Dialysis and Transplantation L15 Flashcards
What are the treatment options for stage 5 CKD?
- renal replacement therapy: dialysis
- transplantation
- palliative care*
*if patient is too frail/unwilling to go through with other treatments
What is dialysis?
an extracorporeal therapy where fluid and solutes are added or removed from patient’s blood. It works by separating the patient’s blood and dialysis fluid by a semi-permeable membrane.
How effective is dialysis?
no way near normal kidney function - only up to GFR of <15ml/min (normal > 90)
What kidney functions can dialysis replace?
- water homeostasis
- electrolyte homeostasis
- acid/base homeostasis
- excrete metabolic waste products
What kidney functions can dialysis not replace?
- hormone control - EPO, Vit D, renin
- can only regulate other functions up to an extent
What kidney functions can transplantation replace?
replaces all kidney functions!
What is ultrafiltration?
use of physical pressure gradient to move things across a semi-permeable membrane
How do solutes move between filtrate and blood in dialysis?
diffusion
What are the two types of dialysis?
- haemodialysis
- peritoneal dialysis
What is the semi-permeable membrane used in haemodialysis?
artificial membrane - a tube with lots of mini tubes inside it; fluid and blood move though tubes in opposite directions
Describe the semi-permeable membrane used in peritoneal dialysis.
Peritoneal membrane:
- full of capillaries
- substances diffuse between peritoneal cavity and capillary blood
- semi-permeable membrane consists of capillary endothelium, interstitial tissue and lining of peritoneum
- small diffusion distance
Describe the peritoneal dialysis procedure.
- insert catheter (tube) into peritoneal cavity
- dialysis fluid enters cavity (from solution bag)
- water + solutes diffuse between blood and fluid
- blood and fluid equilibrate
- drain fluid into drainage bag
- disconnect and replace solution bag
How is a water gradient from the blood into the dialysis fluid achieved?
dextrose (sugar) present in dialysis fluid but can’t pass across membrane
What are the two ways a patient may carry out peritoneal dialysis?
- continous dialysis- continuously hooked up (permanent peritoneal catheter) 2L solution bags changed 4x a day
- overnight dialysis - hooked to machine at night which pumps dialysis fluid in and out of cavity
Describe the haemodialysis procedure.
- insert central venous catheter into forearm*
- heparin injected into tubing to stop blood clotting
- blood enters dialysis filter
- blood moves in opposite direction to dialysis fluid, split by semi-permeable membrane
- waste products removed
- blood returns into body
- waste fluid disposed of
*surgery required beforehand to create AV fistula (connection between artery and vein)
Where is haemodialysis performed?
in hospital - requires machine
How often is haemodialysis done for a patient?
4 hours, 3x a week
why can’t acid be removed from patient’s blood by filtration (during dialysis) alone?
- H+ only present in low concentrations in serum
- most freely diffuses into tissues
- however can only access blood during dialysis
What can be done during dialysis for full acid homeostasis?
alkali (buffer) added to patient from dialysis fluid
- concentration of alkali greater in fluid than in plasma
- usually use bicarbonate (NaHCO3)
How do patients choose which type of dialysis to use?
dependent on circumstances/lifestyle factors
In what circumstances may it be better to use peritoneal dialysis?
- severe heart disease
- young patients with some remaining function (independence)
- older frail patients with carers (do not have to go into hospital)
When is peritoneal dialysis contra-indicated?
if patient has had previous major abdominal surgery
When are patients with CKD started on dialysis?
- when eGFR <10ml/min/1.73m2
- if their symptoms are not being managed through other techniques/treatments
- before patient becomes critically ill (before stage 5)
When are patients with AKI started on dialysis?
- when serum creatinine >500mcmol/L
- if patient is anuric (not producing urine)
- uraemia (build up of toxic waste in blood)*
- if symptoms are not being controlled (hyperkalaemia, metabolic acidosis, pulmonary oedema)
- emergency situations
*build up of toxins in blood can cause inflammation of membranes (pericardium) and collection of fluid > pericardium not stretchy > compression of heart (due to fluid in membrane) > heart cannot fill > decreased CO
what are some of the problems associated with dialysis?
- infection - microorganisms on skin enter body through catheter opening
- cardiac disease
- anaemia
- bone disease
- malnutrition
What are the advantages to having a kidney transplant?
- lifestyle benefits
- replaces ALL kidney functions
- long term costs are much lower than dialysis
- improved life expectancy (if can make it through the first year)
Where in the body is the donor kidney inserted?
- outside peritoneum
- iliac fossa
- connect up to iliac vessels
Are the original kidneys removed during transplant?
no they are left in situ
Who should be allowed to have a kidney transplant?
everyone with CKD stage 5 unless they have ABSOLUTE CONTRAINDICATIONS
What are absolute contraindications that would stop patients from getting a kidney transplant? (3)
- high peri-operative mortality (during surgery)
- poor life expectancy (no more than 3-5years)
- active malignancy
*age is not an absolute contraindication
What are some of the relative contraindications that must be considered before deciding to give a patient a kidney transplant?
- coronary or cerebrovascular disease
- recurrent disease
- non-compliance
Where are transplant kidneys sourced from?
cadaveric donor - people in RTAs etc.
- brainstem dead donors (brain dead but circulation still active)
- non-heart-beating donors (need to be opened within 30mins of death)
living donors (30-50% of transplants) -must ensure that assess donor very carefully to see if medically fit, don't pass on HIV/HBV, tissue compatible, no coercion etc.
Which three things need to be checked to make sure the donor kidney will not be rejected by the recipient?
- ABO blood group match
- Human Leukocyte Antigen (HLA) A, B and DR match
- no anti-donor antibodies in recipient
Which blood group is the universal donor?
group O
Which blood group is the universal recipient?
group AB
Describe the process of HLA matching.
- everyone has two of each type of HLA on their cells (one from mother, one from father)
- 59 variants of HLA-A
- 118 variants of HLA-B
- 124 variants of HLA-DR
- try to match all six HLAs between donor and recipient
- better matching = less chance of rejection
What is the PRA?
panel (percentage) reactive antibody
basically high PRA = high number of different antibodies against lots of different donor cells
What are anti-HLA antibodies?
antibodies that recognise HLA (and other antigens)
In what circumstances are patients more likely to have anti-HLA antibodies? (4)
- dialysis patients
- had blood transfusion
- previous pregnancy
- previous transplant
What is transplant cross-matching and how is it done?
testing for presence of antibodies that are specifically against donor cells. This is done just before operation.
- sample of recipient’s serum antibodies, donor leukocytes and complement factors
- if there is no reaction b/t donor cells and recipient antibodies = negative cross match which is GOOD
- if there is cell lysis/reaction = positive cross match which is BAD
What can be done for a patient who is incompatible with the donor kidney?
If patient has ABO/HLA mismatch or positive crossmatch, they may still be able to have transplant due to immunosuppressive techniques e.g. taking antibodies out of patient to make them suitable for transplant or procedures to make immune system take up kidney. Only done in emergency situations if there is no time to match kidney.
Describe antibody-mediated rejection of a donor kidney. (positive cross-match)
-A/B blood group antigens or HLA antigens on vascular endothelium of donor kidney
-kidney is re-perfused with recipient’s blood
-recipient’s blood contains preformed antibodies
-recipient’s antibodies attach onto donor antigens on cells
-complement activation
-membrane attack complex
-cell lysis and intravascular thrombosis
>dead, necrotic, thrombosed, clot-filled kidney
Describe cell-mediated rejection of a donor kidney. (negative cross-match)
- donor kidney transplanted containing donor antigen-presenting cells/dendritic cells and cellular debris
- kidney re-perfused with recipient’s blood
- APCs and cellular debris enter circulation and are transported to secondary lymphoid tissue
- donor APC presents cellular debris to recipient’s T cells
- T cell activation through CALCINEURIN and NFAT-1 pathway producing IL-2 (autocrine - acts on cell that releases it) > apical IL-2 receptor > TOR (enzyme) > stimulation of cell cycle
- CD4 T cell binds to self-APC > stimulates clonal expansion and cytokine production
- cytokines activate macrophages, B cells, CD8 Tcells
- rejection
How can we suppress T cell activation to stop an inflammatory response and rejection? (5)
- calcineurin inhibitors - Tacrolimus, ciclosporin A
- steroids (block IL-2 mRNA production)
- monoclonal Abs - basilimixab, daclizumab (blocks IL-2 receptors on T cell)
- TOR inhibitors - sirolimus (inhibit cell cycle)
- drugs that inhibit cell cycle directly - azathioprine, mycophenolate, mofetil
What are the complications of steroids used in immunosuppression?
- weight gain
- diabetes
- hypertension
- infection
- osteoporosis
- thin skin
What are the complications of ciclosporin/tacrolimus used in immunosuppression?
- infection
- hypertension
- diabetes
- nephrotoxicity
What are the complications of azathiprine/mycophenolate/mofetil used in immunosuppression?
- infection
- cancer
- bone marrow suppression
