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Clinical Nephrology
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Additive Effect of ACE Inhibition and Angiotensin II Receptor Blockade in Type I Diabetic Patients with Diabetic Nephropathy

Peter Jacobsen, Steen Andersen, Berit R. Jensen and Hans-Henrik Parving
JASN April 2003, 14 (4) 992-999; DOI: https://doi.org/10.1097/01.ASN.0000054495.96193.BF
Peter Jacobsen
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Steen Andersen
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Berit R. Jensen
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Hans-Henrik Parving
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    Figure 1. Albuminuria and BP after blockade of the renin-angiotensin system (RAS) in 18 type 1 diabetic patients with diabetic nephropathy. Albuminuria levels are geometric mean with 95% CI; BP levels are mean with SEM.

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    Figure 2. Individual changes in albuminuria as response to blockade of the RAS in type 1 diabetic patients with diabetic nephropathy.

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    Figure 3. Correlations between treatment response on benazepril and dual blockade of the RAS in type 1 diabetic patients with diabetic nephropathy.

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    Figure 4. Evaluation of carryover effects of treatments on change in albuminuria. Patients receiving placebo treatment in the initial period (—) compared with patients treated with active compounds in the first period (X). Levels are medians, and bars represent range. NS within all treatments.

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  • Table 1. Baseline clinical data before start of study medicationa

    a Mean (SD).
    b Median (range).
    Furosemide, in addition to study medication, was the only drug kept throughout the study.
    Age (yr)43 (7)
    Gender (M/F)13/5
    Duration of diabetes (yr)30 (7)
    Duration of diabetic nephropathy (yr)10 (6)
    Retinopathy (background/proliferative)6/12
    Smokers (no/yes)12/6
    Office BP (mmHg)141 (15)/81 (6)
    Albuminuria (mg/24 h)b362 (80–2628)
    No. of antihypertensive agentsb2 (2–3)
    Previous treatment with ACE-I/ARB (yes/no)18/0
    Dose of furosemide (mg/d)b40 (20–250)
  • Table 2. Effects on kidney function and arterial BP of blockade of the renin angiotensin system in 18 type I diabetic patients with diabetic nephropathy

    ParameterPlacebo ValuesDecline from Placebo
    Benazepril 20 mgValsartan 80 mgBenazepril 20 mg + Valsartan 80 mg
    Placebo values are mean (SEM) and changes are mean (95% CI).
    a Geometric mean (95% CI);
    b P < 0.001 versus placebo;
    c P < 0.05 versus placebo;
    d P < 0.01 dual blockade versus mono-therapy;
    e P < 0.05 dual blockade versus mono-therapy.
    Albuminuria701 (490 to 1002) mg/24 ha65 (56 to 72)%b65 (56 to 72)%b80 (75 to 84)%bd
    GFR (ml/min per 1.73 m2)82 (7)3 (−1 to 7)4 (−1 to 8)10 (6 to 14)bd
    P-creatinine (μmol/L)115 (7)−1 (−8 to 6)2 (−5 to 9)−9 (−16 to −2)ce
    Albuminuria/([p-albumin] × [GFR])172 (109 to 270) 10−6a65 (57 to 72)%b64 (55 to 71)%b78 (73 to 82)%bd
    24-h systolic BP (mmHg)144 (4)15 (9 to 22)b15 (8 to 21)b22 (15 to 28)b
        day (7 to 23)149 (3)15 (8 to 21)b15 (9 21)b22 (15 to 28)be
        night (23 to 7)133 (4)16 (7 to 25)b13 (5 to 22)c21 (13 to 30)b
    24-h diastolic BP (mmHg)79 (2)6 (3 to 9)b6 (3 to 9)b13 (10 to 16)bd
        day (7 to 23)82 (2)7 (4 to 10)b7 (4 to 10)b14 (11 to 17)bd
        night (23 to 7)72 (2)5 (1 to 9)c4 (0 to 8)11 (7 to 15)bd
  • Table 3. Effects on laboratory parameters of blockade of the renin angiotensin system in 18 type I diabetic patients with diabetic nephropathy

    ParameterPlaceboBenazepril 20 mgValsartan 80 mgBenazepril 20 mg + Valsartan 80 mg
    Values are mean (SEM) and a geometric mean (95% CI).
    b P < 0.05 versus placebo;
    c P < 0.01 dual blockade versus mono-therapy;
    d P < 0.05 dual blockade versus mono-therapy;
    e P < 0.05 dual blockade versus benazepril.
    Renina (mU/L)30 (18 to 50)161 (72 to 364)b163 (82 to 325)b331 (133 to 823)bc
    Angiotensin IIa (pmol/L)13 (9 to 17)7 (5 to 10)b44 (26 to 75)b11 (6 to 21)d
    P-potassium (mmol/L)3.7 (0.1)4.0 (0.2)b3.9 (0.1)4.3 (0.1)bc
    Hemoglobin (mmol/L)8.5 (0.3)8.2 (0.2)b8.1 (0.2)b7.8 (0.2)be
    Hemoglobin A1c (%)9.1 (0.2)9.5 (0.2)9.2 (0.2)9.6 (0.2)b
    P-cholesterol (mmol/L)5.5 (0.3)5.3 (0.3)4.9 (0.2)b4.8 (0.2)be
    P-HDL (mmol/L)1.5 (0.1)1.5 (0.1)1.5 (0.1)1.4 (0.1)
    P-LDL (mmol/L)3.4 (0.2)3.3 (0.2)2.9 (0.1)b2.7 (0.2)be
    P-triglyceride (mmol/L)1.3 (0.2)1.2 (0.2)1.1 (0.1)1.3 (0.2)
    U-sodium excretion (mmol/24 h)194 (17)204 (16)187 (13)195 (17)
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Journal of the American Society of Nephrology: 14 (4)
Journal of the American Society of Nephrology
Vol. 14, Issue 4
1 Apr 2003
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Additive Effect of ACE Inhibition and Angiotensin II Receptor Blockade in Type I Diabetic Patients with Diabetic Nephropathy
Peter Jacobsen, Steen Andersen, Berit R. Jensen, Hans-Henrik Parving
JASN Apr 2003, 14 (4) 992-999; DOI: 10.1097/01.ASN.0000054495.96193.BF

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Additive Effect of ACE Inhibition and Angiotensin II Receptor Blockade in Type I Diabetic Patients with Diabetic Nephropathy
Peter Jacobsen, Steen Andersen, Berit R. Jensen, Hans-Henrik Parving
JASN Apr 2003, 14 (4) 992-999; DOI: 10.1097/01.ASN.0000054495.96193.BF
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More in this TOC Section

  • A Randomized, Controlled Trial of Steroids and Cyclophosphamide in Adults with Nephrotic Syndrome Caused by Idiopathic Membranous Nephropathy
  • Lower Progression Rate of End-Stage Renal Disease in Patients with Peripheral Arterial Disease Using Statins or Angiotensin-Converting Enzyme Inhibitors
  • IgACE: A Placebo-Controlled, Randomized Trial of Angiotensin-Converting Enzyme Inhibitors in Children and Young People with IgA Nephropathy and Moderate Proteinuria
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Cited By...

  • Physiology of the Renal Interstitium
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  • Recurrence of Secondary Glomerular Disease after Renal Transplantation
  • Effects of Additive Therapy With Spironolactone on Proteinuria in Diabetic Patients Already on ACE Inhibitor or ARB Therapy: Results of a Randomized, Placebo-Controlled, Double-Blind, Crossover Trial
  • Microalbuminuria in Type 2 Diabetes and Hypertension: A marker, treatment target, or innocent bystander?
  • Are Two Better Than One? Angiotensin-Converting Enzyme Inhibitors Plus Angiotensin Receptor Blockers for Reducing Blood Pressure and Proteinuria in Kidney Disease
  • Renoprotection of Optimal Antiproteinuric Doses (ROAD) Study: A Randomized Controlled Study of Benazepril and Losartan in Chronic Renal Insufficiency
  • Albuminuria Is a Target for Renoprotective Therapy Independent from Blood Pressure in Patients with Type 2 Diabetic Nephropathy: Post Hoc Analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) Trial
  • Dual Blockade of the Renin-Angiotensin System in the Progression of Renal Disease: The Need for More Clinical Trials
  • Progression of Renal Disease: Renoprotective Specificity of Renin-Angiotensin System Blockade
  • ACE Inhibitor or Angiotensin II Receptor Antagonist Attenuates Diabetic Neuropathy in Streptozotocin-Induced Diabetic Rats
  • Systematic Review of Combined Angiotensin-Converting Enzyme Inhibition and Angiotensin Receptor Blockade in Hypertension
  • Long-Term Dual Blockade With Candesartan and Lisinopril in Hypertensive Patients With Diabetes: The CALM II study
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