Biomarcadores renais e endoteliais na doença de Haff

Abstract

Haff disease (HD) is a rare syndrome characterized by the abrupt onset of rhabdomyolysis, manifested primarily by myalgia, darkened urine, and elevated serum levels of creatine kinase (CK) and myoglobin. There are hypotheses suggesting that HD is triggered by thermostable toxins; however, its exact pathophysiological mechanism has not yet been elucidated. Complications arising from HD may progress and culminate in the development of Acute Kidney Injury (AKI). In this context, the evaluation of renal and endothelial biomarkers becomes essential, as it enables the early detection of alterations and contributes to more effective therapeutic strategies and prevention of complications. In this retrospective study, 29 patients diagnosed with HD in the municipality of Itacoatiara, Amazonas State, were evaluated between May 2021 and October 2023. Blood and urine samples were collected at hospital admission for analysis of conventional laboratory parameters and detection of non-conventional biomarkers. The study population presented a mean age of 42 ± 11 years, with a predominance of males (59%) and a mean hospitalization period of 5 ± 1 days. All assessed patients exhibited alterations in laboratory parameters, including elevated CK (100%), CK-MB isoenzyme (100%), lactate dehydrogenase (LDH) (100%), aspartate aminotransferase (AST) (96,6%), alanine aminotransferase (ALT) (89,7%), and the presence of albuminuria. Regarding non-conventional renal biomarkers, Kidney Injury Molecule-1 (KIM-1) and Neutrophil Gelatinase–Associated Lipocalin (NGAL) showed increased levels in some patients, whereas the endothelial biomarker VCAM-1 (vascular cell adhesion molecule- 1) remained within the expected range when compared to levels reported in healthy control groups in previous studies. Among patients without AKI, increases in KIM-1 and albuminuria were observed, in addition to positive correlations between KIM-1 and CK, and between AST and glomerular filtration rate (GFR), as well as a negative correlation between VCAM-1 and GFR. In the group of patients with AKI, a positive correlation between angiopoietin-2 (ANG-2) and CK was identified, along with negative correlations between AST and GFR, among others. Using the newly proposed AKI classification from another study, it was possible to identify that patients previously categorized as non-AKI exhibited a pattern consistent with subclinical kidney injury. These findings indicate that HD may present with subclinical kidney injury, identified by elevations in KIM-1 and albuminuria even in patients who do not meet traditional AKI diagnostic criteria. Moreover, VCAM-1 was associated with unfavorable renal prognosis, reinforcing the contribution of endothelial dysfunction. In patients with AKI, the expression of endothelial biomarkers such as ANG-2 was observed, as well as the inversion of the relationship between AST and GFR throughout disease progression. These findings indicate that traditional markers are insufficient to exclude early renal injury, and that non-conventional biomarkers may improve the detection and clinical management of Haff disease.