hypertension and kidney disease: a nephrologist’s perspective · hypertension and kidney disease:...
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Hypertension and KidneyDisease: a Nephrologist’s
Perspective
Alan Jardine University of Glasgow
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CKD
Dialysis
Tx
Natural history of PRD
GraftFailure
CV Risk
x 3-5
x 10-20
x 3-5
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Incidence of Kidney Failureper million population, 1990-2000, by HSA, unadjusted
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Jardineetal.,Lancet2011:378:1419-27
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Renal Protection
Parving et al; BMJ 1987
The effect of antihypertensive treatment
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ACE INHIBITORS AND RENAL FUNCTION
Lewis et al: NEJM 1993
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Losartan Irbesartan Irbesartan amlodipinevs placebo vs placebo vs amlodipine vs placebo
X2 creat, ESRD, death 16 20 23 -4p=0.024 p=0.024 p=0.006 NS
x2 creat 25 33 37 -6p=0.006 p=0.003 p=0.001 NS
ESRD 28 23 23 0p=0.002 p=0.07 p=0.007 NS
Death -2 “NS” “NS” “NS”
ESRD or death 20 N/A N/A N/A
RENAAL & IDNT Trial Results Comparison of Primary Composite Endpoint and Components
% RR reduction
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Liu Y, et al., JAMA 291: 451-459, 2004
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4D ALERT 4S AURORA
EP Placebo Placebo Placebo Placebo
CD 23% 5.1% 8.5% 23.4%
AMI (NF) 12% 6.3% 22.6% 7.7%
Non-CVD 25% 6.2% 2.2% 19.4%
Is CVD the same in CKD?
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4D ALERT 4S AURORA
EP Placebo Placebo Placebo Placebo
CD 23% 5.1% 8.5% 23.4%
AMI (NF) 12% 6.3% 22.6% 7.7%
Non-CVD 25% 6.2% 2.2% 19.4%
Is CVD the same in CKD?
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Risk Factors – MI
RR CI P .
Age 1.03 (1.00,1.05) 0.0211Diabetes 2.36 (1.42,3.04) 0.0010Smoking 2.31 (1.78,5.63) 0.0017CHD 3.17 (2.08,5.18) 0.0001LDL 1.41 (1.12,1.77) 0.0038
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Risk Factors – Cardiac death
RR CI P . Age 1.05 (1.02,1.08) 0.0001Diabetes 2.82 (1.62,4.91) 0.0002Smoking 1.55 (0.86,2.80) 0.1490CHD 3.60 (1.96,6.63) <0.0001LDL 1.28 (0.99, 1.65) 0.0607SBP 1.01 (1.00,1.03) 0.0506PP 1.01 (1.00,1.03) 0.0034LVH 2.08 (1.11, 3.89) <0.0001ST-T 3.59 (2.07, 6.21) <0.0001
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The Uraemic Heart
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Stewart GA et al., KI 2006;67:217-26
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Mark PB et al., Kid. Int. 2006;69:1839-45
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Mark PB et al., Kid. Int. 2006;69:1839-45
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Rutherford E et al., KI 2016; 90:845-52
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Graham Brown MPM et al., KI 2016; 90:835-44
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Edwards NC et al., Am J Cardiol 2015;115:1311-1317
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Moody WE et al., Hypertension 2016;67:368-72
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Patel RK et al., CJASN 2011;6:519-527
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Stewart GA et al., KI 2006;67:217-26
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Patel R et al. CJASN 2009;4:1477-83
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McQuarrie E et al., NDT 2011;26:933-38
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Sodium & Aldosterone
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Wilkinson R et al., QJM 1970;39:377-394
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McQuarrie EP et al., Hypertension 2014:64:111-117
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Freel EM et al, Circulation CV Imaging 2012;5:740-747
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McQuarrie EM et al., Clin Sci 2012;123:685-694
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McQuarrie E et al., NDT 2003;28:1526-32
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McQuarrie E et al., NDT 2003;28:1526-32
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McQuarrie E et al., NDT 2003;28:1526-32
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Ito Y et al., JASN 2014;25:1094-1102
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Ando K et al., Lancet Diab Endo 2014:2:944-53
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Currie G et al., BMC Nephrology 2016;17:127
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Currie G et al., BMC Nephrology 2016;17:127
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SPRINTNEJM2015;373:2103-2116
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SPRINTNEJM2015;373:2103-2116
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SPRINTNEJM2015;373:2103-2116
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SPRINTNEJM2015;373:2103-2116
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Anything new?
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Lancet Feb 2009
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RelationofMACEwithbaselineSerumPhosphateandHaemoglobin
Even
t ra
te (
%)
16
14
12
10
8
6
Phosphate
Decile
0 2 4 6 8
p<0.0001
Even
t ra
te (
%)
16
14
12
10
8
6
Hemoglobin
Decile
0 2 4 6 8
n.s.
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B.
0
20
40
60
80
100
120
PE1E-5
1.00E-08
3.00E-08
1.00E-07
3.00E-07
1.00E-06
3.00E-06
1.00E-05
3.00E-05
SNP concentration
% R
ela
xa
tio
n
A.
0
20
40
60
80
100
120
PE1E-5
1.00E-08
3.00E-08
1.00E-07
3.00E-07
1.00E-06
3.00E-06
1.00E-05
Carbachol
% R
ela
xa
tio
n
P<0.001
P=0.007
Phosphate– directeffectsonvascularfunction
Stevens KK et al., NDT 2016 (ePub)
Stevens KK et al., Lancet 2015;385:S10
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Oral phosphate loading reduced flow mediated dilatation by over 50% in normal human subjects.
*p<0.001comparedwithbaselinemeasures
*
Stevens KK et al., NDT 2016 (ePub)
Stevens KK et al., Lancet 2015;385:S10
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Stevens KK et al., Int J Nephrol (2011)
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Zinman B et al., NEJM 2015;373:2117-28
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Weber MA et al. Blood Pressure 2015;25:93-103
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Bushinsky DA et al., KI 2015;88:1427-33
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Weir MR et al., KI 2016;90:696-704
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Weir MR et al., KI 2016;90:696-704
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