blood pressure and renal disease ish

8/6/2019 Blood Pressure and Renal Disease ISH

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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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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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Does hypertension cause renal disease?

Does BP treatment reduce progression?



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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?



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?



Differences between European and US

Registry data.

Need renal biopsy studies to resolve


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Does hypertension cause renal disease?

Does BP treatment reduce progression?



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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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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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ACE Inhibition and receptor Blockade reduces

proteinuria 20 40%Meta analysisKunz R; Friedrich C; Wolbers M; Mann JF


What about progression?


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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


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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Does hypertension cause renal disease? Does BP treatment reduce progression?



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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

I


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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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blood pressure and renal disease ish

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