Dataset Information

Hydroxyurea is associated with lower prevalence of albuminuria in adults with sickle cell disease.

ABSTRACT:

Background

Albuminuria is an early manifestation of sickle cell nephropathy. Prior small case series suggests benefit of hydroxyurea in reducing albuminuria, with a similar trend noted in pediatric studies. We aimed to comprehensively evaluate hydroxyurea use and prevalence of albuminuria in adult sickle cell patients.

Methods

We performed a cross-sectional study of 149 adult patients followed between 2000 and 2011 in a comprehensive sickle cell clinic. All patients were assessed for albuminuria either by direct measurement or by urinary chemical strip (dipstick) testing. Urinary albumin-to-creatinine ratios (UACRs) were available for 112 patients. Hydroxyurea exposure was defined as ?3 months of therapy before the assessment of albuminuria. Albuminuria was defined as either UACR ?30 mg/g or ?1+ proteinuria on two separate dipsticks. We constructed a multivariate logistic regression model to assess the association between hydroxyurea and albuminuria.

Results

The prevalence of albuminuria was lower among patients on hydroxyurea (34.7 versus 55.4%; P = 0.01) as was median albumin excretion (17.9 versus 40.5 mg/g; P = 0.04). In multivariate analysis, hydroxyurea was associated with a lower likelihood of albuminuria (odds ratio 0.28, 95% CI: 0.11-0.75, P = 0.01), adjusting for age, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use, tricuspid regurgitant jet velocity, hypertension and acute chest syndrome.

Conclusions

In our population of sickle cell patients, those using hydroxyurea were less than one-third as likely to exhibit albuminuria. Hydroxyurea use may prevent development of overt nephropathy or the progression of sickle cell disease nephropathy to end-stage renal disease, and its use for this indication merits further investigation.

SUBMITTER: Laurin LP

PROVIDER: S-EPMC4038249 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Publications

Hydroxyurea is associated with lower prevalence of albuminuria in adults with sickle cell disease.

Laurin Louis-Philippe LP Nachman Patrick H PH Desai Payal C PC Ataga Kenneth I KI Derebail Vimal K VK

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20130930 6

<h4>Background</h4>Albuminuria is an early manifestation of sickle cell nephropathy. Prior small case series suggests benefit of hydroxyurea in reducing albuminuria, with a similar trend noted in pediatric studies. We aimed to comprehensively evaluate hydroxyurea use and prevalence of albuminuria in adult sickle cell patients.<h4>Methods</h4>We performed a cross-sectional study of 149 adult patients followed between 2000 and 2011 in a comprehensive sickle cell clinic. All patients were assessed ...[more]

PMID: 24084325

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Project description:BackgroundSickle cell disease (SCD) results in severe complications, such as anaemia and pain episodes. Hydroxyurea (HU) is efficacious in SCD, yet adherence remains low.ObjectiveTo assess the relationship of HU adherence to health care utilization and patients' characteristics.MethodsThis is a 5-year retrospective chart review. Patients' demographics and medical history were collected from the electronic medical record (EMR). HU adherence was evaluated using foetal haemoglobin "HbF%", mean corpuscular volume "MCV", and absolute neutrophil count "ANC". Age groups included children (<12 years), adolescents (12-17 years), and young adults (≥18 years).ResultsA total of 113 SCD patients on HU were included (median age 14 years, IQR 10-20; 50% female; 88% HbSS). Young adults had significantly higher HU adherence compared to adolescents and children, including higher median HbF% (24.2 vs. 12.4 vs. 8.6, p = .003), MCV (fl) (106.4 vs. 96.2 vs. 95.4, p = .01) and lower ANC (103/ml) (3.25 vs. 4.9 vs. 4.2, p = .01), respectively. Patients with chronic pain had lower HU adherence (HbF% 15.3 vs. 10.7, p = .04; ANC 3.6 vs. 6.3, p = .002; MCV 102.3 vs. 93.1, p = .1). Patients with higher HbF or MCV and lower ANC had significantly less frequent emergency room visits (rs=-0.26, p = .01; rs=-0.23, p = .01; rs=0.24, p = .01) and hospitalizations (rs=-0.27, p = .01; rs=-0.31, p = .01; rs=0.21, p = .02) as well as shorter length of stays (rs=-0.27, p = .0045; rs=-.34, p = 0.004; rs=0.23, p = .02), respectively. Similar trends in HU adherence and health care utilization were seen in subgroup analysis of only HbSS patients. There was no significant association of HU adherence to patients' sex, socio-economic status, distance from hospital, and HU duration.ConclusionsYoung adults with SCD had significantly higher HU adherence compared to children and adolescents. Patients with lower HU adherence and/or chronic pain had increased health care utilization. Future studies examining barriers to adherence and evaluating interventions to optimize HU adherence in SCD are warranted.KEY MESSAGESYoung adults with SCD had significantly higher HU adherence, as reflected in their laboratory markers, compared to children and adolescents.Patients with higher HU adherence and/or those without chronic pain had lower or less frequent health care utilization.No significant association of HU adherence to patients' sex, socio-economic status and distance from hospital.

Project description:Pediatric patients with sickle cell disease (SCD) have decreased oxygen-carrying capacity in the blood and reduced or restricted cerebral blood flow resulting in neurocognitive deficits and cerebral infarcts. The standard treatment for children with SCD is hydroxyurea; however, the treatment-related neurocognitive effects are unclear. A key area of impairment in SCD is working memory, which is implicated in other cognitive and academic skills. N-back tasks are commonly used to investigate neural correlates of working memory. We analyzed functional magnetic resonance imaging (fMRI) of patients with SCD while they performed n-back tasks by assessing the blood-oxygenation level-dependent (BOLD) signals during working memory processing. Twenty hydroxyurea-treated and 11 control pediatric patients with SCD (7-18 years old) performed 0-, 1-, and 2-back tasks at 2 time points, once before hydroxyurea treatment (baseline) and ~1 year after treatment (follow-up). Neurocognitive measures (e.g., verbal comprehension, processing speed, full-scale intelligence quotient, etc.) were assessed at both time points. Although no significant changes in behavior performance of n-back tasks and neurocognitive measures were observed in the treated group, we observed a treatment-by-time interaction in the right cuneus and angular gyrus for the 2- > 0-back contrast. Through searchlight-pattern classifications in the treated and control groups to identify changes in brain activation between time points during the 2-back task, we found more brain areas, especially the posterior region, with changes in the pattern and magnitude of BOLD signals in the control group compared to the treated group. In the control group, increases in 2-back BOLD signals were observed in the right crus I cerebellum, right inferior parietal lobe, right inferior temporal lobe, right angular gyrus, left cuneus and left middle frontal gyrus at 1-year follow-up. Moreover, BOLD signals elevated as the working memory load increased from 0- to 1-back but did not increase further from 1- to 2-back in the right inferior temporal lobe, right angular gyrus, and right superior frontal gyrus. These observations may result from increased cognitive effort during working memory processing with no hydroxyurea treatment. In contrast, we found fewer changes in the pattern and magnitude of BOLD signals across time points in the treated group. Furthermore, BOLD signals in the left crus I cerebellum, right angular gyrus, left cuneus and right superior frontal gyrus of the treated group increased continuously with increasing working memory load from 0- to 2-back, potentially related to a broader dynamic range in response to task difficulty and cognitive effort. Collectively, these findings suggest that hydroxyurea treatment helped maintain working memory function in SCD.

Dataset Information

Hydroxyurea is associated with lower prevalence of albuminuria in adults with sickle cell disease.

Background

Methods

Results

Conclusions

Publications

Hydroxyurea is associated with lower prevalence of albuminuria in adults with sickle cell disease.

Similar Datasets

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