Kidney transplantation

CKD Stage 5

End stage

Requires RRT (renal replacemetn therapy)

Common indicators of end stage

>35 years

diabetic nephropathy

hypertension

less common indicators

glomerulonephritis

pyelonephritis

congenital abnormailites

renal vascular disease

Transplantation

Not a cure

form of RRT

aim is to keep people from needing dialysis, ideally transplant pre-emptively

Considerations in transplant

Surgical complexity/anatomical deviation

co -morbidities

Examples of surgical complexity

Blood vessel health, bladder health , BMI, Age, frailty, CVD, surgery, HIV/HEP C, history of malignancy, diabtes

what are the two main types of kidney donation

Deceased donor

Live donor

2 types of deased donor

DBD - donated after brain stem death - controlled

DCD - donated after circulatory death - out of hospital - poorer quality - longer to function post surgery

Live donor donation

Directed donation - frined/relative - paired donation

Alturistic donatio - to anyone

How do we increase the donor pool

opt out scheme

marginal donor

paired pooled exchange

desensitisation

exclusion criteria for opt out

<18 yrs

Lived in england <12m

lack capacity to understand

What is a marginal donor

Not considered ideal

may have another condition like hepC

but you can treat it

Tier A national allocation

Pts with matchability score <10 or 100% cRF or had >7 yrs

Tier B allocation scheme

all other pts

Prioritised by point score

What are the factors in the point score

donor/recipient risk index match

waiting time

HLA match and age

location

matchability

total mismatch

blood groups

Matching

Match via HLA, human leukocyte antigens

A, B, DR

mismatch

mismatch of an antigen will cause a reaction therefore numerically scored

which HLA is most inolved in rejection rxn

DR

Medications started

analgesia, gastroprotection, VTE prophylaxis, antiplatelet, laxatives, statin, anti-virals, anti-microbials, surgical abx, electrolyte replacement, immuno suppressant

Medications stopped

all non essential

antihypertensives (not BB - rebound tachycardia)

phospahte binders

alfacalcidol

erthropietin

allopurinol

quinine

What drugs would you continue

diabetes, thyroid, gastroprotection if taken on admission, cholesterol lowering agents (long term prevention)

3 steps of immunosupression

1. Induction - used when kidney is transplanted to prevent rejection

2. Maintenance

3. Treatment of rejection

Why don’t you want to immunosupress

cause cancer and infection

Drug targets

calcinerium, CD25, Sirolimus/erolimus, MPA, anti-CD25, azathiopine

Tc rec. foreign cells we dont want and IS agents wipe out Tc

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

Induction agents

Basiliximab

Alemetuzumab

Basiliximab

IL2 inhibitor

Monoclonal ab

binds to and inhibts interleukin 2 R on surface of T lymphocytes

small risk of hyoersensitivity

Alemetuzumab

used for highly sensitive recpients

more potent inhibitor

increased cancer and infection risk

Maintenance agents

steroids

calcinerium inhibitors

antiproliferative agent

Who would you avoid using steroids

Younger patients

diabetics

serious mental health

how does prednisolone work

prevents production of interleukins 1+6 by macrophages

inhibits all stages of Tc activation

Side effects of steroid

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

Steroid dosing

Start higher (30mg) and reduce down (5mg)

8 weeks

avoid long term high doses

best taken with food in the morning

CNIs

Tacrolimus - better tolerated

ciclosporin

How do CNIs work

inhibit calcinerium activity = prevents Tc proliferation

risk of chronic alllograft nephropathy

two divided doses

Tacrolimus dosing

given on empty stomach

Ciclosporin dosing

oral solution

diluted before taken

How is CNIs dosing determined

Done on blood tests

trough levels very important

adjust based on risks of patient

What are CNIs major disadvantage

Lots of reactions

CYP450 enzyme interaction

polymorphism

Antiproliferative agents

mycophenolate mofetil

Azathioprine

Sirolimus

Mycophenolate moefetil

impair T and Bcell proliferation

GI toxicity = take with food or plit dose throughout the day

prodrug makes little difference

Azathioprine

decreases production of lymphocytes

caution with viral infections and CV19

Sirolimus

can delay wound healing!

should you ever omit immunosuprressants

NEVER with transplantation as it can cause permenant rejection but anti-prolif have the biggest room to hold