Search strategy

Articles were identified through PubMed, PsychInfo, and CINAHL electronic databases using combinations of Medical Subject Heading (MeSH; where appropriate) terms and keywords: peritoneal dialysis; adheren*; complian*; medication*; diet*; fluid*; regimen*; session*; schedule*. Search results were downloaded and imported directly into EndNote X6, after which their bibliographic reference lists were scanned to identify additional relevant studies. The search was carried out in May 2013. Refer to Table 1 for an example of the search strategy for PubMed.

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Table 1. Example Search Strategy (PubMed on 20/05/2013).

https://doi.org/10.1371/journal.pone.0089001.t001

Study selection

We used a three-step process to select the studies. First, using EndNote, duplicate articles were eliminated. Second, to discard irrelevant studies, two authors (HL and KG) screened all titles and abstracts of the papers. Disagreements between the authors were resolved by a consensus. The full paper was obtained where there was insufficient information in the abstract or title to determine eligibility. Third, to select studies that met our inclusion criteria, one analyst (HL) read the full papers identified at abstract screen. If the results of a study were reported in more than one publication, only the publication with the most complete results was retained. Only if publications on the same study focused on different outcomes (i.e. adherence to different aspects of treatment) or different populations were they included in this review.

Publications were included in this review only if full papers met the following criteria:

1. written in English.
2. published in peer-reviewed journals.
3. included measure(s) of (non)-adherence outcome in either dialysis exchanges, medication, diet/fluid restrictions or exercise.
4. explicated criteria/methods or cut offs to calculate and define (non-) adherence.

The papers were required to include details of the methods used to determine non-adherence in any one of the treatment aspects (i.e. dialysis exchanges, medication, diet/fluid restrictions, or exercise) and some numeric results on rates of non-adherence. As there is no gold standard adherence measure, all measures were considered (e.g., self-report, physician/nurse estimate, tablet count, and prescription refill, electronic monitoring, inventory checks/delivery records, built-in software or electronic monitoring systems) as long as the criteria for definition of non-adherence based on these measures and data on frequencies were reported. All definitions of (non-) adherence, such as the percentage of doses taken/exchanges performed over a given time period and percentage of patients achieving a specified adherence level or clinical target, were considered. Where multiple measures were reported, the percentage of patients achieving a specified adherence level was used in this review as this was common to the majority of studies.

Cohort studies, both prospective and retrospective, and cross-sectional designs were all included. For intervention studies, they were only considered if baseline rates were reported. Dissertations, systematic reviews, meta-analyses, case series, editorials, opinion papers, and interventions without any baseline rates on non-adherence were excluded. Studies were also excluded if they did not examine (non-) adherence on either performance of dialysis exchanges, medication, diet/fluid or exercise; did not report on methods to measure or define (non-) adherence; or did not present numerical data on (non-) adherence for PD patients separately to HD. Studies reporting on performance of different steps of PD protocol procedures such as preparation of materials, sterilization, connection/disconnection, or disposal of dialysate bags rather than performance of dialysis exchanges per se were also excluded. These were deemed more related to quality of performance of the recommended procedures among patients who perform PD exchanges rather than (non-) adherence to dialysis exchanges.

Data extraction

Data from the studies were extracted by one analyst (HL) and second analyst (KG) verified all extractions against the original studies. Information extracted included: authors, year of publication, country, study design, PD modality, age, gender, adherence assessment method, definition of non-adherence, non-adherence rates, and factors associated with adherence/non-adherence. Where information on mean age and proportion of male vs. female study participants were unavailable, estimates were calculated based on available data.

We grouped non-adherence into three categories: non-adherence to dialysis exchanges (e.g., missing, shortening or altering schedules), medications (which include not only prescribed phosphate binders but also other medications, e.g., erythropoietin), and dietary/fluid restrictions. When studies did not distinguish between non-adherence rates of their modality sub-population (APD/CAPD), we extracted the available data for the overall study sample.

Quality assessment

The methodological quality of the studies was assessed using a shortened version of the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies [25] employing only the sections pertaining to selection bias, data collection and withdrawals/dropouts. Other sections were not used as they were tailored towards interventional, comparative study designs and were not deemed relevant to many of the studies included in this review. Two researchers (KG and AYL) assessed the quality of the studies independently. Discrepancies were resolved by discussion until consensus was reached.

Search results and study characteristics

Figure 1 shows the flow of literature into this systematic review. We obtained a total of 204 articles from electronic databases and additional searches, of which 147 were excluded at the title/abstract screen stage. Full papers and references lists were reviewed for the remaining 57 studies. A final total of 25 (out of the identified 204) studies were judged to meet the criteria for inclusion in the review (see Table 2). The main reasons for exclusion at both the abstract and full paper screens were that studies: did not clearly define or report the numerical rates of non-adherence, were not written in English, assessed the effects of biochemical markers on clinical outcomes such as survival, were intervention studies aimed at improving adherence without baseline rates reported, or did not distinguish between adherence rates in HD and PD patients among the mixed sample pools.

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Figure 1. Flowchart of Study Selection.

https://doi.org/10.1371/journal.pone.0089001.g001

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Table 2. Non-Adherence Rates Documented in PD Patients.

https://doi.org/10.1371/journal.pone.0089001.t002

Study locations and settings

As seen in Table 2, approximately half (N = 12) of the included adherence-related studies were conducted in North America [3], [4], [23], [26], [27], [28], [29], [30], [31], [32], [33], [34], six were conducted in Europe [35], [36], [37], [38], [39], [40], and six studies were conducted in Asia [41], [42], [43], [44], [45], [46]. One study was conducted in South America [47].

Patient populations and sample sizes

All of studies included patients on PD yet exact PD modality (i.e. CAPD, APD/Continuous Cycle Peritoneal Dialysis; CCPD) was not always clearly stated (N = 12). Of those where modality was specified, N = 4 studies included CAPD only [29], [32], [41], [44], N = 4 included APD only [28], [31], [38], [39] and N = 5 included both CAPD and APD/CCPD patients [3], [23], [26], [37], [46]. More often than not adherence rates were reported for the pooled PD sample and not separately for the different PD modalities with the exception of adherence to dialysis prescription, where rates for APD and CAPD were separately provided [3], [26], [37], [46].

Sample sizes varied greatly from N = 19 in [38] to N = 2001 in [30]; only 20% (N = 5) of the studies had sample sizes of more than 100 participants [27], [30], [37], [40], [44] (Table 2).

More than half (N = 15) of the included studies were cross-sectional [3], [4], [23], [26], [27], [33], [34], [35], [36], [37], [41], [43], [44], [46], [47], with another seven as longitudinal [30], [31], [32], [39], [40], [42], [45]. Two were retrospective investigations [28], [38]. One study reported presented a mixture of cross sectional/retrospective data with some overlap in their sample [29].

While there was no limit to the dates of identification of studies and the earliest was published in 1994 [33], the majority (N = 19) were conducted and published in or after 2000.

Study quality

Overall, the studies were judged as being of moderate quality, as measured using the Effective Public Health Practice Project tool. The most common reasons for being of moderate quality were that non-validated tools were used to assess adherence and that the study recruited small numbers of volunteers, or the selection procedures were not outlined so representativeness could not be inferred.

Definition and measurement of non-adherence

Although some studies report studying adherence and others report non-adherence the studies are implicitly studying both adherence and non-adherence as the one is the converse of the other. Most studies used the same, conceptual definition for non-adherence, namely ‘not following doctor's instructions’. This was operationalized in 20 studies as ‘performing less than prescribed dialysis or deviating from instructions' and in one study as not meeting clinical targets, while four studies used both definitions. Notably, one study [37] chose to avoid the use of term “non-adherence/non compliance” in favor of the term “any modification on PD regime”. Although all studies included some form of definition of non-adherence, the timeframes of measuring non-adherence were not stated in all studies.

The majority of the studies (80%; N = 20) examined adherence with regards to only one aspect of treatment regimen – either dialysis procedures [3], [4], [26], [27], [28], [29], [30], [31], [32], [33], [35], [37], [38], [39], [47], medication [34], [36], [43] or diet/fluid restrictions [42], [45]. Two studies considered at least two of these aspects [23], [40] and another three studies considered all three aspects of treatment (dialysis, medication and diet) [41], [44], [46].

There was a greater degree of research that focused on adherence to dialysis and medication as opposed to dietary recommendations. Adherence to dialysis exchanges was the most commonly assessed treatment aspect (80%; N = 20) [3], [4], [23], [26], [27], [28], [29], [30], [31], [32], [33], [35], [37], [38], [39], [40], [41], [44], [46], [47], eight studies assessed adherence to medication [23], [34], [36], [40], [41], [43], [44], [46] and five studies assessed adherence to diet/fluid restrictions [41], [42], [44], [45], [46]. None of the studies assessed adherence to physical activity despite the fact that it is widely recommended for patients on dialysis and has been found to improve clinical and psychological outcomes.

The methods used to assess non-adherence fell into three categories: (1) subjective measures based on patient self-report, or reporting by nurses/physicians (2) objective/direct measures based on inventory checks/delivery records, built-in software or electronic monitoring systems (e.g. Baxter Home-Choice Pro Card or Baxter PD Link software) and (3) physiological and biochemical indicators that included micronutrients (e.g. serum phosphate, serum potassium), and interdialytic weight gain to evaluate respectively adherence to diet and to fluid intake. Serum creatinine levels were used to quantify adherence to dialysis prescription.

By far, the most frequently used method to assess (non-) adherence across all treatment aspects was self-report either by the patient or healthcare provider (nurse or physician) [3], [4], [23], [26], [27], [32], [33], [34], [35], [36], [37], [40], [41], [43], [44], [45], [46], [47], [48]. Specific methodologies varied across studies. A total of 17 studies used a self-report by interview or an ad hoc (non-validated) patient questionnaire to measure adherence whereas three studies used self-report with a validated questionnaire (Morisky-Green-Levine Test; Dialysis Diet and Fluid Non-adherence Questionnaire) to measure adherence [36], [41], [44].

Biochemical measures/markers were used to quantify adherence to medication (e.g., serum phosphate for phosphate binders [23], [46]) or diet (e.g., protein intake and serum potassium [42], [46]). Only one study used creatinine levels as a marker of adherence to dialysis [33].

Seven out of the 25 reviewed studies used two or more adherence instruments [23], [29], [32], [33], [34], [35], [46], and one [34] combined the different instruments in their analyses to estimate non-adherence rates.

Occurrence of non-adherence

Overall, non-adherence rates ranged from 2.6% to 85.2%. The lowest non-adherence rates were those that measured adherence with built-in software/dialysis delivery records and the highest non-adherence rates measured adherence by either patient self-report or laboratory data. The rates differed across treatment aspects and various definitions for non-adherence. Estimates were typically higher when non-adherence was defined as any deviation from prescribed or recommended activity, and were lower when more specific criteria were applied (e.g. clinical targets for serum biochemistry or duration or numbers of cycles for APD). These issues are presented below.

Non-adherence to dialysis procedures

Non adherence to dialysis was measured in 20 of the 25 studies, and was typically defined as missing exchange(s) [27], [28], [32], [38], [39], [41], [46]; shortening sessions [28], [46] (relevant only to APD/CCPD), or using less than the prescribed amount of dialysate, typically verified by delivery records or built-in software in PD cyclers [3], [4], [23], [26], [28], [29], [31], [32], [47] (e.g. Baxter Home-Choice PRO Card or Baxter PD Link Software) (see Table 2). In the study with the largest sample size, non adherence to dialysis encompassed a range of distinct behaviors and was defined as doing at least three of the following: not attending clinics, not ordering enough supplies, avoiding expedited delivery, or not bringing adequate samples to scheduled outpatient PD appointments [30].

Criteria and the window of observations varied. For 40% of the studies (N = 8/20) that investigated adherence to dialysis, performing less than 90% of prescribed exchanges typically over a period of 1 to 6 months was considered as indicative of non-adherence [3], [4], [26], [28], [29], [30], [31], [47]. The remaining studies had varied criteria to identify non-adherence. Four studies (20%; N = 4/20) adopted more inclusive criteria, i.e. any deviation from regime or procedures [37], [40], [41], [44], or at least one missed exchange during either the past one, two or four weeks [23], [27], [46] while others opted for a more rigid approach in which non adherence was signified by missing 50% of more of the exchanges [32]. Indirect methods based on physiological data (biochemistry or dialysis adequacy data) were also employed mainly in earlier studies [33], [35].

Appreciating the heterogeneity of methods, the observed rates of non-adherence to dialysis procedures ranged from 2.6–53%. In general, rates of non-adherence to dialysis exchanges based on self-report ranged from 2.6–39%, while rates based on objective/direct measures such as inventory/delivery records or built-in software in PD cyclers ranged from 3–53% [28], [29], [31], [32], [35], [38], [39].

Missing PD exchanges/sessions was reported to be in range of 2.5–53% [28], [32], [38], [39], [46], shortening (as in reducing duration of cycles or number of cycles) by 4–15% of patients [23], [28], [46] and performing less than 90% of prescribed exchanges (as per dialysate volume) was evident in 2–40% of patients. Indirect biochemical/physiological measures (e.g. creatinine levels and/or analysis urine/dialysate data and peritoneal equilibration tests) indicate non-adherence rates at 22–26% [33], [35].

Over half of the studies (65%; N = 13/20) reported the rates of non-adherence to dialysis procedures to be higher than 20% [3], [4], [23], [26], [28], [32], [33], [35], [37], [38], [40], [41], [47] suggesting that non-adherence to dialysis prescription estimates are closer to upper bounds estimates reaching 25–30% of patients on PD regimes. In the largest study to date (N = 2001) that employed composite indices, a total 10% of PD patients were found to be non-adherent to dialysis exchanges based on the definition of doing at least three of the following: not attending clinics, ordering enough supplies, avoiding expedited delivery, or bringing in their adequacy samples at scheduled outpatient PD appointments [30].

It is important to note that there is no clear consensus on definitions regarding non-adherence to dialysis sessions, which is likely to have attributed to the high degree of variability in reported non-adherence rates. Missing was defined as absence of one or more session per week, or two or more sessions per month [27]. Definitions were also different between CAPD and APD; non-adherence to the former was conceptualized as missing at least one session during the past week, while for the latter as missing at least one session during the past two weeks [23].

Non-adherence to medication

Non-adherence behaviors to medication included: not completing the full course of a prescribed medication (non-persistence), or incorrectly taking or missing doses of medication.

The range of non-adherence to medication was 3.9–85% (see Table 2 for details). Further investigation revealed that this large spread was due primarily to one outlier, which used more inclusive criteria for non-adherence: i.e., at least one instance of a non-adherent response on the eight-item Morisky-Green-Levine Test (self-report) for anti-hypertensive medication [36]. Removing this paper indicated a range of non-adherence to medication of 3.9–43% for the remaining seven papers.

Both renal specific medications (e.g. phosphate binders, erythropoietin) [23], [34], [36], [43], and other generic/non-renal medications (e.g. medication for extra-renal morbidity such as hypertension) [36] were studied. Several studies assessed non-adherence to medication in general but not to a specific prescribed medication(s) (e.g. [44]). Non adherence rates to generic/non-renal medications ranged from 3.9–37.7% for self-report [41], [44], [46], compared to non-adherence rates of 25% by pill count [40].

Despite the importance of phosphate control in dialysis [49], [50], only three of the studies focused on use of phosphate binders in PD, with self-reported non-adherence rates ranging from 15–85.2% [36], [46] and estimates based on (serum phosphate levels) being more conservative at 10–16% [23], [46].

Non-adherence to diet/fluid restrictions

Out of all identified studies, only a fraction (20%; N = 5/25) investigated dietary non-adherence in PD patients, with 14.4–67% of patients found to be non-adherent to their dietary guidelines. Of these five, two examined fluid adherence presenting the rate of self-reported non-adherence to fluid restrictions as 33.8–55.9% [41], [44]. Studies that used self report showed non-adherence to diet ranging from 14.4–62% [44], [45]. Unintentional and intentional dietary non-adherence behaviors were equally common at 26% [46]. Biochemical indicators of non-adherence produced divergent findings, with rates of dietary non adherence at 16% based on potassium levels [46] while a total of 67% of patients had excessive dietary protein intake in another study [42].

Factors associated with non-adherence

To explore factors associated with non-adherence in the primary studies we have adopted a narrative synthesis approach. The focus was on directionality of associations rather than the magnitude as the variation on type of statistical analyses and inconsistent reporting did not allow a more effective synthesis of results. This involved tabulating factors examined in the included studies, their reported relationship with non-adherence outcomes, defined in terms of significance and direction (negative, positive, or no relationship), and tallying studies falling into each respective grouping with the majority of studies falling into any specific category being considered to indicate a likely relationship.

Nine studies (36%; N = 9/25) [23], [27], [28], [34], [36], [37], [41], [44], [46] identified in this review evaluated factors associated with non-adherence in PD. The focus was mainly on socio-demographic parameters (i.e. age, employment status, education level, sex, race, household income and smoking status), followed by medical/treatment-related factors (duration of renal replacement therapy, presence of carer, number of comorbidities, contact with healthcare professionals) [23], [27], [28], [34], [37], [41], [44], [46]. Psychosocial resources variables (i.e. self-efficacy, perceived burden/control, Quality of Life, satisfaction) have not been examined by more than one study per parameter [23], [36]. Five of the studies that explored factors associated with non-adherence relied on univariate and correlations analyses [28], [36], [37], [44], [46], with four using more rigorous multivariate methods [23], [27], [34], [41].

Although some variables were identified to influence non-adherence, overall there was little agreement between the studies on observed associations to allow identification of high risk sub-groups or determinants in terms of predisposing or maintaining factors. Out of the parameters that have been examined by more than one study, consistent associations with non-adherence were identified for five factors: younger age [23], [34], [37], [41], [44], being employed [27], [37], [41], [44], [46], being male [28], [41], [44], being on treatment for a longer period of time [34], [37], [44], and non-white ethnicity [23], [27], [28]. The correlation between education and adherence levels produced mixed results – lower education was shown to be associated with non-adherence in one study [44], but an opposite trend was observed in three other studies [27], [34], [41].

There is limited evidence for psychosocial factors as each of the various parameters were not examined by more than one of the studies included in this review. The patterns of associations however suggest that non-adherence is associated with low self-efficacy [46], high depression and low quality of life [23] or poor satisfaction with treatment [37]. The presence of a caregiver was found in two studies to be associated with lower rates of non-adherence to dialysis [27], [46].

The association of PD modality with adherence outcomes received very little attention. We are unable to provide clear evidence for the role of PD modality as this issue has not been explored in most studies that have recruited both CAPD and APD patients or studies merged patients on PD modalities and reported overall PD non-adherence rates. Based on the limited number of studies to report rates separately for CAPD and APD patients [3], [26], , non-adherence to APD procedures range from 5–20%, in comparison to 10–47% in CAPD. Although no systematic comparisons have been conducted, a trend of higher non-adherence rates in CAPD compared to APD patients is evident.