Kidney Transplantation

What does CKD stage 5/end stage require

RRT, renal replacement therapy

Common indicators

>35yrs, diabetic nephropathy, hypertension

Less common indicators

Glomerulonephritis, pyelonephritis, congenital abnormalities, renal vascular disease

Considerations

Surgical complexity/anatomical deviation - bv/bladder health

Co-morbidities

2 types of kidney donation

Decreased donor kidney

Live donor kidney

Decreased donor kidney types

DBD, donated after brain stem death - controlled death

DCD, donated after circulatory death - out of hospital- poorer quality = longer post surgery

Live donor kidney types

Directed donation - friend/relative - paired donation

Altruistic donation - donation to anyone

How has th donor pool increased

Optout scheme - exclusion <18, lived in E <12m, lack capacity

Marginal donor - not considered ideal as may have another condition like Hep C but you can still treat it

Paired/pooled exchange

Desensitisation

National allocation scheme

Tier A + B

Tier A

Patients with match ability score = >10 or 100% cRF or >7yrs

Tier B

All other patients prioritised by point score

Factors in points score

Donor/Recipient risk match

waiting time

HLA match and age

Location

match ability

total

blood groups

MIsmatch

Mismatch of antigen wil cause a rxn

numerical score

match = 0

Rejection = 2 mismatch es

HLA

Human leukocyte antigen

A, B, DR DR

DR HLA

Most involved in rejection rxn

Medications started

Analgesia

Gastroprotection

VTE prophylaxis

Anti-platelets

Laxatives - surgery

Statin

Antivirals

Antimicrobials 3/12

Surgical Abx prophylaxis

Electrolyte replacement

Immunosuppressants

Medications stopped

All non essential

Antihypertensives - except BB

Phosphate binders

Alfacalcidol - unless parathyroidectomy

Erythropoietin Allopurinol

Quinine

Why cant BB be stopped

Rebound tachycardia if stopped abruptly

Medications continued

Essential therapy - diabetes, thyroid, gastroprotection, cholesterol lowering agents (long term)

3 elements o Immunosuppression

Induction agents

Maintenance immunosuppression

Treatment of rejection

Why are induction agents used

Prevent rejection

Types of induction agents

Basiliximab

Alemtuzumab

Basiliximab MOA

IL2 inhibitor

Monoclonal antibody

bind to and inhibit interleukin 2 receptor or surface of T lymphocytes

How should basiliximab be administered

First 20mg dose should be given within 2 hours prior to transplant surgery

second dose 4 days later

Why dont you want to over immune suppress

Cancer and infections

Drug target

Calcinerium, CD25, Sirolimus/everolimus, MPA, Anti-CD52, Azathioprine

What do Tc do

Recognise foreign bodies

What do IS agents wipe out

Tc

What is the aim of the drug targets

Aim to knock out a bit of each but not fully squash

Steroids squash all cells !!!

Maintenance agents

Steroids

Calcineurin inhibitors - C/T

Antiproliferative agent - MMF/Azathioprine

Who should steroids not be used in

Avoid in younger as it stops growth

Avoid in DM and serious mental healh

Steroids - how does prednisolone work

Prevents production of interleukins 1+6 by macrophages

inhibits all stages of Tc Activation

Side effects of steroids

moon face, osteoporosis, salt and water retention, diabetes, weight gain, behavioural disturbances, chicken pox exposure P

Prednisolone dosing

Start high and ween down

30mg - 5mg in 8weeks

Avoid long term high doses

best taken with food in the morning

Calcineurin inhibitors

inhibits calcineurin, a calcium-dependent enzyme crucial for activating T-cells.

Tacrolimus

Ciclosporin

What is a risk of taking CNIs

Chronic allograft nephropathy - poison the kidney

take 2 divided doses

Tacrolimus dosing

given on an empty stomach

achieve maximum absorption

Tacrolimus side effects

Alopecia, tremor, glucose intolerance, ginival hyperplasia, hyperlipademia, hypertension, nausea/diarrohea, hyperkalaemia, nurotoxicity

Ciclosporin

Oral solution diluted before taking

Ciclosporin Side effects

Hirsutism, tremor, glucose intol, ginival hyperplasia, hypertension, hyperlipademia, N/V, hyperkalaemia

How is dosing decided for CNIs

Done on blood tests

Adjust based on risks to patient

tremors - aim for 8-10 ug/L

Tacrolimus targetr range

With co-presc of MMF/AZ - -8

Without co presc - 8-10 months 1-3 and then 5-10

Target range for ciclosporin

Months 1-6 - 150-300

Beyond 6 motnhs - 75-150

What are CNIS prone to

drug interactions

CYP450 enzyme interaction - polymorphism - timing is important for trough levels

Antiproliferative agent MOA

Stop proliferation of cells

Mycophenolate

Mycophenolate mofetil MOA

T and Bc proliferation

GI toxicity - take with food or split D throughout the day

Leukopenia, thrombocytopenia, anaemia v common

Taking prodrug has little differences

Mycophenolate sodium/acid

Pro drug of MMF

enteric coated

reduce gastric side effects?

720 = 1g MMF

Azathioprine MOA

Decrease production of lymphocytes

Caution with CV19/viral infectionsS - stop in active cv19

Az side effects

Leucopenia, thrombocytopenia, cholestasis, alopecia

Should you ever ommit immunosuppressants with a transplant

NEVER as it ca cause permenant rejection

anti-proliferative drugs have highest room to hold

Sirolimus MOA

Non calceniurim inhibiting immunosupressant

Inihibit Tc activatio by blocking intracellular signal transduction

Sirolimus side effect

Delays wound healing - dont use post op

SE - hyperlipademia, hypertriglyceridaemia, leucopenia, anaemia and joint pain

Steroid minimising

Increase tacrolimus and MMF

High immunological risk

Increase tacrolimus and MMF

Delayed graft funstion

Decrease tacrolimus and zathioprine

What do different doasages have

Diffeent regimens

Chronic allograft nephropathy Management

Decrease tacrolimus

Alternative agents given post-transplant

Aspirin 75mg - decreased risk of renal vein thrombosis - 1/12 post transplant

PJP prophylaxis - infection risk highest in first 3/12 - co-trimoxazole

CMV prophylaxis - valganciclovir - 3/12

Atorvastatin - CKD increased risk

GI protection - aspirin and steroid (interxn) with tacrolimus but monitor)

TB prophylaxis - iosniazid/pyridoxine 6/13

Hep B prophylaxis - lamivudine - 6/12

Tacrolimus/ciclosporing interactions

Increased by macrolide antibiotic, antifungals, grapefruit juice/pomegranate juice

Decreased by rifampicin, orlistat, st johns wart A

Azathioprine interactions

Allopurinol/feboxustat increases

AVOID

Nephrotoxic meds

Live vaccines T

Treatment for rejection

Methylprednisolone 3 days/500mg IV

ATG (2nd line) - can also be used for induction but cant be used twice - polyclonal antibody - t lymphocyte depletion - anaphylaxis and cytokine rel syndrome so monitor

What happens in rejection

Infiltration of immune cells and it swells and bursts

Nil by mouth patient - steroids

5mg Prednisolone = 20mg Hydrocortisone parentral

Decreased t ½ = splt dose

NBM tacrolymis

give 1/5 of dose as continuous IV infusion

Cant monitor IV trough levels of immunosupression

how do you check for posioning?

use sublingual

Ciclosporin NBM

2/5 or 1/3 oral D as IV

Mycophenolate NBM

licensed liquid

PO:IV

1:1

Mycophenolate sodium

MMF

liquid /IV

Azathioprine

PO:IV

1:1

Generic V Branded

Tacrolimus - brand specific

ciclosporin - brand specific

MMF - can switch

Mycophenolic acid - can switch but not interchangeable with MMF

Az/prednisolone - not brand specific

TWO yellow cards

Regular meds card

prednisolone reducing D card

Patient info

after 3months all meds except IS prescribed by GP (IS by home deliveries)

Transplant Rx not exempt from prescription charge

Travel advice - time zones - must be taken same time

Staying well

Vaccinations - avoid live ones

Avoid nephrotoxic meds

control bp/healthy lifestyle

drug interactions - herbal

avoid food, increase risk of food poisoning

Consider lifestyle

Family planning - cytotoxic drugs

Role of specialist pharmacist

Support to in patient ward

support dialysis units and out patients

Non medical prescription

financial info and horizon scanning

Support for policies and guidelines