Related | Appendix C: Renal Transplant
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Tacrolimus – renal transplant
Recommendations Notes/Evidence
Initiation Post-operative day 1 • Initiation of tacrolimus should start before or at
the time of transplant, rather than delayed until
the onset of graft function (UW Health, Very
Low, Conditional)
Dosing
(initial)
Decreased sensitivity (African-American, >80kg) 0.1 mg/kg/day (use ABW), by mouth divided in 2
doses twice daily, rounded to nearest capsule size
• Capsules and suspension may be taken with or
without food. Since the presence of food affects
the bioavailability of tacrolimus, if taken with
food, it should be taken consistently the same
way each time. (UW Health, Very Low,
Conditional)
• Tacrolimus may be given sublingually in patients
unable to adequately absorb enteral
formulations or in those unable to take oral. If a
patient is being transitioned to tacrolimus
sublingual from tacrolimus IR, each dose should
be divided by 2 and given sublingually. (UW
Health, Very Low, Conditional)
• Use of IV tacrolimus is reasonable for patients
unable to adequately absorb enteral
formulations, and conversion from IV to oral
tacrolimus is recommended as soon as enteral
therapy can be tolerated to minimize risk of
anaphylactic reactions that occur with
injectables containing castor oil derivatives.
(UW Health, Very Low, Conditional)
• Tacrolimus ER may be utilized in patients with
documented intolerable adverse effects with
tacrolimus IR or who are unable to obtain a
therapeutic drug concentration with the IR
formulation. If a patient is being transitioned to
tacrolimus ER (Envarsus®) from tacrolimus IR,
the total daily dose should be multiplied by 0.8,
then rounded to the nearest capsule size. (UW
Health, Very Low, Conditional)
Increased sensitivity (NPO, <80kg) Fixed dose 2 mg by mouth twice daily
Drug-drug
Interactions
(not an all-
inclusive
list)
Increases tacrolimus concentration
*Check Lexicomp for dose adjustments*
Adjust tacrolimus dose empirically:
• Fluconazole
• Posaconazole
• Voriconazole
• Ritonavir
• Letermovir
Monitor tacrolimus levels and adjust as needed:
• Clarithromycin
• Erythromycin
Decreases tacrolimus concentration
*Check Lexicomp for dose adjustments*
Monitor tacrolimus levels and adjust as needed:
• Rifampin
• Phenytoin
• Carbamazepine
• Phenobarbital
Target levels
Dose
Adjustments
Labs
Concurrent use of mycophenolate +/- prednisone
Tacrolimus goals may differ if patient is not on
mycophenolate +/- prednisone regimen. Goal
level should be discussed with provider.
Target TAC Trough Level
DGF 7-9 ng/mL
0-3 months: 8-11 ng/mL
3-6 months: 7-9 ng/mL
6-12 months: 6-8 ng/mL
>12 months: 5-7 ng/mL
Below/Above
Target
>50% Adjust dose by 25-50%
<50% Adjust dose by 25%
*Holding doses may be necessary
Laboratory Monitoring:
Tacrolimus (trough), potassium, and creatinine
Inpatient: Daily
Post-Discharge:
Day Frequency
0-90 Not less than weekly
91-180 Not less than twice
monthly
181-2 years Not less than once
monthly
>2 years Not less than quarterly
As Needed:
• Change in medication formulation, patient
status, or creatinine increase >0.3 mg/dL
above baseline
• 3 to 7 days (ideally 4 days) following dose
adjustment
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Adverse
effects
Acute kidney injury • Assess tacrolimus trough level for correlation with elevated creatinine
• If trough level is above goal and creatinine has increased > 0.3 mg/dL above baseline:
o Decrease tacrolimus dose if trough is <4 ng/mL above goal
o Hold tacrolimus if trough >5 ng/mL above goal and consider increasing current prednisone
dose
Neurological symptoms (tremor, headache) • Assess tacrolimus trough level for correlation with tremors or headache
• If trough level is above goal, adjust tacrolimus dose and follow up with patient
• if trough level within target range, no dose adjustment is recommended, follow-up with patient in 1
week
• If adverse effects are intolerable or interacting with daily activities and there is no other known cause
of symptom:
o Consult the transplant physician to consider converting the patient to tacrolimus ER,
belatacept, cyclosporine, or refer to primary care provider for supportive therapy, such as
addition of low dose beta blocker (propranolol)
New onset diabetes after transplantation
(NODAT)
Diagnosis
• Sx of DM + casual PG concentrations >200
mg/dL
• FPG >126 mg/dL
• 2-hr PG >200 mg/dL during an oral glucose
tolerance test
• No tacrolimus dose adjustment is recommended
• Consider consulting diabetes management & nutrition services
• Diagnosis of new onset diabetes after transplant (NODAT) is defined by the World Health
Organization (WHO) and American Diabetes Association (ADA) that develops for the first time after
transplantation
• If there is no improvement in glucose control 6 months after transplant (NODAT requiring insulin OR
A1c >7% with glucose lowering agent) and there have been 3 months of minimal glucocorticoid doses
o Consult transplant physician and consider converting the patient to cyclosporine
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Cyclosporine – renal transplant
Recommendations Notes/Evidence
Initiation Post-operative day 1 • The initiation of cyclosporine should start before
or at the time of transplantation, rather than
delayed until the onset of graft function (UW
Health, Very Low, Conditional)
Dosing
(initial)
Decreased sensitivity (African-American, >80kg) Fixed dose 150 mg by mouth twice daily • Neoral/Gengraf (cyclosporine modified) and
Sandimmune (cyclosporine non-modified) are not
bioequivalent and cannot be used
interchangeably (UW Health, Very Low,
Conditional)
• Capsules and suspension may be taken with or
without food. However, since the presence of
food affects the bioavailability of cyclosporine, if
taken with food, it should be taken consistently
the same way each time. (UW Health, Very Low,
Conditional)
Increased sensitivity (NPO, <80kg) Fixed dose 100 mg by mouth twice daily
Drug-Drug
Interactions
(not an all-
inclusive
list)
Increases cyclosporine concentration
*Check Lexicomp for dose adjustments*
Adjust cyclosporine dose empirically:
• Fluconazole
• Posaconazole
• Voriconazole
• Ritonavir
• Letermovir
Monitor cyclosporine levels and adjust as needed:
• Clarithromycin
• Erythromycin
Decreases cyclosporine concentration
*Check Lexicomp for dose adjustments*
Monitor cyclosporine levels and adjust as
needed:
• Rifampin
• Phenytoin
• Carbamazepine
• Phenobarbital
Target levels
Dose
Adjustments
Labs
Below/Above
Target
>50% Adjust dose 25% to 50%
<50% Adjust dose by 25%
*Holding doses may be necessary
Goal CSA Level
0-3 months: 200-300 ng/mL
3-6 months: 150-250 ng/mL
6-12 months: 100-200 ng/mL
>12 months: 50-100 ng/mL
Laboratory Monitoring:
Cyclosporine (trough), potassium, and
creatinine
Inpatient: Daily
Post-Discharge:
Day Frequency
0-90 Not less than weekly
91-180 Not less than twice
monthly
181-2 years Not less than once
monthly
>2 years Not less than quarterly
As Needed:
• Change in medication formulation, patient
status, or creatinine increase >0.3 mg/dL
above baseline
• 3 to 7 days (ideally 4 days) following dose
adjustment
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Adverse
effects
Acute kidney injury • Assess cyclosporine trough level for correlation with elevated creatinine
• If trough level is above goal and creatinine has increased > 0.3 mg/dL above baseline:
o Decrease cyclosporine dose if trough is <50 ng/mL above goal
o Hold cyclosporine if trough >50 ng/mL above goal and consider increasing current prednisone
dose
Neurological symptoms (tremor, headache) • Assess cyclosporine trough level for correlation with tremors or headache
• If trough level is above goal, adjust cyclosporine dose and follow up with patient
• if trough level within target range, no dose adjustment is recommended, follow-up with patient in 1
week
• If adverse effects are intolerable or interacting with daily activities and there is no other known cause
of symptom:
o Consult the transplant physician to consider converting the patient to tacrolimus ER,
belatacept, or refer to primary care provider for supportive therapy, such as addition of low
dose beta blocker (propranolol)
New onset diabetes after transplantation
(NODAT)
Diagnosis
• Sx of DM + casual PG concentrations >200
mg/dL
• FPG >126 mg/dL
• 2-hr PG >200 mg/dL during an oral glucose
tolerance test
• No cyclosporine dose adjustment is recommended
• Consider consulting diabetes management & nutrition services
• Diagnosis of new onset diabetes after transplant (NODAT) is defined by the World Health Organization
(WHO) and American Diabetes Association (ADA) that develops for the first time after transplantation
• If there is no improvement in glucose control 6 months after transplant (NODAT requiring insulin OR
A1c >7% with glucose lowering agent) and there have been 3 months of minimal glucocorticoid doses:
o Consult transplant physician
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Belatacept – renal transplant
Recommendation Notes/Evidence
Dosing Induction dosing (starting post-transplant or
converting from CNI <6 months from transplant)
Day 0, day 4: 10 mg/kg/dose
Ends of weeks 2, 4, 8, 12: 10 mg/kg/dose
5 mg/kg/dose every 4 weeks (±3 days)
starting at week 16
• Indicated for use in patients who are EBV
seropositive as a replacement for CNIs or to allow for
CNI minimization (UW Health, Very Low, Conditional)
• EBV serostatus should be evaluated prior to
initiation of belatacept (UW Health, Very Low,
Strong)
Conversion dosing w/ CNI taper (converting from
CNI to belatacept >6 months from transplant)
Initial phase:
- Day 0: 5 mg/kg/dose
- End of weeks 2, 4, 6, and 8: 5 mg/kg/dose
Maintenance phase:
- 5 mg/kg/dose every 4 weeks (±3 days)
starting end of week 12
CNI taper:
- 100% of previous dose on days 1-14
- 50% of previous dose on days 15-28
- 25% of previous dose on days 29-41
- Discontinue CNI on day 42
Conversion dosing with no CNI taper (converting
from CNI to belatacept >6 months from
transplant)
Initial phase:
- Day 0: 10 mg/kg/dose
- End of weeks 2, 4, 6, and 8: 10 mg/kg/dose
Maintenance phase:
- 5 mg/kg/dose every 4 weeks (±3 days)
starting end of week 12
Labs Laboratory Monitoring:
Prior to initiation: EBV serostatus
Adverse
effects
Post-transplant lymphoproliferative disorder
(PTLD)
• Consult transplant provider if concerns for PTLD (weight loss, fatigue, unexplained
anemia/thrombocytopenia/leukopenia, hypercalcemia)
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Mycophenolate – renal transplant
Recommendation Notes/Evidence
Initiation Post-operative day 1 • Full dose mycophenolic acid is the preferred anti-
proliferative medication used for renal transplant
patients (UW Health, Very Low, Conditional)
• IV mycophenolate mofetil is indicated if the patient has
an acute condition that affects gastrointestinal
absorption (i.e., GI bleed or obstruction, malabsorption
syndromes, severe diarrhea or severe vomiting) (UW
Health, Very Low, Conditional)
• Mycophenolate mofetil suspension is utilized for
patients receiving medications via nasogastric or
orogastric tube
Dosing
(initial)
Mycophenolate sodium (Myfortic) 720 mg by mouth twice daily
Mycophenolate mofetil (Cellcept) 1000 mg by mouth twice daily
Drug-drug
interactions
(not an all-
inclusive
list)
Decreases mycophenolate concentration
*Check Lexicomp for dose adjustments*
• Cyclosporine
Target levels
Labs
Goal MPA Trough
CsA based
regimens:
1.3-2.8 mg/L
TAC based
regimens:
1.9-2.8 mg/L
Laboratory Monitoring:
• Lab monitoring of MPA levels is not
recommended to assess for toxicity or
efficacy
• If levels are requested, they are only
appropriate for mycophenolate mofetil
and should be drawn as a trough
• MPA AUC is a better predictor of clinical events than
MPA trough. Trough levels are poorly correlated with
AUC and are not recommended (UW Health, Very Low,
Conditional)
Adverse
effects
Diarrhea
If a patient has ≥50% increase in their frequency of daily
bowel movements for ≥ 5-7 days
• 0-3 months post-transplant:
o C. difficile, C. difficile toxin B PCR
o CMV PCR
• ≥3 months post-transplant:
o CMV PCR
o Complete blood count
o Clostridium difficile toxin B PCR
o Cryptosporidium
o Giardia PCR
o Norovirus PCR
o Rotavirus AG
o Stool culture, with E. Coli (Shiga) toxin
o Stool O&P (parasitology, isospora, cyclospora,
pinworm)
o Consider colonoscopy if diarrhea persists and
all stool studies are negative
• If diarrhea work-up is negative for an infectious cause of diarrhea and it is affecting activities of daily
living or the patient is having limited and/or decreased oral intake:
o Decrease mycophenolate by 25% and increase dosing frequency (ex. 720 mg BID → 360 mg
TID)
▪ If fails, decrease mycophenolate by 50%
o Follow up with patient in 1 week
o If dose is decreased to 180 mg twice daily (MYF) or 250 mg twice daily (MMF) consult provider
to determine if other immunosuppression needs to be adjusted
o Consider adding the following:
▪ Add loperamide (Imodium®) 2 mg as needed after each loose stool (max dose: 16 mg
daily)
▪ Diphenoxylate/atropine (Lomotil®) 5 mg four times daily as needed (max dose: 20
mg/day)
▪ Psyllium fiber (Metamucil®) 3.4 g daily as needed
Heartburn/nausea • Counsel patient on taking MYF or MMF with food if not already doing so
• Convert from MMF to MYF if only upper GI complaints (heartburn, nausea)
• Add calcium carbonate as needed, or the addition of an H2RA or PPI if not already on
• If symptoms continue following 1 week of daily therapy increase H2RA or PPI dose to twice daily,
reassess in 1 week
• If symptoms persist for ≥1 week, consider EGD to rule out infection vs. ulceration
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Azathioprine – renal transplant
Recommendation Notes/Evidence
Initiation Failure to tolerate mycophenolate
Dosing
(initial)
1-2 mg/kg by mouth daily • Azathioprine is recommended for use in patients
unable to tolerate adverse effects of mycophenolate
(UW Health, Very Low, Conditional)
• Azathioprine is considered to be less effective than
MPA in preventing rejection. Prior to initiating
azathioprine, consider the total immunosuppression
for the patient and timing out from transplant
Drug-drug
interactions
(not an all-
inclusive
list)
Increases azathioprine concentration:
*Check Lexicomp for dose adjustments*
Avoid concurrent use:
• Febuxostat
Adjust azathioprine dose empirically:
• Allopurinol
Labs Laboratory Monitoring:
• There is no recommended azathioprine level for monitoring purposes. However, if toxicity is
suspected, check thiopurine methyltransferase (TPMT)
Adverse
effects
Leukopenia • Consult transplant provider if WBC <3
Gastrointestinal
If a patient has ≥50% increase in their frequency of daily
bowel movements for ≥ 5-7 days
• 0-3 months post-transplant:
o C. difficile, C. difficile toxin B PCR
o CMV PCR
• ≥3 months post-transplant:
o CMV PCR
o Complete blood count
o Clostridium difficile toxin B PCR
o Cryptosporidium
o Giardia PCR
o Norovirus PCR
o Rotavirus AG
o Stool culture, with E. Coli (Shiga) toxin
o Stool O&P (parasitology, isospora, cyclospora,
pinworm)
Consider colonoscopy if diarrhea persists and all stool
studies are negative
• See diarrhea work-up algorithm
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Sirolimus/everolimus – renal transplant
Recommendations Notes/Evidence
Initiation For use in patients with:
• CNI toxicity
• Skin cancer
Quadruple therapy
• Sirolimus/everolimus may impair or delay wound healing,
and should be used with caution in the peri-surgical
period (UW Health, Very Low, Conditional)
• Indicated for use in patients with recurrent skin cancers
as a replacement for azathioprine, MPA, or CNIs (UW
Health, Very Low, Conditional)
Dosing (initial) Sirolimus 6 mg load on day 1, followed by 2 mg by
mouth once daily
Everolimus 0.75 mg by mouth twice daily
Drug-drug
interactions (not
an all-inclusive
list)
Increase mTOR concentration (not an all-
inclusive list):
*Check Lexicomp for dose adjustments*
Avoid concurrent use:
• Posaconazole
• Voriconazole
• Ritonavir
Monitor mTOR levels and adjust as needed:
• Fluconazole
• Ritonavir
• Letermovir
• Clarithromycin
• Erythromycin
Decrease mTOR concentration (not an all-
inclusive list)
*Check Lexicomp for dose adjustments*
Monitor mTOR levels and adjust as needed:
• Rifampin
• Phenytoin
• Carbamazepine
• Phenobarbital
Target levels
Dose
Adjustments
Labs
Laboratory Monitoring:
• Recommended once weekly upon initiation and with any dose changes
• When the target trough level has been attained, recommend monitoring levels once
monthly
Goal Trough Levels
(SIRO/EVR+TAC)
Goal Sirolimus Level
(SIRO/EVR+MPA)
0-3 months: TAC: 5-7 ng/mL
SIRO/EVR: 4-7 ng/mL
SIRO/EVR: 8-10 ng/mL
3-6 months: TAC: 5-7 ng/mL
SIRO/EVR: 4-7 ng/mL
SIRO/EVR: 8-10 ng/mL
6-12 months: TAC: 3-5 ng/mL
SIRO/EVR: 3-5 ng/mL
SIRO/EVR: 5-8 ng/mL
>12 months: TAC: 3-5 ng/mL
SIRO/EVR: 3-5 ng/mL
SIRO/EVR: 5-8 ng/mL
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Adverse effects Proteinuria • Monitor at 6 months and then annually post-transplant per standard lab monitoring
• Consider administration of angiotensin-converting enzyme (ACE)-inhibitors and angiotensin II receptor
antagonists and reducing mTOR levels
Mouth ulcers • Development of mouth ulcers also seems to be dose-related, because they usually appear after the
loading dose and often improve after a dose reduction
• Addition of a high-potency topical steroid may be considered
Hyperlipidemia • Monitor cholesterol and lipids
• If hyperlipidemia occurs, follow current guidelines for management (diet, exercise, lipid lowering agents)
• Immunosuppressive strategies minimizing doses of mTORs, CNIs, or corticosteroids may help in
controlling hyperlipidemia
Thrombocytopenia • Consider dose reduction or temporary drug suspension if appropriate
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.
Copyright © 2021 University of Wisconsin Hospitals and Clinics Authority. All Rights Reserved. Printed with Permission
Contact: CCKM@uwhealth.org Last Revised: 07/2021
Prednisone – renal transplant
Recommendations Notes/Evidence
Initiation Post-operative day 4 following dexamethasone taper • Prednisone 30 mg once daily will be
started on POD 4 following
dexamethasone taper and may be
continued on discharge
Dosing
(initial)
Standard steroid taper
• Prednisone taper should occur
following POD4
• Factors that may influence the
duration of prednisone taper:
o Current and historical CNI levels
o Current MPA dose
o Current renal function
o Episodes of rejection
Dexamethasone
100 mg POD0
50 mg POD1
Dexamethasone
or Prednisone
18 mg (dex) or 90 mg (pred) POD2
12 mg (dex) or 60 mg (pred) POD3
Prednisone
30 mg POD4
Discharge on 30 mg and decrease dose by 5
mg each week to a target dose of 10 mg daily
• Steroid withdrawal can be considered
for patients who receive alemtuzumab
for induction (UW Health, Very Low,
Conditional)
• Rapid steroid taper can be considered
for patients who receive alemtuzumab
or thymoglobulin for induction (UW
Health, Very Low, Conditional)
• Prednisone doses should be split to
twice daily dosing for patients requiring
insulin for glucose control (UW Health,
Very Low, Conditional)
Rapid steroid taper
Dexamethasone
100 mg POD0
50 mg POD1
Dexamethasone
or Prednisone
18 mg (dex) or 90 mg (pred) POD2
12 mg (dex) or 60 mg (pred) POD3
Prednisone
30 mg POD4
10 mg POD5
Discharge on 10 mg and consider reduction to
5 mg at week 3 to target dose of 5 mg daily
Early steroid withdrawal
Dexamethasone
100 mg POD0
50 mg POD1
Dexamethasone
or Prednisone
18 mg (dex) or 90 mg (pred) POD2
12 mg (dex) or 60 mg (pred) POD3
Prednisone
30 mg POD4
Steroid withdrawal on POD5
Labs Laboratory Monitoring:
Glucose, bone mineral density
Adverse
effects
Hyperglycemia • Prednisone doses should be split to twice daily dosing for patients requiring insulin for glucose control
Heartburn/reflux • Start a proton pump inhibitor (PPI) at time of transplant
• If a patient complains of heartburn on daily dosing of the PPI, frequency may be increased to twice daily
(pending renal function)
• Discontinue PPI in patients with no history of heartburn/gastroesophageal reflux disease (GERD) prior to
transplant if prednisone is discontinued
Osteoporosis • Recommend calcium 2000 mg daily (based on elemental calcium dosing)
• Recommend vitamin D 2000 units daily
• For patients that are on an early steroid withdrawal maintenance immunosuppression regimen, calcium and
vitamin D supplementation are not required
Effective 6-17-2021. Contact CCKM@uwhealth.org for previous versions.