Hemodialysis induces an acute decline in cerebral perfusion in elderly patients Casper Franssen Dept. of Nephrology University Medical Dutch Nephrology days 2019
Disclosures/ Disclosure belangen spreker (potentiële) belangenverstrengeling Voor bijeenkomst mogelijk relevante relaties met bedrijven Zie hieronder Bedrijfsnamen Sponsoring of onderzoeksgeld Amgen, Fresenius Honorarium of andere (financiële) vergoeding Aandeelhouder - Andere relatie, namelijk - -
Publication J Am Soc Nephrol 2018;29:1317-1325
Major problems with conventional HD Large fluctuations, e.g. in hydration status: frequent hemodynamic instability High cardiovascular morbidity and mortality, mainly cardiac & cerebrovascular
Concept: HD as a risk factor
HD also a risk factor for cerebral damage? Transition to HD is associated with decline in cognitive function 1 rise in stroke incidence 2 Progression of white matter lesions during 1 st year of HD. This was attenuated with cool dialysate 3 1 Kurella Tamura, Int 2017; 2 Murray, JASN 2013; 3 Eldehni, JASN 2015;10:1408-17
Hypothesis The repetitive circulatory stress of HD induces induces (cumulative) ischemic cerebral injury But.. the mechanism by which HD could contribute to brain injury is unknown
Study aims 1. To study the acute effect of hemodialysis on global and regional cerebral blood flow 2. Explore associations between HD-related factors and cerebral blood flow 1 : MAP UF-volume & UF-rate pco 2 & ph Hematocrit Body temperature 1 MacEwen, JASN 2017; Yoon, Front Physiol 2012; Hata, Stroke 1994; Stefanidis, Clin Nephrol 2005; Metry, Am J Dis 2002; Eldehni, JASN 2015
Patients Inclusion criteria: age 65 years arteriovenous fistula without recirculation Exclusion criteria: history of dementia, CVA >70% internal carotid artery stenosis 100000 50000 0 30,000 20,000 10,000 0,000 whole-blood (Bq/cc) 0 100 200 300 Gray Matter (kbq/cc) 0 100 200 300
Methods - [ 15 O] H 2 O PET-CT scans T1: before HD (mean -18 min) T2: early during HD (mean +21 min) T3: at the end of HD (mean +209 min) Dialysis settings: - Constant UF-rate - Dialysate temp. 36.5 C
Results - Patients Patient characteristics N=12 Age 75.4 ± 5.2 Male sex 7 (58%) Dialysis vintage (months) 47 (range 11-319) Diabetes 3 (25%) Fazekas score of white matter lesions: 0 No WML 1 (8%) 1-2 Multiple punctate - confluent WML 9 (75%) 3 Large confluent WML 2 (17%) Microbleeds 7 (58%)
Results - Global CBF change Before (T1) versus at the end of HD (T3): ml/100g/min % Global CBF -4.1 (-7.3; -0.9) * -10.3 * p<0.05
Results - Regional CBF change Before (T1) versus at the end of HD (T3): ml/100g/min % Frontal -5.1 (-9.5; -0.6) * -10.9 Parietal -4.7 (-8.7; -0.8) * -11.3 Temporal -4.0 (-7.4; -0.6) * -9.7 Occipital -4.4 (-8.4; -0.3) * -9.2 Cerebellum -5.0 (-9.2;-0.8) * -9.8 Thalamus -5.5 (-11.1; 0.2) -10.2 * p<0.05
HD-related factors Factors associated with lower cerebral perfusion: Higher UF volume Higher blood ph (only at T2) Higher tympanic temperature
Adverse event A patient lost consciousness due to dialysis hypotension shortly after the 3 rd scan Full recovery without sequelae CBF decreased 20% from T1 to T3
Conclusion 1. Conventional HD induces a decline in global CBF of 10% in elderly patients 2. A higher ph, body temperature and UF volume were associated with lower CBF Repetitive intradialytic decreases in CBF may be one of the mechanisms by which HD induces cerebral ischemic injury
How do our results fit in recent literature? I Mean flow velocity decreased 10% (n=82) JASN 2019 Transcranial Doppler: velocity of art cerebri media Fall in flow velocity correlated significantly with UF-volume & intradialytic decline in cognition At 12 months of follow-up, the decline in CBF correlated with: progression of white matter lesions Lower global and executive function
Open questions 1. Are repetitive HD-induced CBF declines causally related to ischemic brain lesions & cognitive decline? 2. What exactly causes the decline in CBF? Hemodynamic changes/ hypovolemia: - UF - Temperature Acid-base & electrolyte changes - ph Inflammation & endothelial dysfunction - angiopoeitin-2 Polinder et al. J Cerebr blood flow Metabol 2018 On a background of - macro- & microvascular lesions - autonomic dysfunction - endothelial dysfunction
Future research Study the effect of a lower UF rate & slower correction of acidosis on CBF (nocturnal HD) Study link between HD-induced inflammation/ endothelial dysfunction & organ perfusion Ultimate goal: to identify HD-related factors that are involved in CBF decline HD regimen that minimizes cerebrovascular (and cardiac) stress
Cool Warm What can we do in the meantime? 1. Use cool dialysate 2. Renal transplantation Transplantation 2015 JASN 2019 3. Cognitive & exercise training Eldheni et al. CJASN 2015;10:1408-17 KI reports 2017
Acknowledgements This study was financed by a grant from the Healthy Aging Pilot Fund of the University Medical, The Netherlands Dept. Nephrology: Dialysis Students: Dept. Nuclear Medicine: Nuclear Med technologists: Dept. Neurology: Dept. Mathematics: Dept. Radiology: Dept. Neuropsychology: Dept. Epidemiology: Participating patients Casper Franssen - study PI Carlo Gaillard, Ron Gansevoort. Hannie Kuiper, Ralf Westerhuis Rozemarijn, Renske, Marleen, Thom, Brandt, Lara David Vállez García, Antoon Willemsen, Riemer Slart, Gert Luurtsema, Philip Elsinga, Ronald Boelaard, GMP laboratory Johan Wiegers, Eelco Severs, Paul van Snick, Aafke Zeilstra, Yvonne van der Knaap Marcel Aries, Jan Willem Elting Wim Krijnen Peter Jan van Laar Fijanne Strijker Henk Groen
c.f.m.franssen@umcg.nl