hypertension and CRF

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Hypertension In Chronic Kidney Disease
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Introduction
Renal disease
loss of nephrons
Systemic hypertension
Proteinuria
Progressive decline in GFR
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CKD Common pathway in disease progression
RENAL INJURY
?Nephron mass Glomerular capillary
hypertension ?Glomerular permeability to
macromolecules ?Filtration of plasma proteins ?
Proteinuria Excessive tubular protein
reabsorbtion Tubulo-interstitial inflammation
SYSTEMIC HYPERTENSION
RENAL SCARRING
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CKD Common pathway in disease progression

• Therapeutic intervention inhibiting this common
  pathway may succeed in slowing the rate of
  progression of CRF irrespective of the initiating
  cause

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How important is systemic blood pressure control?

• Relative risk of ESRD according to quintile BP

MRFIT study N 332,544 men
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What should be the treatment goal?

• Treatment goal for hypertension in the general
  population has remained relatively the same for
  the last decade.

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What should be the treatment goal for renal
disease?

• Should be lower than the general population
• Should be tailored according to

• the severity of renal failure
• the severity of the proteinuria

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Proteinuria and target BP control

• Aggressive BP control to 125/75 mmHg showed
  better preservation of GFR for those with
  proteinuria gt3g/day.
• No additional benefit if proteinuria is lt 1g/day

Klahr S, Levey AS NEJM 1994 330877
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What should be the treatment goal for renal
disease?
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What should be the treatment goal for non
diabetic renal disease?

• Treatment goal should depend on the severity of
  proteinuria

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Proteinuria

• There is indisputable evidence from animal,
  laboratory and clinical studies that proteinuria
  per se contributes to progressive renal injury

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Proteinuria and renal disease progression
Klahr S, Levey AS NEJM 1994 330877
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Proteinuria and renal disease progression
REIN SUBSTUDY Progression of renal disease
according to severity of proteinuria
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Proteinuria and renal disease progression

• It is now clear that different classes of
  antihypertensive agents have different
  antiproteinuric capacity
• ACEI and ARB have been showed to exhibit the
  highest capacity to diminish protein excretion in
  urine

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ACE Inhibitors In Nephropathy
P0.04
REIN Study KIDNEY SURVIVAL
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ACE Inhibitors In Nephropathy
REIN Study
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ACEI, ARB and combination treatment in
Nephropathy
COOPERATE STUDY Median urinary protein excretion
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ACEI, ARB and combination treatment in
Nephropathy
COOPERATE STUDY proportion reaching endpoints
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Choice of antihypertensive agent for non
diabetic renal disease

• ACEI or ARB should be the first choice
  antihypertensive agent in patient with
  significant proteinuria.

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Choice of antihypertensive agent for non
diabetic renal disease

• Dose of ACEI or ARB should be titrated to
  achieve both target BP and the disappearance of
  proteinuria

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Choice of antihypertensive agent for non
diabetic renal disease

• If target blood pressure is not achieved and
  especially in the presence of persistent
  proteinuria, an ARB should be added.

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Precautions when starting ACEI or ARB

• Check Cr and K within 7-14 days after starting
  treatment especially in the presence of renal
  impairment
• An acute rise in Cr of 30 should be tolerated if
  BP is adequately reduced (lt140/90), hyperkalaemia
  is absent and the patient is euvolaemic
• If Cr continues to rise, or hyperkalaemia
  persist, stop drugs assess for bilateral RAS

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Choice of antihypertensive agent for non
diabetic renal disease

• Choice of combination antihypertensive agents
  depend on the existing comorbidity

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Drug(s) for the compelling indication
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Choice of Anti-Hypertensive drugs in patient
with concomitant disease
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Choice of antihypertensive agent for non
diabetic renal disease

• Since studies have demonstrated that most
  hypertensive patients will require multiple drugs
  to achieve target BP, the argument about which
  one is superior has become almost irrelevant
• We must provide all of the drugs needed to
  achieve maximal protection with the fewest
  adverse effects

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Summary
Control Blood Pressure
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Summary

• Choice of antihypertensives