Dialysis Outcomes and Practice Patterns Study Physical Activity and its Association with Mortality&Quality of Life in Hemodialysis Patients: DOPPS Anna Marti Monros, Antonio Alberto Lopes, Brenda W Guillespie, Yun Li, Patricia Lynn Painter, Stefan H Jacobson, Hugh C. Rayner, Donna L. Mapes, Raymond C Vanholder, Ronald L Pisoni.

The Dialysis Outcomes and Practice Patterns Study The DOPPS is an international prospective cohort study of hemodialysis treatment and patient outcomes: DOPPS 1 ( ): 308 dialysis facilities and 17,034 patients in 7 countries (France, Germany, Italy, Japan, Spain, UK, and US) DOPPS 2 ( ), DOPPS 3 ( ), DOPPS 4 ( ): ≥300 facilities and 11, ,000 patients per study phase in 12 countries (DOPPS 1 countries + Australia, Belgium, Canada, New Zealand, and Sweden) DOPPS 5 ( ): ~465 facilities and 17,000 patients in seven new countries (Bahrain, China, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates) in addition to the 12 countries represented in DOPPS 4

Background –Questions about physical activity in dialysis patients remain unanswered: it is unclear the extent to which the amount or type of physical activity (i.e., aerobic or muscle activities) affects clinical outcomes in hemodialysis (HD) patients. Goal –We describe the relationship between the amount and type of physical activity and mortality and patient-centered outcomes in chronic HD patients.

Methods. Sample: 5,712 chronic HD patients (DOPPS ) including only patients who can walk (assisted or unassisted) and those with complete data for age, sex, vintage, and physical activity. Multiple imputation was used for all other variables (including comorbidities). Analysis: –Outcomes: Mortality, Kidney Disease Quality of Life (KDQOL) Physical / Mental Component Summary (PCS / MCS) scores, Kidney Disease Burden (KD Burden) score, Center of Epidemiological Studies Depression (CESD) scale, and patient-reported post-dialysis recovery time of > 6 hours. –Exposure: Levels of aerobic physical activity and types of muscle activity (strength and/or flexibility) as measured by and calculated using the self- administered Rapid Assessment of Physical Activity (RAPA) survey instrument. –Model: Cox models for mortality, linear models for continuous outcomes, and logistic models for post-dialysis recovery time > 6 hours. –Adjustments:  Minimally adjusted models included geographic region, age, sex, and vintage (years on dialysis), and accounted for facility clustering effects.  Extensively adjusted models included the above plus race, smoking, education, employment status, living status, assistance with walking, body mass index, 14 comorbid conditions, baseline lab values, spKt/V, and blood pressure

Mortality by Level of Aerobic Activity *Model is also adjusted for muscle strength and flexibility activities.

*Model is also adjusted for levels of aerobic activity. Mortality by Type of Muscle Activity

Patient-Centered Outcomes by Aerobic Activity Level *Results shown are from the “extensively adjusted” models. Models are also adjusted for muscle strength and flexibility activity.

Adjusted Aerobic Activity Levels by Patient-Level and Facility-Level Characteristics-1 Type 3 test for sex: p < 0.001; for age p < Aerobic Activity Level by Categories of Age and Gender Adjusted for age, gender, region, vintage, assistance w/ walking = Never or Infrequently = Sometimes or Often = Very Active

Adjusted Aerobic Activity Levels by Patient- Level and Facility-Level Characteristics-2 Aerobic Activity Level by Selected Comorbid Conditions Type 3 test: p = 0.007Type 3 test: p = 0.009Type 3 test: p = 0.16

Adjusted Aerobic Activity Levels by Patient- Level and Facility-Level Characteristics-3 Type 3 test: p < Aerobic Activity Level by Facility Exercise Program Availability

Summary & Conclusions Overall, 29% of patients were classified as never active and 20% were classified as very active with appreciable differences in activity level by age, gender, and comorbidities. Self-reported frequency of aerobic activity was strongly inversely associated with mortality and positively associated with HRQOL outcomes. The benefit was noted even for low activity levels and increased with higher levels of activity. Patients in facilities that offer exercise programs are more likely to be active than are patients in facilities without those programs, adjusting for potential confounders, suggesting a potentially modifiable facility practice to improve patient outcomes. Conclusion(s): Our findings suggest that aerobic activity may improve survival and the quality of life in ambulatory hemodialysis patients, though confounding remains an alternative explanation. Clinical trials to investigate the effectiveness of physical activity interventions, such as facility- based exercise programs, are indicated.

Acknowledgements Our thanks to DOPPS study coordinators, medical directors and participating patients for their dedicated work. The DOPPS Program would not be possible without the support for independent scientific research to improve patient care from the following organizations: Principal Study Support: –Amgen (founding sponsor, since 1996) –Kyowa Hakko Kirin (since 1999, in Japan) –AbbVie (since 2009) –Sanofi Renal (since 2009) –Baxter Healthcare (since 2011) –Vifor Fresenius Medical Care Renal Pharma (since 2012) –Fresenius Medical Care (since 2012) Support for the DOPPS Program is provided without restrictions on publications.

Acknowledgements Also, our thanks to these organizations for their support of program activities in specific countries: –Canada: Amgen, Janssen, BHC Medical, Takeda, Kidney Foundation of Canada (funds distribution) –Germany: Hexal, Shire, WiNe Institute –Japan PDOPPS: JSPD (Japanese Society for Peritoneal Dialysis) Support for DOPPS is provided without restrictions on publications.

Summary (I) In DOPPS, Japan has consistently displayed the highest AV fistula (AVF) use [92-93%, since 2002], with <2% of pts using a catheter The US, led by the Fistula First Initiative, has shown the largest % rise in AVF use from 34% in 2002 to 60% by 2010 AVF use increased in Aus-NZ and the UK to 78% and 74%, respectively, while remaining at ~80% in France Catheter use has either remained stable or declined in Japan, France, UK and US