A Randomized Trial of Captopril for Microalbuminuria in Normotensive Adults with Sickle Cell Anemia

Université Victor Segalen Bordeaux 2, Burdeos, Aquitaine, France
The American Journal of Medicine (Impact Factor: 5). 04/1998; 104(4):339-42. DOI: 10.1016/S0002-9343(98)00056-4
Source: PubMed


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.

13 Reads
  • Source
    • "There was no significant difference in the mean age, body mass index, blood pressure, hemoglobin concentration, serum creatinine, urine albumin excretion and creatinine clearance (Foucan 1998). The authors therefore judged this study to have low risk for these potential sources of bias. "
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Sickle cell disease is a group of disorders characterized by deformation of erythrocytes. Renal damage is a frequent complication in sickle cell disease as a result of long-standing anemia and disturbed circulation through the renal medullary capillaries. Due to the improvement in life expectancy of people with sickle cell disease, there has been a corresponding significant increase in the incidence of renal complications. Microalbuminuria and proteinuria are noted to be a strong predictor of subsequent renal failure. There is extensive experience and evidence with angiotensin-converting enzyme (ACE) inhibitors over many years in a variety of clinical situations for patients who do not have sickle cell disease, but their effect in people with this disease is unknown. It is common practice to administer ACE inhibitors for sickle nephropathy due to their renoprotective properties; however, little is known about their effectiveness and safety in this setting. This is an update of a Cochrane Review first published in 2013. OBJECTIVES: To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects. SEARCH METHODS: The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Hameoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 03 June 2015. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of ACE inhibitors designed to reduce microalbuminuria and proteinuria in people with sickle cell disease compared to either placebo or standard treatment regimen. DATA COLLECTION AND ANALYSIS: Three authors independently applied the inclusion criteria in order to select studies for inclusion in the review. Two authors assessed the risk of bias of studies and extracted data and the third author verified these assessments. MAIN RESULTS: Five studies were identified through the searches, only one met our inclusion criteria. The included study randomized 22 participants (seven males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow up of three months) with captopril or placebo. The overall quality of the outcomes reported was high, since most aspects that may contribute to bias were regarded to be of low risk, although allocation concealment was not reported. At six months, the study reported no significant difference in urinary albumin excretion between the captopril group and the placebo group, although the mean urinary albumin excretion in the captopril group was lower by a mean difference of -49.00 (95% confidence interval -124.10 to 26.10) compared to that of placebo. However, our analysis on the absolute change score showed significant changes between the two groups by a mean difference of -63.00 (95% confidence interval -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean of 45 ± 23 mg/day and the placebo group was noted to increase by 18 ± 45 mg/day. Serum creatinine and potassium levels were reported constant throughout the study. The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure. AUTHORS' CONCLUSIONS: There is not enough evidence to show that the administration of ACE inhibitors is associated with a reduction of microalbuminuria and proteinuria in people with sickle cell disease, although a potential for this was seen. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study
    Full-text · Article · Jun 2015 · Cochrane database of systematic reviews (Online)
  • Source
    • "Proteinuria is more commonly encountered in patients with homozygous (hemoglobin SS) sickle cell disease than in other hemoglobinopathies [6]. Patients with HbSC had also been noted to develop renal insufficiency later than patients with HbSS [19]. A prospective study by Powars et al. showed that severe anaemia, hypertension, proteinuria, nephrotic syndrome, and microscopic hematuria were found to be significant predictor of chronic renal failure [20]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Sickle cell nephropathy is a common presentation in patients with sickle cell disease. End-stage kidney disease is the most severe presentation of sickle cell nephropathy in terms of morbidity and mortality. Sickle cell disease patients with end-stage kidney disease are amenable to renal replacement therapy including kidney transplant. Kidney transplant in these patients has been associated with variable outcome with recent studies reporting short- and long-term outcomes comparable to that of patients with HbAA. Sickle cell disease patients are predisposed to various haematological, cardiorespiratory, and immunological challenges. These challenges have the potential to limit, delay, or prevent kidney transplant in patients with sickle cell disease. There are few reports on the outcome and challenges of kidney transplant in this group of patients. The aim of this review is to highlight the outcome and challenges of kidney transplant in patients with sickle cell disease.
    Full-text · Article · Apr 2013 · Journal of Transplantation
  • Source
    • "Microalbuminuria could be detected long before positive urine test for proteinuria using conventional dipstick like Albustix or Combi 10 Multistix screen which is sensitive to urinary protein excretion that is greater or equals to 300 mg/L [14]. Prolonged period of microalbuminuria precedes persistent proteinuria which is subsequently followed by chronic renal failure (CRF) [15] and occurs with variable frequency in the sickle cell population (4%–20%) [11]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Microalbuminuria is a pre-clinical marker of renal damage in children with sickle cell anaemia and can predict renal failure. Reported prevalence rates increased with age. In Nigeria, burden of disease and prevailing poor health facilities necessitate its screening, determination of prevalence and associated risk factors. It is a cross-sectional as well as descriptive study. Screening microalbuminuria used subjects' early morning urine. Socio-demographic as well as clinical details were ascertained using semi-structured questionnaires and case files. Associations and statistical relationship of prevalence rates and clinical/epidemiological data were ascertained using chi-squared and multivariate analysis (P < 0.05). Two hundred children with sickle cell anaemia (4-17 years) in steady state and 200 age/gender-matched controls were enrolled. Prevalence of microalbuminuria was ,respectively, 18.5% and 2.5% for subjects and controls (P = 0.001). Microalbuminuria was commoner in females (19.8%) than males (17.4%) P = 0.70, increased with age (P = 0.016), significantly associated with haemoglobin level (P = 0.002) and hospitalizations (0.001). Subjects had normal renal function. Hospitalizations and haemoglobin levels showed statistical significance on multivariate analysis. Prevalence of microalbuminuria is 18.5%. Age, haemoglobin concentrations, and higher hospitalizations influenced microalbuminuria among subjects. Screening for microalbuminuria should be incorporated in the case management of subjects with identified risk factors.
    Full-text · Article · Sep 2012
Show more