creatinine 6000 - nwpgmd.nhs.uk this patient have flash... · 73 yr old lady; type 2 diabetes ......
TRANSCRIPT
29/11/2017
1
Does this patient have ‘flash’
pulmonary oedema?
Philip A Kalra
Professor of Nephrology,
Salford Royal Hospital and University of Manchester, UK
Case 1
73 yr old lady; type 2 Diabetes 10 yrs; PVD; hypertension
Acute presentation with 3 day history of pulmonary oedema and anuria (April 2005)
Creatinine 712 mol/l (eGFR 3 ml/min), K 6.1 mmol/l
Needed urgent haemodialysis
Renal U/S : no obstruction, left K 10 cm
Suspected diagnosis : acute left RA occlusion
Serial Creatinine Measurements
0
200
400
600
800
1000
9.4
10.4
10.4
11.4
11.4
13.4
19.4
20.4
21.4 4.
512
.8
Date
Creatinine
Stented
Dialysed
Dialysed
Dialysed
mol/l
2005
British Society for Heart Failure Hypertension/renovascular disease Fibromuscular disease
(FMD) Fibromuscular disease (FMD)
Up to 10% of all renovascular disease
Greatest incidence in women (9:1) aged < 35 years (but also elderly – Pascual, AJKD 2005)
75% have renal involvement, bilateral in 35%; 3% have renal impairment
Associated with pathology in other arterial systems eg carotids (15%)
Familial clustering
Prevalence : data from angiography in kidney donors (3181 patients in 3 studies) – range 3.8%-6.6% (average 4.4% : Cragg et al. 1989; Neymark et al. 2000; Andreoni et al. 2002)
FMD : management
Clinical presentation usually :
hypertension (may be
‘accelerated’) + preserved
renal function
Lesions tend not to progress
over time
Hypertension ‘cure’ rate of
15-30% with angioplasty
(Slovut & Olin 2004), but no
RCT comparing medical
therapy
Angioplasty recommended for
– young
– FMD diagnosed soon after
hypertension onset
– malignant hypertension
– renal impairment
– bilateral disease
Other patients : renin angiotensin
blockade + low dose aspirin (Olin &
Sealove 2011; Plouin et al 2007)
Atherosclerotic renovascular disease
(ARVD) CVS co-morbidity and ARVD
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
CAD CCF PVD AAA CVA
% with RAS
Harding
JASN 1990 MacDowall
Lancet 1998
Choudri
BMJ 1990
Olin
AmJ Med
1990
Kuroda
Stroke 2000
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2
Other CKD
ARVD
Survival after
haemodialysis start
Other CKD
ARVD
Survival – non-dialysis CKD (eGFR 33 ml/min in both groups)
ARVD 2016 : prognosis
still very poor
Why would we consider renal
revascularization in ARVD?
Cardiac
‘Flash’ pulmonary
oedema
Improve ‘congestion’
(cardio-renal disease)
Pre-coronary or
carotid surgery
Blood pressure
Control of severe
hypertension
Renal
Acute kidney injury
Prevention of severe
RAS → RAO
‘Rapid’ deterioration
in renal function
Patients who need
RAA blockade but are
intolerant
Case 2 65 yr old lady with 3 episodes of acute pulmonary
oedema in 12 months
BP 220/88 on 3 agents
Echo – moderate to severe systolic dysfunction (EF 35%) and LVH
Claudication; right carotid stenosis but no history of IHD
↓GFR from 60 to 22 ml/min in 15 months
MRA bilateral 80-90% RAS; right kidney 9 cm, left 11cm
Changes in isoSK-GFR and
cardiac MR parameters
0
5
10
15
20
25
30
35
Left
GFR
Right
GFR
Pre
Post
Pre-
revasc
4
months
EF (%) 42 53
LVEDV
(ml)
200 106
LV mass
(g) 201 133
GFR
(ml/min)
Case 3 : 76 yrs old male
Bilateral 90% RAS – 2 x attempts at revascularization 5 yrs earlier by cardiologists in London
referred with deteriorating renal function
BP 127/53 on verapamil, candersartan, indapamide
Urine PCR 2 g/mol
USS kidneys : right 9.5cm, left 10 cm
creatinine eGFR
– 2 yrs earlier 147 46
– May 2011 203 31
– August 219 26
Case 3 : Renal revascularization August
2011
0
5
10
15
20
25
30
35
40
45
50
2009 Aug-11
eGFR
ml/min
Case 4
Male aged 53
Hypertension (175/90)
Serum creatinine 180mol/l
Kidney sizes : L 9.8cm;
R 11.3cm
Angiogram : L 80% RAS; R
normal
Randomised into ASTRAL :
Successful revascularization Case 4 : Follow-up
Feb 2001 290 mol/l
March 2001 369 mol/l
April 2001 535 mol/l
May 2001 997 mol/l
June 2001 commenced
dialysis
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Renal revascularization : RCTs in ARVD
Level 1 evidence now derived from the following RCTs in ARVD :
- EMMA study (49 patients) – Plouin et al, 1998
- DRASTIC (106) – Van Jaarsfeld et al, 2000
- Scottish and Newcastle (55) – Webster et al, 1998
- STAR (160) – Beutler et al, 2009
- ASTRAL (806) – N Eng J Med, 2009
- CORAL (947) – N Eng J Med, 2013
Many single and multi-centre prospective and retrospective studies showing benefit of revascularization in a proportion of patients
New England Journal of Medicine
2009; 361 : 1953-62
PATIENT CHARACTERISTICS BY
RANDOMISED TREATMENT
Revasc. Medical P-value
Mean age (range) 70 (42 – 86) 71 (43 – 88) 0.7
Male 63% 63% 0.9
Ex-smoker 52% 55% 0.3
Current smoker 20% 22% 0.5
Diabetes 31% 29% 0.5
CHD 49% 48% 0.2
PVD 41% 40% 0.7
Stroke 18% 19% 0.4
Dialysis 0% 0.3% 0.5
LABORATORY and BP DATA BY
RANDOMISED TREATMENT Revasc. Medical P-value
SCr (μmol/l)
88 μmol/l = 1 mg/dl
179
(66 – 551)
178
(64 – 750)
0.9
Rapid increase in SCr 12% 12% 0.9
GFR (ml/min) 40.3
(5.4 – 124.5)
39.8
(7.1 – 121.7)
0.7
Albumin:Creatinine ratio 70.2
(0 – 2740)
71.7
(0 – 2466)
0.9
Systolic BP (mm Hg) 149
(87 – 270)
152
(90 – 241)
0.07
Diastolic BP (mm Hg) 76
(45 – 120)
76
(46 – 130)
0.6
Cholesterol (mmol/l) 4.68
(0.1 – 14.8)
4.71
(1.9 – 9.6)
0.8
Change in Systolic
blood pressure
Change in renal function
Average RAS = 76%;
20% non-compliance with
revascularization
Macrovascular
events
Survival
A Randomized Multicenter
Clinical Trial of Renal Artery Stenting in
Preventing Cardiovascular and Renal Events:
Results of the CORAL Study
Christopher J. Cooper, M.D., Timothy P. Murphy, M.D., Donald E. Cutlip, M.D., Kenneth Jamerson, M.D.,
William Henrich, M.D., Diane M. Reid, M.D., David J. Cohen, M.D., M.Sc., Alan H. Matsumoto, M.D.,
Michael Steffes, M.D., Michael R. Jaff, D.O., Martin R. Prince, M.D., Ph.D., Eldrin F. Lewis, M.D.,
Katherine R. Tuttle, M.D., Joseph I. Shapiro, M.D., M.P.H., John H. Rundback, M.D.,
Joseph M. Massaro, Ph.D., Ralph B. D’Agostino, Sr., Ph.D., and Lance D. Dworkin, M.D.,
on behalf of the CORAL
Investigators
CORAL : Inclusion criteria and primary
outcome measure
INCLUSION CRITERIA Clinical Syndrome:
• Hypertension ≥2 anti-hypertensive
medications, OR
• Renal dysfunction defined as Stage 3
or greater CKD
-AND-
Atherosclerotic Renal Artery Stenosis:
• Angiographic: ≥ 60% and < 100%, OR
• Duplex: systolic velocity of >300
cm/sec, OR
• Core lab approved MRA, OR
• Core lab approved CTA
PRIMARY OUTCOME
• Composite of major
cardiovascular or renal events:
– Cardiovascular or Renal
Death
– Stroke
– Myocardial Infarction
– Heart Failure Hospitalization
– Progressive Renal
Insufficiency
– Permanent Renal
Replacement Therapy
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Medical therapy
Stent plus medical therapy
HR 0.94 [0.76-1.17], p = 0.58
Stent + Medical Therapy 35.1%, 3-years
Medical Therapy 35.8%, 3-years
Results: Primary Endpoint
Clinical Events US Medicare : Trends in
revascularization 1992-2010
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1992 1994 1996 1998 2000 2002 2010
RR
In 2004 approx 30,000 renal stent procedures performed annually in US
↓
ASTRAL published
What have we learned from the RCTs?
Revascularization does not
improve outcomes in majority
of unselected patients with
ARVD
These conclusions only apply
to the patient phenotype
included in the studies
Some patients do benefit
from revascularization – who
are they and can we reliably
identify them?
Don’t forget the benefits of
medical therapy
But at least no more ‘drive-by’
shootings!
Selection of cases for renal
revascularization Haemodynamically
significant RAS with:
– Recurrent unexplained
congestive heart failure (Class I, evidence level B)
– Resistant / malignant hypertension (Class IIa, evidence level B)
– Progressive CKD and bilateral RAS (Class Iia, evidence level B).
2005
Am J Kid Dis 2014; 63(2) : 186-97
Effect of renal revascularization in patients
with RAS > 70% :control versus high-risk* D Vassallo et al; BMC Nephrology (in Press)
Control
n=144; 43 PTRAS
(30%)
P value High-risk
n=131; 55 PTRAS
(43%)
P
value
Death 1.20 (0.61-2.38) 0.60 0.64 (0.33-1.26) 0.20
ESKD 1.00 (0.60-1.66) 1.00 0.64 (0.37-0.96) 0.03
CVE 1.06 (0.65-1.72) 0.82 0.66 (0.42-1.04) 0.07
Any
outcome
1.12 (0.69-1.82) 0.65 0.70 (0.45-1.09) 0.12
Flash pulmonary oedema : HR for death with PTRAS 0.38 (0.15-0.96; p=0.04)
Deteriorating renal function : HR for ESKD with PTRAS 0.44 (0.24-0.82; p=0.01)
*High risk = flash pulmonary edema, rapid deterioration in function or severe hypertension
Techniques to detect
responders to PTRAS
Pressure wire studies
Fractional flow reserve
(FFR)
Duplex ultrasound
MR perfusion imaging
– Volume : GFR
BOLD imaging
Pressure wire criteria
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5
MR perfusion imaging - Parenchymal Volume
(PV) : SK-GFR of stented kidneys
Number Mean PV : SK-GFR
SD Range
Deteriorated
(>15%
Deterioration
renal function)
5
4.86
1.1
3.7- 5.8
Stable (-15 to
15%)
18 6.38 2.5 3.6- 12.7
Improved
(>15%
Improvement
renal function)
7
17.49
15.2
6- 45.4
PV:isoSK-GFR characteristics in improvers (>15% improvement in isoSK-GFR) and non-improvers as compared to normal vessel or insignificant RAS group, *P < 0.05.
Cheung C M et al. Nephrol. Dial. Transplant. 2010;25:1133-1140
© The Author 2009. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: [email protected]
High grade proteinuria =
bad outcome in ARVD
(> 0.6 g/day)
3 main considerations prior to
possible revascularization
Does the patient have a key clinical phenotype (eg
FPE, declining function, severe hypertension)?
Is the RAS physiologically or haemodynamically
significant?
What is the state of the kidney beyond the RAS?
– Renal atrophy (< 7 cm)
– Significant proteinuria = severe parenchymal disease
– Determine kidneys with greatest ischaemic stress yet
viable tissue (‘Hibernating’ kidney tissue)
Beta-blockers
No β-blocker
With β-blocker
• ACE-I/ARB
• Statins
• Anti-platelet
also all effective
Medical therapy
Important :
Where are we now in the management
of Renal Artery Stenosis?
Patients with atherosclerotic RVD have very high
CVS risk
They should all receive comprehensive vascular
protective medication (statin, ACE-I/ARB, anti-
platelet)
An important minority of patients will benefit
from renal revascularization : it is important to
identify them
Revascularization in atherosclerotic RAS is
NOT for all but it should be for some……..
Definite indications
Severe or dialysis
dependent AKI
Patients who require/would
benefit from Renin
angiotensin blockade but
who are intolerant
Recurrent acute heart
failure
Possible indications
Very severe hypertension (eg SBP > 180 on 4+ drugs)
Rapidly deteriorating renal function : individual case basis
If rapidly deteriorating renal function and severe hypertension occur together
Emerging indications Patients with ‘hibernating’ renal
parenchyma ?
Chronic heart failure ?
Preventing renal atrophy long term?