1. MOHAMMED ALSUNAID, MD Section Head, Nephrology Department of Medicine King Faisal Specialist Hospital & Research Centre Riyadh, Saudi Arabia

2. Clinical Scenario Mr Ahmed is 43 years old CKD stage 4 due to FSGS eGFR 18 mL/min He was educated for preservation of vascular access sites Renal replacement therapy options were discussed He chose Hemodialysis (HD)

3. Several years later, he came to the clinic with eGFR 9 mL/min Types of Chronic HD vascular access: A. Native arteriovenous fistulas (AVF), RC AVF B. Grafts (AVG) C. Double-lumen tunneled cuffed catheters Clinical Scenario

4. AVF vs AVG 46.4 20.6 0 10 20 30 40 50 AVF N=139 AVG N=78 P=0.001 Prospective study pre-operative vascular mapping Allon, M, et al KI 2001; 60:2013-2020 Primary Failure Rate %

5. AVF vs AVG 0 10 20 30 40 50 60 70 80 90 AVF N=108 AVG N=52 58 74 69 83 Prospective observational study RC AVF Primary Patency Rate % Silva, Jr, et al J Vasc Surg 1998;27:302-308 12 months 24 months

6. AVF vs AVG Primary Survival Rate % at 2 years 66 52 0 10 20 30 40 50 60 70 AVF N=139 AVG N=78 P=0.005 Prospective study pre-operative vascular mapping Allon, M, et al KI 2001; 60:2013-2020

7. AVF vs AVG P<0.001 0.57 1.67 0 0.5 1 1.5 2 AVF N=139 AVG N=78 Prospective study Total Access Interventions/year Pre-operative vascular mapping Allon, M, et al KI 2001; 60:2013-2020 Access intervention: thrombectomy, angioplasty or surgical revision

8. AVF vs AVG 0 11.5 0 2 4 6 8 10 12 AVF N=108 AVG N=52 Infection Rate % Prospective observational study Mean FU 15.2 months Silva, Jr, et al J Vasc Surg 1998;27:302-308

9. Type of Vascular Access and Mortality 28 38 40 0 5 10 15 20 25 30 35 40 AVF N=1340 AVG N=3129 CVC N=875 2 Years Mortality % Observational study USRDS DMMS Wave 1 Prevalent diabetic pts Dhingra, RK, et al KI 2001; 60:1443-1451 Adjusted RR AVF vs AVG 1.41 (95%CI, 1.13 to 1.77) P<0.003 Adjusted RR AVF vs CVC 1.54 (95%CI, 1.17 to 2.02) P<0.002

10. Type of Vascular Access and Mortality Annual Mortality Rate% 11.7 14.2 16.1 0 2 4 6 8 10 12 14 16 18 20 AVF N=185 AVG N=296 CVC N=603 Adjusted RH AVF vs CVC 1.5 (95%CI, 1 to 2.2) Adjusted RH AVF vs AVG 1.2 (95%CI, 0.8 to 1.8) Analysis from CHOICE Study Incident HD pts Astro, BC, et al JASN 2005;16:1449-1455

11. AVF vs AVG HigherLowerComplication Rate LowerHigherPatency Rate ShorterLongerTime to Use LowerHigherPrimary Failure Rate AVGAVF

12. Clinical Scenario He was referred to vascular surgeon Vascular surgeon referred him to radiologist for left upper extremity vascular mapping by duplex ultrasound

13. Is pre-operative vascular mapping by duplex US should be performed in all patients before vascular access creation? 1.Yes 2.No

14. Pre-operative Vascular Mapping 14 62 24 63 30 7 0 10 20 30 40 50 60 70 Clinical Examination N=183 Doppler US N=172 AVF AVG CVC AVF AVG CVC Doppler US 9/1994-1/1997Clinical Exam 6/1992-8/1994 P<0.05 Creation Rate % Silva, Jr, et al J Vasc Surg 1998;27:302-307

15. Pre-operative Vascular Mapping 40 8.3 0 5 10 15 20 25 30 35 40 Clinical Examination N=25 Doppler US N=108 Clinical Exam 6/1992 – 8/1994 Doppler US 9/1994 – 1/1997 Silva, Jr, et al J Vasc Surg 1998;27:302-308 AVF Primary Failure Rate % P<0.05

16. Pre-operative Vascular Mapping 0 10 20 30 40 50 60 70 80 90 Clinical Examination N=139 Doppler US (DU) N=160 48 63 83 74 Clinical Exam 6/1992 – 8/1994 DU 9/1994-1/1997 Silva, Jr, et al J Vasc 1998; 27:302 - 308 Primary Patency Rate % at 1 yr AVF AVG P<0.05

17. Pre-operative Vascular Mapping 25 5.6 0 5 10 15 20 25 Physical Examination N=52 Doppler US N=72 P=0.002 Primary AVF Failure Rate% RCT CKD5 Mihmanli, I, et al J Ultras Med 2001; 20:217-222

18. The minimal advisable diameter of the anastomosed vessels for the creation of successful AVF is: a.1 mm b.1.5 mm c.2 mm d.2.5 mm e.3 mm

19. Pre-Operative Vascular Mapping 100 19 0 20 40 60 80 100 < 1.6 mm N=7 > 1.6 mm N=47 Primary Failure Rate % Prospective observational study RC AVF Vessel Diameter Wong, V, et al Eur J Vasc Endovasc Surg 1996;12:207-213

20. Pre-operative Vascular Mapping Rate % 83 8.3 0 10 20 30 40 50 60 70 80 90 RC AVFN=108 1 yr Primary Patency Primary Failure Prospective observational study Vein diameter > 2.5 mm Artery diameter > 2 mm Silva, Jr, et al J Vasc Surg 1998;27:302-308

21. Left radiocephalic RC AVF was constructed Nephrologist decided to initiate HD Clinical Scenario

22. The minimum maturation period of AVF should be ideally: a. < 2 weeks b. 2-4 weeks c. > 4 weeks d. > 6 weeks e. > 8 weeks

23. Timing of First Cannulation % of facilities 2 34 37 26 50 29 13 8 74 24 2 0 10 20 30 40 50 60 70 80 90 100 < 1 1-2 2-3 3-4 < 1 1-2 2-3 US EURO JAPAN Observational study 309 HD facilities AVF 2154 MONTHS Saran, R, et al (DOPPS) NDT 2004;19:2334-2340

24. Timing of First Cannulation Adjusted Relative Risk of Access Failure 0.72 1 0.91 0.87 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1 < 11-22-3>3 P=NS MONTHS Observational study 309 HD Facilities AVF 2154 Ref Saran, R, et al (DOPPS) NDT 2004;19:2334-2340

25. Time of First Cannulation Adj. Hazard Ratio for Primary AVF Failure 1.94 1 0 0.5 1 1.5 2 <30>30 DAYS Ref (95% CI, 1.3 to 2.8) P<0.001 Prospective study, MC AVF 513 Ravani, P, et al JASN 2004; 15:204-209

26. Time of First Cannulation Rule of 6s: 1)Access flow > 600 mL/min 2)Vein diameter > 6 mm 3)Vein depth < 6 mm K/DOQI (CPG/CPR 2006) AJKD 2006; 48 (S1): 1

27. Clinical Scenario 6 weeks later, left RC AVF was cannulated smoothly Objective monitoring of access function at regular base was performed

28. The recommended objective monitoring of access function should be performed at regular base by: a.Venous pressure measurement b.Arterial pressure measurement c.Dynamic venous pressure measurement d.Static venous pressure measurement e.Access flow measurement

29. Vascular Access Blood Flow Measurement Duplex US US flow dilution (Transonic) Crit-Line III Crit-Line III TQA Variable flow Doppler In graft Velocitymetry Blood velocity meter Glucose pump test Tordoir, J, et al NDT 2007; 22 (S2) : 88-117

30. Access Blood Flow Measurements Over Dialysis Time Access Blood Flow mL/min 1344 1308 1250 1150 1200 1250 1300 1350 1400 3090150 MINUTES P=0.03 Prospective study 32 HD Pts US dilution (transonic) Rehman, SU, et al AJKD 1999; 34: 471-477 (  7%)

31. Access Blood Flow Measurement and BP Changes 28 50 Decrease in Access Blood Flow% After 90 mins Decrease MAP % 15 25 Prospective Study 32 HD Patients US Dilution (Transonic) Rehman, SU, et al AJKD1999; 34: 471-477

32. Vascular Access Flow Measurement and Number of Catheter Insertions Relative Risk for the No. of Catheter Insertions 0.2 0.59 0 0.1 0.2 0.3 0.4 0.5 0.6 AVF N=60 AVG N=101 P < 0.05 (95% CI, 0.04 to 0.88) P < 0.05 (95% CI, 0.37 to 0.93) Meta-analysis AVF=1 RCT AVG=1 RCT Tonelli, M, et al AJKD 2008; 51: 630-640

33. Vascular Access Flow Measurement and Access Thrombosis Relative Risk for Thrombosis 0.47 0.94 0 0.2 0.4 0.6 0.8 1 AVF N=360AVG N=446 P < 0.05 (95% CI, 0.28 to 0.77) (95% CI, 0.77 to 1.16) Meta-analysis AVF 4RCT AVG 6RCT Tonelli, M, et al AJKD 2008; 51: 630-640

34. Access Flow Measurement and Access Loss 0.65 1.08 0 0.2 0.4 0.6 0.8 1 1.2 AVF N=141AVG N=381 Meta-analysis AVF 2 RCT AVG 4 RCT Tonelli, M, et al AJKD 2008; 51: 630-640 Relative Risk for Access Loss (95% CI, 0.83 to 1.40) (95% CI, 0.28 to 1.51)

35. Clinical Scenario US dilution technique was used at monthly bases for access flow measurement 700 (  22%)840 (  7%) 900Access flow measurement mL/min 7/20086/20082/2007-3/2008Date

36. What Should Be Done Next? a.Repeat access flow measurement b.Perform duplex US c.Perform MRA d.Perform fistulogram + percutaneous transluminal angioplasty (PTA) e.Perform surgical revision

37. Degree of Stenosis and PTA 72 23 65 17 0 10 20 30 40 50 60 70 80 BaselinePost-PTABaselinePost-PTA AVF=33AVG=65 P<0.005 Prospective Observational study, MC US dilution Van der Linden, J, et al JASN 2002; 13:715 - 720 Degree of Stenosis %

38. Access Flow Measurement and PTA 304 638 371 674 0 100 200 300 400 500 600 700 BaselinePost-PTABaselinePost-PTA AVF=33AVG=65 P<0.0001 Prospective observational study, MC US dilution Van der Linden, J, et al JASN 2002; 13:715 - 720 Access Flow mL/min

39. Primary Patency Post-PTA 50 25 0 10 20 30 40 50 AVFAVG P=0.03 Primary Patency Rate Post-PTA at 6/12 % Prospective observational study, MC US dilution Van der Linden, J, et al JASN 2002; 13:715 - 720

40. Repeat PTA Procedures 24 (169 days) 43 (109 days) 0 5 10 15 20 25 30 35 40 45 AVF=25AVG=35 Prospective observational study, MC US dilution Repeat PTA Rate % Van der Linden, J, et al JASN 2002; 13:715 - 720

41. Clinical Scenario PTA was done for 70% stenosis at venous outflow site with good result Access flow measurement improved from 700 to 860 mL/min (within 1 week) Few months later, he underwent kidney transplantation from deceased donor.

42. The indication for pre-emptive percutaneous transluminal angioplasty (PTA) is: a.Decrease of access flow > 10% b.Decrease of access flow > 20% c.AVG flow < 800 mL/min d.AVF flow < 800 mL/min e.AVF flow < 600 mL/min

43. Pre-emptive Intervention Variable EBPG 2007CSN/CPG 2006 Reduction of access flow %> 20 AVF flow (forearm) mL/min< 300< 500 AVG flow mL/min< 600< 650 1. Tordoir, J, et al NDT 2007; 22 (S2) : 88-117 2. Jindal, K, et alJASN 2006; 17 (S1): 1-27

44. Conclusion 1.Upper extremities vein preservation for every patient with CKD (dorsum of the hand) 2.AVF is the preferred type of VA and should be placed as distal as possible 3.Physical examination and vascular mapping with Doppler US of upper extremity should be performed before VA creation 4.Minimal diameter of vessels is 2 mm for AVF creation 5.Minimal period for AVF maturation is one month

45. Conclusion 6. Measuring access blood flow at regular base should be performed (US dilution) 7. Early detection of VA dysfunction (thrombosis) 8. Pre-emptive corrective intervention (PTA) 9. Decrease patient morbidity, hospital admissions and healthcare costs 10. Access monitoring programs should be included as part of routine dialysis care