EARLY URINARY BIOMARKERS OF RENAL DAMAGE IN SICKLE CELL DISEASE PATIENTS

Abstract

Background: Sickle cell disease (SCD) is a genetic monogenic disorder with variable clinical manifestations and is characterized by the presence of the variant hemoglobin S. Renal damage is common in patients with SCD, which begins in childhood, progressing with age, a fact that makes nephropathy one of the possible complications. This can compromise patients’ quality of life and decrease survival. Classical biomarkers such as creatinine, are not able to detect early renal lesions, which makes kidney injury molecule-1 (Kim-1) and N-acetyl-β-D-glucosaminidase (NAG) possible biomarker candidates in the prediction of renal disease in sickle cell anemia patients. Objective: Determine KIM-1 and NAG urine levels in sickle cell anemia patients and a control group. Methods: The study was a cross-sectional study with 56 individuals up to 17 years of age, 32 of whom had sickle cell disease and 24 healthy individuals. All were treated at the Laboratorio de Analises Clinicas da Faculdade de Farmácia da UFBA. The local ethical committee approved the study and blood samples were collected after signing informed consent forms. Hematological analyses were performed with automated protocols. KIM-1 and NAG urine levels were investigated by immunoenzymatic assay (ELISA) as per manufacturer protocols (USCN, USA). All data were analyzed in Epi Info v. 7.2 (CDC, EUA), considering p < 0.05. Results: The results showed that patients with sickle cell anemia have a characteristic hemolytic profile. This is indicated by reticulocyte count and LDH values (mean of 8.7% ± 4.5% and 914.55 ± 382.12 mg/dL, respectively) lipid profile with low HDL, with a mean of 33.29 ± 8.30 mg/dL, compared to 44.47 ± 10.05 mg/dL in the control group. KIM-1 and NAG levels were significantly higher (p < 0.0001 for both) in the patients’ group, compared with the control group (6.95 ± 7.13 pg/mL vs 1.72 ± 1.87 pg/mL for KIM-1 and 0.43 ± 042 ng/mL vs 0, 07 ± 0.11 ng/mL for NAG). Discussion: Previous studies have shown that KIM-1 has been associated with albuminuria and hemolysis and may be a potential biomarker in pediatric SCA patients SCA (Hamideh et al., 2014, Belisario et. 2019). According to Unal and others NAG levels were found to be insufficient for the evaluation of SCA nephropathy in their studies. However, Tchernychev and others (2021) used NAG as a predictor of nephrophathy in Townes HbSS mice. Conclusion: KIM-1 and NAG levels were higher in the patients’ group, which suggests it may be incorporated in a follow up of sickle cell anemia patients in focus to identify early renal damage.