Glomerular filtration rate in children with sickle cell disease in the Eastern Region of Saudi Arabia

Glomerular filtration rate in children with sickle cell disease in the Eastern Region of Saudi Arabia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Glomerular filtration rate in children with sickle cell disease in the Eastern Region of Saudi Arabia Abdalla Mohamed Zayed, Abdalla Zayed, S Almohaimeed, A Eltayeb, and 10 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5337722/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction Sickle cell nephropathy (SCN) is a serious complication of SCD that starts insidiously in childhood, with possible progression to chronic kidney disease in adulthood. Our aim was to study the prevalence and clinical correlates of the glomerular filtration rate, the earliest marker of renal dysfunction, in the Eastern Region of Saudi Arabia (SA). Methods A retrospective cross-sectional study was performed on 114 Saudi children with SCD aged 1-14 years who attended the pediatric hematology clinic in a steady state. Renal function was evaluated via estimated glomerular filtration rate (eGFR). The prevalence of GHF, and the correlation of eGFR with different clinical and laboratory data were investigated. Moreover, a comparison of the clinical characteristics and eGFRs was performed between children from the Southwestern (SW) and Eastern regions of Saudi Arabia (SA) and living in the same Eastern environment. Results A total of 114 children with SCD were included in the study (Male to female ratio: 1.3:1). The mean age was 8.8 ± 3.2 years. They were divided into two groups based on their provenance: Eastern (n: 26/114) and SW (n: 88/114). The mean eGFR was 179.4±52.7 ml/min/1.73 m 2 with a glomerular hyperfiltration (GHF) prevalence of (44.7%). There was no statistical difference between the two groups in terms of the mean GFR or prevalence of GHF (p>0.5). The eGFR correlated with hemolytic markers, including steady-state hemoglobin (HB) (r = −0.25, P 0.003), hematocrit (r=-0.27, p 0.002), HBF (r=-0.28, p 0.001), reticulocytes% (r=0.225, p 0.016), AST(r = 0.32, p 0.000), LDH (r=0.30, p 0.001)and bilirubin (r=0.317, p O.001). In the multivariate regression of the factors determining the eGFR at 95% confidence intervals, only HBF (β =0.216, P = 0.042) remained independently predictive (R 2 = 0.197, p= 0.001). There was no correlation between the GFR and patient age, BP, WBC or platelet count. Conclusion: The prevalence of GHF among Saudi children with SCD in the Eastern region is high, with no significant difference between Eastern and SW patients. The eGFR was correlated with the hemolytic markers, and low HBF was predictive of GHF. Further studies are needed to validate these findings. Figures Figure 1 Figure 2 Figure 3 Introduction Sickle cell disease (SCD) is the most common hereditary blood disorder in humans[ 1 ]. It affects every organ in the body, and kidney abnormalities, known as sickle cell nephropathy (SCN), are common in children[ 2 , 3 ]. The earliest manifestations of SCN are an increase in GFR and defective urinary concentration. GHF starts slowly in infancy, as early as 9–19 months of age, gradually declines to a normal range during the first two decades of life and decreases as the SCN progresses to kidney failure in adulthood[ 4 , 5 ]. GHF may be a cause or a compensatory mechanism in response to early SCN[ 6 ]. The proposed mechanisms for hyperfiltration include a potentially reversible decrease in renal vascular resistance and an increase in renal blood flow. Low oxygen partial pressure, acidic pH, and high osmolality promote sickling of the red cells in the renal medulla, resulting in vaso-occlusion, hemolysis, anemia, inflammation, and oxidative stress. Medullary prostaglandin and nitric oxide secretion due to hypoxia increases the cortical blood flow[ 2 , 4 ]. Concurrently, chronic RBC hemolysis results in severe anemia causing secondary increase in cardiac output and the GFR. Additionally, red cell hemolysis increases heme breakdown into a potent vasodilator (carbon monoxide)[ 7 ]. Moreover, the increase in number, size and selectivity of the glomerular membrane may add to the GHF[ 4 ]. Papillary necrosis may lead to a reduction in functioning renal nephrons, resulting in compensatory hypertrophy and increased filtration of the remaining nephrons[ 6 ]. SCD is relatively common in SA and more prevalent in the Eastern and SW provinces of the country[ 8 ], with marked genetic, clinical and hematological variability. In the Eastern region, the sickle hemoglobin gene is usually associated with the AI haplotype with a mild phenotype, whereas the African (Benin) haplotype predominates in the SW region with a severe phenotype[ 9 ]. Studies on the GFR among Saudi children with SCD are scarce[ 5 ], with limited data on GHF prevalence and risk factors in these children. Given the phenotypic variation among patients with the AI and African SCD haplotypes, we predict that SW children are more predisposed to renal damage than their Eastern counterparts are. Therefore, our aim was to investigate the hypothesis that the prevalence of GHF, as the earliest marker of SCN, is greater in SW children with predominant African haplotypes. Studying the early clinical signs of renal dysfunction in children with different SCD severities may help tailor plans and customize resources for early detection and possible administration of preventive therapy. To address these issues, we conducted a prospective cross-sectional, observational study of children with SCD who attended the out-patient clinic in the steady state. Additionally, we compared the SCD clinical profile including GHF between Eastern children with their SW peers. Material and Methods A retrospective cross-sectional observational study was conducted at King Fahad Military Medical Complex, Dhahran, Eastern Region, Saudi Arabia. All children younger than14 years with SCD who attended the pediatric hematology clinic for routine follow-up in the steady state between July 2021 and August 2022 were included in this study. The diagnosis of SCD was confirmed by hemoglobin electrophoresis via high-performance liquid chromatography (HPLC) method. Children who were S-beta thalassemia, had a pre-existing renal disease, fever, SCD crisis, or acute illness in the preceding two weeks, or who were transfused in the preceding 4 months were excluded. Data were collected from hospital electronic medical records via the case report form. These included: patients' age, sex, place of origin, consanguinity, past medical history and family history of SCD in addition to medications used, including hydroxyurea. Place of origin (provenance)was necessary to determine the patient’s ancestry and hence their SCD haplotype which was confirmed from the patient’s ID attached to their medical file. This was important for comparison between the two groups of SCD patients. Children originally from the SW have African ancestry with the African (Benin) haplotype, whereas those from the Eastern region carry the AI haplotype[ 8 ]. The past medical history included SCD complications such as dactylitis, (vaso-occlusive crisis (VOC), splenic sequestration crisis (SSC), hemolytic crisis, stroke, cholelithiasis, avascular necrosis, stroke, gall stones (GS) and acute chest syndrome (ACS). Weight, height, body mass index (BMI), and both systolic and diastolic blood pressure recordings were among the collected data. Blood pressure readings were compared with the established reference ranges for a pediatric cohort with SCA systolic and diastolic blood pressure (BP)[ 10 ]. The collected standard laboratory parameters included: steady-state hemoglobin, hematocrit, WBCs, reticulocytes, platelets, HBS and HBF in addition to serum creatinine, lactate dehydrogenase (LDH), bilirubin and aspartate transaminase (AST). The estimated glomerular filtration rate (eGFR) was calculated using the updated Schwartz equation as follows: eGFR ( ml / min /1.73 m 2) = 0.413 × height ( cm )/ Serum creatinine ( mg / dl )[ 11 ]. We defined hyperfiltration in our children as an eGFR ≥ 180 mL/min/1.73 m 2 based on the 75th percentile of eGFR identified by the Baby HUG study[ 12 ]. The GFR data were classified into three age groups ( 10 years old) for graph plotting. Statistical Analysis According to their province of origin, we categorized children into two groups: Eastern and Southwestern. Comparison between these groups included demographic, clinical and laboratory data. The Data were uploaded into IBM SPSS 21, New York, USA for analysis. Association between GHF and the independent variables was assessed using Chi square test ( χ 2). Independent t-test was calculated to compare the means which are expressed as ± 1 standard deviation (SD). To determine any correlation with the (eGFR), we performed simple linear regressions for each parameter. For prediction of outcome variables, multiple linear regressions were used. The final result included the variables that remained significantly correlated with eGFR after adjustment for the other variables. R-squares (R 2 ) variables were used as measures of variance. For all outcomes of interest, a P value of < 0.05 was considered significant. Ethical Considerations: The study received scientific and ethical approval from the Armed Forces Hospitals Eastern Province Institutional Review Board (IRB): IRB Protocol No AFHER-IRB-2024-015. This study was conducted in accordance with good clinical practice and the declaration of Helsinki. A field survey was conducted after obtaining approval from the local health authority at our hospital and the Paediatric Department. Results A total of 114 patients with SCD were included in the study, (66 boys, and 48 girls, ratio: 1.3). The mean age was 8.8 ± 3.2 years with a range of (1.5–14) years. Among the 114 patients included in the study, 88 patients (77.2%) originated from the SW province, and 26 patients (22.8%) were from Eastern region. The demographic, clinical and laboratory profiles of the patients is summarized in Table 1. Compared with their Eastern peers, the SW children had significantly more consanguineous parents and more patients used hydroxyurea. On the other hand, the Eastern children had markedly higher HBF levels compared with their SW peers. Notably, SW children have more SCD complications, eGFR and GHF than do their Eastern counterparts, who have higher growth parameters and steady-state HB. However, the differences are not statistically significant. Table (1): Comparison of the demographic, clinical and laboratory data of the SW and Eastern patients Parameter Total (n:114) Southwest (n:88) East (n: 26) P Sex: M (n: 66) F (n: 48) 57.9% 61.4% 46.2% 0.12 42.1% 38.6% 53.8% Consanguinity 67.5% 76.1% 38.5% 0.001* FH of SCD 45.6% 40.9% 61.5% 0.051 H/O dactylitis 13.2% 12.5% 15.4% 0.46 Complicated course 86.8% 87.5% 84.6 0.46 HU Use 61.4% 67% 42.3% 0.02* GHF 44.7% 46.6% 38.5% 0.46 Age, y 8.8 ± 3.2 8.9 ± 3.2 8.6 ± 3.3 0.64 Weight, kg 25.5 ± 11 25.2 ± 10.7 26.7 ± 12 0.31 Height, cm 124.1 ± 18.2 123.8 ± 18.5 125.2 ± 17.5 0.71 BMI, kg/m 2 16 ± 3.7 15.9 ± 3.9 16.1 ± 2.7 0.76 Systolic BP, mm/Hg 107 ± 10 107 ± 10 105 ± 10 0.54 Diastolic BP, mm/Hg 60 ± 8 60 ± 8 62 ± 9 0.31 HB, g/dL 9 ± 1.2 8.9 ± 1.1 9.2 ± 1.3 0.24 Hct % 27 ± 4 27 ± 4 28 ± 4 0.12 MCV 86 ± 16 87 ± 17 81 ± 12 0.09 WBC × 10 9 /L 10.1 ± 4.3 10 ± 4.4 10.6 ± 4.2 0.55 Retics % 7.4 ± 4.5 7.3 ± 4.3 7.7 ± 5.3 0.75 PLT × 10 9 /L 390 ± 181 399 ± 181 359 ± 179 0.32 HBF% 14.3 ± 7.7 13.3 ± 7.3 17.4 ± 8.2 0.03* Total bilirubin 38 ± 31 40 ± 33 33 ± 19 0.16 AST 47 ± 18 47 ± 19 44 ± 17 0.41 LDH, IU/L 494 ± 202 497 ± 215 486 ± 150 0.76 eGFR ml/min/1.73 m 2 179.4 ± 52.7 183.2 ± 54.2 166 ± 45 0.13 * Significant Categorical data are presented as percentage (%) and continuous variables are presented as the means ± standard deviations (SDs). M = male, F = female, FH = family history, H/O = history of, HU = hydroxyurea, GHF = glomerular hyperfiltration, BMI = body mass index, BP = blood pressure, HB = haemoglobin (steady state), Hct = haematocrit, MCV = mean corpuscular volume, WBCs = white blood cells, Retics = reticulocytes, PLT = platelets, HBF: Haemoglobin F, AST = Aspartate transaminase, LDH = lactate dehydrogenase, eGFR: estimated glomerular filtration rate. Patients with a complicated course includes those who experienced at least one episode of SCD crises (VOC, SSC, aplastic and hyper-haemolytic) stroke, ACS, GS and AVN. Figure (1) shows that the prevalence of GHF (GFR > 180 ml/min/1.73 m 2 ) is 44.7%. figure (1): The prevalence of GHF among children with SCD in the Eastern region of SA. Figure (2) compares eGFR between the SW and Eastern Saudi children with SCD. There is no significant difference between the two groups. 183.2 ± 54.2 v.166 ± 45; p > 0.05. Figure (2): The eGFR of SW and Eastern Saudi children with SCD. Figure (3) shows that eGFR increases with age of the patients in the first decade, and then, the rate slows down early in the second decade. However, the difference was not statistically significant, p > 0.05. Figure (3): Mean eGFR rate by a subset of age of children with SCD. Age categories: <5 years (n = 21), 6–10 years (n = 45), 11–14 years (n = 48). Table (2) shows no correlation between GHF and different categorical parameters, including provenance, sex, age group, parental consanguinity, systolic or diastolic hypertension (BP > 90th centile), family history of SCD, past history of dactylitis, VOC or other SCD complications or the use of HU. Table (2): The distribution of glomerular hyperfiltration (GHF) in relation to different categorical data. Clinical Parameter GHF (N:114) P value Yes (N:51 (44.7%) No (N: 63 (55.3%) Provenance SW (n: 88) 41 (46.6%) 47 (53.4%) 0.464 E (n: 26) 10 (38.5%) 16 (61.5%) Gender M (n:66) 29 (43.9%) 37 (56.1%) 0.841 F (n:48) 22 (45.8%) 26 (54.2%) Age group (in years) < 5: (n:21) (18.4%) 9 (17.6%) 12 (19%) 0.973 6–10: (n:45) (39.5%) 20 (39.2% 25 (39.7%) 11–14:(n: 48) (42.1%) 22 (43.1%) 26 (41.3%) Consanguinity n: 77 (67.5%) 35 (45.5%) 42 (54.5%) 0.824 Systolic BP High (n:36) (31.6%) 15 (41.7%) 21(58.3%) 0.690 Normal(n:78) (68.4%) 36 (46.2%) 42 (53.8%) Diastolic BP High(n:12) (10.5%) 4(33.3%) 8 (66.7%) 0.543 Normal(n:102) (89.5%) 47 (46.1%) 55 (53.9%) Dactylitis n:15 (13.1%) 8 (53.3%) 7 (46.7%) 0.472 VOC n :51(44.7%) 18 (35.3%) 33 (52.4%) 0.089 Complications n :99 (86.8%) 43 (43.4%) 56 (56.6%) 0.472 FH of SCD n :52 (45.6%) 24 (46.2%) 28 (53.8%) 0.781 HU use n: 70 (61.4%) 29 (41.4%) 41 (58.6%) 0.370 Table (3) shows that the mean eGFR was significantly higher in children who did not have a past history of VOC. There were no correlations between eGFR and provenance, gender, parental consanguinity, family history of SCD, past history of dactylitis, other SCD complications or the use of HU. Table (3): shows the relationship between the eGFR and different categorical parameters of the study patients. Parameter eGFR (ml/min/1.73 m 2 ) n Mean SD P value Provenance SW 88 183.2 54.2 0.13 E 26 166.8 45.9 Gender Male 66 179.9 51.8 0.94 Female 48 178.7 54.5 Consanguinity Yes 77 183 55.7 0.26 No 37 171.9 45.7 FH of SCD Yes 52 182.7 51.4 0.54 No 62 176.7 54 Dactylitis Yes 15 186.8 50.9 0.55 No 99 178.3 53.1 VOC Yes 52 167.7 45.9 0.02* No 62 189.2 56.3 Complications Yes 99 178.7 48.8 0.77 No 15 184.5 75.5 HU use Yes 70 174.6 43.8 0.25 No 44 187.1 64.1 * Significant Provenance: province of origin, consanguinity = parental consanguinity, FH = family history, Dactylitis = past history of dactylitis, Complications = history of SCD crises and complications, HU = hydroxyurea. Correlations between the eGFR and other clinical measurements taken at the same time were assessed (Table 4). In the univariate analysis, statistically significant associations between the eGFR and markers of hemolysis were observed. Specifically, there was an inverse relationship with steady-state hemoglobin (HB) (r = −0.25, P 0.003), hematocrit (r=-0.27, P 0.002), and HBF (r=-0.28, P 0.001) and a positive correlation with reticulocyte percentage (r = 0.225, P = 0.016), AST(r = 0.32, P 0.000), LDH (r = 0.30, P 0.001)and bilirubin (r = 0.317, P.001). In multivariate regression of the factors determining eGFR at 95% confidence intervals, only HBF (β =0.216, t= -2.054, P = 0.042) remained independently predictive and accounting for 19.7% of the GFR changes (R = 0.444, R 2 = 0.197, F (7,105) = 3.689, P 0.001). Table (4): Univariate analysis of eGFR with measured continuous clinical Parameters: Parameter r p HB − 0.252 0.007* Hematocrit -0.271 0.004* WBCs 0.16 0.055 Reticulocytes% 0.225 0.016* PLT 0.121 0.201 HBF − 0.279 0.003* LDH 0.306 0.001* Age 0.173 0.065 Systolic BP -0.148 0.117 Diastolic BP -0.079 0.405 AST 0.325 0.000* Bilirubin 0.317 0.001* * Significant The Pearson correlation coefficient was calculated for continuous variables. Where non-normal distributions were seen, logarithmic transformation was performed. eGFR: estimated glomerular filtration rate, HB = haemoglobin (steady state), Hct = haematocrit, WBCs = white blood cells, Retics = reticulocytes, PLT = platelets, HBF: haemoglobin F, LDH = lactate dehydrogenase, AST = aspartate transaminase. Discussion There is a dearth of studies carried out in Saudi Arabia on renal function in pediatric SCD patients. The aim of this study was to investigate changes in the eGFR and its clinical correlates as early markers of renal dysfunction on children with SCD living in the Eastern Province of SA. The results indicated a high prevalence of GHF among these children, with no significant difference between children with AI and those with African haplotypes. The study also demonstrated a correlation between the GFR and different hemolytic markers of the disease. It is negatively correlated with low steady-state HB, hematocrit and HBF, and positively correlated with reticulocyte percentage, LDH, AST and bilirubin. According to the multivariate regression analysis, only HBF remained predictive. eGFR: The (eGFR) is a reliable indicator of renal function, as it is widely regarded as the best overall index in both health and disease. The overall mean e GFR in our cohort was 179.5 ± 52.7 mL/min/1.73 m2, in accordance with that previously reported in the pediatric literature (175.8 ± 37.5–184.4 ± 55.5 mL/min/1.73 m2[ 4 , 11 , 12 ]. In the SW group, the mean eGFR was183.2 ± 54.2 ml/min/1.73 m 2 while a study in the Western region reported values of 96–120 ml/min/1.73 m 2 [ 5 ], and another study in the central region reported values of 159.8 ml/min/1.73 m 2 [ 13 ] . GHF: GHF, defined as estimated GFR > 180 ml/min/1.73 m 2 , is appropriate for young patients with SCD[ 12 ]. It is the earliest manifestation of kidney disease and precedes the development of overt SCN. The prevalence of GHF varies widely in different studies, ranging from 16–98%[ 6 , 14 ]. Our results indicated that the overall prevalence of GHF was 44.7% which is comparable to that reported in America (43%)[ 15 , 16 ]. The figure is lower than that reported in the UK (98%)[ 6 ] and higher than that reported in India(16%)[ 14 ]. The main SCD haplotype in India is Arab-Indian (AI) as demonstrated in previous studies. SCD is milder in Indians because of the association of high levels of HBF with the AI haplotype. HBF is responsible for inhibiting erythrocyte sickling, a fundamental step in the pathophysiology of SCN[ 16 ]. Although our children with SCD in Eastern Saudi province carry mainly the AI haplotype, their GHF prevalence is 38.5% which is markedly higher than that reported in India (16%)[ 17 ]. Differences in the environment probably contribute to this difference. The Saudi Eastern and SW regions are different environments that are1500 Km apart. Saudi studies revealed that Eastern patients with SCD have a milder form of the disease than the SW patients do, on the basis of studies conducted independently in each region[ 8 ]. Although HBF is higher in the Eastern group. the current report revealed no significant difference in the studied disease characteristics, including GHF, between the two groups of children. Living in the same environment, our children (Eastern and SW) share the climate (temperature, air quality, humidity, rainfall, and wind speed), altitude, exposure to infection, medical care, and socio-economic status (all of them are military personnel dependents). These factors might have resulted in narrowing the difference in the incidence of many disease complications to an insignificant level between the two groups of patients, including the GHF. Multi-centre studies are needed in different geographic regions of the country to support this hypothesis. Generally, the variation in the reported prevalence could be due to differences in the methods used for determination of the creatinine levels and the GFR by different authors, to different ages of the patients and the influence of haplotypes[ 16 ]. It could also be affected by inconsistency in population characteristics and the definitions of eGFR cut-offs used by various authors, that can sometimes be very low (GFR > 120 ml/min/1.73m2)[ 18 ]. The environmental factors should also be considered. Hemolytic markers: It has been proposed that GHF can be attributed to hemolysis-associated pathophysiology rather than vaso-occlusive pathophysiology. Thus, correlations between GFR and hemolytic markers including total Hb, HBF, reticulocyte count, bilirubin, and LDH were explored[ 4 ]. In the adult literature patients with SCD commonly have GHF associated with severe anemia, the absence of alpha thalassemia, and increased hemolytic markers including lower HBF [ 19 ], and a high reticulocyte count [ 20 ]. To test this hypothesis in the pediatric population, we correlated the eGFR with other clinical measurements. In univariate analysis, statistically significant associations between eGFR and markers of hemolysis were observed. Specifically, there was an inverse relationship with steady-state HB, hematocrit, and HBF and a positive correlation with reticulocyte percentage, AST, LDH, and total bilirubin. According to multivariate regression of the factors determining eGFR, only HBF remained independently predictive which is in line with the findings of a Brazilian pediatric study[ 21 ]. Additionally, in concordance with our results, Brewin et al. reported statistically significant associations between eGFR and markers of hemolysis including an inverse relationship with steady state HB and a positive correlation with reticulocyte percentage, bilirubin, and AST. However, in their multivariate regression, only the steady state HB and reticulocyte percentage remained independently predictive[ 6 ]. Hemoglobin F: HbF is a major SCD modifier which negatively correlates with the severity of complications. Low HbF has been associated with increased hemolysis[ 4 ]. Our results revealed a significant correlation between eGFR and HBF(r=-0.28, p 0.001), which is consistent with the findings of Al-Mosawa’s pediatric study[ 22 ]. Compared to their SW peers, our Eastern children had significantly higher HBF, coupled with lower eGFR and GHF. However, the difference was not statistically significant, possibly due to the weak influence of HBF on the eGFR according to the multivariate regression model (R 2 = 0.197, p 0.001) Hydroxyurea: In SCD patients, HU increases HbF and is recommended for almost all children with SCD starting in the first year of life[ 4 ]. The effect of HU use on GFR and GHF is not yet clear. In the present study, the use of HU was not associated with changes in the GFR, which is consistent with the results of a Saudi study in children[ 5 ]. Roy et al. reported that the evidence that HU improves the GFR or reduces GHF in young children aged 9 months to 18 months is not strong[ 23 ]. Other studies have shown that HU at the maximum tolerated dose (MTD) is associated with a reduction in GHF in young children with SCD (median age 7.5 years)[ 24 ]. However, our study lacked information about compliance, duration of use and whether the MTD has been reached. Age: Generally, the GFR increases in younger children with SCD, plateaus until adolescence and subsequently begins to decrease during adulthood until it reaches the level of renal failure[ 5 ]. Consistent with these findings, our study demonstrated that the mean eGFR increased across age groups until the teenage years, when the rate started to slow. However, the difference was not statistically significant, in consonance with previous studies[ 6 , 25 ], probably due to differences in the sample size of each age group[ 5 ]. Blood pressure: Studies on blood pressure in SCD children have shown conflicting results. While some authors believe that children with SCD have low normal or normal blood pressures[ 26 ], others suggest that they might have hypertension without clear evidence of renal dysfunction[ 27 ]. However, Other investigators reported hypertension in10.3% of children with SCD, on the basis of in-clinic blood pressure measurements. When they utilized ambulatory blood pressure monitoring (ABPM), they reported ambulatory hypertension in 43.6% in their SCD patients. These findings suggest that hypertension may be under diagnosed in SCD children when standard clinic- based measurements are used[ 28 ]. In the present study, 22.8% of the children had an SBP above the 90th percentile and 5.3% had DBP above the 90th percentile. There was no relationship between GHF and either systolic or diastolic BP in accordance with earlier studies[ 29 ]. However, as blood pressure was only recorded at one clinic visit, it should be interpreted cautiously. SCD complications: The relation between the eGFR and complications of SCD is not fully understood. While some researchers reported a weak positive correlation between the eGFR and the frequency of past painful crisis[ 29 ], others reported no correlation with ACS or a high risk for stroke. They postulated that the factors influencing the development of these complications and those contributing to the SCN may differ [ 30 ]. In adults with SCD, Haymann et al. supported the view that GHF could be related predominantly to chronic hemolysis (associated with previous pulmonary hypertension, leg ulcers, priapism, and strokes) than viscosity vaso-occlusive-related complications (including VOC, ACS, and osteonecrosis)[ 20 ]. In the current study, the results indicated no relationship with a past history of dactylitis, but interestingly, patients with a significant history of isolated VOC episodes had a lower eGFR. This finding could support the theory that GHF pathogenesis is dependent mainly on hemolytic rather than the vaso-occlusive process. There was no association between the e GFR and the SCD complications, including ACS, stroke, SSC or hemolytic crisis or even VOC associated with other complications. Further research is needed to support these findings. Limitations: This study had many limitations. First, a retrospective study with incomplete valuable data like the compliance and maximal tolerated dose of hydroxyurea. Second, a single-center hospital-based study would limit the generalizability of its findings. The scarcity of Saudi studies on children with SCD limits the comparative value with similar groups of patients. In addition, blood pressure was only recorded at one clinic visit, making the true prevalence of hypertension less accurate. Moreover, despite the advantages of eGFR method, it may overestimate the GFR due to increased secretion of creatinine resulting from the GHF in SCD. Conclusion The prevalence of GHF among Saudi children with SCD is high, with no significant difference between Eastern patients with the Arab-Indian β-globin haplotype (AI) and their Southwestern counterparts with the African haplotypes. The eGFR was correlated with hemolytic markers including total HB, HBF, hematocrit, reticulocyte percentage, LDH, bilirubin, and AST. According to the multivariate analysis, only HBF remained predictive. Further studies in different regions of the country are needed to validate our findings and develop comprehensive strategies to prevent early renal damage in this population. Abbreviations SCD Sickle cell disease SA Saudi Arabia SW Southwest AI Arab-Indian eGFR estimated glomerular filtration rate GHF Glomerular hyperfiltration SCN Sickle cell nephropathy VOC Vaso- occlusive crisis ACS Acute chest syndrome SSC Splenic sequestration crisis HBF Hemoglobin F LDH Lactate dehydrogenase enzyme AST Aspartate dehydrogenase enzyme BMI Body mass index HU Hydroxyurea Declarations Clinical Trial Number Not applicable Ethical Declaration: The study received scientific and ethical approval from the Armed Forces Hospitals Eastern Province Institutional Review Board (IRB): IRB (Protocol No AFHER-IRB-2024-015). This study was conducted in accordance with good clinical practice and the declaration of Helsinki. According to the study's design, there was no direct interaction with patients or use of tissue samples, eliminating the need for parental or guardian informed consent for minors. In recognition of this, our Ethics Review Board granted a waiver for informed consent. Authors contribution: All authors contributed significantly to this research and reviewed the final version. All were involved in the conception and design of the study, data collection, analysis and interpretation. Acknowledgment We would like to thank Rehab Abdalla Zayed for her contribution in preparation of the graphs and completion of the manuscript. Data availability The raw data of this study contain protected health information. They are therefore not publicly available. Deidentified data may be provided by the corresponding author upon reasonable request, after approval from the ethical review board at King Fahad Military Medical Complex. Any data shared will be fully anonymized for protection of patient confidentiality and privacy according to the regulations. References Babatunde HE et al (2023) Cystatin C-derived estimated glomerular filtration rate in children with sickle cell anaemia. BMC Nephrol 24(1):349 Graf T, Piccone C, Dell KM (2020) Sickle Cell Nephropathy in Children. In: Emma F et al (eds) Pediatric Nephrology. Springer, Berlin Heidelberg: Berlin, Heidelberg, pp 1–15 Ocheke IE et al (2019) Microalbuminuria risks and glomerular filtration in children with sickle cell anaemia in Nigeria. Ital J Pediatr 45(1):143 Afangbedji N, Jerebtsova M (2022) Glomerular filtration rate abnormalities in sickle cell disease. Front Med (Lausanne) 9:1029224 Monagel DA et al (2023) Renal outcomes in pediatric patients with sickle cell disease: a single center experience in Saudi Arabia. Front Pediatr 11:1295883 Brewin J et al (2017) Early Markers of Sickle Nephropathy in Children With Sickle Cell Anemia Are Associated With Red Cell Cation Transport Activity. Hemasphere 1(1):e2 Hariri E et al (2018) Sickle cell nephropathy: an update on pathophysiology, diagnosis, and treatment. 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Saudi J Kidney Dis Transpl 28(3):524–531 Lebensburger J et al (2018) Impact of Hyperfiltration during Early Childhood on the Natural History of Albuminuria in Pediatric Sickle Cell Anemia. Blood 132(Supplement 1):8–8 Ndour EHM et al (2022) Biomarkers of sickle cell nephropathy in Senegal. PLoS ONE 17(11):e0273745 Lakkakula BV et al (2017) Assessment of renal function in Indian patients with sickle cell disease. Saudi J Kidney Dis Transplantation 28(3):524–531 Aloni MN et al (2014) Renal function in children suffering from sickle cell disease: challenge of early detection in highly resource-scarce settings. PLoS ONE 9(5):e96561 Zahr RS, Saraf SL (2024) Sickle Cell Disease and CKD: An Update. Am J Nephrol 55(1):56–71 Haymann JP et al (2010) Glomerular hyperfiltration in adult sickle cell anemia: a frequent hemolysis associated feature. Clin J Am Soc Nephrol 5(5):756–761 Belisário AR et al (2020) Prevalence and risk factors for albuminuria and glomerular hyperfiltration in a large cohort of children with sickle cell anemia. Am J Hematol 95(5):E125–e128 Al-Musawa FE, Al-Saqladi AM (2019) Prevalence and correlates of microalbuminuria in Yemeni children with sickle cell disease. Saudi J Kidney Dis Transpl 30(4):832–842 Roy NB et al (2023) Interventions for chronic kidney disease in people with sickle cell disease. Cochrane Database Syst Rev, 8(8): p. Cd012380. Aygun B et al (2013) Hydroxyurea treatment decreases glomerular hyperfiltration in children with sickle cell anemia. Am J Hematol 88(2):116–119 Zimmerman SA et al (2004) Elevated glomerular filtration rate (GFR) in young patients with sickle cell anemia . 22B-22B Imuetinyan BA, Okoeguale MI, Egberue GO (2011) Microalbuminuria in children with sickle cell anemia. Saudi J Kidney Dis Transpl 22(4):733–738 Bodas P et al (2013) The prevalence of hypertension and abnormal kidney function in children with sickle cell disease -a cross sectional review. BMC Nephrol 14:237 Shatat IF et al (2013) Masked hypertension is prevalent in children with sickle cell disease: a Midwest Pediatric Nephrology Consortium study. Pediatr Nephrol 28(1):115–120 Nnaji UM et al (2020) Sickle Cell Nephropathy and Associated Factors among Asymptomatic Children with Sickle Cell Anaemia. Int J Pediatr, 2020: p. 1286432 Bodas P et al (2013) The prevalence of hypertension and abnormal kidney function in children with sickle cell disease–a cross sectional review. BMC Nephrol 14:1–6 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Complex","correspondingAuthor":false,"prefix":"","firstName":"R","middleName":"Al","lastName":"Abdulrahman","suffix":""}],"badges":[],"createdAt":"2024-10-26 13:37:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5337722/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5337722/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":69355627,"identity":"f2e211fd-41ca-49c1-81b2-2d4bbf962153","added_by":"auto","created_at":"2024-11-19 13:42:43","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":56385,"visible":true,"origin":"","legend":"\u003cp\u003eThe prevalence of GHF among children with SCD in the Eastern region of SA.\u003c/p\u003e","description":"","filename":"image1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5337722/v1/2855bf74e9e375b0de1105b9.jpeg"},{"id":69356465,"identity":"82233019-3635-4f1f-903b-4e8ca08d1c1c","added_by":"auto","created_at":"2024-11-19 13:50:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":10838,"visible":true,"origin":"","legend":"\u003cp\u003eThe eGFR of SW and Eastern Saudi children with SCD.\u003c/p\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-5337722/v1/377e73119dfdd8b0773e8fe4.png"},{"id":69358159,"identity":"316bbcad-5dff-4f01-b55c-93ddb7a8c0ba","added_by":"auto","created_at":"2024-11-19 13:58:43","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":91779,"visible":true,"origin":"","legend":"\u003cp\u003eMean eGFR rate by a subset of age of children with SCD.\u003c/p\u003e","description":"","filename":"image3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-5337722/v1/f9c5e580f0cea551abe09e38.jpeg"},{"id":69557135,"identity":"8679bbc3-fe2c-4925-b6a8-1f09586fd5cc","added_by":"auto","created_at":"2024-11-21 15:39:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":778493,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5337722/v1/bd96d373-5a18-4402-90b1-017d00bc66bf.pdf"}],"financialInterests":"","formattedTitle":"Glomerular filtration rate in children with sickle cell disease in the Eastern Region of Saudi Arabia","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSickle cell disease (SCD) is the most common hereditary blood disorder in humans[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It affects every organ in the body, and kidney abnormalities, known as sickle cell nephropathy (SCN), are common in children[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The earliest manifestations of SCN are an increase in GFR and defective urinary concentration. GHF starts slowly in infancy, as early as 9\u0026ndash;19 months of age, gradually declines to a normal range during the first two decades of life and decreases as the SCN progresses to kidney failure in adulthood[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGHF may be a cause or a compensatory mechanism in response to early SCN[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The proposed mechanisms for hyperfiltration include a potentially reversible decrease in renal vascular resistance and an increase in renal blood flow. Low oxygen partial pressure, acidic pH, and high osmolality promote sickling of the red cells in the renal medulla, resulting in vaso-occlusion, hemolysis, anemia, inflammation, and oxidative stress. Medullary prostaglandin and nitric oxide secretion due to hypoxia increases the cortical blood flow[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Concurrently, chronic RBC hemolysis results in severe anemia causing secondary increase in cardiac output and the GFR. Additionally, red cell hemolysis increases heme breakdown into a potent vasodilator (carbon monoxide)[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Moreover, the increase in number, size and selectivity of the glomerular membrane may add to the GHF[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Papillary necrosis may lead to a reduction in functioning renal nephrons, resulting in compensatory hypertrophy and increased filtration of the remaining nephrons[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSCD is relatively common in SA and more prevalent in the Eastern and SW provinces of the country[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], with marked genetic, clinical and hematological variability. In the Eastern region, the sickle hemoglobin gene is usually associated with the AI haplotype with a mild phenotype, whereas the African (Benin) haplotype predominates in the SW region with a severe phenotype[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStudies on the GFR among Saudi children with SCD are scarce[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], with limited data on GHF prevalence and risk factors in these children. Given the phenotypic variation among patients with the AI and African SCD haplotypes, we predict that SW children are more predisposed to renal damage than their Eastern counterparts are. Therefore, our aim was to investigate the hypothesis that the prevalence of GHF, as the earliest marker of SCN, is greater in SW children with predominant African haplotypes. Studying the early clinical signs of renal dysfunction in children with different SCD severities may help tailor plans and customize resources for early detection and possible administration of preventive therapy. To address these issues, we conducted a prospective cross-sectional, observational study of children with SCD who attended the out-patient clinic in the steady state. Additionally, we compared the SCD clinical profile including GHF between Eastern children with their SW peers.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cp\u003eA retrospective cross-sectional observational study was conducted at King Fahad Military Medical Complex, Dhahran, Eastern Region, Saudi Arabia. All children younger than14 years with SCD who attended the pediatric hematology clinic for routine follow-up in the steady state between July 2021 and August 2022 were included in this study. The diagnosis of SCD was confirmed by hemoglobin electrophoresis via high-performance liquid chromatography (HPLC) method. Children who were S-beta thalassemia, had a pre-existing renal disease, fever, SCD crisis, or acute illness in the preceding two weeks, or who were transfused in the preceding 4 months were excluded.\u003c/p\u003e \u003cp\u003eData were collected from hospital electronic medical records via the case report form. These included: patients' age, sex, place of origin, consanguinity, past medical history and family history of SCD in addition to medications used, including hydroxyurea. Place of origin (provenance)was necessary to determine the patient\u0026rsquo;s ancestry and hence their SCD haplotype which was confirmed from the patient\u0026rsquo;s ID attached to their medical file. This was important for comparison between the two groups of SCD patients. Children originally from the SW have African ancestry with the African (Benin) haplotype, whereas those from the Eastern region carry the AI haplotype[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The past medical history included SCD complications such as dactylitis, (vaso-occlusive crisis (VOC), splenic sequestration crisis (SSC), hemolytic crisis, stroke, cholelithiasis, avascular necrosis, stroke, gall stones (GS) and acute chest syndrome (ACS). Weight, height, body mass index (BMI), and both systolic and diastolic blood pressure recordings were among the collected data. Blood pressure readings were compared with the established reference ranges for a pediatric cohort with SCA systolic and diastolic blood pressure (BP)[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe collected standard laboratory parameters included: steady-state hemoglobin, hematocrit, WBCs, reticulocytes, platelets, HBS and HBF in addition to serum creatinine, lactate dehydrogenase (LDH), bilirubin and aspartate transaminase (AST). The estimated glomerular filtration rate (eGFR) was calculated using the updated Schwartz equation as follows: \u003cem\u003eeGFR\u003c/em\u003e (\u003cem\u003eml\u003c/em\u003e/\u003cem\u003emin\u003c/em\u003e/1.73\u003cem\u003em\u003c/em\u003e2)\u0026thinsp;=\u0026thinsp;0.413 \u0026times; \u003cem\u003eheight\u003c/em\u003e(\u003cem\u003ecm\u003c/em\u003e)/\u003cem\u003eSerum creatinine\u003c/em\u003e(\u003cem\u003emg\u003c/em\u003e/\u003cem\u003edl\u003c/em\u003e)[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. We defined hyperfiltration in our children as an eGFR\u0026thinsp;\u0026ge;\u0026thinsp;180 mL/min/1.73 m\u003csup\u003e2\u003c/sup\u003e based on the 75th percentile of eGFR identified by the Baby HUG study[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The GFR data were classified into three age groups (\u0026lt;\u0026thinsp;5 years old, 6\u0026ndash;10 years old, and \u0026gt;\u0026thinsp;10 years old) for graph plotting.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eAccording to their province of origin, we categorized children into two groups: Eastern and Southwestern. Comparison between these groups included demographic, clinical and laboratory data. The Data were uploaded into IBM SPSS 21, New York, USA for analysis. Association between GHF and the independent variables was assessed using Chi square test (\u003cem\u003eχ\u003c/em\u003e2). Independent t-test was calculated to compare the means which are expressed as \u0026plusmn;\u0026thinsp;1 standard deviation (SD). To determine any correlation with the (eGFR), we performed simple linear regressions for each parameter. For prediction of outcome variables, multiple linear regressions were used. The final result included the variables that remained significantly correlated with eGFR after adjustment for the other variables. R-squares (R\u003csup\u003e2\u003c/sup\u003e) variables were used as measures of variance. For all outcomes of interest, a P value of \u0026lt;\u0026thinsp;0.05 was considered significant.\u003c/p\u003e \u003cp\u003eEthical Considerations:\u003c/p\u003e \u003cp\u003e The study received scientific and ethical approval from the Armed Forces Hospitals Eastern Province Institutional Review Board (IRB): IRB Protocol No AFHER-IRB-2024-015. This study was conducted in accordance with good clinical practice and the declaration of Helsinki. A field survey was conducted after obtaining approval from the local health authority at our hospital and the Paediatric Department.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 114 patients with SCD were included in the study, (66 boys, and 48 girls, ratio: 1.3). The mean age was 8.8 \u0026plusmn; 3.2 years with a range of (1.5\u0026ndash;14) years. Among the 114 patients included in the study, 88 patients (77.2%) originated from the SW province, and 26 patients (22.8%) were from Eastern region. The demographic, clinical and laboratory profiles of the patients is summarized in Table\u0026nbsp;1.\u003c/p\u003e \u003cp\u003eCompared with their Eastern peers, the SW children had significantly more consanguineous parents and more patients used hydroxyurea. On the other hand, the Eastern children had markedly higher HBF levels compared with their SW peers. Notably, SW children have more SCD complications, eGFR and GHF than do their Eastern counterparts, who have higher growth parameters and steady-state HB. However, the differences are not statistically significant.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;(1): Comparison of the demographic, clinical and laboratory data of the SW and Eastern patients\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal (n:114)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSouthwest (n:88)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eEast\u003c/p\u003e \u003cp\u003e(n: 26)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSex: M (n: 66)\u003c/p\u003e \u003cp\u003eF (n: 48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53.8%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConsanguinity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e76.1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFH of SCD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eH/O dactylitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplicated course\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86.8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e84.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHU Use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61.4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42.3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.02*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGHF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e38.5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, y\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight, kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.2\u0026thinsp;\u0026plusmn;\u0026thinsp;10.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.7\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight, cm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e124.1\u0026thinsp;\u0026plusmn;\u0026thinsp;18.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e123.8\u0026thinsp;\u0026plusmn;\u0026thinsp;18.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e125.2\u0026thinsp;\u0026plusmn;\u0026thinsp;17.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI, kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u0026thinsp;\u0026plusmn;\u0026thinsp;3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystolic BP, mm/Hg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e107\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e105\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiastolic BP, mm/Hg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62\u0026thinsp;\u0026plusmn;\u0026thinsp;9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHB, g/dL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHct %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86\u0026thinsp;\u0026plusmn;\u0026thinsp;16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87\u0026thinsp;\u0026plusmn;\u0026thinsp;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e81\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u0026thinsp;\u0026plusmn;\u0026thinsp;4.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.6\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetics %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.4\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.3\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.7\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePLT \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e390\u0026thinsp;\u0026plusmn;\u0026thinsp;181\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e399\u0026thinsp;\u0026plusmn;\u0026thinsp;181\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e359\u0026thinsp;\u0026plusmn;\u0026thinsp;179\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBF%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.3\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.3\u0026thinsp;\u0026plusmn;\u0026thinsp;7.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.4\u0026thinsp;\u0026plusmn;\u0026thinsp;8.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.03*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal bilirubin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38\u0026thinsp;\u0026plusmn;\u0026thinsp;31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u0026thinsp;\u0026plusmn;\u0026thinsp;33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33\u0026thinsp;\u0026plusmn;\u0026thinsp;19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47\u0026thinsp;\u0026plusmn;\u0026thinsp;18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47\u0026thinsp;\u0026plusmn;\u0026thinsp;19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44\u0026thinsp;\u0026plusmn;\u0026thinsp;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.41\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH, IU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e494\u0026thinsp;\u0026plusmn;\u0026thinsp;202\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e497\u0026thinsp;\u0026plusmn;\u0026thinsp;215\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e486\u0026thinsp;\u0026plusmn;\u0026thinsp;150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eeGFR ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e179.4\u0026thinsp;\u0026plusmn;\u0026thinsp;52.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e183.2\u0026thinsp;\u0026plusmn;\u0026thinsp;54.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e166\u0026thinsp;\u0026plusmn;\u0026thinsp;45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e* Significant\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eCategorical data are presented as percentage (%) and continuous variables are presented as the means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations (SDs). M\u0026thinsp;=\u0026thinsp;male, F\u0026thinsp;=\u0026thinsp;female, FH\u0026thinsp;=\u0026thinsp;family history, H/O\u0026thinsp;=\u0026thinsp;history of, HU\u0026thinsp;=\u0026thinsp;hydroxyurea, GHF\u0026thinsp;=\u0026thinsp;glomerular hyperfiltration, BMI\u0026thinsp;=\u0026thinsp;body mass index, BP\u0026thinsp;=\u0026thinsp;blood pressure, HB\u0026thinsp;=\u0026thinsp;haemoglobin (steady state), Hct\u0026thinsp;=\u0026thinsp;haematocrit, MCV\u0026thinsp;=\u0026thinsp;mean corpuscular volume, WBCs\u0026thinsp;=\u0026thinsp;white blood cells, Retics\u0026thinsp;=\u0026thinsp;reticulocytes, PLT\u0026thinsp;=\u0026thinsp;platelets, HBF: Haemoglobin F, AST\u0026thinsp;=\u0026thinsp;Aspartate transaminase, LDH\u0026thinsp;=\u0026thinsp;lactate dehydrogenase, eGFR: estimated glomerular filtration rate. Patients with a complicated course includes those who experienced at least one episode of SCD crises (VOC, SSC, aplastic and hyper-haemolytic) stroke, ACS, GS and AVN.\u003c/p\u003e \u003cp\u003eFigure (1) shows that the prevalence of GHF (GFR\u0026thinsp;\u0026gt;\u0026thinsp;180 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e) is 44.7%.\u003c/p\u003e \u003cp\u003efigure (1): The prevalence of GHF among children with SCD in the Eastern region of SA.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eFigure (2) compares eGFR between the SW and Eastern Saudi children with SCD. There is no significant difference between the two groups. 183.2\u0026thinsp;\u0026plusmn;\u0026thinsp;54.2 v.166\u0026thinsp;\u0026plusmn;\u0026thinsp;45; p\u0026thinsp;\u0026gt;\u0026thinsp;0.05.\u003c/p\u003e \u003cp\u003eFigure (2): The eGFR of SW and Eastern Saudi children with SCD.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure (3) shows that eGFR increases with age of the patients in the first decade, and then, the rate slows down early in the second decade. However, the difference was not statistically significant, p\u0026thinsp;\u0026gt;\u0026thinsp;0.05.\u003c/p\u003e \u003cp\u003eFigure (3): Mean eGFR rate by a subset of age of children with SCD.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAge categories: \u0026lt;5 years (n = 21), 6\u0026ndash;10 years (n = 45), 11\u0026ndash;14 years (n = 48).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;(2) shows no correlation between GHF and different categorical parameters, including provenance, sex, age group, parental consanguinity, systolic or diastolic hypertension (BP\u0026thinsp;\u0026gt;\u0026thinsp;90th centile), family history of SCD, past history of dactylitis, VOC or other SCD complications or the use of HU.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;(2): The distribution of glomerular hyperfiltration (GHF) in relation to different categorical data.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eClinical Parameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eGHF\u003c/p\u003e \u003cp\u003e(N:114)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes (N:51 (44.7%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo (N: 63 (55.3%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eProvenance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSW (n: 88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e41 (46.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47 (53.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.464\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eE (n: 26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (38.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16 (61.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eM (n:66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29 (43.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37 (56.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.841\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF (n:48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22 (45.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (54.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eAge group (in years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;5: (n:21) (18.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (19%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.973\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u0026ndash;10: (n:45) (39.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20 (39.2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25 (39.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u0026ndash;14:(n: 48) (42.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22 (43.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (41.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConsanguinity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en: 77 (67.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e35 (45.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42 (54.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.824\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eSystolic BP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh (n:36) (31.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15 (41.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21(58.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.690\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal(n:78) (68.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e36 (46.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42 (53.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDiastolic BP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh(n:12)\u003c/p\u003e \u003cp\u003e(10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4(33.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (66.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.543\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal(n:102) (89.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e47 (46.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55 (53.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDactylitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en:15 (13.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (53.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (46.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.472\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVOC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en :51(44.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18 (35.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e33 (52.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.089\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en :99 (86.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e43 (43.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56 (56.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.472\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFH of SCD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en :52 (45.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24 (46.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28 (53.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.781\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHU use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003en: 70 (61.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29 (41.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41 (58.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.370\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;(3) shows that the mean eGFR was significantly higher in children who did not have a past history of VOC. There were no correlations between eGFR and provenance, gender, parental consanguinity, family history of SCD, past history of dactylitis, other SCD complications or the use of HU.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;(3): shows the relationship between the eGFR and different categorical parameters of the study patients.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabc\" border=\"1\"\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eeGFR (ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eProvenance\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSW\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e183.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e54.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e166.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e45.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e179.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e178.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e54.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eConsanguinity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e183\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e55.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.26\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e171.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e45.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFH of SCD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e182.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e176.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDactylitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e186.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e178.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e53.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVOC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e167.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e45.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.02*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e189.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e56.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eComplications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e178.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e184.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e75.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHU use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e174.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.25\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e187.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e64.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003e* Significant\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eProvenance: province of origin, consanguinity\u0026thinsp;=\u0026thinsp;parental consanguinity, FH\u0026thinsp;=\u0026thinsp;family history, Dactylitis\u0026thinsp;=\u0026thinsp;past history of dactylitis, Complications\u0026thinsp;=\u0026thinsp;history of SCD crises and complications, HU\u0026thinsp;=\u0026thinsp;hydroxyurea.\u003c/p\u003e \u003cp\u003eCorrelations between the eGFR and other clinical measurements taken at the same time were assessed (Table\u0026nbsp;4). In the univariate analysis, statistically significant associations between the eGFR and markers of hemolysis were observed. Specifically, there was an inverse relationship with steady-state hemoglobin (HB) (r = \u0026minus;0.25, \u003cem\u003eP\u003c/em\u003e 0.003), hematocrit (r=-0.27, P 0.002), and HBF (r=-0.28, P 0.001) and a positive correlation with reticulocyte percentage (r\u0026thinsp;=\u0026thinsp;0.225, P\u0026thinsp;=\u0026thinsp;0.016), AST(r = 0.32, \u003cem\u003eP\u003c/em\u003e 0.000), LDH (r\u0026thinsp;=\u0026thinsp;0.30, \u003cem\u003eP\u003c/em\u003e 0.001)and bilirubin (r\u0026thinsp;=\u0026thinsp;0.317, P.001). In multivariate regression of the factors determining eGFR at 95% confidence intervals, only HBF (β =0.216, t= -2.054, \u003cem\u003eP\u003c/em\u003e = 0.042) remained independently predictive and accounting for 19.7% of the GFR changes (R = 0.444, R\u003csup\u003e2\u003c/sup\u003e = 0.197, F (7,105) = 3.689, \u003cem\u003eP\u003c/em\u003e 0.001).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;(4): Univariate analysis of eGFR with measured continuous clinical Parameters:\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabd\" border=\"1\"\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003er\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;0.252\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.007*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematocrit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.271\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.004*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBCs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.055\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReticulocytes%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.225\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.016*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePLT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.121\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.201\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHBF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e\u0026minus;\u0026thinsp;0.279\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.003*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.306\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.173\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.065\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystolic BP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.148\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.117\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiastolic BP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e-0.079\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.405\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.325\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.000*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilirubin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.317\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.001*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e* Significant\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eThe Pearson correlation coefficient was calculated for continuous variables. Where non-normal distributions were seen, logarithmic transformation was performed. eGFR: estimated glomerular filtration rate, HB\u0026thinsp;=\u0026thinsp;haemoglobin (steady state), Hct\u0026thinsp;=\u0026thinsp;haematocrit, WBCs\u0026thinsp;=\u0026thinsp;white blood cells, Retics\u0026thinsp;=\u0026thinsp;reticulocytes, PLT\u0026thinsp;=\u0026thinsp;platelets, HBF: haemoglobin F, LDH\u0026thinsp;=\u0026thinsp;lactate dehydrogenase, AST\u0026thinsp;=\u0026thinsp;aspartate transaminase.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThere is a dearth of studies carried out in Saudi Arabia on renal function in pediatric SCD patients. The aim of this study was to investigate changes in the eGFR and its clinical correlates as early markers of renal dysfunction on children with SCD living in the Eastern Province of SA. The results indicated a high prevalence of GHF among these children, with no significant difference between children with AI and those with African haplotypes. The study also demonstrated a correlation between the GFR and different hemolytic markers of the disease. It is negatively correlated with low steady-state HB, hematocrit and HBF, and positively correlated with reticulocyte percentage, LDH, AST and bilirubin. According to the multivariate regression analysis, only HBF remained predictive.\u003c/p\u003e\n\u003ch3\u003eeGFR:\u003c/h3\u003e\n\u003cp\u003eThe (eGFR) is a reliable indicator of renal function, as it is widely regarded as the best overall index in both health and disease. The overall mean e GFR in our cohort was 179.5\u0026thinsp;\u0026plusmn;\u0026thinsp;52.7 mL/min/1.73 m2, in accordance with that previously reported in the pediatric literature (175.8\u0026thinsp;\u0026plusmn;\u0026thinsp;37.5\u0026ndash;184.4\u0026thinsp;\u0026plusmn;\u0026thinsp;55.5 mL/min/1.73 m2[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In the SW group, the mean eGFR was183.2\u0026thinsp;\u0026plusmn;\u0026thinsp;54.2 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e while a study in the Western region reported values of 96\u0026ndash;120 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], and another study in the central region reported values of 159.8 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] .\u003c/p\u003e\n\u003ch3\u003eGHF:\u003c/h3\u003e\n\u003cp\u003eGHF, defined as estimated GFR\u0026thinsp;\u0026gt;\u0026thinsp;180 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e, is appropriate for young patients with SCD[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. It is the earliest manifestation of kidney disease and precedes the development of overt SCN. The prevalence of GHF varies widely in different studies, ranging from 16\u0026ndash;98%[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Our results indicated that the overall prevalence of GHF was 44.7% which is comparable to that reported in America (43%)[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The figure is lower than that reported in the UK (98%)[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] and higher than that reported in India(16%)[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe main SCD haplotype in India is Arab-Indian (AI) as demonstrated in previous studies. SCD is milder in Indians because of the association of high levels of HBF with the AI haplotype. HBF is responsible for inhibiting erythrocyte sickling, a fundamental step in the pathophysiology of SCN[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Although our children with SCD in Eastern Saudi province carry mainly the AI haplotype, their GHF prevalence is 38.5% which is markedly higher than that reported in India (16%)[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Differences in the environment probably contribute to this difference.\u003c/p\u003e \u003cp\u003eThe Saudi Eastern and SW regions are different environments that are1500 Km apart. Saudi studies revealed that Eastern patients with SCD have a milder form of the disease than the SW patients do, on the basis of studies conducted independently in each region[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Although HBF is higher in the Eastern group. the current report revealed no significant difference in the studied disease characteristics, including GHF, between the two groups of children. Living in the same environment, our children (Eastern and SW) share the climate (temperature, air quality, humidity, rainfall, and wind speed), altitude, exposure to infection, medical care, and socio-economic status (all of them are military personnel dependents). These factors might have resulted in narrowing the difference in the incidence of many disease complications to an insignificant level between the two groups of patients, including the GHF. Multi-centre studies are needed in different geographic regions of the country to support this hypothesis.\u003c/p\u003e \u003cp\u003eGenerally, the variation in the reported prevalence could be due to differences in the methods used for determination of the creatinine levels and the GFR by different authors, to different ages of the patients and the influence of haplotypes[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. It could also be affected by inconsistency in population characteristics and the definitions of eGFR cut-offs used by various authors, that can sometimes be very low (GFR\u0026thinsp;\u0026gt;\u0026thinsp;120 ml/min/1.73m2)[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The environmental factors should also be considered.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eHemolytic markers:\u003c/h2\u003e \u003cp\u003eIt has been proposed that GHF can be attributed to hemolysis-associated pathophysiology rather than vaso-occlusive pathophysiology. Thus, correlations between GFR and hemolytic markers including total Hb, HBF, reticulocyte count, bilirubin, and LDH were explored[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In the adult literature patients with SCD commonly have GHF associated with severe anemia, the absence of alpha thalassemia, and increased hemolytic markers including lower HBF [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], and a high reticulocyte count [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTo test this hypothesis in the pediatric population, we correlated the eGFR with other clinical measurements. In univariate analysis, statistically significant associations between eGFR and markers of hemolysis were observed. Specifically, there was an inverse relationship with steady-state HB, hematocrit, and HBF and a positive correlation with reticulocyte percentage, AST, LDH, and total bilirubin. According to multivariate regression of the factors determining eGFR, only HBF remained independently predictive which is in line with the findings of a Brazilian pediatric study[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Additionally, in concordance with our results, Brewin et al. reported statistically significant associations between eGFR and markers of hemolysis including an inverse relationship with steady state HB and a positive correlation with reticulocyte percentage, bilirubin, and AST. However, in their multivariate regression, only the steady state HB and reticulocyte percentage remained independently predictive[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eHemoglobin F:\u003c/h3\u003e\n\u003cp\u003eHbF is a major SCD modifier which negatively correlates with the severity of complications. Low HbF has been associated with increased hemolysis[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Our results revealed a significant correlation between eGFR and HBF(r=-0.28, p 0.001), which is consistent with the findings of Al-Mosawa\u0026rsquo;s pediatric study[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Compared to their SW peers, our Eastern children had significantly higher HBF, coupled with lower eGFR and GHF. However, the difference was not statistically significant, possibly due to the weak influence of HBF on the eGFR according to the multivariate regression model (R\u003csup\u003e2\u003c/sup\u003e = 0.197, p 0.001)\u003c/p\u003e\n\u003ch3\u003eHydroxyurea:\u003c/h3\u003e\n\u003cp\u003eIn SCD patients, HU increases HbF and is recommended for almost all children with SCD starting in the first year of life[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The effect of HU use on GFR and GHF is not yet clear. In the present study, the use of HU was not associated with changes in the GFR, which is consistent with the results of a Saudi study in children[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Roy et al. reported that the evidence that HU improves the GFR or reduces GHF in young children aged 9 months to 18 months is not strong[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Other studies have shown that HU at the maximum tolerated dose (MTD) is associated with a reduction in GHF in young children with SCD (median age 7.5 years)[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. However, our study lacked information about compliance, duration of use and whether the MTD has been reached.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eAge:\u003c/h2\u003e \u003cp\u003eGenerally, the GFR increases in younger children with SCD, plateaus until adolescence and subsequently begins to decrease during adulthood until it reaches the level of renal failure[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Consistent with these findings, our study demonstrated that the mean eGFR increased across age groups until the teenage years, when the rate started to slow. However, the difference was not statistically significant, in consonance with previous studies[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], probably due to differences in the sample size of each age group[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eBlood pressure:\u003c/h2\u003e \u003cp\u003eStudies on blood pressure in SCD children have shown conflicting results. While some authors believe that children with SCD have low normal or normal blood pressures[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], others suggest that they might have hypertension without clear evidence of renal dysfunction[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. However, Other investigators reported hypertension in10.3% of children with SCD, on the basis of in-clinic blood pressure measurements. When they utilized ambulatory blood pressure monitoring (ABPM), they reported ambulatory hypertension in 43.6% in their SCD patients. These findings suggest that hypertension may be under diagnosed in SCD children when standard clinic- based measurements are used[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In the present study, 22.8% of the children had an SBP above the 90th percentile and 5.3% had DBP above the 90th percentile. There was no relationship between GHF and either systolic or diastolic BP in accordance with earlier studies[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. However, as blood pressure was only recorded at one clinic visit, it should be interpreted cautiously.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSCD complications:\u003c/h2\u003e \u003cp\u003eThe relation between the eGFR and complications of SCD is not fully understood. While some researchers reported a weak positive correlation between the eGFR and the frequency of past painful crisis[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], others reported no correlation with ACS or a high risk for stroke. They postulated that the factors influencing the development of these complications and those contributing to the SCN may differ [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. In adults with SCD, Haymann et al. supported the view that GHF could be related predominantly to chronic hemolysis (associated with previous pulmonary hypertension, leg ulcers, priapism, and strokes) than viscosity vaso-occlusive-related complications (including VOC, ACS, and osteonecrosis)[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In the current study, the results indicated no relationship with a past history of dactylitis, but interestingly, patients with a significant history of isolated VOC episodes had a lower eGFR. This finding could support the theory that GHF pathogenesis is dependent mainly on hemolytic rather than the vaso-occlusive process. There was no association between the e GFR and the SCD complications, including ACS, stroke, SSC or hemolytic crisis or even VOC associated with other complications. Further research is needed to support these findings.\u003c/p\u003e \u003cp\u003eLimitations:\u003c/p\u003e \u003cp\u003eThis study had many limitations. First, a retrospective study with incomplete valuable data like the compliance and maximal tolerated dose of hydroxyurea. Second, a single-center hospital-based study would limit the generalizability of its findings. The scarcity of Saudi studies on children with SCD limits the comparative value with similar groups of patients. In addition, blood pressure was only recorded at one clinic visit, making the true prevalence of hypertension less accurate. Moreover, despite the advantages of eGFR method, it may overestimate the GFR due to increased secretion of creatinine resulting from the GHF in SCD.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe prevalence of GHF among Saudi children with SCD is high, with no significant difference between Eastern patients with the Arab-Indian β-globin haplotype (AI) and their Southwestern counterparts with the African haplotypes. The eGFR was correlated with hemolytic markers including total HB, HBF, hematocrit, reticulocyte percentage, LDH, bilirubin, and AST. According to the multivariate analysis, only HBF remained predictive. Further studies in different regions of the country are needed to validate our findings and develop comprehensive strategies to prevent early renal damage in this population.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSCD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSickle cell disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSaudi Arabia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSW\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSouthwest\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eArab-Indian\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eeGFR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eestimated glomerular filtration rate\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGHF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eGlomerular hyperfiltration\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSCN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSickle cell nephropathy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVOC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVaso- occlusive crisis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eACS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAcute chest syndrome\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSSC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSplenic sequestration crisis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHBF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHemoglobin F\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLDH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eLactate dehydrogenase enzyme\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAST\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAspartate dehydrogenase enzyme\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody mass index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHU\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHydroxyurea\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eClinical Trial Number\u003c/h2\u003e \u003cp\u003eNot applicable\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eEthical Declaration:\u003c/h2\u003e \u003cp\u003eThe study received scientific and ethical approval from the Armed Forces Hospitals Eastern Province Institutional Review Board (IRB): IRB (Protocol No AFHER-IRB-2024-015). This study was conducted in accordance with good clinical practice and the declaration of Helsinki. According to the study's design, there was no direct interaction with patients or use of tissue samples, eliminating the need for parental or guardian informed consent for minors. In recognition of this, our Ethics Review Board granted a waiver for informed consent.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eAuthors contribution:\u003c/h2\u003e \u003cp\u003eAll authors contributed significantly to this research and reviewed the final version. All were involved in the conception and design of the study, data collection, analysis and interpretation.\u003c/p\u003e\u003ch2\u003eAcknowledgment\u003c/h2\u003e \u003cp\u003eWe would like to thank Rehab Abdalla Zayed for her contribution in preparation of the graphs and completion of the manuscript.\u003c/p\u003e\u003ch2\u003eData availability\u003c/h2\u003e \u003cp\u003eThe raw data of this study contain protected health information. They are therefore not publicly available. Deidentified data may be provided by the corresponding author upon reasonable request, after approval from the ethical review board at King Fahad Military Medical Complex. Any data shared will be fully anonymized for protection of patient confidentiality and privacy according to the regulations.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBabatunde HE et al (2023) Cystatin C-derived estimated glomerular filtration rate in children with sickle cell anaemia. BMC Nephrol 24(1):349\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGraf T, Piccone C, Dell KM (2020) Sickle Cell Nephropathy in Children. In: Emma F et al (eds) Pediatric Nephrology. Springer, Berlin Heidelberg: Berlin, Heidelberg, pp 1\u0026ndash;15\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOcheke IE et al (2019) Microalbuminuria risks and glomerular filtration in children with sickle cell anaemia in Nigeria. Ital J Pediatr 45(1):143\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAfangbedji N, Jerebtsova M (2022) Glomerular filtration rate abnormalities in sickle cell disease. Front Med (Lausanne) 9:1029224\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMonagel DA et al (2023) Renal outcomes in pediatric patients with sickle cell disease: a single center experience in Saudi Arabia. Front Pediatr 11:1295883\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrewin J et al (2017) Early Markers of Sickle Nephropathy in Children With Sickle Cell Anemia Are Associated With Red Cell Cation Transport Activity. Hemasphere 1(1):e2\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHariri E et al (2018) Sickle cell nephropathy: an update on pathophysiology, diagnosis, and treatment. Int Urol Nephrol 50(6):1075\u0026ndash;1083\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJastaniah W (2011) Epidemiology of sickle cell disease in Saudi Arabia. Ann Saudi Med 31(3):289\u0026ndash;293\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAl-Ali AK et al (2021) Sickle cell disease in the Eastern Province of Saudi Arabia: Clinical and laboratory features. Am J Hematol 96(4):E117\u0026ndash;e121\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePegelow CH et al (1997) Natural history of blood pressure in sickle cell disease: risks for stroke and death associated with relative hypertension in sickle cell anemia. Am J Med 102(2):171\u0026ndash;177\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWare RE et al (2010) Renal function in infants with sickle cell anemia: baseline data from the BABY HUG trial. J Pediatr 156(1):66\u0026ndash;70e1\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLebensburger JD et al (2019) Hyperfiltration during early childhood precedes albuminuria in pediatric sickle cell nephropathy. Am J Hematol 94(4):417\u0026ndash;423\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlameer M et al (2021) Epidemiology of sickle cell nephropathy in sickle cell anemia children, Saudi Arabia. Med Sci 25:1486\u0026ndash;1493\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLakkakula B et al (2017) Assessment of renal function in Indian patients with sickle cell disease. Saudi J Kidney Dis Transpl 28(3):524\u0026ndash;531\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLebensburger J et al (2018) Impact of Hyperfiltration during Early Childhood on the Natural History of Albuminuria in Pediatric Sickle Cell Anemia. Blood 132(Supplement 1):8\u0026ndash;8\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNdour EHM et al (2022) Biomarkers of sickle cell nephropathy in Senegal. PLoS ONE 17(11):e0273745\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLakkakula BV et al (2017) Assessment of renal function in Indian patients with sickle cell disease. Saudi J Kidney Dis Transplantation 28(3):524\u0026ndash;531\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAloni MN et al (2014) Renal function in children suffering from sickle cell disease: challenge of early detection in highly resource-scarce settings. PLoS ONE 9(5):e96561\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZahr RS, Saraf SL (2024) Sickle Cell Disease and CKD: An Update. Am J Nephrol 55(1):56\u0026ndash;71\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaymann JP et al (2010) Glomerular hyperfiltration in adult sickle cell anemia: a frequent hemolysis associated feature. Clin J Am Soc Nephrol 5(5):756\u0026ndash;761\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBelis\u0026aacute;rio AR et al (2020) Prevalence and risk factors for albuminuria and glomerular hyperfiltration in a large cohort of children with sickle cell anemia. Am J Hematol 95(5):E125\u0026ndash;e128\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAl-Musawa FE, Al-Saqladi AM (2019) Prevalence and correlates of microalbuminuria in Yemeni children with sickle cell disease. Saudi J Kidney Dis Transpl 30(4):832\u0026ndash;842\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoy NB et al (2023) Interventions for chronic kidney disease in people with sickle cell disease. Cochrane Database Syst Rev, 8(8): p. Cd012380.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAygun B et al (2013) Hydroxyurea treatment decreases glomerular hyperfiltration in children with sickle cell anemia. Am J Hematol 88(2):116\u0026ndash;119\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZimmerman SA et al (2004) \u003cem\u003eElevated glomerular filtration rate (GFR) in young patients with sickle cell anemia\u003c/em\u003e. 22B-22B\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eImuetinyan BA, Okoeguale MI, Egberue GO (2011) Microalbuminuria in children with sickle cell anemia. Saudi J Kidney Dis Transpl 22(4):733\u0026ndash;738\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBodas P et al (2013) The prevalence of hypertension and abnormal kidney function in children with sickle cell disease -a cross sectional review. BMC Nephrol 14:237\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShatat IF et al (2013) Masked hypertension is prevalent in children with sickle cell disease: a Midwest Pediatric Nephrology Consortium study. Pediatr Nephrol 28(1):115\u0026ndash;120\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNnaji UM et al (2020) \u003cem\u003eSickle Cell Nephropathy and Associated Factors among Asymptomatic Children with Sickle Cell Anaemia.\u003c/em\u003e Int J Pediatr, 2020: p. 1286432\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBodas P et al (2013) The prevalence of hypertension and abnormal kidney function in children with sickle cell disease\u0026ndash;a cross sectional review. BMC Nephrol 14:1\u0026ndash;6\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5337722/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5337722/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cu\u003eIntroduction\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eSickle cell nephropathy (SCN) is a serious complication of SCD that starts insidiously in childhood, with possible progression to chronic kidney disease in adulthood. Our aim was to study the prevalence and clinical correlates of the glomerular filtration rate, the earliest marker of renal dysfunction, in the Eastern Region of Saudi Arabia (SA).\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eMethods\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eA retrospective cross-sectional study was performed on 114 Saudi children with SCD aged 1-14 years who attended the pediatric hematology clinic in a steady state. Renal function was evaluated via estimated glomerular filtration rate (eGFR). The prevalence of GHF, and the correlation of eGFR with different clinical and laboratory data were investigated. Moreover, a comparison of the clinical characteristics and eGFRs was performed between children from the Southwestern (SW) and Eastern regions of Saudi Arabia (SA) and living in the same Eastern environment.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cu\u003eResults\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eA total of 114 children with SCD were included in the study (Male to female ratio: 1.3:1). The mean age was 8.8 ± 3.2 years. They were divided into two groups based on their provenance: Eastern (n: 26/114) and SW (n: 88/114). The mean eGFR was 179.4±52.7 ml/min/1.73 m\u003csup\u003e2\u003c/sup\u003e with a glomerular hyperfiltration (GHF) prevalence of (44.7%). There was no statistical difference between the two groups in terms of the mean GFR or prevalence of GHF (p\u0026gt;0.5). The eGFR correlated with hemolytic markers, including steady-state hemoglobin (HB) (r = −0.25,\u0026nbsp;\u003cem\u003eP\u003c/em\u003e 0.003), hematocrit (r=-0.27, p 0.002), HBF (r=-0.28, p 0.001), reticulocytes% (r=0.225, p 0.016), AST(r = 0.32,\u0026nbsp;\u003cem\u003ep \u003c/em\u003e 0.000), LDH (r=0.30, \u003cem\u003ep \u003c/em\u003e0.001)and bilirubin (r=0.317, p O.001).\u0026nbsp; In the multivariate regression of the factors determining the eGFR at 95% confidence intervals, only HBF (β =0.216, \u003cem\u003eP\u003c/em\u003e = 0.042) remained independently predictive (R\u003csup\u003e2\u003c/sup\u003e = 0.197, p= 0.001). There was no correlation between the GFR and patient age, BP, WBC or platelet count.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConclusion:\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe prevalence of GHF among Saudi children with SCD in the Eastern region is high, with no significant difference between Eastern and SW patients. The eGFR was correlated with the hemolytic markers, and low HBF was predictive of GHF. Further studies are needed to validate these findings.\u003c/p\u003e","manuscriptTitle":"Glomerular filtration rate in children with sickle cell disease in the Eastern Region of Saudi Arabia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-19 13:42:37","doi":"10.21203/rs.3.rs-5337722/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1fe8cfef-e26f-4b2d-9a5d-f4784650b654","owner":[],"postedDate":"November 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-11-21T15:30:58+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-19 13:42:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5337722","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5337722","identity":"rs-5337722","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}