2019 Article 816

International Journal of Clinical Pharmacy (2019) 41:630–666
https://doi.org/10.1007/s11096-019-00816-4
REVIEW ARTICLE
Clinical pharmacy practice in the care of Chronic Kidney Disease

patients: a systematic review
Fatma Al Raiisi1 · Derek Stewart1 · Fernando Fernandez‑Llimos2 · Teresa M. Salgado3 · Moustafa Fahmy Mohamed4 ·
Scott Cunningham1
Received: 11 October 2018 / Accepted: 27 March 2019 / Published online: 9 April 2019
© The Author(s) 2019
Abstract
Background Clinical pharmacy services have potential to contribute significantly to the multidisciplinary team providing safe,
effective and economic care for patients. Given recent practice developments (e.g. polypharmacy reviews and pharmacist
prescribing) there is a need to provide a current synthesis of the evidence base for characteristics and outcomes of clinical
pharmacy practice in chronic kidney disease patients. Aim of the review To critically appraise, synthesise and present the
available evidence of the characteristics (structures and processes) and outcomes of clinical pharmacy practice as part of
the multidisciplinary care of patients with chronic kidney disease. Method PubMed, International Pharmaceutical Abstracts
(IPA), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medline and Scopus were searched for peer
reviewed papers using improved search strategy. Included studies were quality assessed using Downs and Black tool for
controlled studies and the mixed methods appraisal tool for all controlled and non-controlled studies. Data were extracted and
synthesised using a narrative approach. Screening, quality assessment and data extraction were performed by two independent
researchers. Ethics approval was not required. Results Forty-seven studies were identified from a variety of countries, with
31 based in a hospital setting. Controlled study designs were employed in 20, with only ten of these using randomisation.
Resources available for service provision were poorly reported in all papers. Positive impact on clinical outcomes included
significant improvement in parathyroid hormone, blood pressure, haemoglobin and creatinine clearance. Pharmacists identi-
fied 5302 drug related problems in 2933 patients and made 3160 recommendations with acceptance rates up to 95%. Impact
on humanistic outcomes was shown through improvement in health related quality of life and patient satisfaction. Economic
benefits arose from significant cost savings through pharmaceutical care provision. Conclusion While there is some evidence
of positive impact on clinical, humanistic and economic outcomes, this evidence is generally of low quality and insufficient
volume. While the existing evidence is in favour of pharmacists’ involvement in the multidisciplinary team providing care
to patients with chronic kidney disease, more high-quality research is warranted.
Keywords Chronic kidney disease · Clinical pharmacy · Pharmacist · Systematic review
Electronic supplementary material The online version of this

article (https://doi.org/10.1007/s11096-019-00816-4) contains
supplementary material, which is available to authorized users.
3
* Scott Cunningham Department of Pharmacotherapy & Outcomes Science,
s.cunningham@rgu.ac.uk Center for Pharmacy Practice Innovation, Virginia
Commonwealth University School of Pharmacy, Richmond,
1
School of Pharmacy & Life Sciences, Robert Gordon VA, USA
University, Aberdeen, Scotland, UK 4
Oman Pharmacy Institute, Ministry of Health, Muscat, Oman
2
Research Institute for Medicines and Pharmaceutical
Sciences (iMed.UL), Faculty of Pharmacy, University
of Lisbon, Lisbon, Portugal
13
Vol:.(1234567890)
International Journal of Clinical Pharmacy (2019) 41:630–666 631
Impacts on practice improved management of anaemia, blood pressure, cal-

cium and phosphate parameters and lipid management [7].
The uncontrolled studies included in the original review
• Understanding fully the structures, processes and rel- shown positive impact of pharmacists’ interventions on
evant outcomes associated with clinical roles of phar- the reduction of transplant rejections and fewer adverse
macists is essential to make best use of resource for events [7]. The reviews main limitations were selection
optimal patient care. and language bias which might affect the quality of the
• There has been a significant volume of research of the systematic review. Salgado et al. concluded that the evi-
clinical role of pharmacists in Chronic Kidney Disease, dence of pharmacists’ interventions in patients with CKD
but it is of limited detail and quality. is scarce, of variable quality and with heterogeneous out-
• There is a need for agreed standard sets of outcomes comes [7]. Since the publication of the original review
for clinical pharmacy practice and research in chronic by Salgado et al., the prescribing practice has continually
kidney disease. developed with new services and models of care being
developed and embedded into clinical pharmacy practice.
Hence, there is a need to update and extend the review.
Given developments in clinical pharmacy globally, it is
Introduction likely that further research has been reported thus an up-
to-date synthesis is warranted.
Chronic Kidney Disease (CKD) continues to be a global
concern with a high risk of mortality, frequent hospitalisa-
tion and reduced life expectancy [1]. Most patients have Aim of the review
co-morbid conditions such as cardiovascular and mineral
bone diseases [2]. Clinical pharmacy services have the The aim of this review was to critically appraise, synthesise
potential to contribute significantly to the multidiscipli- and present the available evidence for the structures, pro-
nary team providing safe, effective and economic care [3]. cesses and related outcomes of clinical pharmacy practice
Key clinical pharmacy roles in the multidisciplinary care as part of the multidisciplinary care of patients with CKD.
of CKD patients were described by two renal pharmacy The specific review questions were:
consultants Mason and Bakus in 2010 [4]. These roles
included specific areas such as managing anaemia, renal • What clinical pharmacy practice related resources (struc-
mineral bone disease and hypertension, as well as more tures, e.g. the multidisciplinary team, clinical pharmacy
general medicines selection and review [4]. Another major skill mix and time allocation) are in place and how are
role pharmacists can play is to contribute to renal drug these matched to healthcare needs and demands to ena-
cost management [5]. An emerging role is the potential for ble provision of care to chronic kidney disease (CKD)
the pharmacist to prescribe and modify medicines, which patients?
has now been implemented into practice in the United • What activities are performed (processes, e.g. medication
Kingdom (UK), United States (USA) and New Zealand review, prescribing) to care for patients with CKD, how
[6]. There is a need to establish the evidence base of the and when are they performed?
impact of clinical pharmacy in the care of CKD patients. • What are the outcomes of the structure and the processes
In 2012, Salgado et al. published a systematic review on the effectiveness (Economic, Clinical, and Humanistic
which included synthesis of the peer reviewed literature up Outcomes (ECHO) model) [8] of care provided?
to March 2010 [7]. The original review identified 37 stud-
ies (38 articles), involving 4743 participants. Majority of
the papers were of uncontrolled design (80%) [7]. Twenty- Method
one articles (55.3%) reported outcome measures and pro-
cess indicators, 4 (10.5%) reported only outcome meas- Data sources
ures, thirteen (34.2%) reported only process indicators and
none reported structures [7]. Pharmacists identified 2683 The systematic review protocol was registered with the
drug-related problems in 1209 patients. The results from International Prospective Register of Systematic Reviews
controlled studies (average quality score 0.57, SD = 0.10) (PROSPERO) (PROSPERO 2017 CRD42017065258). The
reported that pharmacists’ interventions reduced all-cause protocol was constructed in accordance with PRISMA-
hospitalisations, reduced the incidence of end-stage renal P (Preferred Reporting Items for Systematic review and
disease or death in patients with diabetic nephropathy, Meta-Analysis Protocols) standards [9], and the review con-
ducted and reported in accordance with PRISMA (Preferred
13

632 International Journal of Clinical Pharmacy (2019) 41:630–666
Reporting Items for Systematic Review and Meta-Analysis) Title and abstract screening and quality assessment for
standards [10]. inclusion were conducted independently by two reviewers
The Cochrane database was searched to identify any rel- (FA and SC), with any disagreements resolved by discus-
evant systematic reviews. An electronic search of relevant sion with a third independent reviewer (DS).
databases (PubMed, International Pharmaceutical Abstracts
(IPA), Cumulative Index to Nursing and Allied Health Lit-
erature (CINAHL), Medline and Scopus) was conducted Quality assessment
from March 2010 to December 2018 thus providing an
update on the review of Salgado et al. [7]. The search was An independent, duplicate quality assessment of each
carried out using Medical Subject Headings (MeSH) and study was undertaken (DS, TJ, FA & SC). All controlled,
other appropriate subject headings and text words. Scoping uncontrolled and descriptive studies were assessed using
searches were conducted prior to finalising the search strat- the mixed methods appraisal tool (MMAT), a validated
egy. Boolean operators such as truncations (*), wild cards and unique tool for appraising different types of study
($), adjacent search options (e.g. adj2) were used where rel- designs [11]. All controlled studies included in this review
evant. The following grouped terms were initially searched were additionally assessed for quality using the Downs
separately then in combination by two independent review- and Black’s method in line with the original review [12],
ers (FA & SC). The primary search was conducted using the a validated tool with a scoring scale consisting of 27 ques-
improved search strategy of the same terms as the original tions grouped into five domains (reporting, external valid-
review as follows: ity, bias, confounding and power). The total score is 32 and
PubMed, IPA, CINAHL: (“pharmaceutical services” is expressed as rates, the higher the score the better the
[MH+] OR “pharmacy” [MH+] OR “Pharmacies” [MH] quality of the paper in terms of methodology (maximum
OR “Pharmacists” [MH] OR “clinical pharmacist*” [TI/ is 1) [12]. To classify scores, the approach of Machado
AB/SU] OR “clinical pharmacy” [TI/AB/SU] OR “clini- et al. was applied [13] (i.e. < 0.5 was considered ‘weak’,
cal pharmacies” [TI/AB/SU] OR “pharmacist*” [TI/AB/ 0.5–0.69 were ‘fair’, 0.7–0.79 ‘good’ and 0.8–1.0 ‘very
SU] OR “pharmaceutical services” [TI/AB/SU] OR “phar- good’).
macies” [TI/AB/SU] OR “pharmacy” [TI/AB/SU]) AND
(“kidney diseases” [MH+] OR “renal replacement therapy”
[MH+] OR “proteinuria” [MH+] OR “CKD” [TI/AB/SU] Data extraction
OR “nephropathy” [TI/AB/SU]).
Scopus: Data extracted included: primary author, year of publica-
(“Pharmaceutical care” [TI/ABS/KEY] OR “Pharmacist” tion, aim/objectives, design, duration, setting, participants,
[TI/ABS/KEY] OR “Clinical pharmacy” [TI/ABS/KEY]) pharmacist interventions, key findings or main outcomes
AND (“Chronic Kidney Disease” [TI/ABS/KEY] OR “Renal and conclusion. Structures, processes and outcomes were
replacement Therapy” [TI/ABS/KEY] OR “Haemodialysis” adapted from Donabedian’s quality of care model [14].
[TI/ABS/KEY] OR “Kidney failure” [TI/ABS/KEY]). The Structure was defined as the ‘resources required for the
bibliography list of included studies was reviewed to further pharmacist to be able to provide care to renal patients such
identify additional references. as requiring special training, availability of policies and
procedures for practice etc’. Process was defined as ‘the
Study selection and data extraction activities that are performed by the pharmacist on a daily
basis or on specific intervals and how and when they are
Only quantitative studies (randomised and non-randomised performed. These activities may include: daily clinical
controlled and uncontrolled trials, cohort studies and before rounds, involvement in patients’ management plans, medi-
and after evaluations) published in peer-reviewed journals cation reviews, therapeutic recommendations and phar-
were included in the review. Papers published in English and macist prescribing. Outcome measures included clinical
focusing on researching clinical pharmacy practice and the outcomes such as: clinical parameters, medication-related
role of the pharmacist in managing patients with CKD were adverse events, mortality and morbidities, humanistic out-
included. Studies not addressing the topic, literature based comes such as: quality of life and economic outcomes such
only on conceptual models, i.e. lacking empirical evidence, as: rate of hospitalisation and cost of inappropriate thera-
grey literature including conference proceedings, abstracts pies. In addition, pharmacists’ intervention was defined in
and unpublished studies were excluded. Observational stud- the previous review as “any action with the aim of modify-
ies were excluded since they did not address the aim of this ing the process of use of drugs, either in patients’ activities
review. or in medical or health care practitioners’ activities” [7].
13
Data synthesis the inclusion criteria and after quality assessment were of
a standard deemed acceptable for inclusion in the review.
Due to heterogeneity in the data obtained from the included
papers (type of patients, study design, outcomes measured),
Quality assessment
only descriptive and narrative synthesis was possible. All
findings were considered by two independent reviewers to
The Downs and Black’s mean score of the 20 controlled
ensure robustness and consistency in execution of the review
studies was 0.557 (SD = 0.075). All papers presented ‘fair’
process.
quality with the exception of four that scored < 0.5 and was
therefore considered ‘weak’ quality. The quality assessment
of all the included studies using the MMAT tool for the ran-
Results domised (n = 10), non-randomised (n = 20) and descriptive
studies (n = 17) are shown in Figs. 2, 3 and 4.
Study selection and data extraction
No systematic reviews were identified from the Cochrane Data extraction

database and no additional primary studies were identified
from the bibliography lists of included studies. Tables 1 and 2 detail the data extraction characteristics of
Databases searches identified 4140 potential articles to controlled and uncontrolled studies included in the system-
screen further for eligibility (Fig. 1). Only 47 articles met atic review [15–61].
Fig. 1 PRISMA Chart describ-

ing study retrieval and selection
13

Fig. 2 Stacked bar chart representing quality of quantitative Randomized Controlled Trials (n = 10). The % values above represents the propor-
tion for each response as agreed between reviewers for the papers included for each study design
Fig. 3 Stacked bar chart representing quality of quantitative non-randomized studies (n = 20). The % values above represents the proportion for
each response as agreed between reviewers for the papers included for each study design
Fig. 4 Stacked bar chart representing quality of quantitative descriptive studies (n = 17). The % values above represents the proportion for each
response as agreed between reviewers for the papers included for each study design
Study characteristics Thirty-one studies were conducted in hospital settings

(wards, intensive care units (ICU), clinics, departments and
The 47 studies were carried out in a variety of geographic dialysis units) and 16 in primary care settings, including
locations: USA (n = 10), Iran (n = 5), India (n = 7), France clinics and community pharmacies. The follow-up time in
(n = 3), Spain (n = 3), Jordan (n = 2), China (n = 2), Japan all included papers ranged from 4 weeks to 24 months with
(n = 3), Singapore (n = 2), Nigeria, Taiwan, Australia, Saudi a mean of 9.4 (standard deviation, SD = 5.08) months, with
Arabia, Germany, Netherlands, Indonesia, Norway, Canada four studies with unclear duration.
and the UK (n = 1 in each country). Two studies from 2008 The majority of studies (n = 27) used an uncontrolled
to 2009 were not included in the systematic review of Sal- study design, 21 prospective and six retrospective. The
gado et al. [7], hence were considered as part of this review. remaining 20 were controlled, ten of which were randomised
13
Table 1 Characteristics of controlled studies included in the systematic review
Study year Study design Study setting Aim Participants Intervention Control Main clinical outcomes
Country (duration) achieved
N (at baseline) Age (years), mean
(SD)
Santschi et al. Cluster, ran- Primary Care, To evaluates the 90 CKD patients ProFiL group 71.9 (1) A 3-h training Usual care (n = 41) Adjusted mean BP
(2011) domised study Community impact of ProFiL (10.4), and usual workshop for changes, were
Canada [48] (6 months) Pharmacies. on BP control care group 73.3 community phar- (− 6.9/− 0.4 mmHg
Multidiscipli- and management (7.7) macists in ProFiL patients)
nary pre-dialysis of hypertension (2) A communica- compared with
clinic treatment tion network (+ 4.7/+ 2.2 mmHg
to facilitate the in UC) (between
transfer of clini- groups differences, p
cal information value = 0.021/0.348).
between the At 6 months, 44% of
pre-dialysis clinic ProFiL and 24% of
and community UC patients achieved
pharmacists their BP targets.
(3) A pharmaceuti- Patients with written

cal consultation hypertension recom-
service by hos- mendations had a
pital pharmacists greater decrease in
with expertise mean systolic BP
in nephrology (− 11.6 mmHg; p
(n = 48) value = 0.035), and
BP was controlled in
a higher proportion
of them (relative risk,
2.14; p value = 0.011)
Aspinall et al. Non-randomised Primary care To compare the 572 NDD-CKD Pharmacist-Man- Dosing and moni- Usual care More haemoglobin val-
(2012) controlled study setting, Medical quality of ESA patients aged ESA Clinic toring (n = 167) ues were in the target
USA [39] (6 months) centers prescribing and 73.9 (10.9), ESA therapy by range in pharmacist-
monitoring for Usual-Care 78.4 pharmacists managed ESA clinics
patients with (8.8), (n = 314) (71.1% vs. 56.9%
NDD-CKD in Usual Care at Usual care at for usual-care sites;
Veterans Affairs ESA Clinic 76.2 ESA clinic site P < 0.001)
Medical Centers (12.0) (n = 91) Veterans in pharmacist-
with and without managed ESA clinics
pharmacist- had more haemoglo-
managed ESA bin measurements on
clinics average (5.8 vs. 3.6
in usual-care sites
and 3.8 in usual care
at ESA clinic sites;
p = 0.007).
13
635

Table 1 (continued)
636
13
(SD)
Dashti-Khavidaki Cluster, ran- Haemodialysis To assess the 92 HD patients Intervention 55.4 Receive clinical Control group Not reported
et al. (2013) domised study ward of a uni- impact of phar- (15.7), control pharmacist-led (n = 34)
Iran [30] (12 months) versity affiliated maceutical care 48.6 (14.7) pharmaceutical
tertiary hospital on HRQoL of care in addition
haemodialysis to the standard
patients care of the ward
as the case group
(n = 26)
Via-Sosa et al. Non-randomised Community phar- To evaluate the 40 community Intervention 80.8 Pharmacists used a Control group The difference in the
(2013) controlled study macies effectiveness of pharmacies (7.3), control questionnaire to (n = 176) prevalence of dosing
Spain [18] (9 months) the community 354 CKD patients 82.9 (7.1) write a report to inadequacy between
pharmacist GPs detailing the the control and
intervention in DRPs detected intervention group
addressing the and suggest- before the pharma-
problem of dosing changes in cists’ intervention
ing inadequacy therapy. GPs to was 0.73% [95%
as a consequence provide written CI (− 6.0)–7.5] and
of renal impair- reply to the phar- after the pharma-
ment in patients macists within cists’ intervention it
over 65 years that 14 days (n = 178) was 13.5% [95% CI
were taking 3 or 8.0–19.5] (p < 0.001)
more drugs when while the difference
compared with in the mean of drug-
usual care related problems
per patient before
the pharmacists’
intervention was 0.05
[95% CI(− 0.2)–0.3]
and following the
intervention it was
0.5 [95% CI 0.3–0.7]
(p < 0.001).
(SD)
Cabello-Muriel Non-randomised Internal medicine To demonstrate 249 CKD patients Intervention 82.4 Pharmacist inter- Control group Significant differences
et al. (2014) controlled study department of a that the interven- (7.4), Control vention including (n = 125) were noted when
Spain [36] (Unclear) referral hospital tion of a pharma- 81.2 (8.5) patient interview, comparing CrCl
cist in a monitor- medication between discharge
ing program for history taking, and admission in
patients with identification of both the control and
CKD improves inappropriate intervention groups
the outcome of doses of nephro- (5.1 ± 0.9 vs. 6.4 ± 1.0
renal function in toxic drugs, daily p < 0.01). The rate
these patients check of labora- of acceptance of the
tory parameters pharmacists’ recom-
and proposing mendations was 74%
dose adjustments
to physicians
(n = 124)
Debenito et al. Non-randomised Primary care set- To assess adher- 101 CKD patients Intervention 65.6 Clinical phar- Usual care (n = 70) Time to achievement of
(2014) controlled study ting, health care ence to monitor- (pre-dialysis) (14.1), UC 72 macy services haemoglobin target
USA [44] (6 months) system ing guidelines, (13.3) provided to was 28 days in the
along with effi- patients attend- pharmacist-managed
cacy and safety ing the Clinical group compared
outcomes, and to Pharmacy Anti- with 41 days in the
quantify medica- coagulation and usual care group
tion utilization Anaemia Service (p = 0.135), while the
expenditures (n = 31) proportion of patients
among patients achieving target
using ESA haemoglobin was
therapy managed 96.8% compared with
by a clinical 95.7%, respectively
pharmacy service (p = 0.654). Patients
compared with in the pharmacist-
usual care managed group used
less ESA during the
6-month period, lead-
ing to an annualized
savings of 1288 USD
per patient in drug
expenditures
13
637

638
13
(SD)
Jiang et al. (2014a) Non-randomised University To describe the 209 patients on Intervention58.9 The pharmacists No-intervention Suspected adverse
China [35] controlled study affiliated tertiary development and CRRT (17.3), No- assessed the group (n = 103) drug events in the
(12 months) hospital implementation intervention 61.3 patients receiving intervention group
of pharmacist (16.9) CRRT daily dur- were significantly
dosing adjust- ing ICU rounds, lower than the pre-
ment for criti- and then made intervention group
cally ill patients dosage adjust- (35 in 27 patients
receiving CRRT ment interven- versus 18 in 11
and to examine tions when patients, p < 0.001).
the effectiveness needed (n = 106) However, there
of pharmacist was no significant
interventions difference between
length of ICU stay
and mortality after
pharmacist dosing
adjustment, which
was 8.93 days versus
7.68 days (p = 0.26)
and 30.10% versus
27.36% (p = 0.39),
respectively. The
majority of identified
ADEs caused signifi-
cant injury (48.6% in
the pre-intervention
period and 44.4% in
the post-intervention
period) to the patients
involved; the number
of these ADEs dif-
fered significantly
between the two
groups (p = 0.02).
(SD)
Jiang et al. (2014b) Non-randomised University To evaluate the 180 patients on Intervention 62.0 Pharmacists Control group Pharmacists made
China [40] controlled study affiliated tertiary effect of clini- CVVH (18.4), Control assessed criti- (n = 87) 256 antimicrobial
(12 months) hospital cal pharmacist 59.3 (20.6) cally ill patients dosing adjustment
participation in receiving CVVH recommendations
an ICU team on daily during ICU for patients receiving
antimicrobial rounds, and made CVVH, of which 224
dosing adjust- antimicrobial (87.5%) recommen-
ment interven- dosage adjust- dations were accepted
tion for patients ment interven- by physicians.
receiving CVVH tions when In control group,
needed (n = 93) pharmacist dosing
adjustment resulted
in £1637.7 (2669.5
USD) cost savings

per patient, and 2.36
times reduction of
antimicrobial-related
adverse drug events
(ADEs) (11 vs. 26,
p = 0.002), while
length of ICU stay
and mortality in ICU
showed no significant
difference (p > 0.05)
13
639

640
13
(SD)
Joost et al. 2014) Non-randomised Renal transplant To investigate the 74 Tx patients ICG: 51 (13.3), Additional phar- Standard care Adherence was sig-
Germany [47] controlled study unit at a univer- efficacy of a SCG: 54 (11.9) maceutical care group (n = 39) nificantly improved
(12 months) sity hospital pharmaceutical and counselling in patients of the
care programme provided by the ICG (91%) compared
for applying clinical phar- with SCG (75%)
adherence man- macist after the during the first year
agement module transplantation after transplantation
to enhance Additional meet- (p = 0.014). Daily
kidney transplant ings with clinical adherence meas-
patients’ adher- pharmacist ures were already
ence to immu- at out-patient improved within
nosuppressive transplantation 30–40 days after
medication care (minimum start of intensified
once per quarter patientcare. Intensi-
up to maximum fied care patients also
of once a month). showed significantly
(n = 35) better results for
taking adherence
(p = 0.006), pill count
(p = 0.008) and drug
holidays (p = 0.001).
(SD)
Cooney et al. Pragmatic, Primary care To evaluate the 2199 CKD patients Interven- Phone-based phar- Usual care Improvement in the
(2015) randomised, effect of a tion75.5(8.2), macist interven- (n = 1129) primary process out-
USA [15] controlled study pharmacist-based control 75.7(8.2) tion, pharma- come, measurement
(12 months) quality improve- cist-physician of PTH (16.1% in the
ment program collaboration, control arm vs. 46.9%
on 1) outcomes patient education in the intervention
for patients and a CKD regis- arm; p < 0.001). Sub-
with CKD and try (n = 1070) jects in the interven-
2) adherence to tion arm were pre-
CKD guidelines scribed more classes
in the primary of antihypertensive
care setting medications than
those in the control
arm (p = 0.02)
Increased % of subjects
with a phosphorus
and urine albumin to
creatinine ratio meas-
ured for intervention
arm. Satisfaction with
the intervention was
very positive; 92% of
participants
Staino et al. (2015) Non-randomised Renal transplant To determine if a 219 Tx patients Intervention 50, Pharmacists Comparator group Not reported
USA [20] controlled study clinic at a medi- pharmacist-exe- comparator 52 provided recom- (n = 175)
(3 months) cal university cuted compre- mendations via
hospital hensive chart chart review for
review could patients who
serve as sufficient attended the
substitution for transplant neph-
direct par- rology clinic.
ticipation during (n = 170)
outpatient clinic
visits in the post-
discharge follow-
up treatment of
kidney transplant
recipients
13
641

642
13
(SD)
Chang et al. (2016) Pragmatic, cluster, Primary care To examine the 6 primary care MTM 64.0 (13.2), Pharmacist MTM Control group The pharmacist MTM
USA [45] randomised study feasibility of sites, 47 CKD control 70.6 (9.7) arm received (n = 23) intervention did not
(18 months) using pharmacist patients additional sup- significantly improve
MTM to improve port from the total proteinuria
proteinuria pharmacist at the screening at the pop-
screening and clinic site ulation level (OR 2.6,
CKD manage- These pharmacists 95% CI: 0.5–14.0;
ment in a large, received addi- p = 0.3). However,
integrated health tional education it tended to increase
system about KDIGO- screening of previ-
based screening ously unscreened
and manage- patients (78.6% in
ment guidelines the pharmacist MTM
(n = 24) group compared to
33.3% in the control
group; (OR 7.3,
95% CI: 0.96–56.3;
p = 0.05).
Qudah et al. (2016) Randomised Outpatient hae- To evaluate clinical 60 HD patients Intervention 55.3 Physician-pharma- Control group 46% of patients in
Jordan [32] controlled study modialysis units pharmacists role (15.1), and con- cist collaborative (n = 27) the intervention
(6 months) of a university in the manage- trol 51.7 (18.5) care to optimize arm achieved BP
hospital ment of blood antihypertensive target (mean home
pressure in pharmacologic BP ≤ 135/85 mmHg)
haemodialysis therapy (n = 29) compared to only
patients guided 14.3% of patients
by home blood in the control arm
pressure monitor- (p = 0.02). Average
ing decline in weekly
mean home SBP was
10.9 ± 17.7 mmHg in
the intervention arm
(p = 0.004)
Weekly mean home
systolic blood pres-
sure increased by
3.5 ± 18.4 mmHg
in the control arm
(p = 0.396)
(SD)
Chia et al. (2017) Non-randomised, Outpatient neph- To determine 134 patients CC 62 (11.4), UC Pharmacists Usual care CC reduced admissions
Singapore [52] controlled study rology clinic of a whether a col- 60.4 (10.8) performed (n = 190) by 27% (IRR 0.73,
(24 months) tertiary hospital laborative care medication 95% CI 0.54–0.99,
(CC) model review, disease p = 0.047) and
with pharmacist and medication shortened mean LOS
involvement can counselling. by 1.3 days [6.7 (2.6)
reduce admis- They completed versus. 8.0 (3.2),
sions and health- training modules p < 0.001] compared
care utilization in and received to UC. No significant
patients receiving 4 sessions of differences in mortal-
dialysis, com- training with ity (p = 0.189) or
pared to usual an experienced mean healthcare
care (UC) pharmacist utilization cost
before they could (p = 0.165) between

provide the groups
service indepen- Pharmacists identified
dently 515 DRPs with 429
(83.3%) resolved
after review
13
643

644
13
(SD)
Mateti et al. (2017) Open-label, Dialysis centres of To assess the 78 patients PC group 52.78 (1) The PC group Usual care (n = 75) The HRQoL scores
India [53] randomised teaching (TH), impact of (10.45) in TH, received the were significantly
control study government Pharmaceutical 49.15 (12.57) in usual care along improved over time in
(15 months) (GH), and cor- Care (PC) on the GH and 52.97 with pharma- the domains noticed
porate hospitals HRQoL among (15.12) in CH. ceutical care with regard to the
(CH) HD patients Usual care group delivered by a “physical function-
49.40 (12.47) in qualified regis- ing, general health,
TH, 48 (17) in tered pharmacist. emotional well-being,
GH and 53.77 The customized social functioning,
(11.87) in CH care plan was symptom/problem
designed and list, and effects of
delivered to kidney disease” in all
the patients on the three centres of
monthly basis PC group compared
based on the con- to UC group with
dition and need p < 0.05
of the patient by The baseline HRQoL
the WHO-FIP score of KDQoL-
Pharmaceuti- 36 domains such as
cal care model. ESRD-targeted areas
(2) The QoL were not significantly
was assessed different in the UC
using validated group versus PC
KDQoL-36 group in all the three
instrument HD centres
The pharmaceutical
care provided by a
trained pharmacist
had positive impact
in HRQoL of HD
patients
(SD)
Anderegg et al. Cluster randomised 32 medical offices To determine if 227 patients Intervention group Pharmacist inter- 108 patients Intervention group had
(2018) trial from 15 states hypertensive 61.7 (11.6), con- viewed patients significantly greater
USA [54] patients with trol 63.1 (12.2) to review medi- mean systolic blood
comorbid DM cations, assessed pressure reduction
and CKD receiv- knowledge and compared with usual
ing a pharmacist then educated the care at 9 months
intervention patients on HTN. (8.64 mm Hg; 95%,
had improved Individualised CI − 12.8 to − 4.49,
BP control and care plans were p < 0.001). The
greater reduc- prepared and intervention group
tion in mean presented to the had significantly
BP at 9 months physician higher BP control at
compared with 9 months than usual
those receiving care (adjusted odds

usual care ratio [OR] 1.97,
95%, CI 1.01–3.86,
p = 0.047 and OR
2.16, 95% CI 1.21–
3.85, p = 0.0102,
respectively)
Mateti et al. (2018 Open-label, Dialysis centres of To assess the 78 patients As [53] Tailored care Usual care (n = 75) The PC group had sig-
a) randomised teaching (TH), impact of phar- plan has been nificantly reduced its
India [55] control study government maceutical care designed and pro- IDW and BP levels
(15 months) (GH), and cor- on medication vided to the PC in comparison to UC
porate hospitals adherence, Hb group patients group at different
(CH) levels, blood on monthly time intervals with a
pressure (BP), basis based on statistical significance
and interdialytic the situation of of p < 0.05. The Hb
weight gain the patient by levels and medica-
(IDW) among the “WHO-FIP tion adherence rate
HD patients Pharmaceutical scores of HD patients
care model” had significantly
increased in PC
group compared to
UC group at different
time intervals
13
645

646
13
(SD)
Mateti et al. (2018 Open-label, Dialysis centres of To assess the cost- 78 patients As [53] (1)The pharmacist Usual care (n = 75) The incremental cost-
b) randomised teaching (TH), effectiveness of provided PC to effectiveness ratio for
India [56] control study government pharmaceutical the PC group academic, govern-
(12 months) (GH), and cor- care versus usual patients on ment, and corporate
porate hospitals care on treatment monthly basis hospitals HD patients
(CH) costs in the regarding the of PC group com-
patients undergo- knowledge about pared with UC group
ing maintenance the medications, were 86,230 Indian
HD disease, lifestyle Rupee (INR)/Qual-
and medication ity adjusted life year
chart review (QALY) ~ (1223.03
(2) The annual USD), 231,016.66
costs of INR/QALY ~ (3276.6
medications, HD, USD), and
laboratory tests, 87,430 INR/
and travel were QALY ~ (1240.05
collected USD), respectively.
The economic
outcomes were
assessed by
incremental
cost-effectiveness
ratio (ICER)
(SD)
Tuttle et al. (2018) Single-blind, Hospital setting To determine the 72 patients Intervention group A 1- to 2-hour in- 69 patients The primary out-
USA [57] randomized, and home visits. effect of a medi- 70 (12), control home visit from come (composite of
controlled trial cation therapy group 69 (10) a pharmacist for hospitalisation/emer-
(3 months) management a medication gency department/
intervention therapy manage- urgent care centre
on acute care ment (medication visits) occurred in
utilization after review, action 44% of the interven-
hospitalization plan and list) tion group and 41%
in patients with within 7 days in control group
CKD not on of hospital dis- (p = 0.72). Hospital
dialysis charge readmission rate was
n = 19 (26%) in the
intervention group
and n = 18 (26%) in

the control group
(p = 0.95). No differ-
ence in achievement
of goals for BP, hae-
moglobin, phospho-
rus, or parathyroid
hormone
13
647

648
13
(SD)
Xu et al. (2018) Non-randomised, Kidney transplant To evaluate the 43 Tx patients RE group 48.6 The pharmacists 12 Tx patients Patients in the RE
Taiwan [58] controlled study clinics of a medi- behavioural and (8.9). RI group provided face-to- group possessed
(12 months) cal centre. physiological 49.0 (12.8) face interviews, better knowledge for
outcomes of check-ups for self-care (49.6 ± 4.8
pharmaceutical laboratory vs. 38.8 ± 9.1;
care in kidney examinations, p < .001); however,
transplant recipi- and discovery the differences at
ents and documenta- 12 months became
tion of DRPs, insignificant
pharmaceutical (56.4 ± 5.9 vs.
consultation, and 56. ± 4.7; p = 0.72)
education after patients in the
IR group had also
received routine
pharmaceutical
care. Besides, serum
creatinine level of
the RE patients
was stable without
significant varia-
tion (p = 0.93), but it
demonstrated a rising
trend in IR patients
(p < .01). Patients
satisfactory with
the intervention was
95.2%
ADEs adverse drug effects, BP blood pressure, CI confidence interval, CKD chronic kidney disease, CrCl creatinine clearance, CRRT continuous renal replacement therapy, CVVH Continu-
ous Veno-Venous Hemofiltration, DRPs drug related problems, ESA Erythropoiesis stimulating agent, GPs general practitioners, HD haemodialysis, HRQoL health-related quality of life, ICG
intensified care group, ICU intensive care unit, KDIGO kidney disease: Improving global outcomes, MTM medication therapy management, NDD-CKD non-dialysis dependant chronic kidney
disease, OR odds ratio, PTH parathyroid hormone, SBP systolic blood pressure, SCG standard care group, Tx transplantation, UC usual care
Table 2 Characteristics of uncontrolled studies included in the systematic review
Study year Study design (dura- Study setting Aim Participants Pharmacist interven- Main clinical outcomes
Country tion) tions achieved
(SD)
Kelly et al. (2008) Prospective uncon- Diabetes unit of a To offer stepwise 116 diabetic nephrop- 63.4 (8.6) Frequent visits to Significant improve-
United Kingdom [43] trolled study secondary hospital intensive treatment athy patients pharmacist led ments in BP
(18 months) to patients with clinic for treatment (p < 0.001), total cho-
diabetic nephropa- optimisation, check- lesterol (p < 0.001)
thy picked up at the ing of BP, renal and HbA1c (p < 0.05)
traditional second- function, HbA1c,
ary care clinic ACR, FBC, calcium
and phosphate.
Medical history tak-
ing by two sources
Dashti-Khavidaki Prospective uncon- Nephrology and infec- To understand the 1105 CKD patients 52.5 (14.1) Uniform documenta- Not reported
et al. (2009) trolled study tious disease wards types of services tion of all clinical
Iran [51] (12 months) of a large university provided by clinical pharmacy residents
hospital pharmacists in neph- activities and inter-

rology and infec- ventions
tious disease wards,
the acceptance by
physicians and the
clinical significance
of these services
Vessal (2010) Prospective uncon- Nephrology ward of a To determine the 76 CKD patients 47.7 (17.2) CP reviewed medica- Although 89.5% of
Iran [17] trolled study university hospital impact of a clinical tion orders and the detected errors
(4 months) pharmacist on detec- intervention was caused no harm,
tion and prevention made after agree- 4(4.7%) of the errors
of prescription ment of the attend- increased the need for
errors at the neph- ing physician monitoring, 2 (2.3%)
rology ward of a increased length of
referral hospital stay, and 2 (2.3%) led
to permanent patient
harm
Castelino et al. (2011) Prospective uncon- Department of neph- To explore the poten- 308 CKD patients NR Medication history Not reported
India [29] trolled study rology of a teaching tial clinical signifi- interview, clinical
(8 months) hospital cance of the MRPs and medication
and the acceptance review by pharma-
of recommendations cist. Recommenda-
made by clinical tion were reported
pharmacists to the health care
team
13
649

650
13
(SD)
Ohnishi et al. (2011) Retrospective Outpatient haemodial- To explore the role 84 HD patients 62 Pharmacists provided The counselling by
Japan [34] uncontrolled study ysis unit of a tertiary of the pharma- drug information pharmacists sig-
(12 months) hospital cists’ participa- on renal anaemia nificantly decreased
tion, we examined to physicians, haemoglobin levels in
the influence of performed medica- the high group (12 g/
haemoglobin levels tion use evaluations dl) and significantly
anteroposterior the based on laboratory increased them in low
participation data, proposed plans group (10 g/dL)
to change prescrip-
tions based on medi-
cation use evalua-
tions and provided
drug information
and lifestyle care
point to patients
Belaiche et al. Prospective uncon- University hospital To identify DRPs by 67 CKD patients 70 The CP inter- Not reported
(2012a) trolled study based nephrology a trained CP, their viewed patients
France [21] (6 months) clinic frequency and asso- and established a
ciated comorbidities pharmacological
profile, checked for
drug–drug interac-
tions, verified dose
adaptation accord-
ing to the last renal
function tests and
searched for self-
medication and its
potential nephrotox-
icity. The pharma-
ceutical proposals
were validated
with the consulting
nephrologist so as
to optimise therapy
during the following
renal consultation
Belaiche et al. Retrospective Nephrology clinics of To assess the impact 42 CKD patients 64.9 (2.2) Identification of Not reported
(2012b) uncontrolled study a university hospital of clinical pharmacy DRPs by CP and
France [28] (15 months) services in outpa- documentation of
tient nephrology recommendations
clinics
(SD)
Dashti-Khavidaki Prospective uncon- Haemodialysis treat- To assess the impact 86 HD NR CP reviewed patients Serum Calcium was
et al. (2012) trolled study ment centre of a of clinical pharmacy medications and increased in hypocal-
Iran [23] (6 months) teaching hospital services on the man- proposed modifica- caemia patients and
agement of second- tion according to decreased in hyper-
ary complications in laboratory data calcaemia patients
patients who were results to treating until it reached the
on HD, including physicians optimal range in both
bone metabolism groups
disorders, anaemia A decline in serum
and dyslipidaemia Phosphate level was
noted in hyperphos-
phataemia patients
There was an increase
and decrease in serum

iPTH in suboptimal
and supraoptimal
range patients,
respectively
Haemoglobin con-
centration increased
in anaemic patients
and serum ferritin
reached target values
in all patients. Total
cholesterol, low-
density lipoprotein
cholesterol and tri-
glycerides decreased
to near-optimal values
in dyslipidaemia
patients
13
651

652
13
(SD)
Geerts et al. (2012) Prospective uncon- Primary health care To assess the 650 CKD patients 81 (6.7) The pharmacists used Not reported
Netherlands [33] trolled study therapeutic advice a pharmacy medica-
(unclear) formulated by phar- tion alert system to
macists with help of assess the medica-
a pharmacy medication in relation to
tion alert system the reported eGFR
based on the renal and provided an
function of patients alert for target drugs
aged ≥ 70 years with according to the
diabetes or cardio- Dutch guidelines for
vascular disease drug administration
in reduced renal
function
Abu Ruz et al. (2013) Prospective uncon- Nephrology ward of To implement and 130 CKD patients 56.3 (17.8) The pharmacist 17% of all TRPs were
Jordan [37] trolled study a general teaching evaluate the impact Identified TRPs resolved, 5.5%were
(3 months) hospital of pharmaceutical and interventions improved, and
care service for were discussed 37.4%were prevented
hospitalised CKD during ward rounds. through the clinical
patients in Jordan Patients education pharmacist interven-
and interview to tions
improve patient
adherence
Chen (2013) Prospective uncon- Haemodialysis centre To evaluate the 30 HD 62.3 (10.0) Patients requested to Not reported
Singapore [25] trolled study of a general hospital prevalence of DRPs bring their medica-
(5 months) identified and the tion and see the
types of interven- pharmacist before
tions made by MMS the appointment
pharmacists with their physician.
Pharmacist reviewed
patients records,
counsel the patients,
identified and
reported DRPs
(SD)
Jiang et al. (2013) Prospective uncon- Medical and surgical To evaluate the ben- 144 Pre-intervention Pre-intervention: 62.3 Pharmacists com- Dosing adjustments
Japan [38] trolled study ICU of a university- efits that may result (71 patients) (17.0) pleted 1 month of were related to a
(24 months) affiliated hospital from involving phar- Post-intervention (73 Post-intervention: training before the reduced length
macists in the care patients) CRRT 57.9 (15.4) study was started of ICU stay from
of septic patients During the inter- 10.7 ± 11.1 days
receiving CRRT vention period, to 7.7 ± 8.3 days
the pharmacists (p = 0.037) in the
assessed septic intervention group,
patients receiving and to cost sav-
CRRT daily and ings of 3525 USD
adjusted the dosage (13,463 ± 12,045
of antimicrobial vs. 9938 ± 8811,
drugs when needed. p = 0.038) per septic
Recommendations patient receiving

were made to physi- CRRT in the ICU
cians and nurses at Suspected antimicrobial
that time. All phar- adverse drug events
macist recommen- in the intervention
dations were verbal group were signifi-
and recorded on a cantly fewer than in
specially designed the pre-intervention
pharmacist interven- group (19 events vs. 8
tion form events, p = 0.048)
Dosing error events
were significantly
fewer in the post-
intervention phase
than in the pre-inter-
vention phase (54 in
73 patients vs. 194 in
71 patients, p < 0.001)
13
653

654
13
(SD)
Mousavi et al. (2013) Retrospective/ University hospital To evaluate appro- Pre-test phase (375 Pre-test phase 51.2 Pre-intervention Not reported
Iran [22] Prospective based nephrology priateness of acid patients) (18.3) phase: patient chart
uncontrolled study wards suppression therapy Post-test phase (236 Post-test phase 50.2 review by CP,
(12 months) in kidney disease patients) (18.8) develop SUP pro-
patients and to tocol, and provide
assess the role of educational sessions
clinical pharmacists to doctors on SUP
to decrease inappro- Post-intervention
priate SUP prescrib- phase: Clinical
ing and related costs pharmacists accom-
for these patients panied physicians
on the ward rounds
and advised on
starting or stopping
SUP
Rani et al. (2013) Prospective uncon- Dialysis unit of a mul- To assess the medica- 85 HD patients 50.52 (13.28) Patient counselling Not reported
India [50] trolled study tispecialty university tion knowledge of and education (ver-
(3 months) hospital CKD patients under- bally and written).
going HD, to assess Patient interview to
the effect of a CP assess medication
provided continuous knowledge using
patient education in MKAQ. To assess
improving medica- medication adher-
tion adherence ence pattern using
and to evaluate the BMQ
association between
medication knowl-
edge and medication
adherence behaviour
in HD patients
(SD)
Aberger et al. (2014) Prospective uncon- Transplant clinic of aTo describes a 66 Tx patietns 54 Telehealth system Statistically significant
USA [41] trolled study large urban hospital telehealth system encompassing: reductions in average
(4 weeks) approach and home electronic BP systolic and diastolic
preliminary results monitoring designed BP of 6.0 mm Hg and
for the management to assess the efficacy 3.0 mm Hg, respec-
of BP in renal trans- of antihypertensive tively, at 30 days after
plant recipients and therapy. The phar- enrolment (p < 0.01)
to enhance patient macist communi-
engagement and cates BP reading
improve adherence data and dose
to medications via a modifications to the
collaborative care, physician
pharmacist-based,
MTM program
Arrabal-Durán et al. Prospective uncon- Hospital wards and To assess the charac- 181 CKD patients 77.6 (12.5) Medical history of Not reported
(2014) trolled study emergency depart- teristics of pharma- each patient was
Spain [26] (10 months) ment of a general ceutical interven- reviewed by CP,
university hospital tions concerning recommendations
the dose adjustment for an adjustment
of these drugs in were put in writing
patients with CRF for the doctors
who are admitted
into hospital
Barnes et al. (2014) Retrospective Primary care setting, To increase the iden- 146 CKD patients 71.6 (12.2) Review EMRs to Not reported
USA [27] uncontrolled study Patient -Centred tification of CKD as identify CKD
(12 months) Medical Home asso- a medical problem, patients, review
ciated with a major, increase the use of medication list,
academic health aspirin and ACEIs/ estimate CrCl and
system ARBs in patients recommendations
with CKD, and reporting to the
ensure that all medi- physicians
cations prescribed
to patients with
CKD were dosed
appropriately based
on CG calculated
CrCl
13
655

656
13
(SD)
Gheewala et al. Retrospective Aged care facilities To investigate the 847 CKD patients 84.9 (8.8) DRPs identified, and Not reported
(2014) uncontrolled study number and nature recommendations
Australia [19] (12 months) of DRPs identi- made to resolve
fied and recom- those DRPs by CP
mendations made
by pharmacists in
residents of aged
care facilities
To determine the
extent of inappro-
priate prescribing
of renally cleared
medications in resi-
dents with CKD
Holm et al. (2015) Prospective uncon- Internal medicine To describe the use 79 CKD patients 78.7 (10.2) The CP reviewed There was a significant
Norway [24] trolled study department of a of renal risk drugs the patients’ drug correlation between
(6 months) general hospital in a population of regimen to classify the patients’ GFR and
patients with RI in DRPs related to the number of DRPs,
an internal medicine renal function. with an increasing
department and DRPs identified number of DRPs with
investigate possible were discussed with deteriorating renal
risk factors for such the physician function (p = 0.001,
DRPs r = 0.371)
Pourrat et al. (2015) Prospective uncon- Community pharma- (1) To evaluate the 177 CKD patients 78.1 The community Not reported
France [16] trolled study cies ability of commu- pharmacist filled an
(7 months) nity pharmacists to electronic form for
identify drug related each prescription
problems (DRP) in and verify whether
patients at risk for or the drug had to be
suffering from renal adapted to renal
impairment. (2) To function or was
evaluate the propor- contraindicated
tions of recommen- Potential modification
dations by CPs that was proposed to
lead to a modifica- the GP
tion by GP
(SD)
Venkateswararao Prospective uncon- Dialysis unit of a To evaluate the 58 HD patients 46.7 (13.3) Patient counselling Not reported
et al. (2015) trolled study teaching hospital patient percep- once in 2 weeks
India [49] (6 months) tion and degree of (total 3 sessions)
adherence to various was provided.
treatment modalities Printed informa-
(medication use, tion leaflets and
dialysis, life style written information
modifications) by on dialysis note in
renal failure patients regional language
on HD were provided to the
To assess the effect of patients. Adherence
pharmacist’s inter- pattern before and
ventions towards after patient educa-
improving the tional intervention

adherence among was assessed
the study population
Patricia and Foote Prospective uncon- Regional dialysis units To identify the extent 90 HD NR Patients requested to Not reported
(2016) trolled study and type of medica- bring their medica-
USA [46] (17 months) tion discrepancies tion to dialysis
and MRPs experi- unit and medica-
enced by dialysis tion reconciliation
patients during conducted by the
pharmacist-initiated pharmacy team
medication reviews
and determine if the
resulting recom-
mendations made by
the pharmacy team
to the patient’s pro-
vider were accepted
Ramadaniati et al. Prospective uncon- Medical wards and To identify and evalu- 105 CKD NR Identification of DRPs Not reported
(2016) trolled study an ICCU in a major ate drug-related through the direct
Indonesia [31] (3 months) teaching hospital problems (DRPs) in patient interview,
patients with CKD discussion with
nurses and assess-
ment of patients’
medication charts
and medical records
13
657

658
13
(SD)
Adibe et al. (2017) Prospective uncon- Nephrology units To determine the 287 patients with 72.34 (7.56) Identify and report Not reported
Nigeria [42] trolled study of three tertiary prevalence of DTPs, renal illnesses DRPs. Patient
(5 months) hospitals identify the types education and coun-
of DTPs, and assess selling
the outcomes of
DTP interventions
among renal patients
receiving care in
three Nigerian
tertiary hospitals
Alshamrani et al. Retrospective Outpatient haemodial- To determine the 83 HD patients Median age 63, IQR The pharmacy Not reported
(2018) uncontrolled study ysis unit of a tertiary prevalence of poly- (49–1) resident reviewed
Saudi Arabia [59] (3 months) hospital pharmacy and the electronic medical
Medication Related records and analysed
Problems in haemo- each medication
dialysis patients regimen for eligible
patients to identify
MRPs
Chandrasekhar et al. Prospective inter- Outpatient nephrology To evaluate medica- 163 CKD patients – Patient counselling Not reported
(2018) ventional study department tion adherence by pharmacist and
India [60] (12 months) behaviour of patient information
patients using leaflet was carried
questionnaire and out using a proper
enhance adherence management plan
by various cost and with the help
effective interven- of physician and
tions which have feedback informa-
greater effect on the tion was collected
health of patients
with CKD
(SD)
Imamura et al. (2018) Retrospective Hospital To determine whether 150 CKD patients 72.3 (10.5) The multidisciplinary The eGFR significantly
Japan [61] uncontrolled study multidisciplinary care was provided improved between
(unclear) care could help pre- by a team of neph- before and after
vent worsening renal rologists, diabetolo- multidisciplinary
function associated gist, nurses, diabetes care from − 5.46
with CKD educator, dietitians to − 0.56 mL/
and pharmacists min/1.73 m2/year,
respectively
Values for uric acid,
LDL, and HbA1c
were significantly
reduced among
patients with
improved eGFR
ACEi angiotensin converting enzyme inhibitors, ACR albumin:creatinine ratio, ARBs angiotensin receptor blockers, BMQ Brief medication questionnaire, BP blood pressure, CrCl creatinine
clearance, CG Cockcroft-Gault, CKD chronic kidney disease, CP clinical pharmacist, CRF chronic renal failure, CRRT Continuous renal replacement therapy, DRPs drug related problems,
eGFR estimated glomerular filtration rate, EMRs electronic medical records, FBC full blood count, GFR glomerular filtration rate, GP general practitioner, HbA1c glycosylated haemoglobin,
HD haemodialysis, ICCU intensive critical care unit, ICU intensive care unit, iPTH intact parathyroid hormone, IQR interquartile range, MKAQ Medication knowledge assessment question-
naire, MMS medication management service, MRPs medication related problems, MTM medication therapy management, NR not reported, RI renal impairment, SUP stress ulcer prophylaxis,
TRPs therapy related problems, Tx transplantation
13
659

and ten non-randomised. According to Thomson Reuters 25–27, 29, 30, 32–40, 52, 59]; interacting with a member
Journal Citation Report at the time of publication the median of the multidisciplinary team; [15–17, 19–21, 23–25, 27,
impact factor of the journals of articles included was 1.348 31, 32, 34–38, 40–43] requesting and monitoring labo-
(IQR 0.52–2.01), n = 45, two journals did not have an impact ratory parameters; [15, 23, 25, 27, 33, 34, 36, 37, 43]
factor at the time of publication. assessing appropriateness of medications prescribed for
Patient mean age was 46.7–84.9 years, with five stud- hospitalised patients at each point of care; [17, 22, 29,
ies failing to report age [23, 29, 31, 46, 60]. Of the total of 30, 35–38, 40, 57]. Fewer studies described pharmacist
11,122 patients from all studies, 9151 were at various stages processes at out-patient, pharmacist-led clinics relating
of chronic kidney disease not on dialysis, 1036 were haemo- to the management of specific CKD complications, such
dialysis (HD) dependent, 533 receiving other forms of renal as anaemia; [34, 39, 44] hypertension and diabetes; [54]
replacement therapies such as continuous renal replacement managing hypertension through telemedicine; [41] opti-
therapy (CRRT) or continuous veno-venous hemofiltration mising dyslipidaemia management; [37, 45] improving
(CVVH), and 402 were transplant patients. haemoglobin A1c levels (HbA1c); [43] and emphasising
Outcomes were reported in 37 papers, with 25 of these smoking cessation. [37, 43] Development of protocols and
(67.6%) also reporting details of the processes of care, compiling and updating guidelines were also described in
and four (10.8%) reporting structures, processes and out- two studies [22, 34]. Performing medication reconciliation
comes. Outcomes reported were: clinical only (17, 45.9%), [46]; providing patient medication counselling, education
economic with linked clinical (5, 13.5%), humanistic with on disease status or medication, conducting motivational
linked clinical (4, 10.8%), humanistic only (2, 5.4%) and interviews to improve adherence were also reported [15,
economic only (2, 5.4%). The 10 remaining papers did not 25, 27, 29, 30, 34, 36, 37, 42, 43, 47–50, 55, 57, 58, 60].
report outcomes measures with one (2.1%) that reported A number of studies reported pharmacists’ participation in
structure and process indicators only and 9 (19.1%) reported ward rounds [17, 22, 35, 37, 38, 40], providing educational
process indicators only. sessions to healthcare professionals [22, 34] and perform-
ing activities such as medication use evaluations [34].
Resources for care provision: structures There were no reports of pharmacist prescribing activi-
ties; one study described the process of deprescribing to
Structures were poorly reported in all studies, with only two optimise medication use [59].
giving some details of multidisciplinary team involvement Fewer studies provided any data on time spent on specific
[52, 61], while, none on the pharmacist skill mix or time activities. Interaction time between pharmacist and patients
allocation. The only aspect of structures reported relating to were reported in two studies, varying from 15 to 30 min [43,
training which was given in five studies. In one, pharmacists 50] and the timeframe in which the services were provided
and pharmacy residents were engaged in a two-week training ranged from daily [35–38, 40] to every three months [47].
of literature review and patient assessments [35]. A com- Across all studies, the pharmacists identified 5302 drug-
munity pharmacist based study described a workshop cov- related problems in 2933 patients. Pharmacists made 3160
ering clinical presentations of CKD, managing drug-related recommendations to healthcare professionals with an accept-
problems and discussing patient cases [48]. Similar training ance rate varying from 33.3% in a community setting; [16]
was described for community pharmacists, [18] and hospital 46.43% in a dialysis unit; [59] to around 95% in hospital
clinical pharmacists [16], to enable them to identify patients settings [17, 24, 42, 51, 52, 57]. Only three studies reported
with renal insufficiency and perform dose adjustments. A the clinical significance of recommendations. Of these 26%
four session course to all members of the multidisciplinary were of moderate to [29], 48.8% of major clinical signifi-
team prior to the study was described in one article [61]. cance [51] and 47% serious severity [20].
A pharmacist-based quality improvement programme
Characteristics of clinical pharmacy practice: consisting of pharmacists’ interactions with the patients and
processes electronic collaboration with the physicians was associated
with a significant improvement in the measurement of PTH
All studies provided some description of the processes during the study period [15]. Pharmacists’ interventions led
undertaken by the pharmacists, although the detail pro- to medication therapy modifications [16–21, 24–29, 31, 33,
vided varied considerably and was generally lacking. The 37, 42, 46] and resolving medication record discrepancies
majority of processes (often labelled as interventions) [46, 57]. Patients’ compliance with ongoing blood pressure
included medication chart review to identify any drug- (BP) monitoring post kidney transplantation was signifi-
related problems (DRPs) [15–31]. Many studies reported cantly improved with pharmacists’ input [41]. Counselling
pharmacists’ interventions in: modifying drug doses and by pharmacists significantly improved medication adherence
recommending new pharmacotherapy; [16, 19, 21–23, in patients with CKD [47, 50, 60].
13
Clinical outcomes and serum ferritin reaching target values in a prospective

uncontrolled study [23].
The final column of Tables 1 and 2 titled ‘Main outcomes An uncontrolled study of the impact of on managing sec-
achieved’ provides a detailed summary of main results and ondary complications of haemodialysis patients resulted in
statistical significance values related to each of the studies significantly increased median serum calcium in those with
summarised below. Clinical outcomes only were reported hypocalcaemia and decreased values in hypercalcaemia,
in (n = 17) studies. A pharmacist-based quality improve- a decline in serum phosphate in patients with hyperphos-
ment programme in a pragmatic randomised controlled phataemia, and an increase and decrease in serum iPTH in
study reported that patients in the intervention arm were patients with sub-optimal and supra-optimal levels respec-
prescribed more classes of antihypertensive medications tively [23].
than those in the control arm [15]. In a 6-month cluster Pharmacists’ interventions in a pragmatic, cluster ran-
randomised trial, pharmacists attending a structured train- domised study improved screening of proteinuria between
ing and communication-network programme (ProFil) and an interventions compared to control group [45]. A non-
managing hypertension in CKD patients demonstrated randomised controlled study of pharmacist involvement in
larger reduction in systolic blood pressure (BP) of the a monitoring program for CKD reported significant differ-
intervention group compared to the usual care group [48]. ences in CrCl between discharge and admission in both the
Intervention in the management of BP in CKD and hae- control and intervention groups [36].
modialysis resulted in achieving target BP in the inter-
vention versus the control group [32, 54, 55], significant Humanistic outcomes
reductions in mean systolic and diastolic BP in a group of
kidney transplant recipients [41], and significant reduc- In a cluster, randomised study health related quality of life
tion in systolic and diastolic BP in diabetic nephropathy (HRQoL) improved significantly compared to control in a
[43]. Only one article showed that pharmacists’ interven- group of haemodialysis patients receiving pharmacist inter-
tion in an intensive care unit (ICU) setting reduced the vention over a 6-month period [30]. In a non-randomised
length of ICU stay [38]. Another study reported reduc- controlled study, HRQoL domains were not significantly
tion in the length of stay in the intervention group by impacted by the additional pharmacist care in kidney trans-
1.3 days (p < 0.001) and reduced unplanned admission by plants [47]. A multicentre RCT reported significant improve-
27% (p = 0.047) [52]. One further study showed no dif- ment in HRQoL scores in the intervention group compared
ference of pharmacists’ intervention compared to usual to control [53].
care on hospital readmission outcomes [57]. Pharmacists Patient satisfaction reported in two randomised controlled
were also involved in the monitoring of kidney function studies: 92% of patients had positive feelings about pharma-
in patients with CKD and demonstrated significant differ- cists’ involvement in their care and felt that the pharmacist
ences in measuring CrCl between discharge and admission provided beneficial information [15] and 43% of patients
[36]. However, one study demonstrated no difference in were ‘very satisfied’ with the care received and were willing
the mean serum creatinine or estimated glomerular fil- to receive future care from the pharmacist [45]. A cross-
tration rate (eGFR) between the intervention and control sectional prospective study demonstrated that patients were
groups [58]. A retrospective controlled study reported greatly satisfied with the intervention [58].
improvement in eGFR, uric acid, cholesterol and HbA1c in
the intervention group compared to the control group after Economic outcomes
multidisciplinary care, however, pharmacists’ contribution
to the care was not clearly reported [61]. Only seven studies reported economic outcomes resulting
Four studies gave outcomes of pharmacists managing from pharmacist input [22, 35, 38–40, 44, 56]. One study
anaemia in CKD patients [34, 39, 44, 55], with significant reported that pharmacists in the ICU could contribute to
haemoglobin values within target range in pharmacist-led significant cost savings in septic patients, with antimicro-
clinic. Time to achieve target haemoglobin was 28 days in bial prescribing efficiencies accounted for 34.7% of total
the pharmacist-managed group compared with 41 days in savings [38]. In a study investigating an ICU pharmacist
the usual care group [44]. While the proportion of patients dosing adjustment programme, the mean ICU hospitalisation
achieving target haemoglobin was not significant, pharma- costs per patient decreased significantly with total savings of
cist intervention significantly improved haemoglobin and 2669.5 USD per patient [40]. Jiang et al. demonstrated that
iron monitoring by improving compliance to therapy [44]. pharmacist dosing adjustment resulted in drug cost savings
Pharmacist counselling significantly improved haemoglobin per patient of 2345.98 USD with antibiotics accounting for
levels in one study [34], with haemoglobin concentration 64.5% of all cost savings. The presence of an ICU phar-
and Transferrin saturation (TSAT%) increasing significantly macist resulted in 2346 USD savings per patient receiving
13

continuous renal replacement therapy [35]. Debenito et al. of bias generate the highest level of evidence [62]. However,
reported that the mean weekly dose of erythropoiesis-stimu- the availability of quality evidence in this area is limited
lating agents (ESAs) was significantly less in the pharmacist- with only 5 RCTs were included in this review and 4 in a
managed group than the usual care group and the annualised previous review by Salgado et al. [7]. The RCTs in both
ESA cost per patient reduced by 1288 USD [44], whereas, reviews lacked sufficient information on the randomisation
Aspinall et al. reported lower average dose of darbepoetin in process, in addition to poor detail on any blinding process
the pharmacist-managed ESA clinic compared to the usual of the care-giver and the care-receiver (however, it might be
care [39]. Mousavi et al. showed that the cost per patient a challenge to blind in some study designs) so jeopardising
for inappropriate stress ulcer prophylaxis administration the quality of these studies [63]. It is therefore evident that
in patients with insufficient renal function was reduced by there has been a limited amount of high quality research
pharmacists’ intervention [22]. A multicentre RCT reported published for the benefits of clinical pharmacy practice in
that pharmaceutical care costed more per quality adjusted CKD. There is particularly a paucity of evidence from RCTs
life year (QALY) gained compared to usual care [56]. offering a robust evidence base for practice. Despite this
criticism there is a growing body of information in relation
to some aspects of clinical pharmacy practice that offers
Discussion some insights to the developing quality of services provided
making real and significant differences to the outcomes of
There are a number of important key findings that have patients. This, however, needs to be verified through even
arisen from this review and these are outlined below. Forty- more robust RCTs that are better resourced, designed and
seven new studies have been published in the intervening executed.
8 year period since a previous similar review [7]. Ten of The gathering of more gold standard evidence such as
these are of a ‘gold standard’ RCT design and the quality RCTs is essential to enable measuring the impact of clinical
of the controlled studies included is generally poor. Struc- pharmacists’ intervention in patients with CKD compared
tures and processes were very poorly reported and none of to standard care. Furthermore, there is an identified need to
the studies included consideration of pharmacist prescrib- carry out studies with explicit details and accurate defini-
ing—which is considered in several countries, where it has tions including the setting, the participants, the randomisa-
been implemented, to be a significant advance in pharmacy tion process and the interventions of interest.
practice. The process indicators in the original review [7] It is of paramount importance that detailed descriptions
and this review were very similar but this review identified of the interventions, in terms of structures and processes
papers with clear shift from only identifying drug-related and outcomes, are included in publications to allow them
problems to more involvement of the pharmacist in medica- to be reproduced and for readers to consider the studies
tion therapy management. Most of the studies in this review within the context of their own practice [64]. Most papers
continue to focus on and report details of DRPs as an indi- lacked sufficient details of the clinical pharmacy practices so
cator of the process of pharmacy practice. Some of these making it difficult to fully understand the activity. Without
considered the clinical significance of these DRPs but this full insight to practice it is difficult to fully understand the
was not universal. Less focus on clinical, humanistic and context and characteristics of practice and so reproduce the
economic outcomes was observed in majority of the papers structures and processes in wider settings. This is not just
in both reviews. a deficiency of studies in CKD since a study by Schroter
Many of the uncontrolled studies had a variety of quality et al. to assess the replicability of published clinical inter-
deficiencies including; lack of comprehensive explanation ventions, in a variety of clinical settings, reported that 57%
of the pharmacists’ intervention, under-reporting of adverse of the studies had insufficient description of the interven-
events and insufficient information to allow reproduction of interest to make it replicable [65]. A tool produced
tion of the study for interested readers. Few studies lacked by Correr et al. to address the lack of intervention descrip-
some important information leading to poor scoring of the tions in clinical pharmacy research (Descriptive Elements of
study, such as lack of clarity in stating the study aim, [35] Pharmacist Intervention Characterization Tool) DEPICT is
the number of participants, the population from where the a validated instrument for accurately describing the details
sample was drawn, duration of the data collection or the of pharmacist interventions performed as part of clinical
study period, frequency of follow-up, and some studies were pharmacy practice [66]. This tool could be used as a guid-
unable to clearly state the distribution of the confounders in ance to structurally describe the intervention of interest in
both groups [15, 22, 30, 35, 39, 45]. pharmacy practice research.
The majority of the 20 controlled studies were of ‘fair’ Additionally it should be noted that in CKD there are
quality with the exception of four that were considered no studies that have specifically investigated prescrib-
‘weak’ [22, 55, 56, 58]. High quality RCTs with low levels ing as part of clinical pharmacy practice and there are no
13
full description of structure, processes and outcomes as Conclusion

they relate to prescribing practice. A systematic review
by Tesfaye et al. published in 2017 of the prevalence of There is some evidence for the outcomes of pharmacists’
inappropriate prescribing and the impact of pharmacists’ intervention in patients with CKD but this is generally of
interventions reported significant reduction in inappro- low quality and insufficient volume. The controlled studies
priate prescribing when physicians received immediate in this systematic review showed that pharmacist inter-
concurrent feedback from a clinical pharmacist [67]. The ventions improved patients’ clinical outcomes such as Hb
review showed minimal involvement of the pharmacist levels, CrCl, PTH and calcium levels. However, these stud-
in the role of prescribing for patients with CKD. Despite ies lacked detail on reporting of the humanistic outcomes
the increased recognition of prescribing models such as and there remains a paucity of evidence demonstrating
independent, supplementary or collaborative [6], there economic impact of pharmacists’ interventions.
was limited published evidence to lead to the best practice There is some evidence since the last review that shows
model for prescribing. positive contributions of pharmacists’ involvement in the
There is also a need to stimulate more of a research cul- multidisciplinary team to provide care to patients with
ture within clinical pharmacy practice. A paper by Peter- CKD. This includes evidence on the structure, processes
son et al. reported that lack of time, lack of opportunities, of care and the outcomes of pharmacists’ intervention in
lack of training and never being asked to participate in a patients with CKD. More high-quality research in this area
research were major barriers for pharmacists’ engagement is warranted.
in research [68]. A systematic review by Awaisu et al. con-
cluded that pharmacists are aware of the value of research Acknowledgements Ms Tesnime Jebara for input to quality assessment
to enable them advance pharmacy practice and indicate of papers. Mr Hamed Al Naamani for production of graphs and figures
and general technical support in production of the manuscript.
their willingness to be involved in independent research
and in practice-based research networks. However, lack Authors’ contributions All authors were involved in all aspects of this
of time, training and support were the main barriers [69]. work including; conception and design, analysis and interpretation of
A strength for this review is that the protocol was peer data, drafting and revising the article, providing intellectual content
reviewed and registered with PROSPERO. The protocol and final approval of the version to be published.
was devised in accordance with PRISMA-P (Preferred
Funding None.
Reporting Items for Systematic review and Meta-Analysis
Protocols) standards [9] and the systematic review was Conflicts of interest None of the authors has any financial interests or
conducted and reported in accordance with PRISMA (Pre- connections, direct or indirect, or other situations that might raise the
ferred Reporting Items for Systematic Review and Meta- question of bias in the work reported or the conclusions, implications
or opinions stated. In addition, the authors confirm that results pre-
Analysis) standards [10]. In terms of limitations, publi- sented in this paper have not been published previously in whole or
cation bias could potentially affect the selecting process part, except in abstract format.
of the articles, since no study was identified to show the
negative impact of clinical pharmacy services in caring for Ethics approval The Ethics panel of the School of Pharmacy & Life
Sciences, Robert Gordon University indicated that ethics approval was
patients with CKD. One further limitation is the exclusion not required for this systematic review.
of papers in languages other than English potentially lead-
ing to the omission of relevant papers.
Open Access This article is distributed under the terms of the Crea-
In conducting RCTs, it has been recognised that it is tive Commons Attribution 4.0 International License (http://creativeco
vital to be careful in the selection and recording of out- mmons.org/licenses/by/4.0/), which permits unrestricted use, distribu-
comes to build up a coherent dataset [70–73]. Moreover, tion, and reproduction in any medium, provided you give appropriate
consistency in the use of outcomes will aid future users credit to the original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were made.
of the services and those involved in resource alloca-
tion, planning and implementation of clinical pharmacy
services [72]. It is evident from this review that where
RCTs were conducted, there was no consistency in the
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2019 Article 816

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International Journal of Clinical Pharmacy (2019) 41:630–666

Clinical pharmacy practice in the care of Chronic Kidney Disease

Keywords Chronic kidney disease · Clinical pharmacy · Pharmacist · Systematic review

Electronic supplementary material The online version of this

Impacts on practice improved management of anaemia, blood pressure, cal-

No systematic reviews were identified from the Cochrane Data extraction

Fig. 1 PRISMA Chart describ-

Study characteristics Thirty-one studies were conducted in hospital settings

(3) A pharmaceuti- Patients with written

USD) cost savings

before they could (p = 0.165) between

those receiving care (adjusted odds

and n = 18 (26%) in

hospital pharmacists in neph- activities and inter-

and decrease in serum

Recommendations patient receiving

improving the tional intervention

Clinical outcomes and serum ferritin reaching target values in a prospective

full description of structure, processes and outcomes as Conclusion

You might also like

2019 Article 816

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

2019 Article 816

Uploaded by

Copyright:

Available Formats

International Journal of Clinical Pharmacy (2019) 41:630–666

Clinical pharmacy practice in the care of Chronic Kidney Disease

Keywords Chronic kidney disease · Clinical pharmacy · Pharmacist · Systematic review

Electronic supplementary material The online version of this

Impacts on practice improved management of anaemia, blood pressure, cal-

No systematic reviews were identified from the Cochrane Data extraction

Fig. 1 PRISMA Chart describ-

Study characteristics Thirty-one studies were conducted in hospital settings

(3) A pharmaceuti- Patients with written

USD) cost savings

before they could (p = 0.165) between

those receiving care (adjusted odds

and n = 18 (26%) in

hospital pharmacists in neph- activities and inter-

and decrease in serum

Recommendations patient receiving

improving the tional intervention

Clinical outcomes and serum ferritin reaching target values in a prospective

full description of structure, processes and outcomes as Conclusion

You might also like

Fig. 1 PRISMA Chart describ-