Peng et al.

BMC Nephrology (2019) 20:142

https://doi.org/10.1186/s12882-019-1309-y

RESEARCH ARTICLE Open Access

Self-management interventions for chronic

kidney disease: a systematic review and
meta-analysis
Suyuan Peng1,2, Jiawei He3, Jiasheng Huang1, Longwei Lun4, Jiahao Zeng1, Shan Zeng1, La Zhang6,7,
Xusheng Liu4 and Yifan Wu5*

Abstract
Background: Self-management intervention aims to facilitate an individual’s ability to make lifestyle changes. The
effectiveness of this intervention in non-dialysis patients with chronic kidney disease (CKD) is limited. In this study,
we applied a systematic review and meta-analysis to investigate whether self-management intervention improves
renoprotection for non-dialysis chronic kidney disease.
Methods: We conducted a comprehensive search for randomized controlled trials addressing our objective. We
searched for studies up to May 12, 2018. Two reviewers independently evaluated study quality and extracted
characteristics and outcomes among patients with CKD within the intervention phase for each trial. Meta-regression
and subgroup analyses were conducted to explore heterogeneity.
Results: We identified 19 studies with a total of 2540 CKD patients and a mean follow-up of 13.44 months. Compared
with usual care, self-management intervention did not show a significant difference for risk of all-cause mortality
(5 studies, 1662 participants; RR 1.13; 95% CI 0.68 to 1.86; I2 = 0%), risk of dialysis (5 studies, 1565 participants; RR
1.35; 95% CI 0.84 to 2.19; I2 = 0%), or change in eGFR (8 studies, 1315 participants; SMD -0.01; 95% CI -0.23 to 0.21;
I2 = 64%). Moreover, self-management interventions were associated with a lower 24 h urinary protein excretion
(4 studies, 905 participants; MD − 0.12 g/24 h; 95% CI -0.21 to − 0.02; I2 = 3%), a lower blood pressure level (SBP: 7
studies, 1201 participants; MD − 5.68 mmHg; 95%CI − 9.68 to − 1.67; I2 = 60%; DBP: 7 studies, 1201 participants;
MD − 2.64 mmHg, 95% CI -3.78 to − 1.50; I2 = 0%), a lower C-reactive Protein (CRP) level (3 studies, 123 participants;
SMD -2.8; 95% CI -2.90 to − 2.70; I2 = 0%) and a longer distance on the 6-min walk (3 studies, 277 participants; SMD
0.70; 95% CI 0.45 to 0.94; I2 = 0%) when compared with the control group.
Conclusions: We observed that self-management intervention was beneficial for urine protein decline, blood pressure
level, exercise capacity and CRP level, compared with the standard treatment, during a follow-up of 13.44 months in
patients with CKD non-dialysis. However, it did not provide additional benefits for renal outcomes and all-cause mortality.
Keywords: Chronic kidney disease, Self-management, Chronic disease management

* Correspondence: [email protected]
5
Chronic Disease Management Department, Guangdong Provincial Hospital
of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University
of Chinese Medicine, No. 111, Dade Rd, Yuexiu District, Guangzhou,
Guangdong Province, China
Full list of author information is available at the end of the article

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Peng et al. BMC Nephrology (2019) 20:142 Page 2 of 13

Background [11]). The review reported in accordance with the Preferred

Chronic kidney disease (CKD) is a progressive disease that Reporting Items for Systematic Reviews and Meta-Analyses
leads to End-Stage Renal Disease (ESRD: maintenance dia- (PRISMA) [12] statement recommendations.
lysis or kidney transplantation), cardiovascular morbidity
and mortality [1]. Approximately 440,000 patients begin Literature search
dialysis each year worldwide, and annual costs of dialysis Electronic databases were searched using a strategy
and kidney transplants range between US $35,000 and combining selected MeSH terms with keywords related
100,000. This can strain healthcare budgets [2]. Clinical to CKD and self-management intervention. We used
decision making for CKD is challenging [3] due to the het- English and Chinese language restriction [11].
erogeneity of kidney diseases, variability in rates of disease Relevant studies were identified by searching the fol-
progression, and the competing risk of cardiovascular lowing electronic databases from inception to 12th of
mortality, the most common cause of death worldwide May 2018: PubMed, MEDLINE, EMBASE, CINAHL, the
[4]. Furthermore, CKD is not included in the list of prior- Cochrane Library database, the Chinese Biomedicine
ities for most non-communicable diseases (NCD), and few Database (CBM), Chinese National Knowledge Infra-
countries have clear policies or public programs to pre- structure (CNKI), and Wanfang Database. Reference lists
vent and control CKD [5]. from relevant review articles and reviews were also
CKD management includes slowing the progression to searched.
ESRD and decreasing the risk of cardiovascular compli- Studies were first screened according to title and ab-
cations through management of kidney function and stract, and the full texts of any study considered relevant
CKD progression risk factors such as hypertension and according to the selection criteria were assessed for eligi-
diabetes [6]. In addition to medication, managing risk bility by 2 independent reviewers (JS. H and JW. H).
factors is important clinically because it can prevent, or Disagreements between the reviewers concerning deci-
at least minimize, the likelihood of further renal injury. sions to include or exclude studies were resolved by con-
Long-term CKD management requires a high level of sensus, and if necessary, consultation with a third
patient involvement, both in decision-making and in the reviewer (YF. W).
implementation of care. There is growing recognition
that patients want to be involved as equal partners in Selection criteria
their care. The goal of self-management is to identify We included randomized controlled trials of self-man-
strategies that can be used to help patients manage their agement intervention compared with usual care for
condition(s) while leading active and productive lives. adults (age 18 and above) who had been clinically diag-
This includes goal setting, problem solving, symptom nosed with chronic kidney disease. CKD was defined as
management, and shared decision-making, and these a glomerular filtration rate (GFR) < 60 mL/min/1.73 m2
strategies are applicable for a diverse population [7]. For or markers of kidney damage, or both, of at least 3
patients with CKD, this encompasses a spectrum of be- months duration [13]. We included interventions
haviors ranging from adherence to medication, exercise, employing self-efficacy training, empowerment, cognitive
and diet recommendations (self-management mainten- behavioral therapy, or educational programs focusing on
ance) to recognition of early warning signs, and self-management, delivered either face-to-face or
self-adjustment of home-care regimens. through telehealth sessions. Eligible studies had to have
Despite an established tradition of patient self-manage- been published as full-length articles in peer-reviewed
ment of ESRD, and self-management being a well-estab- journals. Patients currently receiving renal replacement
lished treatment strategy for other chronic conditions such therapy [RRT] (dialysis or kidney transplantation) were
as diabetes [8, 9] and hypertension [10], evidence to support excluded.
its use for CKD non-dialysis is limited. To lighten the eco-
nomic burden of ESRD, strategies must be implemented to Outcomes
prevent the progression from early-stage CKD. In this sys- Comparing self-management intervention with the
tematic review and meta-analysis, we synthesized results standard CKD treatment during the follow-up period,
from RCTs to evaluate the effects of self-management inter- the primary outcomes of this systematic review included
vention on major renal outcomes and mortality in all-cause mortality, number of patients progressing to
non-dialysis adults with CKD. We also assessed effect modi- ESRD, change in GFR, change in proteinuria excretion,
fication by proteinuria and blood pressure. and adverse events. Secondary outcomes included health
literacy (diet modifications, exercise capacity) and other
Methods indexes of CKD risk factors, including glycaemia, blood
We performed a systematic review according to a speci- pressure, blood lipid concentration and C-reactive pro-
fied protocol (PROSPERO number: CRD42017059870 tein (CRP) level.
Peng et al. BMC Nephrology (2019) 20:142 Page 3 of 13

Data extraction and quality assessment Results

Data extraction included details on the study character- Search yield
istics (country, study design, sample size and study dur- Computerized and manual searches resulted in 1737
ation), population characteristics (age, sex, CKD stage), unique citations, 1280 of which were excluded after
intervention (intervention format, length and delivery) reviewing their titles and abstracts. In total, 252 poten-
and theoretical frameworks. The comparators and out- tially eligible articles were retrieved for full-text review,
comes assessed were extracted, and then tabulated. and 233 articles were excluded. Both reviewers (HS. H.
We used the recommended Cochrane risk of bias as- and JW. H.) agreed to include 19 publications in the
sessment tool [14], and the following items were present study. See Fig. 1 for details on the review
assessed: random sequence generation, allocation con- process.
cealment, blinding of participants and personnel, blind-
ing of outcome assessment, incomplete outcome data Study and participant characteristics
and selective outcome reporting. Nineteen studies, with a total of 2540 CKD patients,
were deemed eligible. The clinical and methodo-
logical characteristics of each study are summarized
Data synthesis and analysis in Table 1. The follow-up duration across studies
Because of the between-study variance, we used a ranged from 3 months to 60 months, and mean dur-
random-effects model for all analyses [15]. Effects were ation was 13.44 months. All study participants had
reported as the relative risk (RR) and 95% confidence in- CKD, and 10 studies were designed for participants
tervals (CI) for dichotomous outcomes, and mean differ- with CKD and concomitant diabetes or hypertension.
ence (MD) or standard mean difference (SMD) and 95% Studies took place in Europe (2 in the Netherlands,
CI for continuous outcomes. The SMD was used when 2 in the UK), North America (3 in the US, 2 in
all studies had assess the same outcome, but had mea- Canada), Asia (2 in Taiwan, 1 in Hong Kong, 1 in
sured it differently (e.g. GFR was calculated by CKD-EPI Japan), Oceania (4 in Australia, 1 in New Zealand)
equation or CKD-MDRD equation). and Africa (1 in Algeria).
We examined the influence of various characteris-
tics on the study-specific effect estimates by stratify- Intervention features
ing the analysis by self-management type: a) lifestyle Trials in this review comprised various kinds of
modifications; b) medical-behavior modifications; c) self-management. We grouped trials into similar inter-
multi-factorial modifications. ventions (lifestyle modifications; medical-behavior modi-
Statistical heterogeneity across studies was detected fications and multi-factorial modifications). Lifestyle
with the Cochrane Q statistic and an I2 test [14]. In interventions were the most common, followed by med-
cases with substantial heterogeneity, subgroup analysis ical related practice and multi-factorial interventions.
and meta-regression were conducted to explore potential Among the lifestyle intervention trials, 9 studies in-
sources of variation. Subgroup analysis was conducted cluded interventions related to lifestyle modification, tar-
based on intervention format, treatment duration, and geting nutrition management, weight management or
diabetic kidney disease populations. physical exercise. Four studies included in interventions
Funnel plot is a useful tool to visually assess the were related to medical-behavior modification, targeting
potential for publication bias. If publication bias had medicine adherence, disease cognition and complication
been present, then smaller (less precise) studies that control; and 6 were related to multi-factorial modifica-
had failed to show statistical significance would have tions (combined lifestyle and medical behaviors). The
been less likely to have been published. This is programs were delivered either face-to-face in an indi-
reflected as asymmetry in the funnel plot. Publication vidual or group format, or via telehealth sessions (i.e.
bias was also examined by visual inspection of funnel telephone, Digital Versatile Disc). They were conducted
plots for asymmetry and either Egger’s linear regres- by a range of professionals, including nurses, dieticians/
sion test for dichotomous data [16, 17], or Harbord’s nutritionists, certified exercise physiologists (CEP) and
test [18] for continuous data. A p-value less than 0.05 physicians (Table 1).
was considered statistically significant. To assess the Six different self-management intervention theoretical
robustness of our meta-analyses, we conducted a trim frameworks were included in these articles: the Coven-
and fill analysis. The trim and fill method is used to try, Aberdeen, and London—Refined (CALO-RE) tax-
identify, and correct for, funnel plot asymmetry aris- onomy; components of the chronic care (CCM) model;
ing from publication bias. the Trans-Theoretical Model (TTM), the Stanford Pa-
Data were analyzed using RevMan 5.3.3 and STATA tient Education, the SMS program, and the Health Belief
14.0. Model (HBM). When there was insufficient information,
Peng et al. BMC Nephrology (2019) 20:142 Page 4 of 13

Fig. 1 Flow diagram of the stages of article inclusion for this systematic review

we attempted to contact the authors, but the response I2 = 0%) (Fig. 2), risk of dialysis (5 studies, 1565 partici-
rate was poor. pants; RR 1.35; 95% CI 0.84 to 2.19, I2 = 0%) (Fig. 3), or
change in GFR (7 studies, 1315 participants; SMD -0.01;
Quality assessment 95% CI -0.23 to 0.21, I2 = 64%) (Fig. 4). Moreover,
The risk of bias of included studies is summarized in self-management interventions were associated with a
Additional file 1: Figure S1 and S2. The main cause of lower 24 h urinary protein excretion than that of the
potential bias was inadequate allocation concealment. usual care (4 studies, 905 participants; MD − 0.12 g/24 h;
Due to insufficient information, judgement could not be 95% CI -0.21 to − 0.02, I2 = 3%) (Fig. 5).
made in most of the studies regarding either allocation The funnel plots, Egger’s regression asymmetry test,
concealment or selection reporting. and Harbord’s regression asymmetry test each indicated
no significant publication bias for any outcome. There
Effects of self-management intervention on kidney was also no statistical heterogeneity for any of the out-
disease progression comes (Additional file 1: Figure S3).
Figures 2, 3, 4 and 5 shows the pooled estimates for the We also conducted a trim and fill analysis to deter-
primary outcomes. Compared with the standard treat- mine the robustness of our meta-analysis. There was no
ment strategy, self-management intervention showed no effect of replacing missing studies, and the results
significant difference in risk of all-cause mortality (5 showed that these estimates were robust and changed
studies, 1662 participants; RR 1.13; 95% CI 0.68 to 1.86, little (Additional file 1: Table S1).
Table 1 Characteristics of Studies Included in the Systematic Review
Study Participants Age Intervention Format and Delivery Type of Framework Comparator Primary Outcomes Study Country Sample
Characteristics Intervention Duration size
Meuleman 2017 CKD1–4(GFR ≥ 55.6 ± 11.7i; 54.7 ± 16.0c Sodium restriction; Delivered Lifestyle Coventry, Aberdeen Usual care Sodium intake and BP 38 mo NED 67i,
[47] 20)/Hypertension by health psychologists and modifications; and London Refined 71c
dietician Face-to-face (CALO-RE) taxonomy
Rossi 2014 [48] CKD3–4(GFR 67.76 ± 12.4i; 69.26 ± Renal rehabilitation exercise; Lifestyle Usual care Physical Function 3 mo US 59i,
15–59) 12.4c Delivered by exercise modifications; Testing, QoL 48c
physiologist and physical Face-to-face
Peng et al. BMC Nephrology

therapist
Teng 2013 [49] CKD1–3 63.85 ± 12.78 Lifestyle Modification Program; lifestyle Trans-Theoretical Usual care Diet modification, 12 mo Taiwan 52i,
Delivered by clinics’ case modifications; Model (TTM) Exercise 51c
managers Face-to-face
Mustata 2011 [50] CKD3–4 72.5 (59, 79)i; Exercise; Lifestyle Usual care Physical 12 mo CAN 10i,
(GFR15–60) 64 (55, 73)c Delivered by physical therapist modifications; impairment 10c
Face-to-face
(2019) 20:142

Campbell 2008 CKD4–5(GFR<30) 69.75 ± 12.15; Individualized nutritional Lifestyle Usual care SF-36, SGA 3 mo AUS 23i,
[51] counseling: providing modifications; 24c
individualized nutritional Telehealth
counseling (once every 2 weeks),
telephone counseling, and self-
management principles;
Delivered by dietitian
Flesher 2011 [52] CKD3–4(GFR 20– 63.4 ± 12.1i; 63.4 ± Cooking and exercise programs; Lifestyle Stanford Patient Usual care CV risk factors, 12 mo CAN 23i,
60)/Hypertension 11.8c Delivered by certified exercise modifications; Education progression of CKD, 17c
physiologist (CEP), nurse, dietitian, Face-to-face self-efficacy & self-
cook educator and exercise management
physiologist
Leehey 2009 [53] CKD2–4/Diabetes 66 (range 55–81) Aerobic exercise Lifestyle Usual care Proteinuria 6 mo US 7i,
& obesity modifications; 4c
Face-to-face
Mekki 2010 [54] CKD2 61 ± 14 Mediterranean diet Lifestyle Usual care Lipids and 3 mo ALG 20i,
modifications; apolipoproteins 20c
Face-to-face
Howden 2015 CKD3–4(GFR 60.2 ± 9.7i; 62.0 ± 8.4c Exercise training and lifestyle Lifestyle Usual care Efficacy, Adherence 12 mo AUS 36i,
[55] 25–60)/CVD program; modifications; and Safety 36c
Delivered by nurse practitioner, Face-to-face
exercise physiologist, dietitian,
psychologist, credentialed diabetes
educator and social worker
Byrne 2011 [56] CKD1–4(GFR 62.8 ± 11.8 Evidence-based structured group Medical-behavior Usual care Recruitment, uptake 6mo UK 40i,
< 90)/Hypertension educational intervention (CHEERS); modifications; of the intervention 41c
Delivered by nurse Face-to-face and patient satisfaction
van Zuilen 2011 CKD2–4(GFR 58.9 ± 13.1i; 59.3 ± Nurse practitioner (NP) care; Medical-behavior Usual care Composite nonfatal 60 mo NED 352i,
[57] 20–70) 12.8c Delivered by nephrologist modifications; myocardial infarction, 346c
Face-to-face stroke and cardiovascular
mortality
Hotu 2010 [58] DN(> 0.5 g proteinuria/ 60 ± 7.1c; community visi t(medication Medical-behavior Usual care Change in BP. 4.5 mo NZ 30i,
24 h and Scr 63 ± 6.6i adherence and BP control) modifications; 28c
130-300umol/L)& Delivered by healthcare assistant Face-to-face
Hypertension
Page 5 of 13
Table 1 Characteristics of Studies Included in the Systematic Review (Continued)
Study Participants Age Intervention Format and Delivery Type of Framework Comparator Primary Outcomes Study Country Sample
Characteristics Intervention Duration size
Williams 2012b CKD2–4/T1/ 74.31 ± 8.37 multifactorial intervention designed Medical-behavior Health Belief Model Usual care Medication self-efficacy 12 mo AUS 24i,
[59] T2DM&CVD to improve medication self-efficacy modifications; (HBM) & adherence 24c
and adherence; Delivered by nurse Face-to-face &
Telehealth
Joboshi 2017 [60] CKD1–5 67 ± 11.5i; Participants’ behavioral targets Multifactorial Usual care Self-efficacy and self- 3 mo JPN 32i,
70.1 ± 11.1c included blood pressure modifications; management behavior 29c
Peng et al. BMC Nephrology

management, medication Face-to-face

management, and nutritional
management of salt and potassium
intakes; Delivered by nurse
Ishani 2016 [61] CKD3–5(GFR < 60) 75.1 ± 8.1 Telehealth and interprofessional Multifactorial Components of the Usual care Death, hospitalization, 4.5 mo US 450i,
case management (BP, volume modifications; chronic care model emergency department 150c
status, proteinuria, diabetes Telehealth (CCM). visits, or admission to
mellitus, lipid levels, and skilled nursing facilities
(2019) 20:142

depression; health literacy and

patient activation);
Delivered by nephrologist, nurse
practitioner, nurses, clinical
pharmacy specialist, psychologist,
social worker, telehealth care
technician and dietician
Steed 2005 [62] CKD1–5/T2DM and 59.2 ± 8.8i; 60.3 ± 8.6c Diabetes self-management and Multifactorial Usual care QoL 3 mo UK 59i,
microalbuminuria developing problem solving modifications; 65c
techniques (self-monitoring of Face-to-face
blood glucose, diet, exercise and
medication)
Delivered by diabetes nurse,
dietician
Williams 2012a CKD3–5/Diabetes 68 ± 8.3i; 66 ± 10.8c BP & medication adherence; Multifactorial Health Belief Model Usual care BP control, medication 12 mo AUS 36i,
[63] Delivered by renal specialist nurse modifications; (HBM) adherence 39c
Face-to-face &
Telehealth
Chan 2009 [64] Scr 150-350umol/l 65 ± 7.2 Treatment compliance and self- Multifactorial Usual care Death and/or renal end 24 mo HK 81i,
/T2DM care (drug use, insulin injection, modifications; point (Cr > 500umol/L) 82c
self-monitoring of blood glucose, Face-to-face
and lifestyle modification);
Delivered by dietitian and doctor-
nurse team
Chen 2011 [65] CKD3–5 68.39 ± 12.08 Interactive individualized education Multifactorial SMS program Usual care Improved GFR, No. 12 mo Taiwan 27i,
sessions; modifications; ofhospitalizations 27c
Delivered by CKD nursing specialists Face-to-face &
Telehealth
AUS Australia, US United States, GCG Greater China Group (Mainland China, Hong Kong, Macau and Taiwan), CAN Canada, NED Netherlands, UK United Kingdom, ALG Algeria, NZ New Zealand, JPN Japan
T1DM Type 1 Diabetes, T2DM Type 2 Diabetes, Mo Months
Lifestyle modification, targeting nutrition management, weight management or physical exercise; Medical-behavior modification, targeting medicine adherence, disease cognition and complication control; Multi-
factorial modifications, combine lifestyle and medical behavior;
I
intervention; cControl group
Page 6 of 13
Peng et al. BMC Nephrology (2019) 20:142 Page 7 of 13

Fig. 2 Pooled Estimates Comparing Self-management Intervention with Usual Care for All-cause Mortality; M-H, Mantel-Haenszel method; IV,
independent variable method

Fig. 3 Pooled Estimates Comparing Self-management Intervention with Usual Care for Risk of Dialysis; M-H, Mantel-Haenszel method; IV,
independent variable method
Peng et al. BMC Nephrology (2019) 20:142 Page 8 of 13

Fig. 4 Pooled Estimates Comparing Self-management Intervention with Usual Care for Changing on GFR; M-H, Mantel-Haenszel method; IV,
independent variable method

Effects of self-management on risk factors CRP level (3 studies, 123 participants; SMD -2.8; 95%
For the surrogate outcomes, meta-analysis showed that CI -2.90 to − 2.70, I2 = 0%) than that of the usual care.
self-management interventions were associated with a However, there were no statistical differences in HbA1c
lower blood pressure level (SBP: 7 studies, 1201 partic- or total cholesterol (TC) levels. Likewise, for the behav-
ipants; MD − 5.68 mmHg; 95% CI -9.68 to − 1.67; I2 = ioral risk factor outcomes, patients who had received ex-
60%; DBP: 7 studies, 1201 participants; MD − 2.64 ercise management had longer distances on the 6-min
mmHg, 95% CI -3.78 to − 1.50; I2 = 0%), and a lower walk (3 studies, 277 participants; SMD 0.70; 95% CI 0.45

Fig. 5 Pooled Estimates Comparing Self-management Intervention with Usual Care for 24 h Urinary Protein Excretion; M-H, Mantel-Haenszel
method; IV, independent variable method
Peng et al. BMC Nephrology (2019) 20:142 Page 9 of 13

to 0.94; I2 = 0%) than the control group. Regarding body programs in CKD (Stages 1–4) cannot be conclusively
weight and BMI, diet management appeared no better ascertained [26].”
than usual care alone. Cardiovascular disease events, proteinuria and diabetes
In the stratified analysis, it was observed that the are associated with CKD progression, and the former
multi-factorial modification group was associated with have been the major cause of death in those with CKD.
a significant decrease in HbA1c (3 studies, 344 partici- In our study, the results showed a significant drop in
pants; MD -0.68%; 95% CI -0.99,-0.36; I2 = 65%) com- blood pressure and a lower 24 h urinary protein excre-
pared with the usual care. (Additional file 1: Table S2). tion among the self-management group. Long-term
blood pressure drops reduce proteinuria and other indi-
Adverse events of self-management intervention cators of structural damage. Early change in proteinuria
Four studies recorded adverse events (AEs); there were may lead to an increased risk of ESRD and early death,
no specific descriptions for definition of all AEs; and no and may also be associated with slower progression of
AEs occurred during the follow-up periods. kidney disease [27]. In the stratified analysis, it was ob-
served that the multi-factorial modification group was
Meta-regression and subgroup analyses associated with a significant decrease in HbA1c. Com-
Table 2 lists the results of univariate meta-regression pared with CKD patients, co-existing CKD and diabetes
analyses for exploring the potential sources of patients carry a poor prognosis with increased all-cause
between-study heterogeneity. Though this review did mortality and cardiovascular mortality [28].
not find evidence of specific contributors to heterogen- We also found that self-management intervention led
eity, these effects might have differed according to base- to additional kidney protection, due to lower CRP levels
line CKD stage, race, or the prevalence of disease. and better exercise capacity. Evidence shows that exer-
cise training results in improved physical performance
Discussion and functioning among patients with CKD [29]. Also,
Although RRT has been available for decades in wealthy regular participation in moderate-intensity exercise may
countries, most people with kidney failure have insuffi- enhance certain aspects of immune function and exert
cient access to life-saving dialysis and kidney transplants. anti-inflammatory effects [30, 31]. Inflammatory markers
CKD care is an effective alternative, yet it has limita- such as CRP and anti-inflammatory cytokines correlate
tions: underutilization of health professionals in the care with underlying causes and consequences of the in-
of patients with CKD, limited capacity for CKD surveil- flamed uremic phenotype such as oxidative stress, endo-
lance, a general absence of national strategies to support thelial dysfunction, CVD, infections and protein-energy
CKD care, and poor integration of CKD care programs malnutrition (PEM, also referred to as PEW) [32]. As in-
into national NCD control schemes [19]. A global flammatory biomarkers are sensitive predictors of out-
change in the approach to CKD, from treatment to comes in patients with ESRD, inflammation appears to
prevention, is imperative, especially in low- and middle- be a target for preventive and therapeutic interventions
income countries that lack resources for RRT2. in patients with CKD [33, 34]. This is consistent with
our findings.
Results in relation to other studies and reviews
To date, 6 systematic reviews have studied CKD manage- Self-management theoretical frameworks
ment in general. While Lopez-Vargas 2016 [20], and Gal- Patient-oriented self-management is the cornerstone of
braith 2018 [21] provided education-based interventions, chronic disease management, and optimized self-man-
they did not focus on changing participants’ beliefs. Al- agement is fundamental to controlling risk factors and
though interventions might have been necessary for edu- improving disease management. Seeking to facilitate be-
cation, they are often insufficient, on their own, to havioral change rather than providing a purely educa-
produce behavioral change [22]. LEE (2016) [23] and Lin tional program [35], self-management requires patients
(2017) [24] identified CKD as including ESRD patients. In to shift away from passive education, and to become re-
their study, dialysis participants’ self-management sponsible for their own illness [36]. Patients are no lon-
intervention showed significant effects on self-efficacy, de- ger a passive recipient of education; they are an active
pression and health-related quality of life, while the effect- determiner of their health. Self-management interven-
iveness of self-management of non-dialysis CKD patients tion is a vehicle for helping patients develop skills and
is limited. Helou (2016) [25] focused on multi-factorial techniques to enhance self-care of their chronic condi-
management of diabetic kidney disease (DKD) patients. A tions. Changing patients’ beliefs is usually measured by
recent systematic review has identified only 5 studies, and asking “how confident are you” or “how sure are you”
they are of varying methodological quality. This has led that under specific conditions they can achieve certain
the authors to conclude “the effect of self-management behaviors or physiological states.
 Peng et al. BMC Nephrology
(2019) 20:142

Table 2 Univariate Meta-regression for Effects of Self-management Intervention on Primary Outcomes

All-cause mortality Risk of dialysis Change in GFR 24 h urine protein
2 a b 2 2
Covariates No. R,% P Value β (95% CI) No. R,% P Value β (95% CI) No. R,% P Value β (95% CI) No. R2, % P Value β (95% CI)
Age
≥65y 4 0.00 0.56 0.34[−1.37,1.99] 4 0.00 0.38 0.52[− 1.10,2.14] 4 0.00 0.77 −0.09[−0.82,0.63] 3 0.00 0.37 0.49[−1.32,2.29]
<65y 1 1 4 1
Treatment duration
>12 m 3 0.00 0.74 −0.41[−4.09,3.26] 3 0.00 0.276 0.78[−1.08,2.63] 3 0.00 0.76 0.09[−0.63,0.82] 2 0.00 −0.96 −0.36[−2.0,1.25]
≤12 m 2 2 5 2
Diabetic kidney disease
CKD 4 0.00 0.32 −0.64[− 2.37,1.08] 4 0.00 0.902 −0.07[−1.82,1.67] 5 9.11 0.32 −0.30[− 0.97,0.38] 2 0.00 0.44 0.36[−1.25,1.97]
DKD 1 1 3 2
a 2
R indicated the proportion of between-study variance explained by the model. bP value represented to P value of Q model. P<0.05 indicated a between-group difference of the effects of self-management
intervention for the covariate
Page 10 of 13
Peng et al. BMC Nephrology (2019) 20:142 Page 11 of 13

Our study consisted of the following 6 theoretical Second, there was heterogeneity in patient characteristics,
frameworks, with each model having unique aspects. trial designs and risk factor targets (obesity, hypertensive,
These ranged from uni-dimensional variables to complex salt intake, etc.) among the included studies. The number
multi-dimensional constructs. Noar [37] analyzed the of included studies also limited the power for further ex-
components of health behavior frameworks in terms of ploration with multi-variate meta-regression or multi-level
structures appertaining to attitudinal beliefs; self-efficacy subgroup comparisons [43]. Therefore, we could only par-
and behavioral control beliefs; normative beliefs; tially explain the influences of blood glucose on interven-
risk-related beliefs and emotional responses; and tion effects. Third, funnel plots and Egger’s test did not
intention, commitment and planning. We have updated suggest publication bias, owing to the included studies
the table after Noar (see Additional file 1: Table S3) (published studies only); such bias could still exist. Fourth,
showing how the structure and content of the models for the self-management framework, there is extensive
can be understood on multiple levels. The aforemen- heterogeneity in the body of research available, and it is
tioned theoretical frameworks for chronic diseases help uncertain what theory is best to predict (and ultimately to
refine the theoretical basis of intervention evaluations. change) health behavior. Therefore, more integrative ap-
However, at present, none are commonly used outside proaches are needed. Finally, only Chinese and English
of research settings. Furthermore, the effectiveness of language reports were included. Consequently, we may be
self-management for early-stage CKD is limited, and re- missing data from important studies published in other
quires additional large-sample RCTs to assess the effect- languages.
iveness of self-management intervention [38]. The drawback of a manual literature review is the
Additionally, computer-based machine learning algo- time-consuming step of screening articles to select those
rithms can identify intervention at a practice level in real that fulfill the requirements. Accordingly, some studies
time to allow more focused and immediate correction of have leveraged computer-based topic analysis ap-
bias in NCD management [39]. For example, several proaches to support literature review [44, 45]. In the fu-
studies have adopted novel machine learning algorithms ture, these approaches could be leveraged to facilitate
to perform knowledge discovery on management of AEs the efficiency and effectiveness of systematic review [46].
or cancer complications [40, 41]. Therefore, the machine
learning approach provides a general way to discover Conclusion
self-management strategies for NCDs [42]. We observed that self-management intervention pro-
vided additional benefits for neither renal outcomes nor
Strengths of this study all-cause mortality, when compared with standard treat-
This study has several strengths. First, the concept of ments during a follow-up of 13.44 months in patients
self-management is debatable. Many prior studies have with CKD non-dialysis. However, it does show benefits
failed to distinguish it from health education or chronic for urine protein decline, blood pressure level, exercise
disease management. Additionally, there are a variety of capacity and CRP level. Hence, self-management inter-
risk factors for CKD. Our study grouped similar risk fac- vention was beneficial for changing modifiable risk fac-
tors together, and found that the effect of comprehensive tors (e.g. proteinuria, blood pressure level, blood glucose
intervention (lifestyle combined with medical behavior) level, exercise capacity) for the progression of kidney
is more effective. We believe this will be a new trend in disease. It may have been beneficial in optimizing CKD
future self-management intervention. patient outcomes and avoiding progression to ESRD,
Second, current reporting of intervention content in and thus may have improved survival.
published research articles and protocols lacks consist- Integration and ensuring the sustainability of healthcare
ent terminology, making replicability difficult and un- self-management plans requires a large sample of RCT re-
common. We concluded that there are 6 types of search and a unified and precise self-management inter-
self-management frameworks, and this can provide ref- vention framework. These resources will help determine
erence for future self-management decision making. the ideal implementation for interventions.

Limitations Additional file

Our study also has several limitations. First, the effects
of interventions on lifestyle and risk factor modification Additional file 1: Figure S1. Summary for Risk of Bias of Included
may require years for their results to modify surrogate Studies. Figure S2. Risk of Bias Graph of Included Studies. Figure S3.
Funnel Plots, Contour-enhanced Funnel Plots, and Egger/Harbord
and hard outcomes. A methodological limitation of the Regression. Table S1. Association between Self-management Intervention
studies was the short-term follow-up might not distin- and Standard Care by Subgroups. Table S2. Effects of Self-management
guish kidney outcome differences, with most of the in- on CKD Risk Factors. Table S3. Structure and Content of Self-management.
(DOC 268 kb)
cluded studies had a follow-up time shorter than 2 years.
Peng et al. BMC Nephrology (2019) 20:142 Page 12 of 13

Abbreviations Received: 20 September 2018 Accepted: 21 March 2019

AEs: Adverts events; CEP: Certified exercise physiologists; CI: Confidence
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kidney disease; eGFR: Estimated Glomerular Filtration Rate; ESRD: End-Stage
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