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THE RELATIONSHIP BETWEEN BRACHIAL ARTERY FLOW-MEDIATED

DILATATION, BIOCHEMICAL MARKERS OF RENAL FUNCTION AND


RENAL ARTERY RESISTIVE INDEX IN SICKLE CELL DISEASE
Oluwagbemiga Oluwole Ayoola1 Rahman Ayodele Bolarinwa2 Chidiogo Chukwunweike Onwuka1 Idowu Michael Bukunmi1 Aderibigbe
Adeniyi Sunday1

1. Department of Radiology OAUTHC Ile-Ife, Osun state, Nigeria.


2. Department of Hematology and Blood Transfusion OAUTHC Ile-Ife, Osun
state, Nigeria.

Background Results Results (continued) Conclusions


Table 2. Categorization of SCD subjects based on %FMD
Sickle cell disease (SCD) is an inheritable Forty four subjects with Genotype SS and 33 Variables SCD SCD p value Brachial artery FMD is an important test in
genetic disorder of hemoglobin structure with controls with Genotype AA (Ratio 4:3) were %FMD < 5.35 %FMD ≥ 5.35 the management of SCD patients for non-invasive
variable clinical manifestations. Annually, about recruited for the study. The median age of the n = 29 n = 15 assessment of the vascular endothelium status.
312,000 people are born with hemoglobin SS subjects [24.50 years Interquartile range (IQR),
Gender, n (%) There is a relationship between FMD, RARI,
genotype worldwide, with up to 236,000 of these 19.5-32 years] was not significantly different with
Male 14 (48.3) 9 (60.0) 0.535* and biochemical renal indices in SCD patients
in sub-Saharan Africa. Nigeria, which accounts for that of the controls [24.24 years (IQR, 21-27
Female 15 (51.7) 6 (40.0) such that impairment of FMD could also be a
150,000 of these births, has the highest disease years)] [p = 0.305]. The SCD subjects consisted of
proxy marker for the onset of renal impairment in
burden in the world. The prevalence of SCD 23 males (52.3%) and 21 females (47.7%) while Age, years 24.0 (19.0 – 31.5) 26.0 (21.0 – 32.0) 0.637#
this group of patients.
across sub-Saharan Africa is between 10 and the controls consisted of 16 (48.5%) males and 17 Height, m 1.6 (1.5 – 1.7) 1.6 (1.6 – 1.8) 0.102#
(51.5%) females. Even though our findings show
45%. Weight, kg 48.5 ± 11.1 50.3 ± 7.7 0.590** association/relationships rather than causation, we
The vascular endothelium performs BMI, kg/m2 18.1 (16.6 – 20.5) 17.7 (16.8 – 20.2) 0.785# believe it is still a step forward in the on-going
endocrine, autocrine, and paracrine functions and The median % FMD in SCD subjects of 3.44 94.0 (89.0 – 97.5) 95.0 (93.0 – 98.0) 0.178# quest to unravel the mysteries of this genetic
SpO2, %
is the largest organ in the body. It helps to regulate (IQR: 0.00 – 7.08) was significantly lower than that disease. Determining the exact age at which FMD
of controls which was 5.35 (IQR: 3.60 – 6.78); p = Hb conc, g/dl 8.1 ± 1.3 8.3 ± 1.1 0.499**
vascular tone, maintain vascular homeostasis, impairment sets in children with SCD would be the
regulate blood flow, and constitutes an 0.043. No significant gender difference was noted WBC, 103/μL 9.9 ± 4.1 10.0 ± 3.8 0.918**
subject of a future study.
antithrombotic surface for smooth passage of in the % FMD among SCD subjects (p = 0.981) Platelet, 103/μL 302.9 ± 148.6 274.7 ± 146.7 0.552**
blood elements/constituents. Endothelial and among control subjects (p = 0.790). HbF, ng/ml 383.6 (328.8 – 444.5) 349.3 (260.3 – 472.6) 0.421#
dysfunction (ED) is a known feature of SCD which sP-Selectin, ng/ml 79.4 (65.9 – 84.8) 78.5 (76.0 – 82.5) 0.921#
is present both in crisis and in steady state. It has There was significant modest negative HCY, µmol/l 18.7 (11.9 – 32.7) 14.4 (7.4 – 25.6) 0.360#
been demonstrated in both children and adults correlation between %FMD and serum Cys-C
Cys-C, mg/l 4.9 (3.1 – 7.4) 1.6 (1.4 – 9.3) 0.039#
References
with SCD, and is more severe in sickle cell anemia levels (r = -0.372; p = 0.013) and between %FMD
than sickle cell trait patients. Impaired (reduced) and renal artery resistivity index; RARI (r = -0.307; KIM-1, pg/ml 420.0 (297.5 - 540.0) 560.0 (380.0 – 798.0) 0.042# 1. Saraf SL, Molokie RE, Nouraie M, et al.
#
sonographic brachial artery flow-mediated p = 0.042) (Table 1). Creatinine, µmol/l 90.0 (69.0 – 105.5) 78.0 (49.0 – 128.0) 0.766 Differences in the clinical and genotypic
dilatation (FMD) is a recognised biomarker for eGFR, mL/min per 1.73m2 87.0 (60.5 – 115.0) 92.0 (58.0 – 146.0) 0.692# presentation of sickle cell disease around the
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Correlation Coefficient* p value *Chi square (χ2)/Fisher’s exact test statistic was used to compare proportions. Renal function in children suffering from sickle cell
#
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disease: challenge of early detection in highly
Height, m 0.117 0.450 **Independent samples t-test was used to compare the means.
Aim and Objectives Weight, kg -0.063 0.683 BMI – body mass index; SpO2 - Oxygen saturation; HbF – Hemoglobin F; sP-Selectin resource-scarce settings. PloS one.
– soluble P-selectin; Cys-C – cystatin C; KIM-1 – Kidney injury molecule-1; eGFR – 2014;9(5):e96561.
BMI, kg/m2 -0.088 0.571
We aimed at evaluating ED in SCD (HbSS) Estimated Glomerular filtration rate; UACR - urine albumin-creatinine ratio; RARI – 4 Mulumba LL, Wilson L. Sickle cell disease
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ED, biochemical indices of renal function along with sP-Selectin, ng/ml -0.182 0.238 Cystatin-C levels in SCD subjects based on %FMD Gething PW, Dewi M, Temperley WH, Williams
indices of disease severity, and renal arterial HCY, µmol/l -0.204 0.184 category TN, Weatherall DJ, Hay SI. Global epidemiology of
Doppler indices. Cys-C, mg/l -0.372 0.013 sickle haemoglobin in neonates: a contemporary
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eGFR, mL/min per 1.73m2 0.111 0.473
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UACR -0.074 0.632
-0.307
Brachial Artery Diameter as a Predictor of
RARI 0.042
Endothelial Dysfunction in Sickle Cell Disease.
Subjects and Methods BMI – body mass index; SpO2 - Oxygen saturation; HbF – Hemoglobin F; sP-Selectin – soluble P-
selectin; Cys-C – cystatin C; KIM-1 – Kidney injury molecule-1; UACR - urine albumin-creatinine Iraqi Journal of Medical Sciences. 2016;14(4):351-
ratio; eGFR – Estimated Glomerular filtration rate; RARI – Renal artery resistivity index 358.
This was a cross sectional comparative study 7. Blum A, Yeganeh S, Peleg A, et al. Endothelial
in which 44 homozygous SCD (HbSS) along with function in patients with sickle cell anemia during
33 age and sex matched controls (HbAA) were and after sickle cell crises. Journal of thrombosis
enrolled. Brachial artery FMD was done on all and thrombolysis. 2005;19(2):83-86.
subjects using Doppler-enabled MINDRAY DC-7
8. Eltahir MA, Gar-elnabi ME, Omer MA,
ultrasound scanner (Shenzhen Mindray Bio-
Abdelgadir O, Abdallah EA. Impact of Sickle Cell
medical Electronics, Nanshan, Shenzhen, China) Using a %FMD cut-off of 5.35, which is the Disease in Renal Arteries Blood Flow Indices
with a 7.5 to 12 MHz linear array transducer. median value obtained in the control population, Using Ultrasonography. International Journal of
Doppler sonography of the renal arteries was SCD subjects were separated into two groups Medical Imaging. 2017;5(2):9-13.
done for measurement of the Resistive index (RI) (Table 2 and Figure 1).
and Pulsatility index (PI) of the interlobar arteries. 9. Tharaux P-L. Endothelin in renal injury due to
sickle cell disease. Contributions to nephrology.
Venous blood was obtained from all subjects Among SCD subjects with %FMD < 5.35
2011;172:185-199.
to evaluate for homocysteine (HCY), foetal serum Cys-C levels was significantly higher in
hemoglobin (HbF), kidney injury molecule 1 (KIM those with urine albumin-creatinine ratio (UACR) > 10. Ataga KI, Derebail VK, Caughey M, et al.
1), soluble-P-selectin (sPselectin), creatinine, 300mg/g (3.4; IQR = 2.1 – 5.0) than in those with Albuminuria Is Associated with Endothelial
cystatin C (Cys-C), hematocrit levels, platelet and UACR 30-300mg/g (6.4; IQR = 5.6 – 10.5) and Dysfunction and Elevated Plasma Endothelin-1 in
white blood cell (WBC) counts. Urine samples was those with UACR < 30mg/g in that order (13.4; Sickle Cell Anemia. PloS one.
also obtained from all subjects and controls for IQR = 1.6 – 13.4) (Figure 1) with P = 0.006. 2016;11(9):e0162652.
urine albumin-creatinine ratio (UACR). Table 3. Spearman correlation of Cys-C with other variables in the two patient groups
The SCD subjects were further categorized In this subgroup, there was significant UACR, Creatinine, GFR, sP-Selectin, RARI KIM-1, Acknowledgments
into 2 groups based on FMD of 5.35 (the median correlation between %FMD and UACR, %FMD mg/g µmol/l mL/min ng/ml pg/ml
FMD of the control subjects). Those with FMD and serum creatinine levels, %FMD and eGFR per 1.73m2
<5.35 were in one group while those with FMD and between %FMD and serum sP-selectin levels Subjects with %FMD < 5.35 We wish to acknowledge Obafemi Awolowo
≥5.35 were in the second group. The demographic ( (Table 3). Contrariwise, in subjects with %FMD ≥ University Teaching Hospital Complex, Ile-Ife for
and biochemical characteristics of both groups 5.35 there was no significant difference in serum Spearman’s 0.576 0.418 0.430 0.389 0.129 0.032 part sponsorship of the research work.
Cys-C levels based on their UACR values. In Rho
were compared using relevant statistics.
P value 0.001 0.024 0.020 0.037 0.506 0.868
Data analysis was done using IBM Statistical addition, there was no significant correlation
Subjects with %FMD ≥ 5.35
Package for the Social Sciences (SPSS) software between %FMD and UACR, serum creatinine
Version 21. Test of significance was set at p < levels, GFR or sP-selectin (Table 3). Contact
Spearman’s -0.232 -0.268 0.352 -0.396 -0.059 0.566
0.05. Rho Email: oluwagbemiga.ayoola@npmcn.edu.ng
P value 0.406 0.335 0.198 0.144 0.834 0.028
Cys-C – cystatin C; UACR - urine albumin-creatinine ratio; eGFR – Estimated Glomerular
filtration rate; sP-Selectin – soluble P-selectin.

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