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Case History
Mr. RS, a 43yr old male, presented at the Emergency department with a five day history of
fevers and coughing and a 3 day history of nausea and vomiting.
MrRs had a history of diabetic nephropathy secondary to T1DM and had a kidney and
pancreatic transplant in 2000.
Mr RS had a history of T1DM since he was a thirteen years old boy. He was started on
insulin at diagnosis and remained on it until his transplant in 2000. He had a history of poor
control of his diabetes, partly due to heavy alcohol consumption while he was a university
student. He had also trouble taking his insulin and monitoring his blood sugar levels
regularly. His pancreatic and kidney transplants are believed to be as a result of poor control
of his diabetes. RS is a non-smoker and social drinker.
He was diagnosed with acute renal failure due to dehydration secondary to flu-like
symptoms, and at risk of secondary bacterial infection due to immunosuppressive therapy.
No known allergies.
Social History: He is divorced and lives alone.
Table 1: Medication History
Medications Drug
prior to
admission
Tacrolimus
Mycophenolate
Prednisolone
Aspirin
Sodibic
Dosage
Indications
√-Continue
W- Withhold
X- Cease
↑- Increased
↓- Decreased
+ - Added
PO 500mcg
bd
PO 1gm bd
Immunosuppressant for
transplantation
Immunosuppressant for
transplantation
Immunosuppressant
W
Anti-platelet and blood
thinning
Electrolytes
√
PO 25mg
OD
PO 75mg
OD
PO 840mg
OD
W
W
W
Medication
in ED
Ceftriaxone
IV 1gm D
Azithromycin
IV 500mg D Immunomodulator for community
acquired pneumonia
Oseltamavir
PO 75mg
BD
Ondansetron
IV 4-8mg
BD prn
prochlorperazine IV 12.5mg
q8h prn
Morphine
IV 2.5mg
prn
Pantoprazole
IV 40mg
Daily
O2
Table 2: Laboratory Results
Blood results on
admission
Hb
183(H)
WCC
12.4(H)
Na+
133(L)
K+
4.5(N)
Urea
20(H)
Creatinine 229(H)
eGFR
27(L)
Glucose
8.1(H)
Broad spectrum antibacterial,
Empirical treatment effective
against gram positive and gram
negative bacteria.
Prophylactic H1N1 Treatment
Antiemetic for Nausea and
Vomiting
Antiemetic for Nausea and
Vomiting
low dose for Pulmonary Oedema
Pain
Proton pump inhibitor for GORD
and peptic ulceration.
To treat hypoxia and low oxygen
saturation levels.
Most recent blood
results
142(N)
14.2(H)
132
14.8(H)
149(H)
45(L)
8.1(H)
NormalRange
115-165g/L
4-11/L
135-145mmol/L
3.4-4.5mmol/L
7-18 mg/dL
0.6-1.2 mg/dL
75-190ml/min
3-5.4mmol/L
He is not using insulin because has pancreas transplant
Acute Renal Failure
Acute renal failure (ARF) is a disease in which there is a sudden and fast decrease in renal
function resulting in the accumulation of nitrogenous waste in the blood1. ARF rapid decline
in glomerular filtration rate (GFR) over hours to days. ARF complicates approximately 5–7%
of hospital admissions and up to 30% of admissions to intensive care units. ARF could be
classified as pre-renal, intrarenal or post-renal, depending on the causes and locations of the
abnormalities.2
Clinical manifestations and symptoms
ARF is usually asymptomatic and diagnosed with biochemical monitoring of hospitalized
patients reveals a new increase in blood urea and serum creatinine concentrations. In ARF,
the 24hr urine production is reduced to 200-400mL. This is called Oliguria, which is the most
common symptom of ARF.1 Oliguria results in the accumulation of creatinine, urea,
potassium, hydrogen and phosphate ions in the blood which lead to the development of
symptoms such as nausea, vomiting, diarrhea, GI hemorrhage and muscle cramps1.
Diagnosis and Management of ARF
Diagnosis of ARF is through taking the full patient history, physical examination, urinalysis
(concentration and volume), blood analysis (WCC, ESR, CR etc.) and radiological
examinations1.MrRs above blood analysis (WCC, CR), urine analysis ruled out ARF.
Management of ARF should focus on the recovery of kidney functions and keeping patients
alive for longer. The management principles should include early identification of patients at
risk (e.g. diabetic patients), optimization of renal perfusion via infusion of fluid and
electrolyte, diuresis using either loop diuretics or mannitol1.
Therapeutic issues and management
Immunosuperesents are commonly used to prevent transplant rejection and usually more than
one class is used, because of their different mode of action to improve efficacy and reduce
side effects.1Immunosuppressants are started immediately or as soon as possible after
transplantation. Immunosuppressants are used to preserve transplant function and to prevent
organ toxicity and usually prescribed for life time. Infections are more common in patients on
immunosuppressants because they diminish the immune system. Treatment has two phases,
namely induction and maintenance. In the induction regimen monoclonal antibodies
(muromonab-CD3), poly-clonal or anti-CD25 antibodies (basiliximab, daclizumab) are used
for 8 weeks post-transplant and had less nephrotoxicity. In maintenance therapy, triple
therapy with calcineurin inhibitors, mycophenolate or azathioprine and prednisolone are
usually used.3Sirolimus is reserved for those patients who cannot tolerate calcineurin
inhibitors. However, the drugs and dosage vary between individual transplant centers and
patient requirements. Evidence showed that mycophenolate is more effective than
azathioprine in renal transplant patients.3 Immunosuppressant should be maintained at a
lower effective dose after 2-6 months to minimize the side effects.
In RS case, he is appropriately on three immunosuppressant drugs; namely tacrolimus,
mycophenolate and prednisolone. Their dosage and frequency of administration is
appropriate taking in to consideration his ARF and other coexisting conditions. However,
tacrolimus and prednisolone are known to cause an increase in plasma glucose levels and
may compromise his blood sugar control and insulin use.1Regular blood sugar monitoring
and insulin dose adjustment may be required to control his diabetes.
RS is also taking 75mg of aspirin to protect him from blood clots. However, aspirin is mainly
cleared through the kidneys, and in ARF there may be an increased risk of bleeding due to
reduced clearance.
On admission to hospital Mr RS had dehydration secondary to flu-like symptoms, and at risk
of secondary bacterial infection due to immunosuppressive therapy. The common viruses
involved in influenza are influenza A and B (these viruses cause flu-like symtoms).
Therefore, he was started on antibiotics.
Antiboitics: Ceftriaxone belongs to the antibacterial group Cephalosporins and it is one of the
broad spectrum antibiotics. This group of antibiotics contain a beta-lactam ring that interferes
with the bacterial peptidoglycan synthesis.It is therefore bactericidal and effective against
gram-negative and gram positive organisms.
Azithromycin is macrolide antibiotic. This is Bacteriostatic and inhibits bacterial protein
synthesis by binding to the 50S ribosomal subunit. They also have immunomodulatory and
anti-inflammatory effects. Osltamavir used as prophylactic for H1N1. Ondanseton and
prochorperazineare antiemetic for nausea and vomiting.
This patient had history of excessive alcohol consumption and diabetes, which were more
prevalent in the ARF .The studies have been reported that long-term alcohol use of alcohol is
associated with renal dysfunction4 and patients with diabetes are more susceptible to damage
to the kidneys and more prone to infections.5
Drugs that require Therapeutic Drug Monitoring and Precautions
Aspirin and prednisolone
When administered together, corticosteroid drugs decrease the serum concentration of
salicylates6. Therefore monitoring of anti-platelet effect and increasing aspirin dose may be
required. Patients are advised to take these medications with food to avoid gastrointestinal
bleeding. Prophylactic anti-ulcer treatment such as proton pump inhibitors and H2antagonists
can also be used.6
Aspirin and tacrolimus
Co-administration of aspirin and tacrolimus may increase the risk of renal impairment due to
synergistic effect on the kidney. Renal function should be monitored when using this
combination both during and after treatment.6
Morphine and prochlorperazine
Moderate interactions have been found between Morphine and prochlorperazine, creating a
synergistical depressant affect and therefore monitoring is required.6
Aspirin & Sodium Bicarbonate
Alkalinisers (i.e. sodium bicarbonate) increase aspirin renal elimination – monitor for
possible dose adjustment.7
Tacrolimus& Sodium Bicarbonate
Sodium bicarbonate reduces tacrolimus absorption and plasma level when taken together,
therefore separate doses by at least 2 hours8.
Immunosuppressed patients are more prone to get infection and require annual pneumococcal
and influenza vaccinations.1Mycophenolate is more prone to cause infection, monitor
complete blood count each week for one month then every 1-3 months.
Tacrolimus is renally cleared; renal function test is recommended every 2-3 months. Blood
concentration drug monitoring is recommended because of its low therapeutic index and
variable bioavailability.9
Immunosuppresant drugs increase the risk of malignancy and other proliferative
disordersespecially of the skin.Regular examination for skin cancers and avoiding sun
exposure by using SPF 30+ sunscreen and protective clothing is recommended.1
Continuation of care:
 The role of the pharmacist is to watch the right dosage, strength and if there is any
interaction between the drugs, should discuss with patients.
 Based on the patient’s previous medication history, Pharmacist should assist this
patient after discharge from hospitaleducate the patient about the immunosuppressant
medication and about that he is more prone to infections.
 Patient is divorced and single. For future care we may want to ask the patient how
long ago this happened and how he is coping. We may think about depression and
patient’s compliance towards his medications.
 He may also benefit from a home medicine review. Educate the patient how to use
blood glucose monitoring and keep the readings of them. This would help to establish
if the medication non-compliance and educate the patient on the role of her
medications to prevent further complications.
 Educate the patient on the importance of regular blood test, renal function test,
followed by regular visit to the doctor.
 Promote healthy eating habitse.g increase the intake of green vegetables and fruits.
References:
1. Walker R and Whittlesea C, editors. Clinical Pharmacy and Therapeutics 4thed,
Edinburgh: Churchill Livingstone; 2007.
2. Acute renal failure The Merck Manual of Diagnosis and Therapy; last reviewed 25
March 2011. [Online www.merck.com/mmpe/sec10/ch111/ch111b.html
3. Australian Medicines Handbook (AMH), 2009, Australian Medicines Handbook Pty
Ltd, Adelaide.
4. Cecchin E, De Marchi S. Alcohol misuse and renal damage. Addict Biol 1996; 1(1):
7–17.
5. Weisberg LS, Kurnik PB, Kurnik BR. Risk of radiocontrast nephropathy in patients
with and without diabetes mellitus. Kidney Int 1994; 45(1): 259–26
6. MIMS Online MIMS Australia Pty Ltd 2003. [Online] 2008 [Cited 2011, march19]:
Available from: http://www.mims.com.au.
7. Vicari-Christensen M, Repper S, Basile S, and Young D.Tacrolimus. Review of
pharmacokinetics, pharmacodynamics, and pharmacogenetics to facilitate
practitioners' understanding and offer strategies for educating patients and promoting
adherence. Prog Transplant. 2011 Sep;19(3):277-84
8. Shastri RA. Effect of antacids on salicylate kinetics,International Journal of Clinical
Pharmacology Therapy & Toxicology. (1985) 23, 480–84.
9. Venkataramanan R, Swaminathan A, Prasad T, Jain A, Zuckerman S, Warty V,
McMichael J, Lever J, Burckart G, Starzl T. Clinical pharmacokinetics of tacrolimus,
Clinical Pharmacokinetics (1995) 29, 404–30.