blood pressure and renal disease ish
TRANSCRIPT
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Blood Pressure and the Kidney
Renal Disease as a CV risk factor
Does hypertension cause renal disease? Does BP treatment reduce progression?
Practical guidelines for management
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Blood Pressure and the Kidney
Why the interest?
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RAISED BLOOD PRESSURE >160/90.
Very Common in Renal Disease
DIABETES
GOMERULONEPHRITIS
POLYCYSTIC
PYELONEPHRITIS
90%
85%
80%
30%
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Not really surprising
Fluid retention Vasoconstrictors e.g. angiotensin
Vasodilators e.g. prostaglandins
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Hypertension is a strong risk factor for
Cardiovascular Disease.
.....so is Renal Disease
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Richard Bright
1789-1858
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Richard Bright
1789-1858
And when the urine
coagulates, the pulse does
harden.Richard Bright 1815
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Incidence of Fatal Stroke in Renal Failure
1981-85
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Blood Pressure and the Kidney
Renal Disease as a CV risk factor
Does hypertension cause renal disease?
Does BP treatment reduce progression?
Practical guidelines for management
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MRFIT Klag et al NEJM 1996
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Cause or Effect?
Does essential (non malignant) HTN ever
cause renal failure in the absence of RenalDisease?
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Benign hypertension does not cause clinically
significant renal damage. The kidney in benignhypertension remains normal in both size and
function
Pricilla Kincaid-Smith 1982
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Cause or Effect?
Does essential (non malignant) HTN ever
cause renal failure in the absence of RenalDisease?
Differences between European and USRegistry data.
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PRIMARY RENAL DIAGNOSIS
in National Renal Registries
USRDS 2003 - 07
25% HYPERTENSION
4% UNKNOWN
UK RENAL REGISTRY 2006
5% HYPERTENSION
22% UNKNOWN
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PRIMARY RENAL DIAGNOSIS
in National Renal Registries
USRDS 2003 - 07
25% HYPERTENSION
4% UNKNOWN
28% BLACK
UK RENAL REGISTRY 2006
5% HYPERTENSION
22% UNKNOWN
5% BLACK
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Hypertension and Renal Disease are both
more common and more aggressive in black
patients
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Increased Renal Deaths in
Hypertensive Black PatientsMRFIT Am J Kid Dis 1993
Flack JM et al Am J Kid Dis 1993
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Cause or Effect?
Does essential (non malignant) HTN ever
cause renal failure in the absence of RenalDisease?
Differences between European and US
Registry data.
Need renal biopsy studies to resolve
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Blood Pressure and the Kidney
Renal Disease as a CV risk factor
Does hypertension cause renal disease?
Does BP treatment reduce progression?
Practical guidelines for management
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Does treatment of Hypertension
reduce progression of renal failure?
Can we slow it down, reverse or even prevent it?
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BLOOD PRESSURE CONTROL & RENAL FUNCTIONMogensen C.E. BMJ, 1982
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Blood Pressure Control and Renal Function
Parving et al
Lancet 1983
n = 11
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Angiotensin Inhibition and Diabetic
Nephropathy
Taguma Y, Kitamoto Y, Futaka G, Ueda H, Monma H, Ishizaki
M, Takahashi M, Sekino H, Sasaki,Y. NEJM 1985
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Taguma Y, Kitamoto Y, Futaka G, Ueda H, Monma H, Ishizaki M, Takahashi M, Sekino H, Sasaki,Y.
NEJM 1985
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Exciting because.....
Degree of proteinuria generally reflects the
extent of glomerular damage (intraglomerularpressure) and likelihood of progression.
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Was this just an effect of blood pressure
reduction?
Would it result in long term protection of
renal function?
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We needed controlled studies
Ed Lewis et al. NEJM 1993, 329
Captopril v placebo (ie non- ACEI antihypertensives)
in type 1 diabetics
Equal BP lowering
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Renal End Points after 4 yearsLewis et al NEJM 1993. 329
Captopril n=207
Death 8
Dialysis or
Transplantation 20
Death, dialysis or
transplantation 23
Others n=202
14
31
42
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Non diabetic Renal Disease
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Non diabetic Renal Disease
ACE Inhibition and receptor blockade reduces
proteinuria 20 40%Meta analysisKunz R; Friedrich C; Wolbers M; Mann JF
Ann Intern Med. 2008 Jan 1;148(1):30-48
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Non diabetic Renal Disease
ACE Inhibition and receptor Blockade reduces
proteinuria 20 40%Meta analysisKunz R; Friedrich C; Wolbers M; Mann JF
Ann Intern Med. 2008 Jan 1;148(1):30-48
What about progression?
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Non diabetic Renal Disease
Effect of ACEI on Renal Function
Ramipril Efficiency in Nephrology (REIN) Study.Lancet 1997. 349, 1857. 352 non diabetic, proteinuric renal disease
Double blind randomised controlled trial of
ramipril againstplacebo(conventional)
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Progression of Renal Failure in the
REIN study
ramipril
control
ff i h i i i
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Greater Effect with Heavier Proteinuria
REIN Study. Ramipril v placebo
Lancet 1998. 352, 1252
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PROGRESSION OF RENAL FAILURE
REVERSED REIN FOLLOW UP TRIALRUGGENENTI P et al. J Am Soc Nephrol 10: 9971006, 1999
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ACEI in advanced diseaseHou FF et al. N Engl J Med. 2006 354:131-40.
Placebo controlled. Benazapril v placebo
Group 1 creatinine 1.5 3.0 mg/dl (132 264um/l)
Group 2 creatinine 3.1 5.0 mg/dl (273 440um/l)
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ACE Inhibition or Angiotensin Receptor
Blockade (ARB)?
Reduction in proteinuria equivalent.Meta analysisKunz R; Friedrich C; Wolbers M; Mann JF
Ann Intern Med. 2008 Jan 1;148(1):30-48
Probably true also for renin inhibitors
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How to Enhance the Effect?
Combine ACEI and ARBProduces further reduction in proteinuria.
Meta analysis. Kunz R et al. Ann Intern Med. 2008 Jan 1;148(1):30-48
Effect on progression uncertain COOPERATE Study. Withdrawn
Concerns over adverse effectsON TARGET Study. Mann JF; Schmieder RE et al. Lancet. 2008 Aug 16;372(9638):547-53.
Supramaximal dose
Low Na diet and diuretic
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Effect of Supramaximal doses of
Candesartan in Proteinuric Renal Disease.Burgess et al. J Am Soc Nephrol 2009
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How to Enhance the Effect?
Combine ACEI and ARBProduces further reduction in proteinuria.
Meta analysis. Kunz R et al. Ann Intern Med. 2008 Jan 1;148(1):30-48
Effect on progression uncertain COOPERATE Study. Withdrawn
Concerns over adverse effectsON TARGET Study. Mann JF; Schmieder RE et al. Lancet. 2008 Aug 16;372(9638):547-53.
Supramaximal dose
Low Na diet and diuretic
E h d Eff t f A i t i I hibiti
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Enhanced Effect of Angiotensin Inhibition
by Na restriction and diuretics
Voit et al J Am Soc Nephrol 2008. 999
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Blood Pressure and the Kidney
Renal Disease as a CV risk factor
Does hypertension cause renal disease? Does BP treatment reduce progression?
Practical guidelines for management
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Guidelines
For proteinuric CKD JNC 7 and the K/DOQIClinical Practice and British Guidelines
< 130/80
Include ACEI or ARB in the antihypertensiveregime
But not less than 120/80Lowest systolic blood pressure is associated with stroke in stages 3 to 4 chronic kidney disease.
Weiner DE; et al. J Am Soc Nephrol. 2007. 960-6
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Conclusions
Renal Disease is a risk factor for cardiovascular
morbidity and mortality
Blood Pressure reduction reduces progression
of proteinuric chronic kidney disease
Inhibition of the renin angiotensin system
enhances this effect
Progression of proteinuric CKD is preventable
and possibly reversible
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