Avaliação da associação entre marcadores inflamatórios plasmáticos e albuminúria nos pacientes com doença falciforme

Abstract

Sickle cell disease (SCD) is a hereditary hemoglobinopathy caused by a mutation in the beta- globin gene, which leads to the substitution of glutamic acid for valine, culminating in the production of Hemoglobin S (HbS). The characteristic polymerization of HbS during periods of oxidative stress leads to changes in red blood cell morphology, which assumes a sickle-like shape, predisposing to endothelial damage, blood stasis, vaso-occlusion, and hemolytic anemia. One of its complications with the highest morbidity and mortality in adulthood is nephropathy. The chronic inflammatory state resulting from persistent hemolysis and vaso- occlusion appears to be related to the development of glomerulopathy, with albuminuria being an early clinical marker of kidney damage, but there are few studies that explore the specific pathophysiology of this complication. The objective of this cross-sectional study was to evaluate the association of plasma inflammatory markers with the presence of albuminuria in SCD. The study included 85 patients with SCD followed at the Hematology service of Pedro Ernesto University Hospital, in steady state, who underwent blood and urine sample collection. Clinical information was collected from medical records. According to the urinary albumin-to-creatinine ratio (ACR), these individuals were initially categorized into two groups: absence of albuminuria (ACR < 30 mg/g) and presence of albuminuria (ACR ≥ 30 mg/g). The control group included 11 individuals without SCD, matched by sex and age. Patients with SCD, regardless of subgroup, presented significantly higher plasma levels of IL- 4, IL-5, IL-6, IL-17, TNF-α, CXCL8/IL-8, and CCL3/MIP-1α, and patients with albuminuria also had higher levels of IL-9, CCL4/MIP-1β, CCL11/eotaxin, CXCL10/IP-10, and G-CSF when compared to the control group. IL-12p70 levels were higher in the group with SCD and presence of albuminuria than in the group with SCD and absence of albuminuria. Analysis was also performed according to a categorization of patients into 3 subgroups: normal (ACR < 30mg/g); microalbuminuria (ACR between 30-299mg/g); and macroalbuminuria (ACR ≥ 300mg/g). Patients with macroalbuminuria presented higher median levels of G-CSF, GM-CSF, IL-12p70, TNF-α compared to the group with normal ACR, and higher G-CSF, TNF-α, and IL-17 compared to patients with microalbuminuria. In multiple linear regression analysis, it was observed that TNF-α and IL-6 levels showed a positive correlation and IL-1ra levels showed a negative correlation with urinary ACR. The results suggest a possible relationship between the intensity of pro- inflammatory immune responses, particularly involving TNF-α and IL-6, and the severity of kidney involvement in SCD