Treatment of Diabetic Nephropathy and Proteinuria Background

1
Treatment of Diabetic Nephropathy and
ProteinuriaBackground

• End stage renal disease is a major cause of death
  and disability among diabetics
• Blood pressure reduction is an important initial
  step in slowing the progression of diabetic
  nephropathy
• Randomized, blinded outcomes trials that
  demonstrate a clear renoprotective benefit of ACE
  inhibitors in diabetes have been conducted only
  in type 1 diabetics
• Three recently completed randomized blinded
  trials address the previously unanswered
  questions of whether ARBs delay the progression
  of diabetic nephropathy (RENAAL, IDNT) or reduce
  proteinuria (IRMA II) in patients with type 2
  diabetes

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2
Angiotensin II Receptor Blockers in Type 2
Diabetics With NephropathyProgression of Renal
Insufficiency
In combination with conventional
antihypertensive therapy (excluding ACE
inhibitors)
RENAALThe Reduction of Endpoints in NIDDM with
the Angiotensin II Antagonist Losartan
StudyIDNTThe Irbesartan in Diabetic Nephropathy
Trial
Brenner BM, et al. N Engl J Med.
2001345(12)861-869. Lewis EJ, et al. N Engl J
Med. 2001345(12)851-860.
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3
Angiotensin II Receptor Blockers in Type 2
DiabeticsProgression of Microalbuminuria
Albumin excretion rate of 20 to 200 ?g per
minute in 2 of 3 consecutive, sterile, overnight
urine samples Urinary albumin excretion rate
gt200 ?g per minute and at least 30 higher than
baseline in at least 2 consecutive
measurements In combination with conventional
antihypertensive therapy (excluding ACE
inhibitors)
IRMA IIThe Irbesartan Microalbuminuria Type 2
Diabetes in Hypertensive Patients Study
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Parving HH, et al. N Engl J Med.
2001345(12)870-878.
4
Angiotensin II Receptor Blockers (ARBs) in Type
2 Diabetes and NephropathySummary of Findings (I)

• RENAAL, IDNT and IRMA II present the strongest
  evidence to date for the efficacy of specific
  types of treatment to slow the progression of
  nephropathy in type 2 diabetes
• The ARBs losartan and irbesartan compared to
  placebo have been shown to reduce the
  progression of renal insufficiency beyond the
  benefit of similarly achieved blood pressures
• Irbesartan compared to placebo has been shown to
  reduce the progression of microalbuminuria to
  diabetic nephropathy

In combination with conventional
antihypertensive therapy (excluding ACE
inhibitors)
Brenner BM, et al. N Engl J Med.
2001345(12)861-869. Lewis EJ, et al. N Engl J
Med. 2001345(12)851-860. Parving HH, et al. N
Engl J Med. 2001345(12)870-878.
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5
Angiotensin II Receptor Blockers in Type 2
Diabetes and NephropathySummary of Findings (II)

• Good blood pressure control in earlier studies
  has proven critical to slow the progression of
  nephropathy in type 2 diabetes
• New guidelines for good blood pressure control
  are
• lt130/80 mmHg (American Diabetes Association)
• lt125/75 mmHg for patients with renal
  insufficiency with greater than 1 g/d of
  proteinuria (JNC VI)
• Multiple antihypertensive agents will be needed
  to achieve good blood pressure control
• ARBs now are indicated for the treatment of type
  2 diabetes with nephropathy

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