Renal Replacement Therapies

1. Renal Replacement Therapies Dr Dana Ahmed Sharif

2. Median 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 2000-2007UK renal registry data, annual report 2011

3. 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

4. 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

5. Principles of dialysis Salt Water Electrolytes Acidosis Toxins

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

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

8. Haemodialysis access Tunnelled dialysis line A-V fistula

9. Haemodialysis 1- Diffusion: Diffusionof solutes between solutions across a semipermeable membrane down a concentration gradient

10. Principles of dialysis

11. Principles of dialysis • Determining factors: - Concentration gradient • Size + protein binding of molecule removed • Permeability + surface area of membrane

12. 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

13. 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

14. Haemofiltration

15. 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

16. Haemodialysis(HD) Haemofiltration(HF)

17. Haemodialysis(HD) Haemofiltration(HF)

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

19. Haemodialysis- complications • Access complications: - Thrombosis - Infection - Lack of access • Dialysis complication: - Reactions (hypersensitivity, inflammation) - Hypotension - Haemorrhage - Air embolism - Cardiac arrhythmias

20. Peritoneal Dialysis

21. CAPD: principles

22. Peritoneal dialysis • Partly relies on residual renal function • Home based • Ambulant • Flexible • Continuous / intermittent

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

24. Automated Peritoneal Dialysis • Night time exchanges only • Convenient for people in employment

25. Peritoneal dialysis • Advantages: - continuous, independence - home based, flexible • Disadvantages: - patient competence - peritonitis - membrane failure - ultrafiltration failure - catheter exit site infection - sclerosing peritonitis

26. Transplantation

27. Compatibility • Blood group • HLA – tissue type • Antibodies

28. 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

29. 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

30. 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

31. Anti- HLA Antibodies (sensitization) • Previous mismatched organ transplant • Mismatched paternal HLA antigen in Pregnancy • Blood transfusion

32. Donor type • Live donor - related - non related • Cadaveric donor - Heart beating ( brain death) - Non heart beating

33. Medication post transplant • Immunosuppressive drugs: - Calcineurin inhibitors (Ciclosporin, Tacrolimus) - Antiproliferative ( Mycofenolatemofetil MMF, azathioprine) - mTOR inhibitors (sirolimus, Everolimus) - Steroids

34. Complications • Infections - Bacterial - Fungal - Viral – EBV, CMV - atypical • Cancer - Skin - Lymphomas – PTLD ( post transplant lympho-proliferative disorder) - Solid tumours • Metabolic - Diabetes - Hypertension - Osteoporosis

35. 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