IN THE NAME OF GOD Renal Replacement Therapy Dr. M Mahdavi-Mazdeh

1. IN THE NAME OF GOD Renal Replacement Therapy Dr. M Mahdavi-Mazdeh Associate professor of Nephrology (TUMS)

2. Renal Function& Approach Level 1. Healthy Kidney : Preventive Programs Level 2. Chronic Kidney Disease (CKD) Management Level 3. End – Stage Renal Disease (ESRD) Level 4. RRT Hemodialysis & PD & Renal Tx

3. ESRD in Iran 12% In 5 Years, the Number of ESRD Patients Will Be Doubled.

4. 3% 3% 9% DM 43% 18% HT Other 28% GN PCKD IN Causes of ESRD

5. Causes of ESRD in the last 10 years in Iran

6. Modalities of renal replacement therapy Interchangeable, depends on residual renal function Ramesh Khanna & Karl D. Nolph

7. ESRD Status in IRAN 1380-1385

8. Kidney Failure, and Diabetes; Number of patients and costs; USA 2002 Numbers Costs 19% 5.8% 25.1% 41.3% 1.1% 7.8% Dialysis/Tx Total Medicare Diabetes Collins AJ; USRDS database

10. Ultrafiltration: The process by which plasma water is removed due to a pressure gradient between the blood and dialysate compartments Diffusion: solute exchange separated by a semipermiable membrane. Molecules move from a region of higher solute concentration to a region of lower solute concentrations

11. to waste Dialysate Out Blood In (from patient) Dialysate In Blood Out (to patient) HIGH CONC LOW CONC Hemodialysis

13. Jd = D . A . T ( dc / dx ) D = Diffusivity Coefficient T = Temperature A = Surface Area dc = Concentration gradient dx = Diffusion distance

14. Solute Clearance Depends upon : • Concentration gradient • Blood flow rate • Dialysate flow rate • Properties of dialysis membrane • Size and physicochemical properties of solutes

15. Solute Clearance

17. Installation of water pre-treatment and RO system Reverse osmosis with mechanical Filter Mechanical Filter Carbon filter Water meter Sand filter Softener Salt tank

18. Dialysis Solution Biff F. Palmer

19. The main function of the dialysate, is to remove waste material from the blood and to keep useful material from leaving the blood. Electrolytes and water are some materials included in the dialysate so that their level in the blood can be controlled

20. Organ Reservoirs of urea

21. Each patient Has his own Membrane for PD

22. Principles of peritoneal dialysis

27. Model of transport - 3 sorts of pores Ramesh Khanna & Karl D. Nolph

28. Urea concentration in dialysate, rate of equalization of solute concentration depends on molecular size of solute

30. Relative contraindications of PD • diverticulosis • colostomy • blindness • pleuro-peritoneal leakage • hernias • significant loin pain • big polycystic kidneys • severe deformant arthritis • psychosis • significant decrease of lung functions

31. Transplantation HLA Ags

32. Benefits Of Successful Renal Transplantation • Optimal treatment for most patients with End Stage Renal Disease • Improved quality of life • Reduced medical expenses • Survival advantage

33. Sources of Donor Kidneys • Living Donors • - Related • - Genetically Unrelated • Deceased Donors

34. Who is the Best Kidney Donor? • Monozygotic Twin • HLA identical Sibling • One-haplotype Living Donor • Other Living Donor • Deceased Donor

35. Inheritance of HLA–antigenes

36. Human Leukocyte Antigen (HLA) also referred to as Major Histocompatibility Complex (MHC) plays a role in intercellular recognition and discrimination between self and non-self.

37. Goals of Post-transplant Management • Prevention of graft loss due to rejection • Prevention of “death with a functioning graft” - Early detection & appropriate management of complications - Minimizing side effects of immunosuppressive medications

38. There are three classes of MHC molecules. • Class I- encodes glycoproteins expressed on the surface of nearly all nucleated cell; the major function of the class I gene is presentation of peptide antigens to cytotoxic T-cells • Class II- encodes glycoproteins expressed primarily on antigen-presenting cells, examples: macrophages, dendritic cells and B-cells, where they are present processed antigenic peptides to T helper cells. • Class III- encodes various secreted proteins that have immune function including components of the complement system; C2,C4, Factor B, &TNF, and molecules involved in inflammation.

39. Late Causes of Late Allograft Loss Pascual M, et al NEJM 2001; 346: 580-590

40. HLA In Transplantation • There are two characteristics of the HLA genes that make them special for organ transplantation: • high degree of polymorphism • strong immune reactions that their products can produce in other individuals.

41. Biological functions of Class I and Class II molecules • Class I • Present peptides derived from endogenously synthesized proteins • Responding T cells express CD8+ • Complex interactions with NK cells http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/HLA.html#cd8

42. Biological functions of Class I and Class II molecules • Class II • Present peptides derived from exogenously synthesized proteins • Responding T cells express CD4+ http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/H/HLA.html#class_II

43. Risks of Immunosuppression • Immunodeficiency state - Infections - Post-transplantation lymphoproliferative disease • Non-immune drug toxicity - Hypertension - Diabetes mellitus - Hyperlipidemia - Bone marrow depression - Nephrotoxicity

44. Modalities of renal replacement therapy Ramesh Khanna & Karl D. Nolph

45. One thing I can't recycle is wasted time