Secondary renal failure affects 5-–20% of adult patients with SCD, and the progression of renal disorder begins in childhood.19 Microalbuminuria is one of the earliest manifestations of SCN. Hence, many studies have aimed to determine the prevalence of microalbuminuria among SCD patients as an indicator of the severity of the condition.20,21 In this study, we determined a prevalence of microalbuminuria of 9.6% among pediatric patients with a mean age of 12.4 years. This condition emerged at a very young age (2 years) and increased continuously to the highest percentage among young adults (15–18 years), who exhibited a prevalence of 51.6%. The mean age and average prevalence of microalbuminuria among older patients in our study were consistent with the prevalence rates of 46% as reported by Dharnidharka et al20 and of 39–43% in adults with SCD as reported by McBurney et al.16 However, the overall prevalence of microalbuminuria among all patients (9.6%) was lower than the average prevalence reported by those previous studies. Additionally, Alkhunaizi et al22 determined that the prevalence of microalbuminuria among adult Saudi Arabian patients (>18 years) was 25%, which was very similar to our findings in the same age group.
Dharnidharka et al20 and McBurney et al16 reported that no microalbuminuria was detected in children <7 years old. Conversely, 9.7% of microalbuminuria patients in our study were aged 2–5 years. Our findings were supported by those of Aloni et al,23 who confirmed the presence of microalbuminuria in patients aged <7 years. This early deterioration of glomerular function could be explained by the presence of certain factors, including a genetic predisposition, the fetal hemoglobin (HbF) level, environmental factors, the efficacy of medical care, and lifestyle factors associated with developing countries.24 However, the small sample size in our study may also reasonably explain these contradictory results. Still, the studies by Dharnidharka et al20 and by McBurney et al,16 enrolled 104 and 151 patients, respectively. Interestingly, when we compared the microalbuminuria and non- microalbuminuria groups, we observed no statistical difference in terms of age (P=.432), indicating that this was not a defining variable in either group. However, age was a defining variable in the progression of microalbuminuria in the affected group.
Previous publications have reported a female predominance of microalbuminuria. Jones et al reported a microalbuminuria prevalence of 9.7% among female patients and 6.1% among male patients,8 while Okpere et al25 also reported results consistent with female predominance (45.3% vs. 20.4% of males). However, we did not observe a significant difference in sex between the microalbuminuria and non-microalbuminuria groups in our study, consistent with the findings of McBurney et al16 and Dharnidharka et al.20 Consequently, additional research evidence is needed to clarify these contrasting results.
Our findings demonstrated that microalbuminuria occurs in association with most hemoglobin genotypes. The highest percentage was observed with the Hb-ss genotype (74.2%) in the microalbuminuria group, similar to the results of a previous study conducted by Wigfall et al.26 However, no microalbuminuria was detected in the HB-Sβ0 (Beta-Zero) thalassemia sub-group. Most previous studies included few patients with Sβ-thalassemia, and only a few studies have published mixed results regarding this patient group. Becton et al21 reported that only one patient with Sβ-thalassemia had microalbuminuria.
We further examined the frequencies of several clinical complications that may be associated with microalbuminuria (Table 3). We compared the microalbuminuria and non-microalbuminuria groups to identify definitive variables that varied significantly between the groups. Interestingly, we found that most patients in the microalbuminuria group experienced acute chest syndrome, gallbladder stones, osteomyelitis, pneumonia, and spleen sequestration, whereas none reported priapism, avascular necrosis, aplasia, stroke, acute coronary syndrome (ACS), or dactylitis. These findings were consistent with those reported by Dharnidharka et al20 and McBurney et al,16 who observed no significant correlation between microalbuminuria and stroke, and McBurney et al16 and Kalpathi et al,21 who reported no significant correlation with ACS. Our observation of a significant association between acute chest syndrome and microalbuminuria (P=.005) was consistent with the findings reported by Alvarez et al.27 In contrast, Bodas et al28 reported that the glomerular filtration rate was not correlated with episodes of either stroke or acute chest syndrome, suggesting that the etiologies of these complications may differ from the etiologies underlying the development of SCN. However, that study included only 48 patients, and the relatively small sample size likely influenced the significant correlation between the two conditions.
We further identified found a significant correlation between microalbuminuria and the development of gallbladder stones (P=.014%). Our findings were consistent with those of Alexander-Reindorf et al29 and Bond et al,30 who reported significantly higher morbidity and more hospital admissions among SCD patients with gallbladder stones. Additionally, the mean age in our microalbuminuria group was 13.74 years, consistent with a study by Martins et al31 with age 11- and 29-year-old, with a higher prevalence of cholelithiasis and gallbladder stones.
In our study, the number of BTs was significantly and negatively associated with microalbuminuria, suggests that BTs are a renoprotective process in the management of SCD. Alvarez et al27 reported similar results and indicated that the early initiation of transfusion could protect the kidney and hinders deterioration of the SCN. However, the side effects of transfusion, such as iron overload, must be considered before starting this process. In contrast, Aloni et al23 reported that BT is not a significant factor with respect to microalbuminuria.
Kalpathi et al21 stated that 36% of SCD patients presented with hematuria. However, the authors reported no significant difference in the frequency of hematuria between the microalbuminuria and non- microalbuminuria groups. In contrast, we observed a statistically significant difference in the frequency of hematuria between patients with and without microalbuminuria (P=.007). Our results were consistent with the findings of Sesso et al,34 who reported higher frequencies of hematuria in the Hb-ss and Hb-as groups. The authors stated that hematuria is caused by the increased sickling of RBCs in the renal medulla, resulting in extravasation and ischemia. We further determined that most patients with SCD had O RhD+ blood, and that this variable differed significantly between the two groups (P=.022). This result was consistent with the findings of Alagwu et al,35 who reported a an O blood group frequency of 63% among Hb-ss patients. This finding could be explained by the fact that the O Rh+ blood group is the most prevalent group in humans.
In conclusion, our findings highlight the importance of early investigations (e.g., urinalysis) for the assessment of microalbuminuria and hematuria, as well as the determination of the degree of SCN. The observation that the average number of BTs was significantly higher in the non-microalbuminuria group than in the microalbuminuria group could suggest a protective role of transfusion against the development of microalbuminuria. However, further investigations are needed to confirm our results. We additionally reported significantly higher rates of acute chest syndrome and gallbladder stones in patients with microalbuminuria patients. These factors must be considered, and special care should be provided to affected patients. We recommend the routine screening of SCD patients for microalbuminuria and hematuria.