1. I will not discuss off label use and/or investigational use in my presentation. I have financial relationships to disclose: Employee of: Fresenius Medical Services Consultant for: N/A Research support from: Amgen and Abbott Honoraria from: N/A Presenter Disclosure Information

2. Raymond M. Hakim, M.D., Ph.D. April 25, 2009 ESRD: State of the Art Charting the Challenges for the Future

3. Background ESRD patients <65 years old do not receive Medicare coverage until 91 days of ESRD therapy. In order to make results comparable across age groups, USRDS reports mortality rates for all patients after 90 days of ESRD therapy. Several studies have highlighted multiple co-morbidities and risk factors that are present in the majority of patients starting dialysis therapies. Nevertheless, few studies have focused on the mortality of dialysis patients during these initial 90 days, or on processes to reduce it.

4. Published Data for Initial 90 Day Mortality 1990 USRDS (Held et al): reported a 12% mortality rate in the initial 90 days (48 deaths/100 pt years at risk) in patients starting dialysis. Khan et al (AJKD 1995): reported a 12.6% mortality rate during the initial 90 days (50 deaths per 100 pt years at risk). Soucie and McClellan (JASN 1996): reported avg mortality rate of 24 deaths per 100 pt yrs at risk, based on data supplied by facility staff. RCG has reported a 10% mortality during that initial 90 day period of time, or an annualized 40 deaths per 100 pt years at risk; this compares to 20 deaths per 100 pt years at risk for prevalent patients.

5. Co-Morbidities and Risk Factors Associated with Early Mortality  Co-Morbidity Age Nutritional Status Diabetes Cardiovascular Disease LVH Depression  Reversible Risk Factors Anemia Low albumin High Phosphorus High catheter rate  Reversible Risk Factors Anemia Low albumin High Phosphorus High catheter rate  Risk Factors Unplanned start (w/o permanent access) Short (<4 months) prior nephrological care Low residual renal output  Risk Factors Unplanned start (w/o permanent access) Short (<4 months) prior nephrological care Low residual renal output

6. At Initiation of Dialysis in the U.S. 57% had albumin concentration below lower limit of normal 80% of patients with Hct <28% were not receiving EPO 50% had no visit with dietitian (21% had one visit) 25% had a permanent access 30 days before starting dialysis 33% used temporary access 60 days after initiation

7. Outcomes for Patients Initiating Dialysis Month 1 Month 2 Month 3 Month 4+ Percent URR > 70% N=562 Percent Hct > 33% N=682 Percent Albumin > 3.7 g/dL N=696 123 4+123 123

8. RightStart ® Goals Defined goals for each healthcare team member General Goals Ongoing individualized Patient Education & Self-Care, Medication Reviews, care plans, recommendation for a liberal diet Protocol-driven outcomes Specific Goals Week 2:URR >=70% Weeks 3-4:Target EDW Hct >=30%, T. Sat >=20% Transplant referral & permanent access planning Weeks 5-6:Stable BP Weeks 7-8:Hct >=33% PO4 3.5-5.5 mg/dL Use Permanent Access Weeks 9-10:Review Goal Achievement Weeks 11-12:HgbA1C =3.7 g/dL PTH 150-300 (BiPTH 75-150)

9. Week: 1/2 3/4 5/6 7/8 9/10 11/12 Goals M.D. Nursing S.W. R.D. RightStart ® Grid

10. Enrollment Process RightStart ®, N=923 Prospective enrollment of ALL new patients within one to three weeks of dialysis initiation Exclusions:  Seasonal or transient patients  Nursing home residents  Patients with cognitive dysfunction that precludes ability to learn Time-Concurrent Control Group, N=1,047 Retrospective data retrieval of all new patients in non- RightStart ® clinics in same geographic area for one year concurrent with the RightStart ® program

11. Demographics VariableRightStart ® Control Group p Value Age (years)61.8 + 16.062.0 + 17.2NS 1 Male/Female45.8%/54.2%46.6%/53.4%NS 2 Diabetes (I & II)53.8% NS 2 Caucasian57.2%47.8%P<0.05 2 AA/Hispanic36.5%36.2%NS 2 Other6.3%16%NS 2 1 = Student’s t-test 2 = Chi-square

12. Laboratory Parameters Percent of Patients with Hematocrit >33% Percent of Patients with Albumin >3.5 g/dL

13. paricalcitol PTH>300 Supplements on HD Alb < 3.7 megesterol Alb < 3.2 Teaching (Eat, Eat, Eat!) Binders Phos >5.5 Renal Dietitians Star Plan RightStart

14. URR and Vascular Access Outcomes Percent Reduction of Catheters Percent of Patients with URR >70%

16. What Do Patients Say They Want? (I CARE) Information Compassion Attitude Responsiveness Expertise

17. Right Start Outcome Data Percent of Patients Physically Active

18. All Patients KDQOL by Weeks Average Mental Component Score (MCS)

19. Survival Curve, 1 st 365 Days Adjusted Cox-proportional hazards regression model P<0.001 by Cox Log- rank, Breslow, and Tarone-Ware tests at 90, 180, and 365 day exposure levels. RightStart ® Control Adjusted by age, race, gender, diabetes

20. Mortality Hazard Ratios Mortality Period Unadjusted Hazard Ratio 1 (95% CI) Adjusted 2 Hazard Ratio 1 (95% CI) P Value (Adj. Hazard Ratio) RightStart ® (deaths per 100 pt yrs) Control (deaths per 100 pt yrs) 90-days 0.52 (0.35-0.76) 0.60 (0.37- 0.97) 0.0370.200.39 180-days 0.55 (0.40-0.75) 0.60 (0.40- 0.91) 0.0150.180.33 365-days 0.60 (0.46-0.79) 0.66 (0.46- 0.95) 0.0260.170.30 1 = Control used as reference group 2 = Adjusted for age, gender, race, diabetes

21. Hospital Days per Patient Yr at Risk

22. Summary 1. Patients initiating dialysis present with several co- morbidities and risk factors, and knowledge deficits that are associated with a high initial 90-day mortality rate, (generally not reflected in published data). 2. Several of these risk factors can be attenuated or reversed more rapidly with an intensive team effort during the initial 90 days of therapy. 3. The RightStart ® program, consisting of focused attention on reversible risk factors and patient education, resulted in a significant reduction in mortality and hospitalization during those initial 90 days, which extended up to 1 year following initiation of dialysis.

23. Combine RightStart and Diabetes Programs - Primary Areas of Patient Care Patient Education/Modality Options Vascular Access Medication Reviews Nutrition Rehab/SW referrals Foot Exams/Shoes Glucose control – home records Prevention (eye exams) Case Follow-up and input Self-Care Electronic Documentation/Outcomes RSCM (follow pts x4 months) All Patients Included Nursing home pts Non-English speaking pts Spouse/significant other for confused pts

24. Preventing Infection and Amputations

25. Facts About the Diabetic Foot 1 ESRD pts with diabetes have 10X the rate of amputations as normal population Up to 86% of amputations start from a minor injury i.e. blister, callus, poorly fitting shoes Amputations linked to decreased survival rate - 51% of ESRD pts survive 1 yr after amputation - 34% of ESRD pts survive 2 yrs after amputation 1 Eggers et al. Kidney International

26. Diabetes Foot Check Procedure INITIAL FOOT CHECK- (Annually) includes: Observation of shoes, skin condition, integrity, temperature Check Pedal Pulses Sensory testing Patient Education ROUTINE FOOT CHECK – (Monthly) includes: Observation of shoes, skin condition, integrity, temperature Reinforce Patient Education

27. 2008 RightStart Analysis: Case Control Matching 2 Patient DataSets Analyzed: RCG (aka AMI) Clinics (5/2004 – 5/2008) and FMS Clinics (3/2006 – 5/2008) Incident HD pts in facilities that agreed to participate in the RightStart Program Each case matched to a non-RightStart pt (control) per the following criteria Same facility Age, gender, diagnosis Control started dialysis before RightStart program was started in that facility Control survived # of days it took to enroll matched pt into RightStart

28. RightStart vs. Case-Control Matching: Demographics VariableControlRightStartp Value AMI Patient Group # of Pts3,392 Age (years)63.1 + 0.2462.6 + 0.25NS Male (%)55.9 + 0.5655.7 + 0.56NS Diabetes (1 & 2)51.8 + 0.5857.0 + 0.58p<0.0001 FMS Patient Group # of Pts1,042 Age (years)63.4 + 0.4463.3 + 0.46NS Male (%)56.7 + 1.154.7 + 1.1NS Diabetes (1 & 2)64.3 + 1.165.9 + 1.0NS Avg + Standard Error

29. Outcomes Analysis Anemia/Cycle Time Nutrition Dialysis Adequacy Vascular Access Foot Checks Survival

30. Cycle Time: Efficiency of Epogen Management Time (Days) from Date of 1 st Outpatient Dialysis to Date of 1 st Epogen Order Components Measured Days to 1 st Lab Draw Days to 1 st EPO Order

31. Days to First Lab Draw for Incident Patients **p<0.0001 **

32. Days to First EPO Order for Incident Patients **p<0.0001 **

33. Percent of Pts with Epogen Orders at 120 Days **p<0.0001 * **

34. Percent of Pts with T. Sat 20-50% at 120 Days **p<0.0001 **

35. Percent of Pts with Hgb 11-12 g/dL at 120 Days *p<0.001 *

36. Percent of Pts with Albumin >=3.5 g/dL at 120 Days **p<0.0001 **

37. Percent of Pts with Phosphorus 3.5-5.5 mg/dL at 120 Days *p=0.02 *

38. Percent of Pts with spKt/V >=1.4 at 120 Days (eKt/V >=1.2 for FMS pt group) **p=0.0001 **

39. Percent of Pts with AV-Fistula at 120 Days **p<0.0001 **

40. Average Number of Foot Checks Done During First 120 Days (diabetic pts only) **p<0.0001 **

41. One Year Survival of RightStart Pts vs. Case- Control matching, All Pts n=approx 8,000 120 Days Hazard Ratios at 120 days: 0.66 At 1 year: 0.78 RightStart Patients Matched non-RightStart patients P<0.0001

42. Mortality Hazard Ratios for RightStart vs. Matched Controls, All Pts **p<0.0001 ** Ref. (matched controls)

43. Top 10 Lessons Learned from RightStart for Incident Dialysis Patients 1. Reduce cycle time a) Lab panel on 1 st treatment b) Lab follow-up by MD and RN next (2 nd ) treatment 2. Make early “emotional” connection with new pt. Recognize grieving process and empathize, support pt to reach acceptance phase & empowerment/self-management 3. Delay heavy (intensive) teaching until 2-3 weeks after start 4. Team-driven “curriculum” 5. Emphasize good nutrition- “Eat well and we’ll dialyze you well” 6. Provide oral nutritional supplements early on 7. Get rid of catheters ASAP 8. Include family members or next of kin in education 9. Focus on pt as most important team member 10. Assure TOPS program participation before starting dialysis

44. Advantages of the RightStart Program 1. To the Patient Number of new (incident) patients in US100,000 Number of new (incident) patients in FMS33,000 Current 1 st Year Mortality (USRDS)25.4% Number incident pts at end of 1 st year without RightStart 24,618 Expected 1 st Year Mortality with RightStart (HR = 0.75) 19.0% Number incident pts at end of 1 st year with RightStart 26,730 Lives Saved/Lives Extended from RightStart~ 2100 pts/Yr

45. Mortality Rates, by modality & year of treatment Incident hemodialysis patients Year

46. Adoption of RightStart in the Nephrology Community 1. CJASN Manuscript, Nov 2007 2. DaVita IMPACT Program Incident Management of Pts Actions Centered on Treatment 3. NKF Booklets 4. Kidney Times 5. Canadian Trial 6. CMS Pt Ed Regulations 7. KCP goal of reducing 1 st year morality of 20% in 3 years

47. RightReturn

48. Re-Hospitalization after discharge from Hospital (Medicare fee-for-service) (N=3 million) Medical Discharges% Cumulative Re-Hospitalizations 0-30 days21.1% 30-60 days30.3% 61-90 days36.6% 91-180 days47.9% 181-365 days59.4% S. Jencks et al, NEJM 360, 1418, 2009

49. Predictors of Re-Hospitalization Age <55 yr1.0 (ref) 55-69 yr0.99 70-791.07 ESRD 1.42 No of Re-Hospitalization 01.0 11.37 21.75 ≥32.5 S. Jencks et al: NEJM 360, 1418, 2009

50. Impact of hospitalization on hemoglobin, albumin, and weight by length of stay

51. Impact of hospitalization on the prevalence of EPO and vitamin D usage by length of stay

52. Hazard ratios for repeat hospitalization within the specified number of days after discharge from hospital

54. Laboratory Outcomes Following Initiation of Dialysis (N = 7,658) HCFA Data from Q4, 1997 Rocco: AJKD, 2001

55. A Special Group: New Patients Have Special Needs New HD Pts Arrive: Anemic Malnourished Underdialyzed (uremic) With catheter Inflammatory state (catheter) Inactive Jobs threatened Overwhelmed More likely to be hospitalized More likely to die

56. RightStart Pilot Program – Primary Areas of Patient Care Patient Education Vascular Access (surgeon appt 1 st mo. if catheter) Medications Nutrition Facilitate overall medical care Rehab/SW referrals Physical activity program Self-Care Collaborate with staff Documentation

57. Advantages of the RightStart Program 2. To FMS Relative increase in (incident) patient growth rate (2/33) 6.4% Absolute increase in (incident+prevalent) patient growth rate (2/120) 1.7% Cost of RightStart Implementation 1 Case Manager/200 Pts/Yr x 60K (including benefits) $9.9 M Return on Investment Increase in revenues from RightStart (2100 pts x $350/tx x 150 tx/yr) $110 M Increase in EBIT from RightStart (0.17 x Revenue)$18.7 M ? Increase in revenue from earlier start of EPO & Vit D ? CFC Mandated ‘Patient Ed’ Related Nursing Time (10 hr/pt) ((10 x 33000) / 2080) $8.0 M

58. Patient Stories Louise Gene

59. Current RightStart Participation by Business Units Number of Case Managers BURSCMs CBU10 NEBU1 SBU6 SEBU5 SWBU3 WBU5 ALL30

60. Mortality Hazard Ratios for RightStart vs. Matched Controls by Business Unit ** Ref. (matched controls) NE excluded due to small # of pts

61. Mortality Hazard Ratios for RightStart vs. Matched Controls, All Pts **p<0.0001 ** Ref. (matched controls)

62. One Year Survival of SPIDER Pts vs. Case-Control matching, All Pts n=approx 8,000 120 Days Hazard Ratios at 120 days: 0.66 At 1 year: 0.78