Global trends in ESRD epidemiology and impact on Vascular Access

Global trends in ESRD epidemiology and impact on Vascular Access Wolfgang Meichelboeck, Dipl.-Ing. Pentenried Germany wolfgang.meichelboeck@t-online.de Please respect the copyright when using slides or parts of this presentation 5 th Svenska Accessmötet, Stockholm, Feb 2-3, 2017

End Stage Renal Disease (ESRD) and Vascular Access ESRD 3 replacement therapy options: Kidney transplant (Tx) Peritoneal dialysis (PD) Hemodialysis (HD) To perform HD the creation and maintenance of a permanent vascular access (AVF, AVG/shunt or dialysis catheter) is necessary. Picture: courtesy M.K. Widmer, Bern

Worldwide ESRD / RRT 2001-2015 2015 ~ 3.572 pat. on RRT 4.000 3.500 3.000 2.500 2.000 1.500 1.000 500 0 All numbers (n) in.000 3.360 3.200 3.010 2.786 2.632 2.455 2.305 1.783 1.479 2001 2004 2008 2009 2010 2011 2012 2013 2014 2015 TX PD HD Moeller S, et al. Nephrol Dial Transplant 2002 Grassmann, NDT 2005, 2014 estimated Fresenius Medical Care, Ann Report 2009, 2010, 2011, 2012, 2013, 2015

Worldwide ESRD Treatment Modalities / 2001 2015 100% Almost no change in RRT treatment modality! 80% 60% 22,9% 23,1% 23,0% 22,8% 22,5% 22,3% 21,7% 21,2% 20,6% 20,1% TX 8,5% 8,4% 8,5% 8,3% 8,3% 8,4% 8,4% 8,5% 8,8% 9,2% PD 58,4% 40% 20% 68,6% 68,5%68,5%68,9%69,2% 69,2% 70,0% 70,3% 70,5% 70,6% HD 8,7% 0% 32,9% 2001 2004 2008 2009 2010 2011 2012 2013 2014 2015 2015 Moeller S, et al. NDT 2002, Grassmann, NDT 2005, 2014 estimated Fresenius Medical Care, 2009, 2010, 2011, 2012, 2013, 2015, SVENSKT NJURREGISTER - ÅRSRAPPORT 2016

Dialysis population by geographical split (n) in.000 3.000 Annual Growth rates 2.500 2.000 42% 43% 42% 43% Others China ~ 9% ~ 15% 1.500 1.000 500 0 38% 12% 13% 8% 9% 34% 3% 2000 2005 2010 2011 2012 2013 Japan EU USA ~ 1-2% ~ 2% ~ 3-4% Data Fresenius Medical Care 2014 Others = Asia, Latin America, Middle East, Africa

The 15 largest dialysis countries 2013 - HD vs PD USA China Japan Brazil Mexico Germany India Taiwan Turkey Thailand Korea Italy France Egypt Malaysia HD % PD % 40% 75% 88% 86% 92% 90% 93% 92% 91% 93% 91% 94% 97% 95% 100% 0% 20% 40% 60% 80% 100% 4 European countries Data Fresenius Medical Care 2014 n (%) dialysis population 0% 1.309.000 (52%) 576.000 (23%) 52% 75%

SUMMARY EUROPE

ESRD and RRT in Europe Approx. 50 Mill. Patients with chronic kidney disease (10% of the population) CKD stages 3 5 prevalence varied from 1.0% to 5.9% (approx. 36 Mill.) 100% 80% 36% TX Approx. 350.000 Patients with ESRD on HD in 2013 Approx. 5.400 dialysis centers 60% 4% PD Annual growth rate of Dialysis population approx. 2 % 40% 60% 20% HD Data Fresenius Medical Care 2014, ERCPA providers Info Chart 0% 2013

Incidence of RRT in Europe 2005-2009 & 2012-2013 - 2014 300 250 2005 2006 2007 2008 2009 2012 2013 2014 200 150 100 50 0 Incidence (pmp) day 1 - Adjusted for age and gender van de Luijtgarden M. Clin Kidney J (2012)5: 109-119, updated with data from ERA-EDTA report 2012, 2013, 2014 + TR registry data (unadjusted)

Prevalence of RRT in Europe 2005-2009 & 2012-2013 - 2014 1600 1400 2005 2006 2007 2008 2009 2012 2013 2014 1200 1000 800 600 400 200 0 Prevalence (pmp) - Adjusted for age and gender van de Luijtgarden M. Clin Kidney J (2012)5: 109-119, updated with data from ERA-EDTA report 2012, 2013, 2014 + TR registry data (unadjusted)

Distribution of the main pathologies contributing to Chronic Kidney Disease (CKD) DM, HT, GN DM DM, HT GN, DM, MS, HT DM, GN, HT, UD DM, GN, HT DM Diabetes Mellitus HT Hypertension GN GN, HT, DM, UD DM, HT GN Glomerulonephritis MS Metabolic Syndrome UD Urological Diseases Nugent RA. Nephron Clin Pract (2011)118:c269-c277

The Lancet 2012 - Global Burden of Disease study - 7 large publications on Global disease trends 1990 vs 2010 Published Dec 15, 2012 12 http://www.thelancet.com/themed/global-burden-of-disease

Global death ranks with 95% UIs for the top 25 causes in 1990 and 2010, and the percentage change with 95% CIs between 1990 and 2010 1990 2010 Diabetes 15 9 HT 18 14 Chronic Kidney Disease 27 18 Lozano R, Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010 Lancet 2012; 380: 2095 128

Trends for major underlying diseases/factors 14

Trends for major underlying diseases 15

Trends in Diabetic disease worldwide 2010 to 2030 Adult only 20-79 years 6,4 % of the adult population 285 Mill. diabetics in 2010 + 154 Mill. 7,7 % of the adult population 439 Mill. diabetics in 2030 estimated in 2010 Shaw JE, Diab Res Clin Pract (2010) ;87:4-14

Diabetes: A global emergency 700 600 500 400 300 200 100 0 World Diabetes Prev. (Mill.) 415 642 2015 2040 IDF Diabetes Atlas 2015

Diabetes prevalence estimates in European Region 2010 2030 Mill 70,0 only in age groups 20-79 years 66,5 Mill 60,0 50,0 40,0 30,0 55,4 Mill 30,0 Mill 54,3% 40,8 Mill 61,3% 60-79 years 40-59 years 20,0 10,0 20-39 years 0,0 http://www.idf.org/diabetesatlas/ Europe 2010 Europe 2030 pop 646,4 Mill. pop 659,3 Mill.

Diabetes prevalence Europe / country - 2010-2030 only in age groups 20-79 years 16,0% 14,0% National - 2010 National - 2030 12,0% 10,0% 8,0% 6,0% 4,0% 2,0% 0,0% Portugal Germany Switzerland Austria Liechtenstein Cyprus Slovenia Latvia Estonia Malta Lithuania Ukraine France Poland Georgia Croatia Belarus Monacoa Bosnia and Herzegovina Russian Federation Bulgaria Andorra Italy Greece Hungary Moldova Spain Czech Republic Serbia Montenegro Romania Finland Macedonia, the Former Belgium San Marino Netherlands Denmark Slovakia Turkey Sweden Israel Azerbaijan Luxembourg Ireland Kazakhstan United Kingdom Albania Norway Kyrgyzstan Turkmenistan Channel Islands Uzbekistan Tajikistan Iceland http://www.idf.org/diabetesatlas/

Trends for major underlying factors 20

The global ageing of the population up to 2050 and its impact on ESRD 2030 2050 2002

population [billion] 10 9 8 7 6 5 4 3 2 1 0 The Global ageing and population 2002-2050 The elderly population is projected to grow most rapidly! 7% 38% 8% 41% 10% 2002 2010 2020 2030 2040 2050 year Source: U.S. Census Bureau, An aging world International population Reports, Nov 2001 12% 15% 17% 42% 43% 42% 42% 65 y + 30-64 y of age 15-29 y of age 0-14 y of age

Population age structure EU-27 1990-2060 100 90 80 3,1 3,3 4,7 5,8 10,6 12,3 12,7 14,4 7,0 8,9 11,0 12,0 16,6 18,0 17,6 17,5 % 70 60 2017 50 40 66,8 67,2 67,0 64,3 61,7 59,0 57,0 56,2 30 20 10 0 19,5 17,2 15,6 15,5 14,7 14,2 14,3 14,2 1990 2000 2010 2020 2030 2040 2050 2060 0-14 years 15-64 years 65-79 years 80+ years (1) Excluding French overseas departments in 1990; 2010, provisional; 2020-2060 data are projections (EUROPOP2010 convergence scenario). Source: Eurostat (online data codes: demo_pjanind and proj_10c2150p)

Incidence of ESRD RRT per million age related population (pmarp) at Day 1 in 2009 2.000 1.800 1.600 1.400 1.200 1.000 800 600 400 200 0 by age group (pmarp) 75+ y 65 74 y 45 64 y 20 44 y 0 19 y van de Luijtgarden M. Clin Kidney J (2012)5: 109-119

Median Age incident & prevalent ESRD population Europe - 2012 75 Average 62,3 y Average 67,7 y Belgium, Dutch-speaking * Greece 70 67,1 y Italy (12 of 20 regions) # Spain, Castile and Leon * France 65 61,3 y Belgium, French-speaking * Austria Spain, Valencian region Denmark Sweden Croatia The Netherlands 60 55 Germany - prev.: 1996: 59 years 2006: 66 years 2014: 71 years Prevalent pat. - Median Germany - incid.: 1996: 63 years 2006: 70 years 2014: 72 years Incident pat. - Median Norway Slovakia United Kingdom, All countries * Finland Estonia Bosnia and Herzegovina ERA-EDTA Register Report 2012 selected countries Germany: Quasi-Niere Report 2006/2007

Age structure + ESRD Significant increase of the older population over the next 35 years Life longer Increase in age specific diseases (mainly non communicable diseases) many of them also causing ESRD Diabetes Hypertension Cardiovascular Diseases ESRD / HD population is getting older

Trends for major underlying diseases 27

Trends in hypertensive (HT) disease worldwide - 2000 to 2025 26% of the adult population + 588 Mill. 29% of the adult population 1,560 Bill. HT adults in 2025 972 Mill. HT adults in 2000 2017 Kearney PM Lancet (2005)365:217

Prevalence of high Blood pressure by sex (%) - 2015 Men more likely have high BP Central and Eastern Europe High Income Western Men % Sub-Saharan Africa Women more likely have high BP Others Women % NCD Risk factor Coll. Lancet (2017)365:217

Global prevalence of Hypertension (2000 and 2025) Hossain M, American Journal of Kidney Diseases (2009)53: 166-174 (data from Kearney PM Lancet (2005) 365:217)

Prevalence of HT and Overweight/Obesity HYDRA Study n = 38.873; http://www.hydra-studie.de 100% 16-29 y 30-44 y 45-59 y 60-74 y >75 y 80% 60% 40% 20% 0% Normal BMI 18.5 24.9 Overweight BMI 25 29.9 Obesity grade 1 BMI 30 34.9 Obesity grade 2 BMI 35 39.9 Obesity grade 3 BMI > 40 Bramlage P. Hypertension in Overweight and Obese Primary Care Patients Is Highly Prevalent and Poorly Controlled. Am J Hypertens 2004;17:904 910

Trends for major underlying factors

Facts on Worldwide Obesity - 2014 % Obese BMI 30 www.metrocosm.com

Age-adjusted Prevalence of Obesity and Diagnosed Diabetes Among US Adults Obesity (BMI > 30 kg / m²) 1994 2000 2014 Diabetes 1994 2000 2014 26% 9%

WHO facts on Europe Overweight Obese BMI 25 kg/m² BMI 30 kg/m² Several direct and indirect effects on the kidney WHO 07/2013 WHO 03/2014 www.euro.who.int/obesity http://www.euro.who.int/en/health-topics/noncommunicable-diseases/obesity.

Europe Obesity - 2014 Blue more obese Men Purple more obese Women Data from WHO World health statistics 2015

Association between obesity and KD based on cohort studies in the general populations (Metaanalysis) Overweight (BMI 25 BMI 30) vs normal weight Obese (BMI 30) vs normal weight Test for heterogeneity: Q=37.11, P=0.003; Pooled RR (95% Cl): 1.40 (1.30 1.50). Strong correlation with Kidney Diseases Wang Y, Kidney International (2008) 73, 19 33 Alice RZ, Advances in Chronic Kidney Disease (2013)20:121-127. Test for heterogeneity: Q=40.96, P=0.001; Pooled RR (95% Cl): 1.83 (1.57 2.13).

Body Mass Index (BMI) and Risk for End-Stage Renal Disease (ESRD) Adjusted Relative Risk for ESRD 10,0 1,0 0,1 Higher BMI was a risk factor for ESRD in adjusted multivariable models. <18,5 18,5-24,9 25,0-29,9 30,0-34,9 35,0-39,9 >40 BMI in kg/m² 320.252 adult members of Kaiser Permanente who volunteered for screening health checkups between 1964 and 1985 and who had height and weight measured. Hsu C. Ann Intern Med. 2006;144:21-28.

Diabetes CHD Cardiac paod Cerebrovascular Maglignoma Infections COPD Other chronic diseases CO-MORBIDITY

HD - Dialysis patients and Comorbidity Dialysis population (HD) prevalent comorbidities 30% diabetes mellitus needing treatment 27% CHD 54% other cardiac diseases, 13% peripheral arterial occl. disease (paod), 11% cerebrovascular diseases, 9% malignoma, 4% chronic infections, 2% demecia, 3% Polyneuropthia, 3% depression 46% had other chronic diseases 2015 Germany Only 14% of the dialysis patients had no additional diseases Zusammenfassender Jahresbericht QS-Dialyse Germany 2015

Comorbidities in Sweden 2014/2015 Komorbidita sjukdomar vid inklusion i CKD-registret 2014-2015 SVENSKT NJURREGISTER - ÅRSRAPPORT 2016

Co-morbidities / Multimorbidity Elderly nephrologic / ESRD patients Difficult vessel situation Multimorbidity Malnutrition More complications Compliance issues Often no transplant candidates Social and psychological issues Picture: courtesy M.K. Widmer, Bern Vascular access challenges More complex access revisions

OUTLOOK

The 4 bad guys for the kidney will grow further 44

RRT prevalence 25 largest countries in 2014 represent 75% of the world population (= 7.200 Mill.) Only 11 out of these 25 countries provide RRT above the 2013 world average of 450 pmp 1.600 1.400 1.200 1.000 1.367 1.265 6 countries (China, India, USA, Indonesia, Brazil, Pakistan) 50% of world population population in Mill. ESRD is existing: but often not adequately treated! 800 600 400 200 320 255 204 187 185 158 146 127 121 101 93 91 88 81 81 81 71 68 66 64 62 54 56 0 CHN IND USA IDN BRA PAK NGA BGD RUS JPN MEX PHL VNM ETH EGY DEU IRN TUR COD THA FRA GBR ITA ZAF MMR various sources

Dialysis Patients 2013 & 2030 (Millions) In the next 13 years PLUS 4 Million dialysis patients 7 6 Asia-Pacific +2.300.000 5 North America +632.000 4 Europe +319.000 3 Latin America +308.000 2 1 0 2013 2030 Middle East Africa +210.000 +156.000 Fresenius Medical Care internal estimate (2013)

Conclusion Epidemiologics Aspects Further increase prevalent HD population High prevalence of Diabetes, HT and Obesity Increasing Age of the incident and prevalent patients Elderly multimorbid nephrologic patient with ESRD More complex cases / challenges in Vascular Access Interdisciplinary Challenge Adequate training and education IMPORTANT role

Future Vascular Access Challenges The access challenge is individual and locally different in the various regions or countries in the world The biggest challenge is however how can we provide adequate and high standard vascular access for all HD patients worldwide!

ESRD 2017 ESRD 2020 ESRD 2025 ESRD 2030 ESRD 2040

Thank you very much for your attention Acknowledgement: All people around the world who run and contribute to the various ESRD registries