This document discusses a study examining the relationship between brachial artery flow-mediated dilation (FMD), markers of renal function, and renal artery resistive index in patients with sickle cell disease. Forty-four patients with sickle cell disease and 33 controls were recruited. FMD was significantly lower in patients compared to controls. FMD showed a modest negative correlation with serum cysteine-C levels and renal artery resistive index, suggesting FMD may serve as a proxy for early renal impairment in sickle cell disease. The findings provide insight into endothelial dysfunction in sickle cell disease and its relationship to renal function.
This document discusses a study examining the relationship between brachial artery flow-mediated dilation (FMD), markers of renal function, and renal artery resistive index in patients with sickle cell disease. Forty-four patients with sickle cell disease and 33 controls were recruited. FMD was significantly lower in patients compared to controls. FMD showed a modest negative correlation with serum cysteine-C levels and renal artery resistive index, suggesting FMD may serve as a proxy for early renal impairment in sickle cell disease. The findings provide insight into endothelial dysfunction in sickle cell disease and its relationship to renal function.
This document discusses a study examining the relationship between brachial artery flow-mediated dilation (FMD), markers of renal function, and renal artery resistive index in patients with sickle cell disease. Forty-four patients with sickle cell disease and 33 controls were recruited. FMD was significantly lower in patients compared to controls. FMD showed a modest negative correlation with serum cysteine-C levels and renal artery resistive index, suggesting FMD may serve as a proxy for early renal impairment in sickle cell disease. The findings provide insight into endothelial dysfunction in sickle cell disease and its relationship to renal function.
This document discusses a study examining the relationship between brachial artery flow-mediated dilation (FMD), markers of renal function, and renal artery resistive index in patients with sickle cell disease. Forty-four patients with sickle cell disease and 33 controls were recruited. FMD was significantly lower in patients compared to controls. FMD showed a modest negative correlation with serum cysteine-C levels and renal artery resistive index, suggesting FMD may serve as a proxy for early renal impairment in sickle cell disease. The findings provide insight into endothelial dysfunction in sickle cell disease and its relationship to renal function.
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 endothelial dysfunction in SCD. The assessment world. Paediatric respiratory reviews. UACR, mg/g of FMD was introduced as a noninvasive 2014;15(1):4-12. n (%) approach to examine vasodilator function in vivo <30 17 (58.6) 9 (60.0) 0.920* 2. Weatherall DJ, Clegg JB. Inherited and has been used as a surrogate marker of haemoglobin disorders: an increasing global <30 - 300 9 (31.0) 5 (33.3) vascular health. health problem. Bulletin of the World Health >300 3 (10.3) 1 (6.7) Organization. 2001;79(8):704-712. RARI 0.70 (0.67 – 0.73) 0.69 (0.62 – 0.71) 0.160# Table 1. Spearman correlation of %FMD with other variables in SCD subjects 3. Aloni MN, Ngiyulu RM, Gini-Ehungu J-L, et al. 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 # Age, years 0.153 0.322 Independent samples Mann-Whitney U test was used to compare the median.; 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 SpO2, % 0.127 0.410 subjects using sonographic brachial artery FMD, Renal artery resistivity index among children in Africa: an integrative literature Hb conc, g/dl 0.125 0.418 compare the FMD in SCD patients to that of WBC, 10 /μL 3 0.077 0.620 review and global recommendations. International controls with HbAA genotype, and to determine any Platelet, 103/μL -0.182 0.238 Journal of Africa Nursing Sciences. 2015;3:56-64. possible association/relationship among the trio of HbF, ng/ml 0.011 0.945 Figure 1: Clustered Bar chart showing the median 5. Piel FB, Patil AP, Howes RE, Nyangiri OA, 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 KIM-1, pg/ml 0.179 0.245 geostatistical model-based map and population Creatinine, µmol/l -0.166 0.281 estimates. The Lancet. 2013;381(9861):142-51. eGFR, mL/min per 1.73m2 0.111 0.473 6. Al-Janabi HO, Al-Saadi WI, Hamdani FB, et al. 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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