with validity is reflected by the lack of correlation 53,57 or weak correlation (r = ) 56 of potassium and phosphate values with self-reported dietary nonadherence. Medication Nonadherence Nonadherence with the medication regimen is usually assessed by using self-reports or predialysis serum levels of phosphate, although the degree to which the results of assessment of phosphate-binding medication can be extrapolated to the rest of the medication regimen (calcium supplements, vitamins B and C, folic acid, cardiovascular drugs) is not known. The weak correlation between self-reports and phosphate measurements (r = -0.24) 53 may be due to the fact that factors other than taking medication (dietary adherence, for example) also affect serum levels of phosphate. 56 Assessment of serum calcium, which is generally low in cases of nonadherence, is a complementary method for evaluating adherence to use of phosphate binders. Other methods for assessing medication nonadherence such as pill counts, prescription refills, and electronic monitoring are used infrequently. With electronic monitoring systems, the date and time of each cap opening of a pill bottle is recorded via a microprocessor. Although in other populations of patients (eg, transplant recipients) the system is an effective method for assessing nonadherence with the medication regimen, 73,74 we found only 1 study 71 in which electronic monitoring was used with hemodialysis patients. Use of a combination of methods to assess medication nonadherence (ie, assay, self-report, and electronic monitoring) would be preferable to increase the reliability and validity of the results. 62 Studies listed in Table 3 and those on serum levels of phosphate in Table 2 present an overview of the estimated nonadherence prevalences 51,53,54,57-59,70 with medication taking in hemodialysis studies. The estimated prevalences ranged from 19% to 99%. 51,53,71 Part of the variation can again be attributed to the chosen method of measurement and the cutoff value used. Appointment Nonadherence Appointment nonadherence refers to data gathered by the dialysis staff about missed and shortened treatments, along with the total treatment time missed. Missed treatments, the percentage of nonattendance, are the number of sessions skipped compared with the number of sessions prescribed during a specific time. Shortened treatments are the 228 AJCC AMERICAN JOURNAL OF CRITICAL CARE, May 2007, Volume 16, No. 3

8 Dichotomization adherent vs nonadherent Prevalence of nonadherence, % No cutoff score reported 17 No cutoff score reported 27 Perfect adherence Minor nonadherence: <20% of prescribed medications not taken Major nonadherence: >20% of prescribed medications not taken Perfect adherence Minor nonadherence: <20% of prescribed medications not taken Major nonadherence: >20% of prescribed medications not taken Perfect adherence Minor nonadherence: <20% of prescribed medications not taken Major nonadherence: >20% of prescribed medications not taken Anthypertensives: 7% adherence, 45% minor nonadherence, 47% major nonadherence Phosphate binders: 2% adherence, 25% minor nonadherence, 73% major nonadherence Anthypertensives: 9% adherence, 49% minor nonadherence, 42% major nonadherence Phosphate binders: 1% adherence, 28% minor nonadherence, 72% major nonadherence Anthypertensives: 80% adherence, 9% minor nonadherence, 11% major nonadherence Phosphate binders: 54% adherence, 38% minor nonadherence, 8% major nonadherence percentage of the prescribed time of the attended sessions a patient actually receives dialysis or the percentage of appointments shortened by a certain amount of time. The total missed treatment time covers both the skipping and the shortening dimensions of appointment nonadherence; this time is the percentage of time a patient received dialysis compared with the total time prescribed in both attended and unattended sessions. These definitions provide a clear and easy measure of nonadherence and are therefore recommended. Table 4 presents an overview of appointment nonadherence studies. In the absence of agreed cutoff points to classify patients as adherent or nonadherent, the percentage of patients who are nonadherent through skipping varied from 0% to 35% 29,54,59,70,75-78 and through shortening from 7% to 32%. 54,59,70,75 Most studies on appointment nonadherence were done in the United States. These results might not be representative of other healthcare systems. Consequences of Nonadherence Adherence with the prescribed medical regimen is a crucial factor for achieving good therapeutic results in dialysis patients and contributes to better outcomes by reducing morbidity and mortality 11 and the side effects of hemodialysis (eg, muscle cramping, malnutrition, sepsis, infection). In the following sections, we summarize the existing evidence on the relation between nonadherence and the different aspects of hemodialysis therapy and clinical outcome. Our literature search yielded 13 articles on the clinical consequences of nonadherence with 1 of the 4 aspects. 24,27,30-32,47,54,66,79-83 Table 5 is an overview of the results of 8 of the studies. Fluid Nonadherence Nonadherence with fluid restrictions can cause shortness of breath, muscle cramping, dizziness, anxiety, panic, lung edema, and hypertension. Although hypertension is a known risk factor for cardiovascular disease, which is the most important cause of mortality in patients receiving hemodialysis, 5,24,30,84 the results of studies on the relationship between nonadherence with fluid restrictions and mortality were inconsistent, showing positive 27,54,79 as well as negative 30,66 or no relationships. 31 These results may indicate that other variables, such as nutritional status and age, act as mediating factors. 27,30 Higher IWGs or IWLs may reflect a good nutritional status, and thus be protective, at least in younger patients, who can tolerate larger IWGs and IWLs. 27,30 High IWGs and IWLs seem to be particularly risky in patients with low nutritional status. 27 Further research is needed to disentangle the role of the different variables involved in determining IWG and IWL and to determine the exact conditions under which IWG and IWL are related to survival or to mortality. Dietary and Medication Nonadherence Nonadherence with the dietary and medication regimens can result in chronically elevated serum levels of phosphate, which play an important role in the development of secondary hyperparathyroidism and renal osteodystrophy. 33 Elevated levels of phosphate also may increase coronary artery disease, even in young patients, 80 leading to a significantly Skipping at least one dialysis session is associated with a 25% to 30% increase in the risk of death. AJCC AMERICAN JOURNAL OF CRITICAL CARE, May 2007, Volume 16, No

9 Table 4 Prevalence of appointment nonadherence in hemodialysis patients Reference Sample and setting Measurement method Sherman et al, n = 860, United States and Puerto Rico, 54 centers Number of sessions skipped: 3 measurements over 3 months Number of sessions shortened: 3 measurements over 3 months Total time of nonadherence: 3 measurements over 3 months DeOreo, Leggat et al, n = 1000, United States, 3 centers n = 6251, United States, US Renal Data System Number of sessions skipped Number of sessions skipped: measurement over 1 month Number of sessions shortened: measurement over 1 month Block et al, Bleyer et al, Kutner et al, n = 6407, United States, US Renal Data System United States, 49 centers, n = 415 Japan, 21 centers, n = 194 Sweden, 16 centers, n = 84 n = 119, United States, 26 centers Number of sessions skipped Skipping: number of missed treatments per 100 patient months (when no prior arrangement was made and the skipping was not due to lack of transportation because of severe weather disturbances or hospitalization) Number of sessions skipped in the 4 weeks before enrollment in the study Shortening sessions in the 4 weeks before enrollment in the study Hecking et al, Random sample of units and patients France, 20 units, n = 672 Germany, 21 units, n = 571 Italy, 20 units, n = 600 Spain, 20 units, n = 576 United Kingdom, 20 units, n = 620 Number of sessions skipped in the month before enrollment in the study Shortening sessions in the month before enrollment in the study Taskapan et al, n = 40, Turkey, 1 center Skipping sessions during the measurement period of 2 months There are no standardized methods for measuring nonadherence to the hemodialysis regimen. increased risk for mortality. 47,54,81,82 Serum levels of phosphate greater than the reference range (ie, >2.10 mmol/l [>6.5 mg/dl]) were associated with an increased adjusted relative mortality risk. 54,79,82 Appointment Nonadherence Skipping or shortening dialysis sessions decreases the delivered dialysis dose and thus the adequacy of the dialysis. The dose is assessed by using the following indicators: (1) Kt/V (K = dialyzer clearance of urea, t = dialysis time, and V = patient s total body water), a dimensionless index based on the urea clearance rate, and (2) the urea reduction ratio, the decrease in the serum urea nitrogen concentration during the dialysis session. 85,86 A lower delivered dose, as assessed by calculating Kt/V or the urea reduction ratio, has been reported to increase mortality, 32,87 although the exact details of this relationship are controversial. 88 In studies in which the delivered dialysis dose was determined by assessing appointment nonadherence, the relationship between the dose and higher mortality 54,79,83 or higher blood pressure 24 was significant. Skipping at least 1 dialysis session per month has been associated with a 25% to 30% higher risk of death. 54,79 Shortening frequently more than 10 minutes ( 3 times per month) also has been associated with increased mortality. 54 Conclusion In this literature overview, we focused on nonadherence to hemodialysis treatment. Nonadherence with fluid intake restrictions has received the most attention in the dialysis literature. Few researchers have explored medication adherence by using a 230 AJCC AMERICAN JOURNAL OF CRITICAL CARE, May 2007, Volume 16, No. 3

10 Dichotomization adherent vs nonadherent Prevalence of nonadherence, % Percentage of patients missing 1 dialysis sessions per month Percentage of patients shortening 1 dialysis sessions per month Percentage of patients missing 10% of prescribed total treatment time Skipping 2 dialysis sessions per month Percentage of patients skipping 1 dialysis session per month Percentage of patients shortening a dialysis session 10 minutes in 1 month Skipping 1 dialysis session per month Skipping at least 1 treatment Percentage of patients skipping 1 dialysis session per month Sweden: 0 Japan: 0 United States: 28.1 (=2.3% of all sessions; about 147 or 35% of the patients missed 1 treatment) 19 Percentage of patients shortening a dialysis session 10 minutes in 1 month Percentage of patients skipping 1 dialysis session per month Percentage of patients shortening a dialysis session 10 minutes per month Number of patients skipping 31 France: 0.3 Germany: 0.9 Italy: 8.8 Spain: 6.6 United Kingdom: 12.6 France: 7.3 Germany: 9.5 Italy: 8.8 Spain: 6.6 United Kingdom: (n = 1) skipped a session method other than assays of serum phosphate. No study to date has included all 4 aspects of the hemodialysis regimen, namely adherence related to fluid restrictions, dietary guidelines, medication, and dialysis appointments. The prevalence of nonadherence with the different aspects of the dialysis regimen seems considerable. However, assessment of nonadherence has 2 major obstacles: inconsistencies in definitions and invalid measurement methods. Little consensus exists among researchers about standardized methods for measuring nonadherence. Without uniformly applied standardized criteria, the literature on the prevalence and consequences of nonadherence remains difficult to interpret. Development of these standards by linking adherence levels to clinical outcomes should result in clinically relevant definitions of nonadherence; operational definitions should indicate which level and type of adherence are associated with adverse outcomes in terms of morbidity and mortality. Despite problems with the validity of the current assessment methods of fluid, diet, and medication nonadherence, excessive nonadherence is associated with higher morbidity and mortality. Also, appointment nonadherence, especially skipping hemodialysis sessions, is associated with higher morbidity and mortality. This evidence indicates that the behavioral dimension of hemodialysis must be considered to guarantee adequate treatment results. Nurses are in an excellent position to target this behavioral dimension by assessing adherence as an important clinical parameter and by implementing adherence-enhancing interventions that have the ultimate goal of improving clinical outcomes. FINANCIAL DISCLOSURES None reported. AJCC AMERICAN JOURNAL OF CRITICAL CARE, May 2007, Volume 16, No

11 Table 5 Clinical consequences of nonadherence with hemodialysis treatment Reference Sample and setting Nonadherence measurement Leggat et al, Rahman et al, Kimmel et al, Sezer et al, Szczech et al, Saran et al, n = 62, Hong Kong, 1 center n = 5369, United States, US Renal Data System n = 283, United States, 3 centers n = 68, Turkey, 1 center n = , United States, Frenius Medical Care database n = , United States, United Kingdom, France, Germany, Japan, Italy, Spain Fluid nonadherence: mean IWG, up to 6 consecutive monthly measurements Dietary/medication nonadherence: baseline serum phosphate level Appointment nonadherence: skipping (measurement over 1 month) Appointment nonadherence: shortening (measurement over 1 month) Appointment nonadherence: skipping (measurement over 1 month) Appointment nonadherence: shortening (measurement over 1 month) Fluid nonadherence: (mean IWG over 3 months/dry weight)/number of interdialytic days, expressed as the percentage of change per day (3 sessions per week) Fluid nonadherence: mean daily IWG as percentage of the dry weight measured during 3 months (3 sessions per week) Fluid nonadherence: IWL percentage = percentage of weight loss relative to the dry weight (estimated by using the mean postdialysis weight) Fluid nonadherence: IWG as percentage of the dry weight Dietary/medication nonadherence: serum phosphate level >2.42 mmol/l (>7.5 mg/dl) Dietary/medication nonadherence: serum potassium level >6 mmol/l Appointment nonadherence: skipping 1 session per month Block et al, n = 6407, United States, US Renal Data System Appointment nonadherence: shortening a session by 10 minutes Dietary/medication nonadherence: baseline serum phosphate level Lopez-Gomez et al, n = 59, Spain, 1 center Fluid nonadherence: mean IWG as percentage of the dry weight during 4 weeks (3 sessions/week) Abbreviations: IDWG, interdialytic daily weight gain; IDWL, intradialytic daily weight loss; IWG, interdialytic weight gain; IWL, intradialytic weight loss. eletters Now that you ve read the article, create or contribute to an online discussion about this topic using eletters. Just visit and click Respond to This Article in either the full-text or.pdf view of the article. SEE ALSO To learn more about treating patients with renal disease, visit and read the article by Broscious and Castagnola, Chronic Kidney Disease: Acute Manifestations and Role of Critical Care Nurses (Critical Care Nurse, August 2006). REFERENCES 1. European Renal Association-European Dialysis and Transplant Association. ERA-EDTA Registry 2004 Annual Report. Amsterdam, the Netherlands: Department of Medical Informatics, Academic Medical Center; US Renal Data System. USRDS 2006 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. Bethesda, Md: National Institute of Diabetes and Digestive and Kidney Diseases; Locatelli F, Marcelli D, Conte F, et al. Survival and development of cardiovascular disease by modality of treatment in patients with end-stage renal disease. J Am Soc Nephrol. 2001;12: AJCC AMERICAN JOURNAL OF CRITICAL CARE, May 2007, Volume 16, No. 3

12 Outcome IWG >7.5% 35% higher mortality risk Serum phosphate >2.42 mmol/l (>7.5 mg/dl) 13% higher mortality risk Skipping 1 dialysis session 25% higher mortality risk Shortening a session 3 times per month for >10 minutes 20% higher mortality risk Higher diastolic and systolic blood pressure if skipping 1 session Higher diastolic blood pressure if shortening 1 session for 10 minutes No relationship found Longer survival if IDWG 3% of dry weight/day Increasing IDWL percentage associated with higher mortality at 1 year 1.12 relative mortality risk if IWG >5.7% Hospitalization: no relationship detected 1.17 relative mortality risk if serum phosphate >2.42 mmol/l (>7.5 mg/dl) 1.07 relative risk to be hospitalized if serum phosphate >2.42 mmol/l (>7.5 mg/dl) No relationship detected 1.30 relative mortality risk if skipping 1.13 relative risk to be hospitalized if skipping No relationship detected 1.18 relative mortality risk if serum phosphate between 2.13 and 2.52 mmol/l (6.6 and 7.8 mg/dl) 1.39 relative mortality risk if serum phosphate between 2.55 and 5.46 mmol/l (7.9 and 16.9 mg/dl) 5-year survival higher for higher IWGs 4. 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