Lacquaniti Antonio, Campo Susanna, Falliti Giuseppe, Caruso Daniele, Gargano Romana, Giunta Elena, Monardo Paolo
Nephrology and Dialysis Unit, Papardo Hospital, 98158 Messina, Italy.
Clinical Pathology Unit, Papardo Hospital, 98158 Messina, Italy.
J Clin Med. 2022 Nov 23;11(23):6904. doi: 10.3390/jcm11236904.
Background: Uremic toxins are associated with immune dysfunction and inflammation. The inadequate removal by hemodialysis (HD) of serum free light chains (FLCs) determines their accumulation. This study evaluated FLCs in HD patients, analyzing their relations with other biomarkers, such as serum high mobility group box 1 (HMGB1). Methods: FLC and HMGB1 were evaluated in a cohort of 119 HD patients. κFLC and λFLC were summated to give a combined (c) FLC concentration. Patients were followed prospectively until the end of the observation period of four years, or until the endpoint: the patient’s death. Results: cFLC values in HD patients were 244.4 (197.9−273.5) mg/L. We detected a significant reduction in CD8+ cells and a decreased CD4+/CD8+ ratio. HMGB1 levels were 94.5 (55−302) pg/mL. After multivariate analysis, cFLCs correlated with β2-microglobulin and the CD4+/CD8+ ratio. Subjects with cFLC values above 263 mg/L and with sHMGB1 values < 80 pg/mL experienced a significantly faster evolution to the endpoint (mean follow-up time to progression of 27.5 and 28.5 months, respectively; p < 0.001). After an adjusted multivariate Cox analysis, cFLCs were associated with 11% increased risk of death, whereas low sHMGB1 increased this risk by 5%. Conclusions: cFLCs and HMGB1 reflect the inflammation and immune dysfunction in HD patients representing two strong and independent risk markers of mortality.
尿毒症毒素与免疫功能障碍和炎症相关。血液透析（HD）对血清游离轻链（FLC）清除不充分导致其蓄积。本研究评估了HD患者的FLC，分析其与其他生物标志物，如血清高迁移率族蛋白B1（HMGB1）的关系。方法：对119例HD患者队列进行FLC和HMGB1评估。κFLC和λFLC相加得出组合（c）FLC浓度。对患者进行前瞻性随访，直至4年观察期结束，或直至终点：患者死亡。结果：HD患者的cFLC值为244.4（197.9−273.5）mg/L。我们检测到CD8+细胞显著减少，CD4+/CD8+比值降低。HMGB1水平为94.5（55−302）pg/mL。多变量分析后，cFLC与β2-微球蛋白和CD4+/CD8+比值相关联。cFLC值高于263 mg/L且sHMGB1值<80 pg/mL 的受试者向终点进展明显更快（分别为平均随访至进展时间27.5个月和28.5个月；p<0.001）。经过校正的多变量Cox分析后，cFLC与死亡风险增加11%相关，而低sHMGB1使该风险增加5%。结论：cFLC和HMGB1反映了HD患者的炎症和免疫功能障碍，是死亡率的两个强有力的独立风险标志物。
