ELEVATED SYSTEMIC IMMUNE-INflAMMATION INDEX (SII) IS ASSOCIATED WITH GLOMERULAR HYPERfiLTRATION IN ADULTS WITH SICKLE CELL ANEMIA

Sickle cell anemia (SCA) is characterized by hemolytic anemia, vaso-occlusive manifestations and inflammation, leading to progressive kidney injury. Hematological indices as neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-platelet ratio (NPR), Systemic Immune-Inflammation Index (SII), and Systemic Inflammation Response Index (SIRI), have been reported as clinical outcomes predictors in various diseases. To evaluate the hematological indices NLR, d-NLR, LMR, PLR, NPR, SII, and SIRI in adults with SCA, in association with renal parameters such as proteinuria and glomerular hyperfiltration. A cross-sectional study was performed with participants ≥ 18 years with SCA recruited from the Hematology outpatient clinic at Hospital Universitário Antonio Pedro, Universidade Federal Fluminense. Blood and urine samples were collected for routine laboratory assessment. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI 2021 equation and the protein-to-creatinine ratio (PCR) was also determined. The following indices were calculated: NLR; d-NLR (total number of neutrophils divided by the difference between the total leukocyte and the neutrophil count); LMR; PLR; NPR; SII (multiplying the platelet count by the neutrophil count and dividing the result by the lymphocyte count); and SIRI (multiplying the neutrophil by the monocyte count and dividing the result by the lymphocyte count). Participants were stratified according to the presence of glomerular hyperfiltration (defined as eGFR > 130mL/min/1.73m² for women and > 140 mL/min/1.73m² for men) and proteinuria (defined as PCR > 200 mg/g). A total of 48 individuals (66.7% women) with SCA were included. The median age was 33 years (IQR: 26–46 years). No participant had an eGFR below 60mL/min/1.73m². However, 12 participants (25.0%) presented glomerular hyperfiltration and 13 individuals (27.1%) presented proteinuria. Patients with glomerular hyperfiltration had significantly higher SII values (P = 0.013) and a trend toward higher SIRI values (P = 0.092) in comparison to those without hyperfiltration. In addition, participants with proteinuria showed a trend toward higher d-NLR (P = 0.062), NPR (P = 0.053), and SII (P = 0.070) when compared to those without proteinuria. Hematological indices are increasingly studied due to their cost-effectiveness and because they are easily calculated using routine blood tests. They also have been studied in conditions marked by prominent inflammatory processes. However, data in SCA are limited. Here, we observed higher SII levels in patients with glomerular hyperfiltration, as well as trends toward higher d-NLR, NPR, and SII in SCA patients with proteinuria. These findings suggest a potential contribution of inflammation to kidney injury and support further research to assess the role of inflammatory indices as markers of renal damage in SCA. Therefore, we conclude that in adults with SCA, glomerular hyperfiltration is significantly associated with higher SII levels, whereas proteinuria may be linked to elevated d-NLR, NPR, and SII.