Renal Replacement Therapy - Dialysis and Transplant Flashcards
What is end-stage renal disease - HCFA definition?
Irreversible damage to a person’s kidneys so severely affecting their ability to remove or adjust blood wastes that, to maintain life, he or she must have either dialysis or a kidney transplantation
What is uraemia?
The syndrome of advanced CSK
What are the symptoms of uraemia?
Until stage 4 or 5 CKD the patient may be asymptomatic
Uraemia can involve almost every organ system but the earliest and cardinal symptoms are malaise and fatigue
Other symptoms: Nausea Vomiting Anorexia Weight loss Muscle cramps Pruritis Visual disturbances Increased thirst Exacerbation of CVS conditions Mental status changes
What are the signs of uraemia?
Anaemia Acidaemia Electrolyte abnormalities Hypertension Fluid retention Muscle wasting Arrhythmias Exacerbation of CVS conditions Mental status changes
What is renal replacement therapy?
The means by which life is sustained in patients suffering from end-stage renal disease
This is usually indicated when eGFR is less than 10ml/min
What are the types of renal replacement therapy?
Haemodialysis
Peritoneal dialysis - continuous ambulatory peritoneal dialysis (CAPD, or intermittent peritoneal dialysis (IPD)
Renal transplant
What is dialysis?
A process whereby the solute composition of a solution, A, is altered by exposing solution A to a second solution, solution B, through a semi-permeable membrane
What are the main principles of dialysis?
Diffusion
Ultrafiltration - pressure gradient across the membrane is increased
What does an increase in transmembranous pressure allow?
Allows water to be pushed across the membrane and therefore allows removal of excess water
What are the pre-requisites for dialysis?
Semi-permeable membrane - artificial kidney in HD or peritoneal membrane
Adequate blood exposure to the membrane - extracorporeal blood in HD, mesenteric circulation in PD
Anticoagulation for HD
Dialysis access - vascular in HD, or peritoneal in PD
What are the access options for haemodialysis?
Arteriovenous vistula - anastomosis of artery and vein, usually the end of vein to the side of artery
This short-circuits arterial blood into the vein to increase the size and thickness of the vein wall after around 6 weeks
Arteriovenous prosthetic graft
Tunnelled venous catheter - subcutaneous so cannula doesn’t come straight out of the neck, removed via subcutaneous tunnel
Temporary venous catheter
What are the complications of haemodialysis?
Clotting of vascular access Hypotension and cramps Cardiovascular problems Heparin-related problems Allergic reactions to dialysers and tubing Catastrophic dialysis accidents (rare)
What are the restrictions for dialysis patients?
Fluid restriction - dictated by urine output, interdialytic weight gain
Dietary restriction - sodium, potassium and phosphate
How is peritoneal dialysis done?
Balanced dialysis solution is instilled into the peritoneal cavity via a tunnelled, cuffed catheter using the peritoneal mesothelium as a dialysis membrane
After a dwell time, the fluid is drained out and fresh dialysate is instilled
How often is continuous ambulatory peritoneal dialysis done?
4 exchanges a day
When is automated peritoneal dialysis done?
Cycles done at night while patient is asleep
What is the main advantage and disadvantage of peritoneal dialysis?
Advantage of being done at home
Disadvantage of large infection risk
What does the dialysate used for PR contain?
A balanced concentration of electrolytes
What is the most common osmotic agents used for ultrafiltration of fluid?
Glucose
What are dwell times adjusted according to?
Transport characteristics - peritoneal transport characteristics can vary from high transporter to low transporter
What are the complications of peritoneal dialysis?
Peritonitis Exit site infection Ultrafiltration failure Encapsulating peritoneal sclerosis Tunnel infection Abdominal wall hernia
What are the types of peritonitis seen due to PD?
Gram positive - skin contaminant
Gram negative - bowel origin
Mixed - suspect complicated peritonitis e.g. due to perforation
What are the indications for commencing dialysis in end-stage renal disease?
Advanced uraemia, usually GFR < 5-10ml/min
Severe acidosis, bicarbonate < 10 mmol/l
Hyperkalaemia, K > 6 mmol/l
Fluid and salt retention not controlled with diuretics
What is the recommended protein dietary intake for a dialysis patient?
1.2-1.4 g/kg/24 hours
What is the recommended calorie dietary intake for a dialysis patient?
35-40 kcal/kg/24 hours
What vitamins are supplemented in dialysis patients?
Water soluble vitamins
How is phosphate controlled in dialysis patients?
Dietary phosphate restricted
Use of phosphate binders
What is the fluid restriction in dialysis patients?
Haemodialysis patients usually restricted to 500-800 ml/24 hours
Intake allowed = urine output + insensible loss
Peritoneal dialysis usually more liberal intake as continuous ultrafiltration is often achieved
What drugs are usually prescribed for dialysis patients?
Erythropoietin injections Either alpha vitamin D or calcitriol Phosphate binders with meals Iron supplements Water soluble vitamins Possibly antihypertensives Possibly lipid-lowering drugs
What are the factors that determine the choice of dialysis modality?
Patient-related Cost Remuneration Perceptions of effectiveness Patient choice
What are the limitations of dialysis?
Not a complete substitute for the kidneys but only means of keeping patients with end-stage renal disease alive
How is renal transplantation carried out?
Transplanted kidney is placed into iliac fossa and anastomosed to the iliac vessels
Native kidneys usually remain in situ
What are the indications for native nephrectomy?
Size e.g. polycystic kidneys
Infection e.g. chronic pyelonephritis
When are deceased donors used for renal transplantation?
Donation after brain death or after cardiac death (according to criteria)
What living donors can be used for renal transplantation?
Living related donor
Living unrelated donor - spousal, altruistic, Paired/pooled
ABO incompatible/HLA incompatible
What are the brain death criteria which must be met for a patient to be allowed to donate their kidneys?
Coma, unresponsive to stimuli
Apnoea off ventilator despite build up of CO2
Absence of cephalic reflexes e.g. pupillary, oculocephalic, oculovestibular, corneal, gage, purely spinal reflexes may still be present
Body temperature above 34 degrees Celsius
Absence of drug intoxication - ethanol, anaesthetic agents or paralysing drugs
When are extended criteria used for deceased donor kidneys?
Donor aged > 60
Donor aged > 50 with history of hypertension or stroke as cause of death
What are the features of donation using living unrelated kidney donor?
Usually poorly matched
Heavier immunosuppression
Higher rate of sensitisation if it fails
High degree of donor/recipient satisfaction
What are the outcomes of kidney donation?
Life span of donors is similar to general population
No increase in ESRD risk, rates of ESRD reduced
Good quality of life
Uninephrectomy leads to compensatory increase in GFR of remaining kidney to 70% of pre-donation values
Compensatory increase is greater in younger donors
What are the complications of renal transplantation?
Rejection - cell mediated, humeral (Ab mediated)
Cardiovascular - underlying renal disease, CRF, hypertension, hyperlipidaemia, PT diabetes
Infective - bacterial, viral, fungal
Malignancy - skin, lymphoma, solid cancers
What are the types of acute rejection following renal transplantation?
Hyperacute rejection - pre-existing alloreactivity to donor
Acute T cell-mediated rejection
Acute antibody mediated rejection
What are the features of type I acute rejection?
Lymphocyte infiltrate
Tubilitis
What are the features of type II acute rejection?
Endarteritis
Endothelialitis
What are the features of humeral rejection?
Neutrophil infiltration - glomeruli, peritubular capillaries
Endothelial swelling
Positive C4d - peritubular capillaries
What immunosuppression can be used in renal transplantation?
Non-specific e.g. prednisolone, azathioprine
T-cell activation specific e.g. cyclosporine, tacrolimus, MMF
mTOR inhibitors e.g. rapamycin
Anti-IL2 receptor antibodies
T-cell antibodies e.g. ATG, OKT3
What is the side effect of sicrolimus (rapamycin)?
Hyperlipidaemia
What are the side effects of CNIs?
Hyperglycaemia
Hypertension
Chronic kidney disease
What is the side effect of lymphoid depletion?
Malignancy
What is the side effect of glucocorticoids and anti-metabolites e.g. MMF, AZA?
Infections
Why is cytomegalovirus important in renal transplantation?
Major problem following transplant
Most common opportunistic infection after transplant
Incidence of clinically apparent CMV disease between 20% and 80%
What are the complications of cytomegalovirus infection?
High mortality if untreated - up to 90% CMV syndrome Gastroenteritis Nephritis Hepatitis Pneumonitis Retinitis
What does BK virus cause?
Nephropathy in renal transplant recipients
Haemorrhagic cystitis in AIDs patients and in those who have undergone bone marrow transplantation
What does JC virus cause?
Associated with progressive multifocal leukoencephalopathy
How do human polyoma viruses infect cells?
Viral particles bind to specific cell surface receptors on a permissive cell - T antigens early in the infection cycle
These bind intracellular proteins to promote viral replication and block tumour suppressor proteins
What are the clinical manifestations of BK virus infection?
Renal transplantation
- ureteral stenosis
- interstitial nephritis
- end stage renal failure
Bone marrow transplantation
- haemorrhage cystitis
- pneumonitis
- hepatitis
AIDS
- nephritis
- end stage renal failure
- retinitis
- meningoencephalitis
- pneumonitis
What are the risk factors for BK virus Allograft Nephropathy ?
Intensity of immunosuppression - tacrolimus, mycophenolate mofetil, antilymphocyte globulins
Patient determinants
- older age
- male
- white ethnicity
- DM
- negative BKV serostatus
Organ determinants
- graft injury
- HLA mismatches
- ureteral stents
Viral determinants
- changes in epitopes of viral capsid protein VP-1
What is the outcome of BKAN?
Allograft dysfunction, loss of graft in 45-80%
What is the treatment of BKAN?
Modification of immunosuppression
Antiviral therapy - cidofovir +/- probenecid, leflunomide
What is the relative risk of colon, lung or breast cancer after renal transplantation?
2%
What is the relative risk of testicular or bladder cancer after renal transplantation?
3%
What is the relative risk of melanoma, leukaemia or cervical cancer after transplantation?
5%
What is the relative risk of renal malignancy after transplantation?
15%
What is the relative risk of non-melanoma skin cancer, Kaposi sarcoma or non-Hodgkin lymphoma after transplantation?
20%
