Renal Replacement Therapies Dr Dana Ahmed Sharif

Median life expectancy on RRT by age group Median life expectancy on RRT by age group incident 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 well 2- 55 years old female with GFR 12, K: 5.2 with nausea, itching and anorexia 3- 48 years old female with GFR 9, K: 5.0 good urine output, BP 155/90mmHg 4- 52 years old male with GFR 8, K: 5.0 with tiredness

When to start dialysis? GFR < 15ml/min with uraemic symptoms GFR < 10ml/min whether symptomatic or not Refractory 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/ 2010

Principles of dialysis Salt Water Electrolytes Acidosis Toxins

Haemodialysis Largely hospital based Efficient Requires access to circulation Limited by staff and space

Haemodialysis Artificial membrane used for exchange Extracorporeal circuit Direct access to blood

Haemodialysis access Tunnelled dialysis line A-V fistula

Haemodialysis 1- Diffusion: Diffusion of solutes between solutions across a semipermeable membrane down a concentration gradient

Principles of dialysis

Principles of dialysis Determining factors: - Concentration gradient Size + 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 principles Haemodialysis Solute removal by diffusion of substances between blood + dialysate Fluid removed by filtration (driven by pressure gradient across membrane) Haemofiltration Fluid removal by filtration Solute removal by convection of substances in filtrate

Haemodialysis(HD) Haemofiltration(HF)

Haemodialysis(HD) Haemofiltration(HF)

Haemodiafiltration Combines both HD and HF Set for HD with high TMP Both dialysate and fluid replacement required

Haemodialysis- complications Access 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 based Ambulant Flexible Continuous / intermittent

Peritoneal dialysis- CAPD 4 x 2L exchanges a day Each exchange takes ~ ½ - 1 hour Complications - Peritonitis - Loss of membrane function

Automated Peritoneal Dialysis Night 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 kidney Naturally occurring anti-blood group antibodies develop at 6 months of age , possibly in response to bacterial carbohydrate antigens The 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 –B Class II: HLA –DR So 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 MM

Benefits of well matched graft Lower acute rejection rate Better 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