Carmine Zoccali Carmine Zoccali Hypertension in ESRD Hypertension in ESRD
Lancet; 2002; 360:1903 This specification is This specification is important because the important because the Ischemic Heart Disease association can be association can be Mortality 8 th used to predict risk used to predict risk 7 th only in populations only in populations low risk populations low risk populations having the same risk having the same risk 6 th profile. profile. 5 th 4 th Usual systolic BP mmHg
� .high risk populations �� a different story.. � .high risk populations �� a different story.. Rotterdam Heart Study Rotterdam Heart Study Prognostic models apply Prognostic models apply Paradoxical? Paradoxical? 4 year 4 year just to the population just to the population Cardiac death Cardiac death � .This is what we expect in � .This is what we expect in whereupon whereupon they they were were 2.31 2.31 RR RR � patients with pump failure � patients with pump failure derived .. derived .. 2.0 2.0 1.52 1.52 1.5 1.5 1.0 1.0 0.65 0.65 0.5 0.5 0.0 0.0 80 80 100 120 140 160 180 100 120 140 160 180 Systolic BP (mmHg) Systolic BP (mmHg) Drawn from data reported in the study Drawn from data reported in the study
Risk Risk Patients with HF and Patients with HF and high risk patients in high risk patients in general general Mixed Populations Individuals without CV Individuals without CV complications to start with complications to start with BP BP
48:606- 48:606 -615. 2006 615. 2006 56.000 incident dialysis patients, Fresenius MC 56.000 incident dialysis patients, Fresenius MC Survivors >1year Survivors >1year HR Non- Non -survivors survivors HR 6 6 Syst. BP Syst. BP 20 20 4 4 0 0 These data are clearly in These data are clearly in line with the hypothesis that line with the hypothesis that -20 - 20 the link between low BP and the link between low BP and 2 2 ⇑ risk of death is an ⇑ risk of death is an epiphenomenon of epiphenomenon of 1 1 deterioration pump function deterioration pump function -40 - 40 0 0 <120 <120 <120 <140 <160 <180 <200 > >200 200 <120 <140 <160 <180 <200 ) (mmHg ) Pre- Pre -dialysis Systolic dialysis Systolic Pre Pre- -dialysis Systolic dialysis Systolic (mmHg
Basic mechanism(s) of hypertension in ESRD Basic mechanism(s) of hypertension in ESRD Therapy Therapy
GFR ml.min.1.73m 2 120 CKD 80 40 ESRD 0 Prevalence % 100 90% 80 60 40 20 0
Systolic BP mmHg Systolic BP mmHg GFR ml.min.1.73m 2 Risk Reduction Risk Reduction 170 170 % ⇑ LVMI for Death or ⇑ LVMI for Death or 0 120 160 160 CKD -10 Conventional E-pub, ahead of print, 20 ° Nov 2010 150 150 80 -20 140 140 Frequent 40 -30 130 130 -39% ESRD -40 0 120 120 Prevalence Baseline 1- Baseline 1 -year year % 100 90% 80 Short dialysis, no surveillance of salt intake 60 40 Centers applying a policy 20 based on long/frequent dialysis and low salt 0 intake
⇓ restraint of central sympathetic activity 0 or � 0 ability to excrete Na VOLUME expansion Sympathetic fibers, ESRD Sympathetic fibers, peroneal nerve peroneal nerve afferent nerves High sympathetic activity
⇓ restraint of central sympathetic activity 0 or � 0 ability to excrete Na VOLUME expansion 327:1912-18, 1992 MAP MAP Sympathetic fibers, ESRD Sympathetic fibers, peroneal nerve mmHg mmHg peroneal nerve Bursts/min Bursts/min 60 60 100 100 90 90 40 40 High sympathetic activity 80 80 20 20 70 70 0 0 60 60 Healthy Healthy HD HD HD HD subjects subjects patients patients Patients Patients Post- Post -nephrectomy nephrectomy
⇓ restraint of central ⇑⇑ sympathetic activity sympathetic activity 0 or � 0 ability Airways narrowing Airways narrowing to excrete Na due to pharingeal pharingeal due to VOLUME edema and and edema recumbency recumbency expansion VOLUME expansion has Nocturnal Nocturnal ESRD indirect influences on hypoxemia hypoxemia sympathetic activity RENALASE Sleep Sleep Apnea Apnea ⇓⇓ ⇓⇓ RENALASE RENALASE (monoaminoxidase) (monoaminoxidase) ⇓⇓ ability to degrade ⇓⇓ ability to degrade catecholamins catecholamins Volume Expansion, sleep apnea (nocturnal hypoxemia) and Sympathetic Overactivity are among the most solidly established factors underlying Hypertension in ESRD
� ESRD � Also beyond BP, nocturnal hypoxia is a strong risk factor in ESRD Also beyond BP, nocturnal hypoxia is a strong risk factor in Fatal and non- -fatal CV events fatal CV events Fatal and non 1.0 1.0 non hypoxemic (SO 2 >95%) non hypoxemic (SO 2 >95%) 0.8 0.8 0.6 0.6 hypoxemic (SO 2 <95%) hypoxemic (SO 2 <95%) 0.4 0.4 Independent of BP and Independent of BP and other risk factors other risk factors 0.2 0.2 0.0 0.0 0 16.7 33.3 50.0 0 16.7 33.3 50.0 time (months) time (months) Zoccali C et al J Am Soc Nephrol. 2002;13:729-33.
� .independently of BP, high sympathetic activity is a strong � .independently of BP, high sympathetic activity is a strong predictor of CV events in ESRD predictor of CV events in ESRD CV Death (%) CV Death (%) 60 60 Nor- -Epi > median value Epi > median value Nor 40 40 Nor Nor- -Epi < median value Epi < median value 20 20 0 0 0 10 20 30 40 50 55 0 10 20 30 40 50 55 months months Zoccali C et al., Circulation 105: 1354, 2002 Zoccali C et al., Circulation 105: 1354, 2002
Basic mechanism(s) of hypertension in ESRD Basic mechanism(s) of hypertension in ESRD Therapy Therapy
Diaphane Registry Degoulet P. Proc Eur Dial � - � Transplant Assoc. 1980;17:149-54. 70- 80 70 80 � � HR 2.0 Stroke mortality CV mortality 1.5 All cause mortality Dialysis patients in the seventies were a selected, relatively young population (diabetics and those with CV complications often excluded) 1.0 0.5 0.0 First Second Third <138 139-155 >155 mmHg
Normal LV mass or mild LVH Normal LV mass or mild LVH but no alterations in systolic but no alterations in systolic function. function. TODAY, about 15% TODAY, about 15% Young, Young, relatively healthy relatively healthy In primary prevention in In primary prevention in apparently healthy persons apparently healthy persons we aim at <140/90, possibly at we aim at <140/90, possibly at normotension by a non normotension by a non- - pharmacological approach pharmacological approach
ESRD ESRD old Age old Age BP BP a composite parameter a composite parameter Volume expansion Volume expansion (either occult or (either occult or Information on components of Information on components of manifest) manifest) BP and cardiac function BP and cardiac function fundamental in some contexts. fundamental in some contexts. One size may not fit all One size may not fit all high proportion of high proportion of pts with ⇑ ⇑ PP PP pts with ~ 40% with past MI ~ 40% with past MI and/or HF and/or HF
Salt- -Vol Vol Salt Can hypertension in ESRD be controlled by simply intensifying UF? F? Can hypertension in ESRD be controlled by simply intensifying U Salt- -Vol Vol Salt Salt- -Vol Vol Salt Hypertension in ESRD Hypertension in ESRD & Carmine Zoccali NEJM 2001;344:102-7 E-pub, ahead of print, 20 Nov 2010 Apnea Hypopnea Index Apnea Hypopnea Index Systolic BP mmHg Systolic BP mmHg 100 100 170 170 80 80 160 160 60 60 150 150 Conventional 40 40 140 140 Frequent 20 20 130 130 0 0 120 120 Conventional Nocturnal Conventional Nocturnal Baseline 1- Baseline 1 -year year
2009;53:500-507 150 patients 150 patients randomized randomized 100 patients ( ⇑ ⇑ UF) UF) 100 patients ( 50 patients (standard HD) 50 patients (standard HD) Additional UF, as Additional UF, as tolerated, without tolerated, without changing changing HD HD duration duration Follow up 8 weeks Follow up 8 weeks 91 patients 91 patients 43 patients 43 patients
2009;53:500-507 Systolic BP Systolic BP mmHg mmHg 150 150 control control 140 140 UF UF - 7 mmHg 7 mmHg - 130 130 diastolic mmHg diastolic mmHg Very short term Very short term No outcome data (death, CV events) No outcome data (death, CV events) 85 85 The usefulness of this intervention still unproven The usefulness of this intervention still unproven 80 80 - 4 mmHg 4 mmHg - 75 75 0 4 8 weeks 0 4 8 weeks
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