Renal Replacement Therapies

Renal Replacement TherapiesDr Dana Ahmed SharifMedian life expectancy on RRT by age group Median life expectancy on RRT by age groupincident patient starting RRT from 2000-2007 incident of diabetic patient starting RRT from 2000-2007

UK renal registry data, annual report 2011

When to start dialysis?1- 50 years old male with GFR 13, K 5.4, mild leg oedema otherwise well2- 55 years old female with GFR 12, K: 5.2 with nausea, itching and anorexia3- 48 years old female with GFR 9, K: 5.0 good urine output, BP 155/90mmHg4- 52 years old male with GFR 8, K: 5.0 with tiredness When to start dialysis?GFR < 15ml/min with uraemic symptomsGFR < 10ml/min whether symptomatic or notRefractory hyperkalaemia, acidosis, pulmonary oedema, pericarditis, encephalopathy and neuropathy ( all need urgent dialysis)There is no clear evidence that an early start to dialysis confers a survival benefit*Pre-emptive transplant is the treatment of choice of ESRF. Consider when GFR < 15ml/min

*RCT of Early versus late initiation of dialysis, N Engl J Med 2010; 363:609-619, August 12/ 2010Principles of dialysis Salt Water Electrolytes Acidosis Toxins Haemodialysis Largely hospital basedEfficient Requires access to circulation Limited by staff and space Haemodialysis Artificial membrane used for exchange

Extracorporeal circuit

Direct access to blood Haemodialysis accessTunnelled dialysis lineA-V fistula

Haemodialysis

1- Diffusion: Diffusion of solutes between solutions across a semipermeable membrane down a concentration gradientPrinciples of dialysis

Principles of dialysisDetermining factors: -Concentration gradientSize + protein binding of molecule removed Permeability + surface area of membrane

Haemodialysis

2- Ultrafiltration:

- Water can be driven through the membrane by hydrostatic force - By varying the trans-membrane pressure (TMP) the amount of water removed can be controlled Haemofiltration Convection - Flow of water + dissolved solutes (convection) down a pressure gradient caused by hydrostatic or osmotic forces - Rate of filtration depends on pressure gradient

Haemofiltration

Basic principlesHaemodialysisSolute removal by diffusion of substances between blood + dialysateFluid removed by filtration (driven by pressure gradient across membrane)

HaemofiltrationFluid removal by filtrationSolute removal by convection of substances in filtrate

Haemodialysis(HD) Haemofiltration(HF)

Haemodialysis(HD) Haemofiltration(HF)

Haemodiafiltration Combines both HD and HFSet for HD with high TMPBoth dialysate and fluid replacement required

Haemodialysis- complicationsAccess complications: - Thrombosis - Infection - Lack of access

Dialysis complication: - Reactions (hypersensitivity, inflammation) - Hypotension - Haemorrhage - Air embolism - Cardiac arrhythmias

Peritoneal Dialysis

CAPD: principles

Peritoneal dialysis Partly relies on residual renal function Home basedAmbulant Flexible Continuous / intermittent Peritoneal dialysis- CAPD4 x 2L exchanges a dayEach exchange takes ~ - 1 hour

Complications - Peritonitis - Loss of membrane function

Automated Peritoneal DialysisNight time exchanges only Convenient for people in employment

Peritoneal dialysis Advantages: - continuous, independence - home based, flexible

Disadvantages: - patient competence - peritonitis - membrane failure - ultrafiltration failure - catheter exit site infection - sclerosing peritonitis Transplantation Compatibility Blood group

HLA tissue type

Antibodies Blood group ABO antigens are expressed on endothelial cells in the kidneyNaturally occurring anti-blood group antibodies develop at 6 months of age , possibly in response to bacterial carbohydrate antigensThe same role apply for transplantation and blood transfusions (ie blood group O are universal donor and AB are universal recipient)ABO incompatible transplant are generally avoided Tissue typing Class I : HLA -A and BClass II: HLA DRSo HLA identical donors have 0,0,0 mismatch(MM)Whereas those pairs which share 1 HLA- A, 1 HLA B and 1 HLA DR have 1,1,1 MMBenefits of well matched graft Lower acute rejection rateBetter long term graft survival Fewer subsequent anti HLA antibodies Lower incidence of delayed graft function Anti- HLA Antibodies (sensitization) Previous mismatched organ transplant

Mismatched paternal HLA antigen in Pregnancy

Blood transfusion Donor type Live donor - related - non related

Cadaveric donor - Heart beating ( brain death) - Non heart beating Medication post transplant Immunosuppressive drugs:

- Calcineurin inhibitors (Ciclosporin, Tacrolimus) - Antiproliferative ( Mycofenolate mofetil MMF, azathioprine) - mTOR inhibitors (sirolimus, Everolimus) - Steroids Complications Infections - Bacterial - Fungal - Viral EBV, CMV - atypical

Cancer - Skin - Lymphomas PTLD ( post transplant lympho-proliferative disorder) - Solid tumours Metabolic - Diabetes - Hypertension - Osteoporosis Contraindication to renal transplant Absolute: 1- Active malignancy, a period of 2 years of complete remission recommended for most tumors 2- Active vasculitis or recent anti-GBM disease 3- Severe heart failure 4- Severe occlusive aorto-iliac vascular disease

Relative: 1- Age: not routinely offered to < 1 yr or >75 yrs 2- High risk of disease recurrence in the transplant kidney 3- Disease of the lower urinary tract such as bladder dysfunction 4- Significant comorbidity