Impact of Hydroxyurea therapy on albuminuria among children with sickle cell anemia Open Access

Tehseen, Sarah (2016)

Permanent URL: https://etd.library.emory.edu/concern/etds/fx719n204?locale=en
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Abstract

Background: The process of renal damage in sickle cell anemia (SCA) is progressive and leads to end stage renal disease in 12% of adult sickle cell patients. Hydroxyurea (HU) is known to successfully reduce many complications of sickle cell disease. However, its role in sickle cell nephropathy remains uncertain.

Objectives: To investigate the effect of HU on progression of sickle cell nephropathy as estimated by urine albumin to creatinine ratios (ACR) in children with HbSS/Sβ0 phenotype. AIM 1: Compare the urine ACR levels post- vs. pre-initiation of HU among patients with SCA. AIM 2: Among SCA patients with albuminuria, compare the urine ACR levels between SCA patients on HU and age-matched SCA patients not on HU.

Methods: This retrospective cohort study was conducted in tertiary care children's hospital between 2010 and 2013, with up to 2 years of follow-up. The main outcome was urine ACR. Other covariates included age, mean hemoglobin levels, indices of HU compliance and blood pressure. A paired t test or appropriate non-parametric test was used to compare urine ACR levels post- vs. pre-initiation of HU. An independent sample t test was used to compare change in urine ACR levels between exposed and unexposed patients. Multiple linear regression models were used to investigate the impact of HU therapy on change in ACR while adjusting for other covariates (AIM 2).

Results: AIM 1: The final number of patients included was 81. Urine ACR levels were significantly lower ~2 years after initiation of HU compared to levels pre-HU (7±15 two years post HU vs. 11.4±24 pre-HU; p=0.02 N=65). This change was most pronounced among patients who had abnormal ACR levels before initiation of HU (N=21; 23.4±39 2 years post-HU vs. 95±103 pre-HU; p=0.02). AIM 2: The final number of patients included was 48. HU therapy was associated with a significant reduction in ACR over ~1 year of follow up compared to patients not on HU, controlling for age and baseline hemoglobin.

Conclusion: HU therapy in SCA is associated with lower urine ACR levels over time.

Table of Contents

TABLE OF CONTENTS

INTRODUCTION…………………………………………………………………… 1

BACKGROUND……………………………………………………………………... 3

METHODS………………………………………………………………………….... 8

RESULTS…………………………………………………………………………….. 18

DISCUSSION………………………………………………………………………… 24

REFERENCES……………………………………………………………………….. 30

FIGURES AND TABLES..………………………………………………………….. 33

LIST OF FIGURES AND TABLES

Figures

Figure 1A. Flow sheet of patients' selection for AIM 1……………….….……...... 33

Figure 1B. Flow sheet for patient selection for AIM 2……...………….….…........ 34

Figure 2A Data collection schema AIM 1………………...………….…...,.………35

Figure 2B. Data collection schema AIM 2……………...…..................................... 35

Figure 3. Change in mean ln (ACR) values over time……………………………39

Figure 4. Proportion of patients with albuminuria over 2 years of HU therapy ………………………………………...…………...………………..….40

Figure 5. Individual patient trajectories showing change in ln (ACR) levels after starting HU therapy …………………………………………………… 41

Figure 6. Changes in mean ln (ACR) values on Hydroxyurea (HU) therapy among patients with albuminuria pre HU………………………………………45

Figure 7. Proportion of patients with albuminuria over 2 years of HU therapy ….46

Figure 8. Individual patient trajectories showing change in ln (ACR) levels after starting HU therapy (patients with albuminuria pre HU) …….………...47

Figure 9. Changes in mean ln (ACR) values over ~1 year among patients with and without HU therapy …………………………………………….……….52

Figure 10. Change in proportion of patients with albuminuria over ~ 1 Year among exposed and unexposed patients…………………………………...……53

Tables

Table 1. Baseline characteristics of SCA patients who started Hydroxyurea (HU) between 2011 and 2013…………….………....................................... 36

Table 2. Comparison of median ACR values pre and post HU for patients with 2 years of data ………………………….………….…….……..……... 37

Table 3. Results of multivariable analysis of the effect of covariates on ln(ACR) using mixed effects……………………………….………….……….38

Table 4. Comparison of baseline characteristics of SCA patients (normal vs. albuminuria group) in study……………………...…..….….………...42

Table 5. Comparison of median ACR pre and post HU-among SCA patients with albuminuria pre HU ……………… ………….…...............................43

Table 6. Result of multivariable analysis of the effect of HU on ln (ACR) using a mixed effects model among patients with albuminuria pre HU…..….44

Table 7. A comparison of baseline characteristics of SCA patients with albuminuria exposed versus unexposed to hydroxyurea therapy for at least 6 months…………………………………………………………..…….48

Table 8. A comparison of change in ACR values (ΔACR) over ~1 year exposed versus unexposed ……………………………………………….…….49

Table 9. Result of univariate analysis of the association of covariates with difference in ln (ACR) values among SCA patients …………………50

Table 10. Result of multivariable analysis of the effect of HU therapy on Δ ln (ACR) values among SCA patients while adjusting for covariates………......51


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