Actuarial Survival

Division of Organ Transplantation

Resident Manual

Rhode Island Hospital

A Lifespan Partner
Tacrolimus + Mycophenolate regimen

Compiled by:
Paul Morrissey, MD

Revised: December 2011

Available at: http://intra.lifespan.org/surgery.

Table of Contents

Administrative issues
Transplant office and clinic
APC 921
444-5285 or 444-8345
Transplant surgeons
Kevin Charpentier
350-3848 (b)
Paul Morrissey
350-1385 (b)
Transplant physicians
Reg Gohh
350-5553 (b)
Terri Montague
350-7227 (b)
Staci Fischer
350-9022 (b)
Transplant Manager
Bette Hopkins-Senecal 350-5523 (b)
Transplant Clinical Coordinators
Nancy McNamara, RN 444-3186
Mary Ellen Espanola, RN 444-3284

ORDERS
Admissions to the Transplant Surgical and Medical Services
ORDERS after donor nephrectomy
ORDERS for renal transplant patients
Post-op
MEDICATIONS
Transplantation historical timeline
Immunosuppressive medications Mechanism of Action
Transplant medications - routine dosing and prescriptions
Steroids
GRAFT DYSFUNCTION
Early considerations after renal transplant
Algorithm for work-up of rising creatinine
Infectious complications
Late complications after transplantation (Ciba)
Clinical rejection
Hyperacute
Acute rejection
Chronic rejection

Rounds
The team meets at 9:00 (8:30 on Thursday for Journal Club) to
discuss patients. Walk rounds begin at 4:00 PM on 4A or 5ISC.
Clinic (Surgery residents attend one clinic per week)
Tuesday - Dr. Morrissey (1:00 PM)
Friday - Dr. Charpentier (9:30 AM)

GENERAL INFORMATION
Success of renal transplantation
Live donor versus Cadaver Renal Transplant (CRT)
Organ Donation

Surgery
Renal transplant with Senior Resident or AR-III (cadaveric)
Donors by AR-II; AV access with AR I or II
PD catheters and PermCaths with AR I or II

Dialysis Access Game Plan

Resident Duties Routine care of in-house transplant surgical
patients, discharge summaries, admissions, consultations and inhouse pre-ops.

ASTS WEBSITE (Resident Education in Transplantation)

http://www.asts.org/FellowshipTraining/ResidentEducati
on/Resident1.aspx

Kidney Donors

Donors
There are two sources of kidneys: either a living donor (relative,
spouse or friend, e.g.) or a deceased donor (brain dead or donor
after circulatory death (DCD)). Live donors are preferred for many
reasons, especially the reduced time on dialysis for the recipient.

Donor nephrectomy is unique among surgical procedures as the patient is

undergoing major surgery with all its risks (1% incidence of major
complication, 0.03% incidence of mortality) for no medical benefit.
Therefore, special attention to detail is required for the donors safety.
Eligible donors are in good health, ABO compatible with the recipient
and have normal renal function. Spouses and close friends are potential
unrelated donors. Pre-op testing consists of physical exam, labs, 24-hr.
urine collection for creatinine clearance, renal ultrasound and CT
angiogram (for renal anatomy). The surgery is performed (1)
laparoscopically, (2) mini-open nephrectomy via an anteriorretroperitoneal approach or (3) via a flank incision (over 11th rib).

Item

Live donor

Deceased donor

Allograft half-life

12-14 years

8-9 years

Waiting time

2 - 4 months

18 - 48 months

18 - 65

4 - 70

Excellent

Fair to excellent

Immediate function

97 %

50 %

DGF*

2%

30 %

5 - 7 days

5 - 14 days

Planned

Urgent

Lower doses

Standard

5 - 10 %

15 - 20%

Donor Age
Quality of kidney

POST-OP Typical course through discharge

Prophylactic Rx: Spirometer, heparin 5000U sc bid x 48 hr
Sequential compression devices (Venodyne boots)
Pain management: PCA for 1-2 days
Clear liquid diet

Hospital LOS
Surgery

POD #1
Heplock or KVO I.V. when tolerates adequate P.O.
D/c Foley catheter; d/c Venodyne boots when ambulating
Advance to regular diet as tolerated.
Check CBC, BUN/creatinine

Immunosuppression
Risk of acute rejection

*Delayed graft function requires dialysis after transplant.

Requirements for live donor renal transplants
1. Compatible blood type ABO, HLA matching not required
2. Excellent health low operative risk
3. Normal renal function 24 hour urine collection, U/S and CT
4. Proper motivation (voluntary donation)

POD #2
Check CBC, BUN/creatinine
POD #3
D/c PCA
Vicodin (or Percocet) for analgesia
Laxative prn (begin P.O., then use suppository if no effect)
D/c to home today or next day
F/U 10-14 days in Transplant Clinic
One week supply of analgesics (usually 20-30 tablets)

Risks to the Donor

Hyperchloremic metabolic acidosis (Kellum JA. CCM 2002; 30: 259.)
Major complication < 1 % (e.g. - bleeding, injure adjacent structure,
AMI, DVT or PE, significant injury to donor kidney)
Lifetime risk of HTN, ESRD same as general population.

DECEASED ORGAN DONORS

KIDNEY TRANSPLANT RECIPIENT ORDERS

Expected LOS 5 days (longer with delayed graft function, DGF)

Brain Dead Donor

Standard criteria donor (SCD) other than ECD
Expanded criteria donor (ECD)
1. Donor age > 60 years or
2. Donor age > 50 with 2 of the following:
a. Pre-retrieval creatinine > 1.5 mg/dL
b. Death from CVA
c. History of hypertension
Donor after Circulatory Death (DCD)
Donor with irreversible brain injury, family decides on CMO
status, organs (usually kidneys liver) are recovered after
extubation and progression to circulatory arrest (5 minutes).

ORDERS FOR PATIENT CARE

ADMIT to PACU, then 5ISCU
DIAGNOSIS: S/P renal transplant
VITALS: Hourly BP; target SBP > 130. Use neosynephrine PRN
for BP support if SBP and urine output are low.
ACTIVITY: OOB to chair POD #1, then ambulate
NURSING:
Strict I & O
CXR in PACU R/O pneumothorax if new line placed.
Foley to gravity, d/c Foley catheter on POD #5
MEDS:
Induction: Thymoglobulin (high immune risk or high risk
of DGF) or basiliximab (Simulect).
Immunosuppression: usually tacrolimus (Prograf),
mycophenolate mofetil (CellCept) or EC-MPA (Myfortic)
and steroid taper as below.
Day 1 Solumedrol 250 mg IV times one, then

TRANSPLANT RECIPIENT MANAGEMENT - FLUIDS

0.9 % Saline
Volume - most patients get 2-3 L in the OR and cc/cc
replacement of UO thereafter. Hypovolemia is unusual postop. The CVP is a rough (though inaccurate) measure;
however aiming for a CVP > 10 is a reasonable guide.
Urine output most live donors have an initial UO of 200-1000
cc/hr, while a deceased donor with ATN might be expected
to be oliguric.
BP - high normal or slightly elevated BP is best for renal
reperfusion. Even low normal BP can result in ATN and
requirements for dialysis post-op. Goal > 130 mm Hg.

Prednisone taper as follows:

STANDARD
Day 2-6
Prednisone 30 mg po BID
Day 7-14
Prednisone 20 mg po BID
Day 15-21
Prednisone 10 mg po BID
Day 22-28
Prednisone 10 mg po AM, 5 mg PM
Day 29 onward Prednisone 10 mg po QD.
or
RAPID TAPER
Day 1
Solumedrol 250 mg
Day 2
Prednisone 40 mg po BID
Day 3
Prednisone 20 mg po BID
Day 4
Prednisone 10 mg po BID
Day 5 onward.
Prednisone 10 mg po QD

BP MANAGEMENT POST-OP
The short-term effects of hypotension (ATN, DGF) complicate
patient care after renal transplantation. The short-term effects
of hypertension are minimal, especially in this population with
> 85% incidence of hypertension. SBP <100 should be treated
promptly with IV fluids or a vasopressor (Neosynephrine qtt).
Pre-operative -blockers should be continued as tolerated. .

BP medications 85% of recipients have HTN. Blood pressure

at the time of discharge is often high (due in part to immunosuppression and volume overload) and BP is gradually adjusted
as an outpatient.

POM contains order sets for the donor and recipient. Some
explanations and instructions are given below.
LABS:
Every 6 hours x 24 hours, then q 12 hr on POD#2, then QD.
Tacrolimus level or CsA level QD beginning day after
medication begins.
Ca, Mg, PO4 may become depleted with high volume diuresis.
CBC with differential (lymph count guides Thymoglobulin
dosing)

Insulin Type I DM or patients on oral agents at the time of

transplant invariably require insulin therapy on discharge.
Managing BS after transplant is optimally done with a QD
Lantus regimen and Humolog sliding scale transitioned to premeal short-acting insulin. Minimally elevated FSBS (120
200s) can initially be controlled with sliding scale insulin and
adding an oral agent or longer-acting preparation as indicated.
Prudent use of peri-operative Lantus (for patients on insulin pretransplant) and sliding scale insulin should limit the need for an
insulin drip in most patients.

IV Fluids:
Replacement cc/cc of urine output due to tubular injury
Replacement IVF is NS (similar [Na+] to urine)
D5 NS is maintenance until adequate PO intake
Other management issues:
JP Drain d/c when output < 50 cc/ day
Foley d/c on POD #5
PCA d/c on POD # 2
Dressing change prn and always by POD # 2
Daily weights
CVL d/c on AM of discharge
RN may draw labs from CVL
Rationale for ancillary medications after renal transplant
Antacids Ulcer prophylaxis due to steroids and for dyspepsia
due to Cellcept (common side effect)
Bactrim Single Strength PCP, Nocardia and UTI prophylaxis
Mycelex Thrush prophylaxis
Ketoconazole - Fungal prophylaxis and CYT p450 3A
inhibition (used when CsA is 1* immunosuppressant).
Valganciclovir - CMV and EBV (Mononucleosis and
lymphoma) prophylaxis.

Preferred peri-operative and long-term blood pressure management:

Class
Beta-blocker
CaCB (Dihydropyridine)
Alpha blocker
Diuretic

Example
Atenolol, Toprol
Norvasc
Cardura
Lasix

seizure, and retinopathy with papilledema. Focal signs and

symptoms are uncommon. Renal disease presents as proteinuria,
microscopic hematuria, red blood cell casts, and oliguric renal
failure.

Note
First line
Second line
QHS dosing
Volume overload

Differential Diagnosis: complications of pregnancy; cocaine;

withdrawal of alcohol, beta-blockers, or alpha-stimulants; renal
artery stenosis, pheo, Ao coarctation, and hyperaldosteronism.
Treatment of Hypertensive Urgency/Emergency borderline cases
requiring more than gradual increasing of Htn medication.

Treatment of Hypertensive Urgency vs. Emergency

A hypertensive emergency is a condition in which elevated blood
pressure results in acute target organ damage. The systems primarily
involved are the CNS, the CV system, and the kidneys. In order to
diagnose malignant hypertension, papilledema must be present.
Accelerated Htn is defined as a recent significant increase over
baseline blood pressure that is associated with target organ damage.
Funduscopic exam may show vascular damage (flame-shaped
hemorrhages).

Labetalol (alpha and beta-blocker) is a safe and effective agent to

consider, provided that the patient does not have asthma, heart
failure, or heart block.
Add 2 vials of Labetalol (40ml) to 250 ml D5W and start at
3ml/min. The BP should start to drop within half an hour. Labetalol
can also be given as a 20mg bolus over 2 minutes; repeated with a
40 mg dose every 10 minutes until the desired BP is reached or 300
mg have been given. Response is usually within 5-10 minutes.

Hypertensive urgency must be distinguished from emergency.

Urgency is defined as severely elevated blood pressure (systolic
>220 mm Hg or diastolic >120 mm Hg) with no evidence of target
organ damage.

Hypertensive Emergency (Encephalopathy, AMI, CHF or unstable

angina) - Admission to ICU is warranted.

Hypertensive emergencies require immediate therapy to decrease

BP within minutes to hours. No evidence suggests a benefit from
rapidly reducing BP in patients with hypertensive urgency. Such
aggressive therapy may harm the patient, resulting in cardiac, renal,
or cerebral hypo-perfusion. Increasing the dose of an existing BP
med or adding another medication is the best approach.

Nitroprusside (Nipride, 0.25 ug/kg/min). It dilates both arteries and

veins and is not associated with tachyphylaxis. It's onset of action is
rapid and minute by minute BP monitoring is required.
Hydralazine 5-25 mg IV, coupled with a beta blocker to prevent
reflex tachycardia is a safe alternative. Hydralazine may be repeated
q4h as necessary.

The cardiac presentation of malignant Htn is angina, AMI or CHF.

Neurological presentations are occipital headaches, cerebral infarct,
cerebral hemorrhage, or hypertensive encephalopathy. Hypertensive
encephalopathy is a symptom complex of severe hypertension,
headache, vomiting, visual disturbance, mental status changes,

Esmolol is also a reliable drug in this situation and can be

administered by IV infusion.

Timeline of Immunosuppressive Agents in Transplantation

Drug Protocols and Rationale

Triple Therapy: a three-drug combination for immunosuppression,
which allows for adequate immunosuppression with modest doses
of all three drugs. In theory, side effects of each drug are
minimized.

1954 None available (Identical twin transplant - PBBH)

1959 - Total body irradiation and cancer chemotherapeutics
Fraternal Twins in Boston and Paris are first successful

Prograf (tacrolimus)
Cellcept (mycophenolate mofetil) of Myfortic (MPA)
Prednisone

transplants with immunosuppression.

1960 - 6-mercaptopurine

Prograf (tacrolimus)
Imuran (azathioprine, if Cellcept not tolerated)
Prednisone

1961 Azathioprine (imidazole derivative of 6-MP)

First successful Cadaver Renal Transplant reported.
1962 - Prednisone

Neoral (cyclosporine)
Azathioprine or Cellcept
Prednisone

1965 Polyclonal antibodies to T-cells: ALG / ATGAM with

serum obtained from horses, goats, and rabbits.

Rapamune may be substituted for Prograf, Neoral or Cellcept

1975 - Donor specific transfusions given pre-transplant

Induction Therapy Antibody (Simulect, Thymoglobulin (rabbit

antithymocyte globulin) or OKT3) used at the time of the initial
transplant as prophylaxis rather than therapy for acute rejection.
Currently, we offer Ab induction to patients with a PRA > 20%,
repeat transplant, high likelihood of delayed graft function or a plan
to limit other immunosuppression (steroid withdrawal, e.g.).

1975 - OKT3 (mouse monoclonal Ab versus CD3)

CD3 = receptor expressed on all T cells
1978 - Cyclosporine (available clinically in 1983)
1994 - Tacrolimus (FK506)
1995 - Mycophenolate mofetil (Cellcept)

OKT3 monoclonal Ab to CD3 (First mAb ever in clinical use.)

Used for the treatment of severe acute rejection. Associated with
cytokine release syndrome (fever, hypotension, CHF).
Basiliximab chimeric mouse-human mAb to IL-2 receptor (CD25)
Benefit in reducing acute rejection (40% versus 20% at 6
months) and allowing safe steroid minimization.
rATG polyclonal Ab against many T-cell antigens produced by
immunizing rabbits with human thymocytes. Pre-medicate with
steroids, diphenhydramine (25 mg) and acetaminophen (650 mg) to
prevent cytokine release syndrome.

1998 - IL-2R monoclonal Ab (Simulect, Zenapax)

1999 Thymoglobulin Rabbit ATG)*
1999 - Sirolimus (Rapamune)

* FDA approved for treatment of rejection versus other agents

approved for the prevention of organ rejection following
renal transplantation.
7

Standard taper (10 mg by day 29) = 500, 250, 30 bid x 5

days, 20 bid x 7 d, 10 bid x 7 d, 15 mg/d x 7, then 10 mg/d.
Pancreas: see taper (including methylprednisolone x 3 d) to
10 mg/d on POD #7.

TYPICAL IMMUNOSUPPRESSION PLAN

INDUCTION
Basiliximab (Simulect)
Dose: 20 mg on POD #0 and #4
Indications: Low immunologic risk, future Thymoglobulin
exposure planned (PAK), high medical risk for overimmunosuppression
Utility: A meta-analysis of randomized trials. Transplantation
2004; 77: 166.

NOTES:
1. Pancreas Transplantation: as above with routine
Thymoglobulin induction.
2. 0-MM allograft: consider no induction, rapid steroid taper or
two-drug regimen.
3. DSA present consider IVIG at induction and
Plasmapheresis.

rATG (Thymoglobulin)
Dose: 1.5 mg/kg/d (round to 25 mg increments; maximum dose
150 mg) via CVL
Higher immunologic risk (High PRA, DSA) or high likelihood
of DGF
Usual dose: 1.5 mg/kg on day of surgery and 2 more doses
(4.5 mg/kg)
DGF or high immunologic risk: 1.5 mg/kg for 4-5 doses
(6.0-7.5 mg/kg)

PROPHYLAXIS
Bactrim SS begin post-op day #3 and continue for one year.
Clotrimazole troches begin post-op day #3 and continue for
one month.
Valganciclovir 900 mg QD* x 3 months for D+R+, D-R+. Rx
D+R- for six months. D-R- (Donor and Recipient negative
for CMV IgG): obtain serial CMV PCR every 2-4 weeks for
6 months, pre-emptive therapy if PCR > 500 copies.

MAINTENANCE
Prograf (Tacrolimus)

(*450 mg/d for creatinine > 2.5, leukopenia, $$$ issues or low
body weight.)

Dose: Target 7-10 ng/ml first 2 months, 6-8 ng/ml 2-6 months,
5-8 ng/ml after 6 months.

Pancreas Transplant - Steroid Taper:

Mycophenolic acid (EC-MPA, Myfortic)

Methylprednisolone 70 mg IV 2XD for one day then

Methylprednisolone 35 mg IV 2XD for one day then
Methylprednisolone 17.5 mg 2XD for one day then
Prednisone 15 mg PO 2XD for one day then
Prednisone 25 mg PO daily for one day then
Prednisone 20 mg PO daily for one day then
Prednisone 10 mg PO daily until discontinued

Dose: 720 BID

Consider: 540 BID less than 50 kg or 360 BID for elderly
patients, prior GI symptoms, or current leukopenia.

Methylprednisolone / Prednisone
Rapid taper (10 mg by day 5) = 500, 250, 40 bid x 1 day, 20
bid x 1 day, 10 bid x 1 day, 10 QD.

1.
2.
3.
4.
5.

CORTICOSTEROIDS (Prednisone, Solumedrol)

Rapid taper to 10 mg daily
Bind intracellular receptors blocking DNA/RNA synthesis
Inhibit IL-1 secretion (costimulator); Inhibit MAC chemotaxis
Anti-inflammatory
Apoptosis at high doses (pulse therapy lympholysis)
Toxicity: Steroid side effects
Hypertension, Sodium / fluid retention
Psychosis / emotional instability
Peptic ulcer disease
Delayed growth, Amenorrhea, Osteopenia
Centripetal obesity (Cushingoid appearance)
Glucose intolerance, Hyperlipidemia
Glaucoma / cataracts
Neutrophil dysfunction / sepsis

1.
2.
3.
4.

AZATHIOPRINE (Imuran)
2-3 mg / kg / day
1. Blocks the synthesis of purine nucleotides
2. Toxicity: leukopenia (common), GI upset (rare)

1.
2.
3.
4.

MYCOPHENOLATE MOFETIL (Cellcept)

500 - 1000 mg BID

1.
2.
3.
4.
5.
6.

Enteric Coated - MYCOPHENOLIC ACID (Myfortic)

360 - 720 mg BID
Inhibitor of inosine monophosphate dehydrogenase (IMPDH)
Blocks de novo synthesis of purine nucleotides
Most cells, but not lymphocytes, can make purines via a salvage
pathway
Increased activity against Type II IMPDH which is abundant in
active lymphocytes
Efficacy: reduced AR to 20% compared to 40% with Imuran
Toxicity - leukopenia (common), gastritis, diarrhea.

1.
2.
3.
4.
5.
6.

CYCLOSPORINE (Sandimmune, Neoral)

Dose to achieve trough levels of 100-400 ng/ml
Peptide derived from fungus Tolypocladium inflatum
Blocks the mRNA (transcription) for IL-2 and INF-g
IL-2 formerly called T cell growth factor stimulates the
proliferation of T lymphocytes
Toxicity:
Nephrotoxic in high dose
Hypertension
Neurotoxic (tremor, parethesias)
HyperK+
Renal tubular acidosis
Gout
Excess hair growth
Gum hyperplasia
TACROLIMUS (Prograf, "FK506")
Dose to achieve trough levels or 5-15 ng/ml
Macrolide ABx derived from Strep . tsukubaenis
Inhibits transcription of IL-2 similar to CsA (Also IL-3, 4, 5,
INF-g, TNF, GM-CSF, IL-2R)
Similar toxicity profile to CsA
Differences from CsA: More post-transplant diabetes
No cosmetic or lipid SE
Can reverse acute rejection
SIROLIMUS (Rapamune)
Dose to achieve trough levels 5-15 ng/ml
Derived from Streptomyces hygroscopicus (Easter Island)
Inhibits IL-2 signal; arresting T-cell in G1-S phase
Synergistic with CsA or tacrolimus (which fx in G0-G1 phase)
Not nephrotoxic (board question) !
Toxicity: hyperlipidemia, low cell counts, delayed healing,
lymphocele formation, Pneumonitis
Less mutagenic; actually in trials as CA chemotherapeutic

Immunosuppression - DOSING
DRUG
CsA
Prograf

Low dose
80-150
3-6 ng/ml

Moderate
150-250
6 - 10

High
250-400
10 - 15

Steroid equivalents

Too much
Greater 400
Greater than 15

Duration
Short
Hydrocortisone
Intermediate
Prednisone*
Methylprednisolone
Long
Dexamethasone

Azathioprine (Imuran): 1-3 mg/kg once daily.

Mycophenolate mofetil (Cellcept, Myfortic): 500 1000 mg/ BID
depending on body size, GI side effects (heartburn, gastritis,
diarrhea) and WBC (reduce dose if < 3.0)

Potency

t1/2

Equivalent

8-12 hr

20 mg

4
5**

18-36
12-36

5 mg
4 mg

25

36-54

0.75 mg

* Physiologic equivalent is 7.5 mg per day

** For simplicity we usually convert methylprednisolone
(Solumedrol) 1:1 with prednisone when patients can not take PO.

Steroids slow taper to 10 mg/d at one month or rapid taper to 10

mg/d at POD #5 (see orders). If there is no history of acute
rejection continue taper to 5 mg/d after 3-6 months.

Stress steroids

TRANSPLANT PRESCRIPTIONS:

Stress doses of steroids are not required for mild-moderate medical

illnesses (infections, MI, etc.) or for surgery after transplant (reoperations, catheter removals, elective general surgery). Patients
require only their usual maintenance dose of prednisone. Stress
steroids may be beneficial in severely ill patients on long-term
steroids (sepsis in the ICU, severe asthma attacks, major multiple
trauma victim). Patients with evidence of adrenal insufficiency
(low BP, low sodium, unexplained MS changes, etc.) should
receive stress steroids.

Most patients use a mail-order pharmacy and Rx are filled by

our Transplant RNs, otherwise please discharge from the
hospital with a six-month supply of all meds (one month supply
with 5 refills). Pain med (narcotic) scripts must be written.
Immunosuppression
Prograf (tacrolimus) - supplied as 1 and 5 mg capsules
Neoral (cyclosporine) - supplied as 100 and 25 mg capsules
Cellcept - supplied as 250 or 500 mg capsules, 180 or 360 for MPA.
Prednisone - discharge with 10 mg capsules (#100)
Prophylaxis
Axid QD or bid; Protonix (pantoprazole) if previous Hx of PUD
Bactrim SS (for PCP and UTI) - QD (6 months); then every MWF
Mycelex (for thrush) QID with meals for 1 month.
Valganciclovir (for CMV) - 450 or 900 mg QD for 3-6 months.

References:
(1) Stress steroids are not required for patients receiving a renal
allograft and undergoing operation. JACS 1995, 180:532.
(2) Corticosteroid therapy in severe illness. NEJM 1997, 337:
1285.

10

Early Considerations after Renal Transplantation

Algorithm: renal transplant dysfunction
The one and five year allograft survivals are:
1-year
Live donor renal transplant 95 %
Cadaver renal transplant* 88 %
*(immediate function)
Cadaver renal Tx (DGF*) 70 %

Hx and PEx
Weight gain / edema
Oliguria
Hypertension
Allograft pain
Fever, chills, myalgias

5-year
88 %
70 %
50 %

DGF delayed graft function defined as oliguria necessitating dialysis

after transplantation.

Differential Dx
Dehydration
Drug toxicity
Infection
Hydronephrosis
Rejection
Technical pblm

Stricture
Lymphocele
Compression

EVALUATION
Labs: Chem 7, CBC, LFTs, CsA or Tacrolimus level, U/A + C &
S, Urine sediment (ATN, PMN).
Pre-biopsy labs: PT, PTT, CBC, T & C 2U, bleeding time.

Surgical considerations
Bleeding - anastomotic, hematuria, peri-graft.
Thrombosis - renal artery or vein (1%)
Ureteral or urethral (Foley) obstruction - use of stent
Urine leak - immediate or delayed (weeks)
Ureteral stricture weeks to years later
Obstruction by compression (lymphocele, urinoma)

Usual approach:
Hydrate overnight, thorough history (new meds such as ACEI,
NSAIDs, Abx; recent illness, change in BP, glucose control).
Check labs, urinalysis, and urine sediment.
Renal consult to assist with assessment and perform biopsy.
Ultrasound to R/O technical problem.
Renal biopsy (2 U/S-guided 18G core biopsies of renal cortex).

Early renal transplant dysfunction

Immediate function with high output diuresis due to fluid
overload, osmotic diuresis from inadequate hemodialysis,
intraoperative diuretics, proximal renal tubular injury
Delayed function due to ischemia-reperfusion injury
Risks: donor age, donor hypotension and vasopressor use,
cold and warm ischemic times
SE: cardiac, pulmonary edema
Cytokine release syndrome with use of ATG
ATN
Hypovolemia (CVP), hypotension, MI, CHF, seizure,
sepsis
Cyclosporine or tacrolimus (CNI) toxicity

Common surgical complications after renal transplantation

Ureteral complications (10%) leak or stricture (obstruction)
Lymphocele (5%) may be incidental or cause compression
Wound infection (3%), Hernia (3%)
Colon perforation (diverticulitis - 3%)
Pathologic fractures
Tertiary hyperparathyroidism most resolve in 6-12 months. Some
require cinacalcet or parathyroidectomy (one gland or 3 glands).
Progressive vascular disease including amputation
Cancer skin, renal and other solid tumors.

Rejection unusual in the first week after transplantation.

11

Polyoma (BK) virus affects the urinary tract and causes renal
transplant dysfunction. The inflammatory infiltrate mimics acute
rejection.

Infectious complications after transplantation

Early
(0 - 6 weeks)

Middle
(6 weeks - 6 months)

Late
(> 6 months)

Wound infection
Line sepsis
UTI / urosepsis
Herpes
Pneumonia
Thrush
Dialysis access

CMV disease
PCP*
Candidiasis
Nocardia
Polyoma virus
EBV
Legionella

PCP*
Cryptococcus
Pneumonia
UTI
PML
Viral infections**
Mycoplasma

Pneumonia evaluation
Sputum or induced sputum
Bronchoscopy PRN
AFB
Fungal stains and cultures
PCP DFA
Legionella urinary Ag
Histoplasmosis serology (P. Rico and Ohio River Valley)
Coccidioidomycosis (Southwestern USA)
Cryptococcus serum Ag
Nocardia smear and stain
Respiratory viral cultures
CMV biopsy
Chlamydia

* Incidence <0.1 % with Bactrim prophylaxis.

** CMV most likely in middle period. RSV, HSV, adenovirus, influenza
can occur in middle and late periods.

Routine work-up is based on Hx, PEx, post-op period, etc., but may
include bacterial, fungal, and viral cultures, mycoplasma and acid
fast (TB), Legionella cultures, silver stains for PCP, cryptococcal
Ag.

Open lung biopsy - PRN

CMV is diagnosed by rapid spin-amplified viral culture, IgM

antibody, CMV PCR or by inclusion bodies in a tissue biopsy. The
diagnosis is suspected when the triad of leukopenia, unexplained
fevers and flu-like symptoms is noted.
Pneumonia is evaluated by appropriate sputum samples. If these
can not be obtained within 6-12 hours of admission, proceed to
bronchoscopy. PCP is extremely rare with Bactrim prophylaxis.

12

Chronic Renal Failure A Vasculopathic State (NEJM 1998;

339:841.)

Success Rates for Renal Transplantation

Allograft survival based on donor source and HLA matching.
Graft survival
Category
N
1-year
3-year
HLA-ID sibling
1984
97
95
Spouse donor
368
95
85
Other living unrelated
129
97
81
Parent donor
3368
95
82
Cadaver donor
43,341
85
70
CRT with DGF
11,060
70
60

2/3 of ESRD patients have DM or Htn

Reasons are multi-factorial
Renal dysfunction
Chronic inflammatory state
Hyperhomocysteinemia
Syndrome X
Anemia
Chronic volume overload
Elevated oxidized low-density lipoprotein
Secondary hyperparathyroidism
Endothelial cell dysfunction: excess ET-1 and diminished NO
LVH, impaired cardiac microcirculation, tendency to
arrhythmias.

Terasaki et al. High survival rates of kidney transplants from spousal and
unrelated donors. NEJM 1995; 333: 333-6.

Long-term Survival after AMI in Dialysis Patients

Category
Patients on hemodialysis
Dialysis + DM
Dialysis + Htn
Transplant recipients*
Renal Tx + DM

Overall mortality after AMI (%)

1-yr
2-yr
3-yr
4-yr
59
73
81
90
62
77
86
93
61
73
81
90
24
29

30
36

36
43

47
54

* Differences persisted after adjustment for age and other demographic

factors, cause of renal failure, duration of ESRD and coexisting illnesses.
Herzog et al. NEJM 1998; 339: 799-805.

13

Rejection Banff Schema (Am J Tx: 2008 8(4):753-60.)

Pancreas transplantation
Since the first performance of pancreatic transplantation (PTx) in
1966 the procedure has come of age. As of June 2003, the
International Pancreas Transplant Registry (www.iptr.umn.edu) had
recorded more than 19,600 PTx, out of which over 14,300 were
done in the USA. Most PTx are performed in patients with diabetic
nephropathy requiring kidney transplantation. These patients
already require chronic immunosuppression and a functioning
pancreas transplant provides the most efficacious method for
achieving a normal glucose and hemoglobin A1C. In this setting
there are two options:
SPK - simultaneous pancreas and kidney transplantation
where one deceased donor provides kidney and pancreas or
PAK - pancreas after a previously performed kidney
transplant (PAK), usually after a LDRT.

Borderline changes: Suspicious for acute cellular rejection. No

intimal arteritis is present, but there are foci of mild tubulitis (1
4 cells/tubular cross-section) and mild inflammation.
Acute/active cellular rejection
T-cell-mediated rejection graded by histopathological findings:
IA Cases with significant interstitial infiltration (>25% of
parenchyma affected) and foci of moderate tubulitis (>4
mononuclear cells/tubular cross section or group of 10 tubular cells)
IB Cases with significant interstitial infiltration (>25% of
parenchyma affected) and foci of severe tubulitis (>10 mononuclear
cells/tubular cross-section or group of 10 tubular cells)
IIA Cases with mild-to-moderate intimal arteritis (v1)
IIB Cases with severe intimal arteritis comprising >25% of the
luminal area (v2)
III Cases with transmural arteritis and/or arterial fibrinoid
change and necrosis of medial smooth muscle cells also with
lymphocytic inflammation (v3).

Less common is pancreas transplant alone (PTA), performed in a

patient without diabetic nephropathy, where the trades off of
achieving normoglycemia with the possible complications of
chronic immunosuppression have to be weighed closely. Each year
in the U.S., approximately 900 SPK and 500 solitary pancreas
transplants are performed (compared with 16,000 kidney Tx).

Chronic/sclerosing allograft nephropathy

Fibrosing changes in the allograft, with or without features of true
alloimmune injury to the graft. Histopathological findings
reveal IFTA interstitial fibrosis and tubular atrophy which is
graded mild, moderate and severe, usually with features of
glomerular injury or sclerosis.

Currently the whole organ obtained from a cadaver donor is used.

The organ is placed in the pelvis opposite to the kidney transplant
and receives its blood supply through the iliac vessels with the
exocrine secretions drained into the small intestine or the bladder.
A newer surgical innovation has been portal venous drainage of the
pancreas allograft. The traditional systemic venous drainage
achieves euglycemia at the expense of hyperinsulinemia. Portal
venous drainage replicates the physiological state and due to the
first pass effect achieves euglycemia with normal insulin levels.

Humoral rejection (B cell (Ab) mediated):

Allo-Ab may cause immune injury to the allograft kidney. The
diagnosis requires (1) renal transplant dysfunction, (2) presence
of circulating anti-donor Ab (donor specific Ab) and (3) C4d
detected by immunoperoxidase. Evidence of acute cellular with
occult humoral rejection is often identified with late AR
episodes.

14

Patient survival at one year for 1999-2003 US cadaveric pancreas

transplants was at least 94% in all categories (SPK 95%; PAK 94%;
PTA 98%). After SPK, pancreas graft survival rate at one year for
1996-2000 was 84.7%; kidney graft survival was 92%. For solitary
pancreas transplants, pancreas graft survival at one year was 78.5%
for PAK and 78.2% for PTA.

7. Ongoing substance abuse (drug or alcohol).

8. Major ongoing untreated psychiatric illness.
9. Recent history of medical noncompliance.
10. Inability to provide informed consent.
11. Any systemic illness that would severely limit life expectancy or
compromise recovery.
12. Significant, irreversible hepatic or pulmonary dysfunction.
13. Positive lymphocytotoxic cross-match.

Indications for pancreas transplantation

1. Presence of insulin-requiring diabetes mellitus*.
2. Ability to tolerate surgery and immunosuppression.
3. Adequate cardiopulmonary function.
4. Absence of organ system failure (other than kidney: creatinine
clearance < 30mL/min for SPK; for PAK > 40 mL/min.).
5. Emotional and psychosocial suitability.
6. Presence of 2 or more diabetic complications
Proliferative retinopathy
Nephropathy (hypertension, proteinuria, decreased GFR)
Peripheral or autonomic neuropathy
Microangiopathy
Accelerated atherosclerosis
Glucose hyperlability, hypoglycemia unawareness

Relative contraindications
1. Age less that 18 or greater than 50 years.
2. Recent retinal hemorrhage.
3. Symptomatic cerebrovascular or peripheral vascular disease.
4. Absence of appropriate social support network.
5. Extreme obesity (greater that 150% ideal body weight).
6. Active smoking.
7. Severe, untreatable peripheral vascular (aorto-iliac) disease.
Risk factors
1. History of myocardial infarction, congestive heart failure, or
previous open heart surgery;
2. History of major amputation or peripheral bypass graft;
3. History of cerebrovascular event or carotid endarterectomy;
4. History of hypercoagulable syndrome.

* As a general rule, most candidates have absolute insulin deficiency as

determined by an undetectable c-peptide, rather than a component of
insulin resistance (Type II DM).

Absolute contraindications
1. Insufficient cardiovascular reserve (coronary angiography with
uncorrectable or untreatable CAD, or recent MI).
2. Active infection.
3. History of malignancy treated within the past 3 years (excluding
nonmelanoma skin cancer).
4. Positive HIV serology.
5. Positive hepatitis B surface antigen serology.
6. Active, untreated peptic ulcer disease.

15

Scopolamine patch PRN

PCA for pain
Home beta blocker and statin meds

Care for the Pancreas Transplant Recipient

POST-OP Typical course through discharge
Immediate Postop Orders:
-Basic orders: NPO, IVF, SCD/TEDs, Foley, NGT, Clinical
Nutrition consult, OOB and ambulate > TID with help
starting POD 1, Physical therapy consult, case management,
may take meds with sips, clamp NGT for 1hr after meds

POD#2:
-Induction with Thymoglobulin (1-2mg/kg) dose.
Premedicate 30 -60 min before with solumedrol, Tylenol
650mg PR, and 50mg IV Benadryl. Run Thymo over 6 hrs.
-DC arterial line.

-Daily Labs: Chem 10, Amylase, Lipase, CBC w/Diff,

Tacrolimus level (if tacrolimus has been started)

POD#3:
-Flag to 4A/4AE if clinically appropriate

-Radiology: First thing in the AM patient should have an

abdominal US and put in the comment that it should be the
pancreas transplant protocol. Must call ultrasound first
thing in the AM to make sure patient is scheduled first.

POD#4:
-Induction with Thymoglobulin (see POD#2)
POD#5-7:
-DC home with services

-Medications:
Fluconazole 100mg IV 1XD
Bactrim SS PO 1XD
Valcyte 900mg PO 1XD (Adjust based on GFR)
Tacrolimus PO 2XD (dose to be determined)
Myfortic or Cellcept IV 2XD (Ask re: dose)
Steroid taper as follows:
POD 1 Methylprednisolone 70mg IV 2XD
POD 2 - Methylprednisolone 35mg IV 2XD
POD 3 - Methylprednisolone 17.5mg IV 2XD
POD 4 Prednisone PO 15mg 2XD
POD 5 - Prednisone PO 25mg 1XD
POD 6 - Prednisone PO 20mg 1XD
POD 7 - Prednisone PO 10mg 1XD

**Refer to the pancreas transplant manual on the Lifespan intranet

for a more detailed description of the procedure and protocols.

Aspirin 81mg PO
Heparin 5000 units SQ 3XD
Zofran PRN

16

GAME PLAN FOR HEMODIALYSIS ACCESS

Graft (6-mm PTFE or Bovine carotid artery) considered if

dialysis required in fewer than 6 weeks, no reasonable vein, or
patient with limited life expectancy. (NEJM 2009; 360:2191).

Renal replacement therapy

Hemodialysis (HD): Catheter, fistula or graft (PTFE)
Peritoneal dialysis (CAPD)
Renal transplantation (Cadaver or Live Donor)

OPTIONS:
Fistula: RCF, BCF below the antecubital fossa, BCF above
the elbow, TPBVF (transposed basilic vein fistula).
Graft: Forearm loop, upper arm, subclavian artery, femoral.
Catheter: highest likelihood of sepsis, clotting, inadequate
flow.

CAPD (developed in the 1970s) is available to individuals with the

direction and ability (physical and emotional) to perform dialysis at
home. Most patients prefer HD. Less than 10% opt for CAPD in RI

Evaluation for hemodialysis access includes:

Pulse Bilateral brachial artery and radial artery pulses
Suitable vein
Superficial cephalic or basilic
Deep basilic vein in upper arm

Uncommon (last resort) options:

Translumbar or transhepatic catheter
HERO: hybrid AVG-central catheter.
Work-up: CBC, Chem 7, EKG OR. Dialysis access is an
urgent surgery; only acute medical issues (CHF, hyperkalemia >
6.5, active angina, new arrhythmia, active bleeding, etc.) require
investigation or treatment prior to surgery.

Two questions must be answered before access surgery:

1. Is the patient medically stable for surgery?
No CHF, chest pain, K+ > 6.5, sepsis, etc.
2. What access operation should be done?
Wrist fistula, BCF, Basilic vein fistula (TPBVF), leg loop,
AV graft, PermCath or consider peritoneal dialysis.

Note:
Patients on routine dialysis should have a recent K+.
Patients with dialysis access problems (poor flow, incomplete
dialysis treatment prior to surgery); those with a history of high K+
or patients not yet on dialysis should have the K+ checked on the
day of surgery.

Access considerations
Prefer non-dominant arm in case of paresthesia or steal.
Ask the RN to place a red band on the arm indicating No IV
placement or blood draws.
Transposed basilic vein fistula if no superficial vein noted on
exam.
Ultrasound or venogram multiple prior access procedures or
evidence of central stenosis (arm swelling, collateral veins,
etc.).

Cardiac pacers: when possible document the type, make and

model of the pacer. This information is useful for re-programming
after surgery. Consider placing access on the opposite side of the
pacer as SCV stenosis is fairly common 2* to pacing wires.

17