Drugs that aim to prevent the loss of protein or albumin through urine in people with sickle cell disease

Review question

We reviewed the evidence on the effect of drugs that aim to prevent loss of protein or albumin through urine in people with sickle cell disease.

Background

Sickle cell disease is a group of inherited disorders that often lead to kidney damage. High protein or albumin levels in urine is a strong predictor of subsequent kidney failure. It is common practice to give angiotensin-converting enzyme (ACE) inhibitors to reduce the level of protein or albumin in urine, thus protecting the kidneys from damage. However, little is known about how effective and safe these are in people with sickle cell disease.

Search date

The evidence is current to: 03 June 2015.

Study characteristics

One study (22 adult participants) was included in the review. The participants with sickle cell disease had proteinuria or microalbuminuria and were selected randomly to be treated for six months with either captopril (an angiotensin-converting enzyme inhibitor) or placebo (dummy drug with no active medication).

Key results

The results from this small study were not convincing, with minor analysis changes leading to very different study conclusions. This study did not show that angiotensin-converting enzyme (ACE) inhibitors could reduce the level of protein or albumin in the urine. The level of creatinine and potassium in the blood were reported constant throughout the study. No serious adverse events were noted, although the potential for causing low blood pressure should be highlighted. More long-term studies involving multiple centers and larger numbers of participants are needed.

Quality of the evidence

Overall, the study appeared to be well run, although the actual method used to assign participants to treatment groups was not reported, nor whether it was concealed which group they were assigned to.

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.

Read the full 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 strategy: 

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.

Share/Save