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Effects of Pharmaceutical Care Intervention by Clinical Pharmacists in

Renal Transplant Clinics


H.Y. Wang, A.L.F. Chan, M.T. Chen, C.H. Liao, and Y.F. Tian
ABSTRACT
Renal transplantation is an established treatment for end-stage renal disease. Most renal
transplant patients take multiple medications for a long period of time to maintain
immunosuppression as well as to treat concomitant chronic diseases. Since some medications prescribed for these patients have narrow therapeutic ranges, optimal pharmacotherapy is vital. However, pharmacists can qualify the role in assisting patients and
physicians to solve and reduce drug-related problems. The purpose of this trial was to
investigate the effects on treatment outcomes by clinical pharmacists joining renal
transplant clinics to provide pharmaceutical care. We enrolled 37 renal transplant patients
who visited the renal transplant clinic in our medical center from May 2005 through
August 2006. The responsibility of the clinical pharmacist was to interview patients, review
medication regimens, and make therapeutic recommendations for 3 hours every Tuesday
morning. According to potential clinical impacts, pharmacist recommendations were
divided into 6 scales, evaluating physician acceptance of pharmacist recommendations and
impact on treatment outcomes. Fifty-five pharmacotherapy recommendations were made
for the 37 renal transplant patients during the trial period, of which 81.8% were classified
as clinically significant. The drug classes most commonly involved were cardiovascular
medications, immunosuppressants, and antimetabolites (32.6%, 23.9%, and 26.1%, respectively). Physician acceptance rates of recommendation types and drug classes were
96.0% and 97.1%, respectively. Among the cases in which the recommendations were
accepted, 94.2% of patients showed improved conditions. We concluded that clinical
pharmacists joined to renal transplant clinics provide pharmaceutical care with a positive
potential impact on physician prescriptions and patient outcomes.

ENAL TRANSPLANTATION is one of the treatments for patients with end-stage renal disease. In
Taiwan, approximated 100 patients receive renal transplantations every year. Most renal transplant patients take
multiple medications for a long period of time to maintain
immunosuppression as well as to treat concomitant chronic
diseases, such as hypertension, hyperglycemia, and hyperlipidemia. The polypharmacy increases the possibility of
drug interactions, adverse reactions, and even repeated use
of medications. These factors decrease patient compliance,
resulting in an increase in reject reactions.1,2 Therefore,
good medication care is important. Pharmacists can assist
patients and physicians to reduce drug-related problems.
The literature has documented remarkable effects of pharmacist participation in the joint care team for hospitalized
patients.35 However, this experience in the field of renal
transplantation is limited in Taiwan. In order to investigate

the influence on physician prescriptions and patient outcomes after pharmacist participation in the renal transplant
clinic, we designed this trial. The clinical pharmacists
provided information to patients, made medication recommendations to physicians, and evaluated their influence on
physician prescriptions and patient outcomes based on the
following 3 viewpoints: (1) document the quality and quantity of recommendations suggested by the pharmacist to the
physician; (2) determine physician acceptance rates of the
From the Department of Pharmacy (H.Y.W., A.L.F.C.), Division
of Transplantation Surgery (M.T.C., Y.F.T.), and Division of
Urology (C.H.L.), Department of Surgery, Chi-Mei Medical Center, Tainan, Taiwan.
Address reprint requests to Yu-Feng Tian, Department of
Surgery, Chi Mei Medical Center, 901, Chang Hwa R.D., Yung
Kang City, Tainan, Taiwan. E-mail: van0112@hotmail.com

2008 by Elsevier Inc. All rights reserved.


360 Park Avenue South, New York, NY 10010-1710

0041-1345/08/$see front matter


doi:10.1016/j.transproceed.2008.06.050

Transplantation Proceedings, 40, 2319 2323 (2008)

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WANG, CHAN, CHEN ET AL

recommendations; and (3) determine the influence of pharmacist recommendations on patient outcomes.
MATERIALS AND METHODS
This prospective trial enrolled subjects who visited the renal
transplant clinic for post-renal transplantation follow-up from May
2005 through August 2006 using 3-hours sessions on Tuesday mornings. The renal transplant clinic has 2 adjacent diagnosis rooms.
During the clinic hours, the pharmacist interviewed patients and
reviewed their medication regimens and relevant laboratory test data
in the first diagnosis room seeking to identify, solve, and prevent
medication-related problems and make therapeutic recommendations. After interviewing patients in the first diagnosis room, the
pharmacist recorded the patients subjective complaints, laboratory
test results, and medication recommendations on the pharmacotherapy evaluation-recommendation form in duplicate one copy
was sent to the second diagnosis room along with the medical chart
and the other copy was kept with the clinical pharmacists records.
After receiving the pharmacotherapy evaluation-recommendation
form, the physician provided appropriate advice to patients according to the recommendations make by the pharmacist. Each recommendation was recorded on the medication record regardless of
whether accepted; patient outcomes were also recorded. The
quality of the recommendations made by the pharmacist was based
on clinical importance: negative recommendation, ambiguous
recommendation, slightly significant recommendation, significant recommendation, very significant recommendation, and extremely significant recommendation, namely the 6 categories defined by Strand et al.6 The criteria of Hatoum et al7 were used in
this assessment (Table 1). To reduce deviations, the quality of each
recommendation was coevaluated by the pharmacist participating
in renal transplantation as well as another physician. The evaluation of treatment for each renal transplant patients was conducted
based on laboratory test results and subjective symptoms. If the
laboratory test results improved for 2 successive months or the
subjective symptoms were improved at the follow-up visit, the evaluation was recorded as improved; in contrast, the evaluation was
recorded as regressive or maintained if the condition was not
obviously improved. Descriptive statistics were employed to evaluate the quality of the recommendations, acceptance rates by
Table 1. Scale for Recommendations and Potential Impact on
Patient Care5,17
Recommendation Scale

Evaluation Criteria

Adverse significance

Recommendation may lead to adverse


outcomes
Recommendation is informative (not
specifically related to patient in
question)
Benefit of recommendation for patient
may be neutral, depending on
professional interpretation
Recommendation would bring care to
a more acceptable and appropriate
level
Recommendation qualified by
potential or existing major organ
dysfunction
Information qualified by life-and-death
situation

No significance

Slight significance

Significance

Much significance

Extreme significance

Fig 1.

Time distribution of post-renal transplant patients.

physicians, and patient outcomes after pharmaceutical care interventions.

RESULTS

The 37 post-renal transplant patients followed during the


trial period included 17 males and 20 females of age range
22 to 60 years. The time post-renal transplantation was 2 to
5 years for 21 patients (56.4%; Fig 1). The overall major
causes of renal failure were: hypertension (n 11; 20%),
glomerulonephritis (n 5; 9.1%), pyelonephritis (n 5;
9.1%), drug-induced (n 3; 5.5%), polycystic kidney (n
3; 5.5%), diabetes (n 1; 1.8%), and lupus erythematosus
(n 1; 1.8%). The cause for 26 patients (47.3%) was
unknown. The pharmacist made 55 recommendations for
pharmaceutical care. The recommendations were categorized as slightly significant (18.2%) versus 81.8% as
significant, very significant, or extremely significant at
the rates of 58.2%, 21.8%, and 1.8%, respectively (Table 2).
The recommendations, classified into 8 types according to
their character, were primarily for medication selection
(n 19; 84.5%). The other recommendations were 7 times
for improper laboratory data, 8 times for dosage adjustment, 6 times for adverse drug reaction, 5 times each for
untreated indications and medication use without an
indication, 3 times for failure to receive medication, and
2 times for others. The mean physician acceptance rate
for types of recommendations was 96.0% (Tables 3, 5). The
pharmacist made 46 medication recommendations: 11 for
immunosuppressive agents (23.9%); 15 for cardiovascular
agents (32.6%); 12 for antimetabolites such as uric acidreducing or hypoglycemic agents (26.1%); 2 for anti-infective
drugs (4.4%); and 6 for other medications (13%). The
mean acceptance rate for drug class recommendations was
97.1% (Tables 4, 5). Among the recommendations accepted
by physicians due to the pharmacists intervention, the
conditions of 94.2% of patients improved (n 49) and
5.8% were maintained (n 3; Table 6).
DISCUSSION

The chronic diseases observed in renal transplant patients


may have existed preoperatively and may not disappear,
such as metabolic diseases (eg, hyperuricemia and hypertension) which may be exacerbated by immunosuppressive
agents. Post-renal transplant patients take multiple medi-

PHARMACISTS IN RENAL TRANSPLANT CLINICS

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Table 2. Recommendation Quality


Recommendation Scale

No.
%

Adverse Significance

No Significance

Slight Significance

Significance

Much Significance

Extreme Significance

Total

10
18.2

32
58.2

12
21.8

1
1.8

55
100

to drug intolerance or because of poor blood pressure


control were suggested to change to another class of medication. Immunosuppressive and antimetabolite agents were
recommended the most (Table 4). Most of the metabolic
disorders were immunosuppressant-related, such as hyperuricemia and hyperlipidema. It has been shown that the hyperuricemia predisposing to gout occurs among 7% to 24%
renal transplant patients. Cardiovascular disease as a result
of hyperlipidemia occurs in more than 50% of transplant
patients. The occurrence rate of diabetes among patients
receiving transplantations in the United States increases
16% every year.1113 Because there are diseases relevant to
medications, selection posttransplantation is more complicated, due to drug interactions (eg, cyclosporinediltiazem
combination increases the level of cyclosporine, resulting in
nephrotoxicity)14 and drug side effects (eg, calcium blockerassociated ankle edema and the choice of hypoglycemic
drugs; that is, avoid administration of metformin in patients
with insufficient graft kidney function to prevent lactic
acidosis.15,16 Therefore, it is necessary to immediately provide the physician with ideas for proper medication selection. Although infection is one of the risks of taking
immunosuppressants, the probability of an unanticipated
infection is not high; recommendations for anti-infective
drugs were relatively few (n 2; 4.4%). The 3 unaccepted
recommendations were as increased dosage of hypoglycemic agent (metformin); the selection of a statin hypolipidemic drug (simvastatin switch to fluvastatin); and a laboratory test (monitoring of fasting blood sugar level). The
main reason for not being accepted may have been that the
patients condition was stable without an adverse reaction.
Most reasons to adjust the dosage of an immunosuppressive agent were adverse drug reactions: headache and
hepato- or nephrotoxicity. Change in immunosuppressive
agents was recommended due to suspicion of a rejection
reaction (from cyclosporine to tacrolimus). The occurrence
of adverse reactions was greatly related to drug interactions,
especially of cyclosporine, tacrolimus, and sirolimus , all of
which are metabolized via cytochrome P-450. Therefore,
medications relevant to cytochrome P-450-dependent metab-

cations to maintain the function of the transplanted kidney


and to control the adverse effects of immunosuppressive
agents. In addition, some agents have a narrow therapeutic
index or proclivity to interactions, thus increasing the
possibility of adverse drug reactions compared with nonrenal transplant patients. Furthermore, the complex regimen is associated with reduced patient compliance. In
addition, most patients feel a certain degree of nervousness
when facing physicians plus the restricted clinic time; thus
they usually cannot completely and timely tell physicians about
their problems during the medication process, resulting in
dysharmonious doctorpatient relationships. Nevertheless, the
pressure for patients will be reduced if they face the pharmacist; hence, it may be beneficial for patients who need longterm care to review their medication conditions through the
pharmacist to the physician. This strategy allows the pharmacist to evaluate the medication conditions and the laboratory results in advance of the physicians clinic time, so as to
make medication recommendations and assist physician
prescription behavior.
We made 55 pharmacotherapy recommendations during
the trial period, including 18.2% adjudged to be slightly
significant. There were no adverse or nonsignificant
recommendations. Only one case was extremely significant, because the patients red blood cell counts were
high for 6 months, which may have been related to a
blood disorder. The patient was transferred to the Division of Hematology-Oncology after the pharmacists recommendation to have a definite diagnosis and was found to
have polycythemia. Most recommendations were classified
as significant (58.2%) and very significant (21.8%;
Table 2). Most recommendations were for medication
selection (34.5%), the item for which physician acceptance
was the highest (Table 3). Most recommendations for
medication selection were cardiovascular agents, especially hypotensive agents. According to the literature, more
than 50% of patients experience hypertension due to immunosuppressive agents.8,9 Their control to lower blood
pressure is beneficial for long-term graft survival.10 Patients
who experienced adverse reactions (eg, ankle edema) due

Table 3. Types of Pharmacist Recommendations and Physician Acceptance Rates


Types of Recommendations

No. of recommendations (%)


Acceptance rate (%)

Untreated
Indications

Dosage
Adjustment

Medication Use
Without an
Indication

Adverse Drug
Reaction

Medication
Selection

Failure to
Receive
Medication

Improper
Laboratory
Data

Others

Total

5 (9.1)
100

8 (14.5)
87.5

5 (9.1)
100

6 (10.9)
100

19 (34.5)
94.7

3 (5.5)
100

7 (12.7)
85.7

2 (3.6)
100

55 (100.0)

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WANG, CHAN, CHEN ET AL


Table 4. Drug Classes of Recommendations and by Acceptance Rate by Physician
Drug Class
Immunosuppressive
Agents

Cardiovascular
Agents

Antimetabolite
Agents

Anti-infective
Agents

Others

Total

11 (23.9)
100

15 (32.6)
93.3

12 (26.1)
91.7

2 (4.4)
100

6 (13)
100

46 (100.0)

No. of recommendations (%)


Acceptance rate (%)

olism interact with them.14 During the trial period, one


patients cyclosporine level dropped abruptly due to prescription of carbamazepine, resulting in the occurrence of a
rejection reaction. The rejection reaction stopped after the
pharmacist reminded the physician of the interaction between these 2 drugs and recommended session of carbamazepine.
Clinical pharmacists in the renal transplant clinic need to
monitor tests/examinations. Post-renal transplant patients
receive routine biochemical (serum creatinine, BUN, total
cholesterol, triglyceride, uric acid, SGOT, SGPT, and glucose AC), blood (RBC, WBC, Hb, and platelet), and urine
tests at least once a month. In addition to monitoring graft
renal function, liver function was also routinely examined to
ensure whether immunosuppressive agents influenced laboratory examinations. This type of recommendation was
made by the pharmacist 7 times, the third in ranking (Table 3).
Most recommendations reminded physicians of the tests/
examinations that had not been conducted or to cancel
unnecessary routine tests/examinations. Among those recommendations, only one was not accepted: in this case
there was a family history of diabetes, but the patients
blood sugar level had not been monitored for 3 months
after the transplantation. The pharmacist suggested to
measure the patients fasting blood sugar, but the recommendation was not accepted. This patient was subsequently
sent to the hospital for urgent treatment at 4 months
posttransplantation due to diabetic ketoacidosis; the patients blood sugar level was controlled after proper treatment. Some patients had abnormal values due to incorrect
urine sampling, and incorrect time to take medications and
to draw blood. After the pharmacist confirmed with the
patients and provided information to the physician, the
physician performed further management.
Pharmaceutical recommendations may be evaluated
based on the type of recommendations and the drug class
recommendations; the mean acceptance rates were 96.0%
and 97.1%, respectively (Table 5), which implied that the
recommendation quality of the pharmacist was good
enough to let the physician trust in and accept them. This
Table 5. Pharmacist Recommendations and Physician
Acceptance Rates

No. of recommendations
No. accepted
Mean acceptance (%)

Types of
Recommendations

Drug Class
Recommendations

55
52
96.0

46
44
97.1

acceptance rate was similar to the 96% previously reported


from the renal transplantation team by Chisholm et al17 and
higher than the 88% acceptance rate for pharmacist recommendations by Galt.18 Among the 52 interventions and
accepted recommendations, the function of the transplanted kidney improved in 8 cases, which was related to
patient compliance, where the dosage of immunosuppressive agents was proper, and when the blood sugar level was
controlled. If higher levels of total cholesterol, triglycerides,
and uric acid were related to immunosuppressants, in
addition to adding medications to correct the current
metabolic disorder, the pharmacist educated the patient
with mild symptoms and advised diet adjustment. The
common adverse reactions included ankle edema, which
was caused by cardiovascular agents, increased blood sugar
level, increased liver indices relevant to hypolipidemic
agents, and symptoms caused by immunosuppressants such
as baldness, tremors, and imbalanced electrolytes. Blood
pressure increase was effectively improved by changing
the dosage/type of medication or adding the symptomcontrolled medications. In this trial, 94.2% of the treatment
results of patients were improved, while the patients condition was maintained for 3 individuals (5.8%), and there
was no regressive case for patients who had been followed
up by the end of this trial after pharmaceutical care
interventions (Table 6). In addition, the patients also
expressed that they were satisfied with the post-transplant
care directly provided by the pharmacist.
In conclusion, the experience from this trial showed that
clinical pharmacists can directly help physicians in the clinic
or medication selection and detection of adverse reactions.
Pharmacist participation in transplantation care teams

Table 6. Patient Outcomes After Pharmaceutical Care


Intervention
Improved

Renal function
Blood sugar
Total cholesterol/
triglycerides
Blood pressure
Uric acid
Adverse drug
reaction
Compliance
Others
Total (%)

Maintained

Regressive

8
5
6

2
0
0

0
0
0

4
5
5

0
0
1

0
0
0

3
13

0
0

0
0

49 (94.2%)

3 (5.8%)

Total

52 (100%)

PHARMACISTS IN RENAL TRANSPLANT CLINICS

showed a positive influence on physician prescriptions and


patient treatment outcomes.
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