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Intervention Review

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Angiotensin-converting enzyme (ACE) inhibitors for proteinuria and microalbuminuria in people with sickle cell disease

  1. Teguh H Sasongko1,*,
  2. Srikanth Nagalla2,
  3. Samir K Ballas3

Editorial Group: Cochrane Cystic Fibrosis and Genetic Disorders Group

Published Online: 28 MAR 2013

DOI: 10.1002/14651858.CD009191.pub2


How to Cite

Sasongko TH, Nagalla S, Ballas SK. Angiotensin-converting enzyme (ACE) inhibitors for proteinuria and microalbuminuria in people with sickle cell disease. Cochrane Database of Systematic Reviews 2013, Issue 3. Art. No.: CD009191. DOI: 10.1002/14651858.CD009191.pub2.

Author Information

  1. 1

    Universiti Sains Malaysia, Human Genome Center, School of Medical Sciences, Kota Bharu, Kelantan, Malaysia

  2. 2

    Thomas Jefferson University, Department of Medicine, Division of Hematology, Philadelphia, Pennsylvania, USA

  3. 3

    Jefferson Medical College, Thomas Jefferson University, Cardeza Foundation for Hematologic Research, Department of Medicine, Philadelphia, USA

*Teguh H Sasongko, Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kota Bharu, Kelantan, Malaysia. teguhharyosasongko@yahoo.com. teguhhs@usm.my.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 28 MAR 2013

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This is not the most recent version of the article. View current version (04 JUN 2015)

 
Characteristics of included studies [ordered by study ID]
Foucan 1998

MethodsDouble-blind, randomized, parallel, placebo-controlled trial.


Participants22 patients were enrolled into the study, in which 12 were in the treatment group and 10 were in the placebo group. All were homozygous for hemoglobin SS. Ages >18 years. Urinary albumin excretion between 30 mg and 300 mg per 24 hours on 3 different occasions in the 6 months prior to the study.


InterventionsPatients were were randomized into either:

1. captopril 6.25 mg/day for month 1, 12.5 mg/day for months 2-3 and 25 mg/day for months 3 onward; or

2. placebo.


OutcomesPrimary outcomes include: urinary albumin (24 hr), serum creatinine, sodium (results not stated), potassium
Secondary outcomes include: hemoglobin concentration; blood pressure.


Notes-


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandom assignment. No process of generating allocation sequence was described.

Allocation concealment (selection bias)Unclear riskNot stated.

Incomplete outcome data (attrition bias)
All outcomes
Low riskIntention-to-treat analysis was used. 2 patients were withdrawn from the study. Full reasons for withdrawal were given in the published paper.

Selective reporting (reporting bias)High riskResults for sodium level were not reported. Exact serum creatinine level and hemoglobin concentration were not reported.

Other biasLow riskNo difference in baseline characteristics between the captopril group and placebo group.

Blinding of participants and personnel (performance bias)
All outcomes
Low riskParticipants were blinded. Treating physicians were blinded.

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessors were blinded.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Aoki 1995Observational, not randomized, no control group.

Falk 1992Interventional but not randomized, no control group.

Fitzhugh 2005Observational, not randomized, no control group.

McKie 2007Observational, not randomized, no control group.

 
Comparison 1. ACE inhibitors versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Urinary protein or albumin excretion (per hour)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    1.1 Total albumin excretion at 6 months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    1.2 Absoulte change in total albumin excretion at 6 months
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Adverse effects1Risk Ratio (M-H, Fixed, 95% CI)Totals not selected

    2.1 Dry cough
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 Pain in shoulder
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.3 Clinical proteinuria
1Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Summary of findings for the main comparison.

ACE inhibitors compared with Placebo for proteinuria and microalbuminuria in people with sickle cell disease

Patient or population: People with proteinuria or microalbuminuria due to sickle cell disease

Settings: Any

Intervention: ACE inhibitor

Comparison: Placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

PlaceboACE inhibitor

Albumin excretion in 1 month (mg/day)---22(1)⊕⊕⊕⊕
high
No significant change

Albumin excretion in 3 months (mg/day)Increase from baselineDecrease from baseline-22(1)⊕⊕⊕⊕
high
-

Albumin excretion in 6 months (mg/day)125 + 11476 + 45-49 (-124.1 to 26.1)22(1)⊕⊕⊕⊕
high
-

Serum creatinine (umol/L)ConstantConstant-22(1)⊕⊕⊕⊕
high
-

Sodium---22(1)-Done but not reported.

PotassiumConstantConstant-22(1)⊕⊕⊕⊕
high
-

Mean blood pressure (mmHg)ConstantDecrease by 5 mmHg-22(1)⊕⊕⊕⊕
high
-

Systolic blood pressure (mmHg)ConstantDecrease by 8 mmHg-22(1)⊕⊕⊕⊕
high
-

Diastolic blood pressure (mmHg)Increase by 3 mmHgDecrease by 5 mmHg-22(1)⊕⊕⊕⊕
high
P < 0.01.

Hemoglobin concentration (g/dL)ConstantConstant-22(1)⊕⊕⊕⊕
high
-

Dry cough1 out of 12 patients in ACE inhibitor group2.54 (0.11 to 56.25)22(1)⊕⊕⊕⊕
high
-






Pain in shoulder1 out of 12 patients in ACE inhibitor group2.54 (0.11 to 56.25)22(1)⊕⊕⊕⊕

high
-






Clinical proteinuria1 out of 10 patients in Placebo group0.28 (0.01 to 6.25)22(1)⊕⊕⊕⊕
high
-






Note: in future we will again contact trial authors regarding outcomes where no exact value was indicated in the study manuscript

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk Ratio

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.