Evidence for interactions between inflammatory markers and renin-angiotensin system molecules in the occurrence of albuminuria in children with sickle cell anemia.

Sickle cell anemia (SCA) is an important cause of chronic kidney disease, but its pathophysiology is not completely understood. The aim of this study was to compare inflammatory biomarkers in urine samples of SCA children with and without albuminuria, and to explore correlations with renin-angiotensin system (RAS) molecules. A cross-sectional study of 213 children selected from the Minas Gerais state cohort were assigned to two groups: Group 1-89 children with SCA who had albuminuria; Group 2-124 children with SCA and normal albuminuria matched by age and sex with group 1. A subset of 89 children was prospectively followed for a median time of 1.1 year. Inflammatory biomarkers (chemokines and cytokines) in urine were measured using cytometric beads array, and RAS molecules were measured by ELISA. Children with albuminuria had significantly higher urinary levels of IP-10/CXCL10, MCP-1/CCL2, MIG/CXCL9, IL-8/CXCL8, IL-12p70, TNF, IL-10, and IL-6 than patients with normal albuminuria. In the correlation analysis, albumin/creatinine ratio was significantly and positively correlated with IP-10/CXCL10, MCP-1/CCL2, MIG/CXCL9, IL-8/CXCL8, TNF, IL-10, and IL-6. Significant correlations were found between inflammatory and RAS molecules. In the prospective analysis, cumulative risk of persistent albuminuria was higher for children with urinary levels of IP-10/CXCL10 or IL-6 above the 50th percentile. Our data showed that inflammatory markers and RAS molecules might contribute to the occurrence of albuminuria in children with SCA, suggesting that both pathways interact in sickle cell nephropathy.

Association between inflammatory molecules, nitric oxide metabolites and leg ulcers in individuals with sickle cell anemia.

INTRODUCTION: Leg ulcers (LUs) are relatively common in patients with sickle cell anemia (SCA). The role of inflammation and nitric oxide (NO) pathways in the pathophysiology of the LU is not understood. OBJECTIVE: The aim of this study was to verify the association between inflammatory molecules and nitric oxide metabolites (NOx) and the occurrence of the LU in patients with SCA. METHOD: It was a cross-sectional study on adult participants with SCA followed at Fundação Hemominas, a public blood center in Brazil. Eligible participants were recruited and included in one of two groups: Group 1, comprised of cases with SCA (Hb SS) and at least one LU at the time of inclusion in the study and Group 2, comprised of controls with SCA without a history of LU, matched by sex and age to cases. Participants were interviewed to obtain sociodemographic data and blood samples were collected. Clinical and laboratory data were abstracted from medical records. Nitric oxide metabolites (NOx) and inflammatory molecules were quantified using an immunoassay and Multiplex xMAP® technology, respectively. Eighty-seven individuals were included, ranging in age from 17 to 61 years (mean 40 ±â€¯10.7 years); 30 had LU and 57 were controls without LU. RESULTS: Participants with LU had significantly higher levels of interleukin 8 (IL-8), IL-10, IL-15, NOx and platelet and white blood cell (WBC) counts, when compared to those without LU. Participants with LU had a significantly higher risk of having a history of osteomyelitis and a higher use of antiseptic soap in bathing, when compared to those without LU. CONCLUSION: In conclusion, our results showed that NOx, inflammatory molecules and hematological features were associated with LU in Brazilian adults with SCA.

Association between inflammatory molecules, nitric oxide metabolites and leg ulcers in individuals with sickle cell anemia

Abstract Introduction Leg ulcers (LUs) are relatively common in patients with sickle cell anemia (SCA). The role of inflammation and nitric oxide (NO) pathways in the pathophysiology of the LU is not understood. Objective The aim of this study was to verify the association between inflammatory molecules and nitric oxide metabolites (NOx) and the occurrence of the LU in patients with SCA. Method It was a cross-sectional study on adult participants with SCA followed at Fundação Hemominas, a public blood center in Brazil. Eligible participants were recruited and included in one of two groups: Group 1, comprised of cases with SCA (Hb SS) and at least one LU at the time of inclusion in the study and Group 2, comprised of controls with SCA without a history of LU, matched by sex and age to cases. Participants were interviewed to obtain sociodemographic data and blood samples were collected. Clinical and laboratory data were abstracted from medical records. Nitric oxide metabolites (NOx) and inflammatory molecules were quantified using an immunoassay and Multiplex xMAP® technology, respectively. Eighty-seven individuals were included, ranging in age from 17 to 61 years (mean 40 ± 10.7 years); 30 had LU and 57 were controls without LU. Results Participants with LU had significantly higher levels of interleukin 8 (IL-8), IL-10, IL-15, NOx and platelet and white blood cell (WBC) counts, when compared to those without LU. Participants with LU had a significantly higher risk of having a history of osteomyelitis and a higher use of antiseptic soap in bathing, when compared to those without LU. Conclusion In conclusion, our results showed that NOx, inflammatory molecules and hematological features were associated with LU in Brazilian adults with SCA.