1. Infections in the dialysis population: A major communicable disease issue! Allan J. Collins, MD, FACP Professor of Medicine University of Minnesota Director, USRDS Coordinating Center

2. USRDS 2008 ADR Disclosures Institutional research funding: NIH, CDC, National Kidney Foundation, Amgen, Baxter, Sigma Tau, NxStage, Genzyme, BMS, AMAG Pharmaceuticals Advisory boards in last year: WHO Advisory Panel on NCDs, Kidney Disease Improving Global Outcomes (KDIGO), International Federation of Kidney Foundations (IFKF), Epidemiology consulting: NxStage, Amgen, Affymax

3. USRDS 2008 ADR Infectious complication in dialysis patients: an old yet new communicable disease challenge Trends in overall mortality show reductions in death rates in years 2-5 after onset of ESRD Death rates in the first year have not changed in 12 years raising concerns about the underlying morbidity contributing to the early death rates Cardiovascular and Infectious hospitalizations are the leading cause of morbidity yet little is known about the trends in the first months of dialysis Here we review the trends in hospitalization rate with particular emphasis on infections as a contributor to morbidity and mortality in the first year of treatment

4. USRDS 2008 ADR Mortality rates, by modality Figure 6.1 (Volume 2) Incident ESRD patients; adjusted for age, gender, race, & primary diagnosis. Incident ESRD patients, 2005, used as reference cohort.

5. USRDS 2008 ADR Change in all-cause & cause-specific hospitalization rates, by modality Figure p.16 (Volume 2) Period prevalent ESRD patients; adjusted for age, gender, race, & primary diagnosis. ESRD patients, 2005, used as reference cohort. Vascular access hospitalizations are “pure” inpatient vascular access events. New vascular access codes for peritoneal dialysis patients appeared in late 1998; therefore, peritoneal dialysis vascular access values are shown as changing since 1999 rather than 1993.

6. USRDS 2008 ADR Adjusted admissions for principal diagnoses, by modality Figure 6.5 (Volume 2) Period prevalent ESRD patients; adjusted for age, gender, race, & primary diagnosis. ESRD patients, 2005, used as reference cohort.

7. USRDS 2008 ADR Trends in hospitalization surveillance data in the dialysis population Overall, hospitalization rates have changed little over the last 10-12 years However, there have been significant changes in the types of hospitalizations with vascular access events transitioning to the outpatient setting with increases in cardiovascular disease and infectious hospitalizations Hospitalization secondary to pneumonia have increased but have begun to plateau since 2003 Vascular access infectious event have more than doubled in the last 10 years an area of major concern!  By most standards this would be considered a major communicable disease problem yet the CDC stopped its survey in 2004!!!!  Who and what is responsible for this trend?

8. USRDS 2008 ADR Infectious complications in dialysis patients Infectious hospitalizations have increased in part related to the increases in pneumonia but this trend appears to be reversing with increased evidence of pneumococcal pneumonia vaccinations Preventive care in the form of influenza vaccinations needs attention and is clearly within the domain of the providers! Yet other sources of infectious events likely contribute to the increased hospitalization rates

9. USRDS 2008 ADR Vascular access use at initiation, 1 st outpatient access, 2006 (From Medical Evidence Form 2728) Figure 3.1 (Volume 2) incident hemodialysis patients, 2006. 82% Catheters

10. USRDS 2008 ADR First access at initiation, by nephrologist care, 2006 Figure 3.4 (Volume 2) incident hemodialysis patients, 2006, with new (revised edition) Medical Evidence forms.

11. USRDS 2008 ADR Pre-ESRD nephrologist care, 2006 Table 3.a (Volume 2) incident ESRD patients, 2006, with new (revised edition) Medical Evidence forms.

12. USRDS 2008 ADR Cumulative probability of catheter placement Figure 1.8 (Volume 2) Medicare: hemodialysis patients who initiate dialysis at age 67 or older during the year specified. Includes those with Medicare as primary payor during the two years prior to initiation & through the first six months of ESRD; pre-ESRD claims used for months prior to initiation date. Medstat (EGHP): patients with first date of regular & continuous dialysis in 2000 or 2005, regardless of age. Only one year of claims prior to the start of dialysis was available for the 2000 cohort.

13. USRDS 2008 ADR Cumulative probability of multiple catheter placements determined from service claims Figure 1.9 (Volume 2) Medicare: hemodialysis patients who initiate dialysis at age 67 or older during the year specified. Includes those with Medicare as primary payor during the two years prior to initiation & through the first six months of ESRD; pre-ESRD claims used for months prior to initiation date. Medstat (EGHP): patients with first date of regular & continuous dialysis in 2000 or 2005, regardless of age. Only one year of claims prior to the start of dialysis was available for the 2000 cohort.

14. USRDS 2008 ADR Per person per year vascular access costs, by physician specialty Figure 11.24 (Volume 2) period prevalent hemodialysis patients. Costs determined as the payment amount for each line-level access procedure billed through physician/ supplier claims.

15. USRDS 2008 ADR Catheter events & complications Figure 5.27 (Volume 2) Prevalent hemodialysis patients age 20 & older, ESRD CPM data; only includes patients who are also in the USRDS database. Year represents the prevalent year & the year the CPM data were collected. Access is that listed as “current” on the CPM data collection form.

16. USRDS 2008 ADR Arteriovenous fistula events & complications Figure 5.28 (Volume 2) Prevalent hemodialysis patients age 20 & older, ESRD CPM data; only includes patients who are also in the USRDS database. Year represents the prevalent year & the year the CPM data were collected. Access is that listed as “current” on the CPM data collection form.

17. USRDS 2008 ADR Arteriovenous graft events & complications Figure 5.29 (Volume 2) Prevalent hemodialysis patients age 20 & older, ESRD CPM data; only includes patients who are also in the USRDS database. Year represents the prevalent year & the year the CPM data were collected. Access is that listed as “current” on the CPM data collection form.

18. USRDS 2008 ADR lla illi lla illi Period prevalent hemodialysis patients with or without simple fistulas. Data from physician/supplier claims. Some patients may have more than one access at a given point in time. Access procedures in prevalent hemodialysis patients, by diabetic status Figure hp.13 (Volume 2) Change to cuffed catheters

19. USRDS 2008 ADR Vascular access utilization and infectious complications Arteriovenous fistula utilization rates have increased during the same time as the Fistula First initiative has been stressed The Fistula First effort is also associated with reductions in the use of grafts and changes in catheter utilization rates Infectious complication are highest with catheters and lowest with fistulas but there are similar rates with grafts. What are the trends in infectious hospitalizations that may relate to vascular access complications

20. USRDS 2008 ADR Change in all-cause & cause-specific hospitalization rates, by modality: prevalent Figure p.22 Period prevalent ESRD patients; adjusted for age, gender, race, & primary diagnosis. ESRD patients, 2005, used as reference cohort. Vascular access hospitalizations are “pure” inpatient vascular access events, as described in Appendix A. New vascular access codes for peritoneal dialysis patients appeared in late 1998; therefore, peritoneal dialysis vascular access values are shown as changing since 1999 rather than 1993.

21. USRDS 2008 ADR Trends in cardiovascular Hospitalizations in the First Year by months Adjusted for age, gender, race and cause of ESRD Rate per 1,000 Pt Yrs Incident Cohort Year Increased cardiovascular hospitalizations

22. USRDS 2008 ADR Trends in Infectious Hospitalization rates in the 1 st year by month Adjusted for age, gender, race and cause of ESRD Rate per 1,000 Pt Yrs Incident Cohort Year Increased infectious hospitalizations

23. USRDS 2008 ADR Trends in cardiovascular Hospitalizations in the First Year by months Adjusted for age, gender, race and cause of ESRD Rate per 1,000 Pt Yrs Incident Cohort Year CardiovascularInfections

24. USRDS 2008 ADR Trends in CVD and Infectious Hospitalization rates in the first month Adjusted for age, gender, race and cause of ESRD Rate per 1,000 Pt Yrs Incident Cohort Year Infectious hospitalizations now approach CVD for the 1 st time!

25. USRDS 2008 ADR Percent change in hospital admissions from Day 90: 1993 to 2005 Incident dialysis patients age 20 and older *Model based adjustment for age, sex, race, cause of ESRD: Interval Poisson regression (ASN 2008 poster)

26. USRDS 2008 ADR Percent change in hospital admissions from day 1: 1993 to 2005 Incident hemodialysis patients age 65 and older *Model based adjustment for age, sex, race, cause of ESRD: Interval Poisson regression (ASN 2008 poster)

27. USRDS 2008 ADR Adjusted admissions for principal diagnoses, by modality Figure 6.5 (Volume 2) Period prevalent ESRD patients; adjusted for age, gender, race, & primary diagnosis. ESRD patients, 2005, used as reference cohort. *early data noted decline but must be confirmed

28. 2004 ADR Incident dialysis patients with 90-day rule, Medicare as primary payor, & Part A & B claims, 1992–2000 combined; adjusted for age, gender, race, & primary diagnosis. Reference cohort: patients without corresponding diseases in the first year after ESRD initiation + 90 days. Adjusted relative risk of mortality after pneumonia: dialysis Figure 6.29 Foley RN, Guo H, Snyder JJ, Gilbertson DT, Collins AJ: Septicemia in the United States Dialysis Population, 1991 to 1999. Journal of the American Society of Nephrology 15 (4): 1038-1045, 2004

29. 2004 ADR Incident dialysis patients with 90-day rule, Medicare as primary payor, & Part A & B claims, 1992–2000 combined; adjusted for age, gender, race, & primary diagnosis. Reference cohort: patients without corresponding diseases in the first year after ESRD initiation + 90 days. Adjusted relative risk of mortality after VA event: dialysis Figure 6.30 Foley RN, Guo H, Snyder JJ, Gilbertson DT, Collins AJ: Septicemia in the United States Dialysis Population, 1991 to 1999. Journal of the American Society of Nephrology 15 (4): 1038-1045, 2004

30. USRDS 2008 ADR Trends in Infectious hospitalizations Infectious hospitalizations have substantially increased over the last 10-13 years The increase in infectious hospitalizations is more than 4 times greater compared to cardiovascular events in the first months The increase in infectious hospitalization rates is approaching that of cardiovascular events which is a new finding and they appear to be interrelated The risk of death after an infectious hospitalization event is significant and is associated with CVD events (The infection/inflammation multiplier hypothesis)!

31. USRDS 2008 ADR Conclusions Death rates in the first months of dialysis are high and need to be addressed Infectious hospitalizations in the 1 st months of dialysis have increased nearly 2 fold Vascular access infectious hospitalizations are up nearly 3 fold The consequences of late referral and delayed vascular access planning result in the use of catheters with the accompanying complications and risk of infection and premature death! The high rates of catheter utilization and associated infectious complications suggest a major effort is needed to reduce catheter utilization (Catheter Last!). CMS under the QIO scope of work should act to increase early referral and a “Planned Transition” to dialysis consistent with the MIPPA CKD Stage 4 education benefit! CMS should implement a similar effort for planned transition as was done for Fistula First by engaging health plans, physicians, hospitals and public health infection control officials to reduce the use of catheters!

32. USRDS 2008 ADR Acknowledgements The USRDS Coordinating Center produced the material in this talk based on contributions from the entire staff of  SAS programmers  Biostatistians  Epidemiologist  Physcians  Pharm Ds  Co-investigators  Graphics designers and editors We would like to thank CMS and the NIH project officers for their support and oversight of the USRDS and the entire kidney disease community for the hard work they do and providing the data!