A randomized trial of captopril for microalbuminuria in normotensive adults with sickle cell anemia.
ABSTRACT Nephropathy is a common complication of sickle cell anemia and is often preceded by proteinurea. Our aim was to evaluate the effect of angiotensin-converting enzyme inhibition on microalbuminuria in sickle cell patients.
We performed a randomized, double-blind, placebo-controlled trial in 22 normotensive patients with sickle cell anemia and persistent microalbuminuria. Patients received captopril (25 mg/day) or placebo and were followed up for 6 months. Albuminuria, blood pressure, and serum creatinine and hemoglobin concentrations were measured at baseline and at 1, 3, and 6 months. The primary outcome variable was the 6-month change in albuminuria between the two groups.
Baseline albuminuria was 121 (SD 66) mg per 24 hours in the captopril group and 107 (SD 86) mg per 24 hours in the placebo group. Microalbuminuria decreased from baseline in the captopril group but increased in the placebo group. The mean absolute change and the mean percentage change in microalbuminuria were significantly different between the two groups at 6 months (absolute change -45 mg per 24 hours in the captopril group versus +18 mg per 24 hours in the placebo group, P <0.01; and percentage change -37% in the captopril group versus +17% in the placebo group, P <0.01). The 95% confidence intervals (CI) for the difference in albuminuria between the two groups were 63 (CI 40 to 86) mg per 24 hours for the mean absolute change and 54% (CI 22% to 85%) for the mean percentage change. Blood pressure decreased slightly from baseline in captopril-treated patients and did not change in the placebo group. The change was significantly different between the two groups only for diastolic blood pressure at 6 months (P <0.01).
Captopril reduces albuminuria and slightly decreases blood pressure in patients with sickle cell anemia. More studies are required to demonstrate the sustained benefit on protein excretion.
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ABSTRACT: Aims: Sickle cell disease (SCD) pathogenesis leads to recurrent vaso-occlusive and hemolytic processes, causing numerous clinical complications including renal damage. As vasoconstrictive mechanisms may be enhanced in SCD, due to endothelial dysfunction and vasoactive protein production, we aimed to determine whether the expression of proteins of the renin-angiotensin system (RAS) may be altered in an animal model of SCD. Main methods: Plasma angiotensin II (Ang II) was measured in C57BL/6 (WT) mice and mice with SCD by ELISA, while quantitative PCR was used to compare the expressions of the genes encoding the angiotensin-II-receptors 1 and 2 (AT1R and AT2R) and the angiotensin-converting enzymes (ACE1 and ACE2) in the kidneys, hearts, livers and brains of mice. The effects of hydroxyurea (HU; 50-75 mg/kg/day, 4 weeks) treatment on these parameters were also determined. Key findings: Plasma Ang II was significantly diminished in SCD mice, compared with WT mice, in association with decreased AT1R and ACE1 expressions in SCD mice kidneys. Treatment of SCD mice with HU reduced leukocyte and platelet counts and increased plasma Ang II to levels similar to those of WT mice. HU also increased AT1R and ACE2 gene expression in the kidney and heart. Significance: Results indicate an imbalanced RAS in an SCD mouse model; HU therapy may be able to restore some RAS parameters in these mice. Further investigations regarding Ang II production and the RAS in human SCD may be warranted, as such changes may reflect or contribute to renal damage and alterations in blood pressure.Life Sciences 09/2014; 117(1). DOI:10.1016/j.lfs.2014.08.021 · 2.30 Impact Factor
Article: Sickle cell nephropathyDisease-a-Month 10/2014; 60(10). DOI:10.1016/j.disamonth.2014.08.004 · 0.54 Impact Factor
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ABSTRACT: Sickle cell disease (SCD) produces many structural and functional abnormalities in the kidney, including glomerular abnormalities. Albuminuria is the most common manifestation of glomerular damage, with a prevalence between 26% and 68% in adult patients. The pathophysiology of albuminuria in SCD is likely multifactorial, with contributions from hyperfiltration, glomerular hypertension, ischemia-reperfusion injury, oxidative stress, decreased NO bioavailability and endothelial dysfunction. Although its natural history in SCD remains inadequately defined, albuminuria is associated with increased echocardiography-derived tricuspid regurgitant jet velocity, systemic blood pressure and hypertension, as well as history of stroke, suggesting a shared vasculopathic pathophysiology. While most patients with albuminuria are treated with angiotensin converting enzyme inhibitors/angiotensin receptor blockers, there are no published long-term data on the efficacy of these agents. With the improved patient survival following kidney transplantation, SCD patients with end-stage renal disease should be considered for this treatment modality. Given the high prevalence of albuminuria and its association with multiple SCD-related clinical complications, additional studies are needed to answer several clinically important questions in a bid to adequately elucidate its pathophysiology, natural history and treatment.American Journal of Hematology 09/2014; 89(9). DOI:10.1002/ajh.23762 · 3.48 Impact Factor