Clementi Anna, Virzì Grazia Maria, Manani Sabrina Milan, de Cal Massimo, Battaglia Giovanni Giorgio, Ronco Claudio, Zanella Monica
Department of Nephrology and Dialysis, Santa Marta and Santa Venera Hospital, 95024 Acireale, Italy.
IRRIV-International Renal Research Institute, 36100 Vicenza, Italy.
J Clin Med. 2023 Aug 28;12(17):5616. doi: 10.3390/jcm12175616.
Cell-free plasma DNA (cfDNA) is circulating extracellular DNA arising from cell death mechanisms (apoptosis, necrosis, etc.). It is commonly existent in healthy individuals, but its ranks increase in diverse clinical circumstances, such as kidney disease, sepsis, myocardial infarction, trauma and cancer. In patients with advanced chronic kidney disease, cfDNA is connected to inflammation, and it has been associated with higher mortality. Caspase-3 plays a dominant role in apoptosis, a mechanism of programmed cell death involved in the pathogenesis and progression of chronic kidney disease (CKD). The aim of this pilot study was the evaluation of cfDNA levels and caspase-3 concentrations in patients with chronic kidney disease, in order to investigate the potential role of these molecules, deriving from inflammatory and apoptotic mechanisms, in the progression of renal damage.
We compared cfDNA and caspase-3 levels in 25 CKD patients and in 10 healthy subjects, evaluating their levels based on CKD stage. We also explored correlations between cfDNA and caspase-3 levels in CKD patients and between cfDNA and caspase-3 levels and serum creatinine and urea in this population.
We observed that cfDNA and caspase-3 levels were higher in patients with CKD compared to healthy subjects, in particular in patients with advanced renal disease (CKD stage 5). A positive correlation between cfDNA and caspase-3 levels and between cfDNA and caspase-3 and creatinine and urea were also noticed.
Patients with chronic kidney disease show higher levels of cfDNA and caspase-3 levels compared to the control group. Based on these preliminary results, we speculated that the worsening of renal damage and the increase in uremic toxin concentration could be associated with higher levels of cfDNA and caspase-3 levels, thus reflecting the potential role of inflammation and apoptosis in the progression of CKD. Future studies should focus on the validation of these promising preliminary results.
游离血浆DNA（cfDNA）是由细胞死亡机制（凋亡、坏死等）产生的循环细胞外DNA。它在健康个体中普遍存在，但在多种临床情况下其水平会升高，如肾脏疾病、败血症、心肌梗死、创伤和癌症。在晚期慢性肾脏病患者中，cfDNA与炎症相关，并且与较高的死亡率有关。半胱天冬酶-3在凋亡中起主导作用，凋亡是一种程序性细胞死亡机制，参与慢性肾脏病（CKD）的发病机制和进展。这项初步研究的目的是评估慢性肾脏病患者的cfDNA水平和半胱天冬酶-3浓度，以研究这些源自炎症和凋亡机制的分子在肾损伤进展中的潜在作用。
我们比较了25例CKD患者和10名健康受试者的cfDNA和半胱天冬酶-3水平，并根据CKD分期评估其水平。我们还探讨了CKD患者中cfDNA与半胱天冬酶-3水平之间以及该人群中cfDNA和半胱天冬酶-3水平与血清肌酐和尿素之间的相关性。
我们观察到，与健康受试者相比，CKD患者的cfDNA和半胱天冬酶-3水平更高，尤其是晚期肾病（CKD 5期）患者。还注意到cfDNA与半胱天冬酶-3水平之间以及cfDNA和半胱天冬酶-3与肌酐和尿素之间存在正相关。
与对照组相比，慢性肾脏病患者的cfDNA和半胱天冬酶-3水平更高。基于这些初步结果，我们推测肾损伤的恶化和尿毒症毒素浓度的增加可能与cfDNA和半胱天冬酶-3水平升高有关，从而反映了炎症和凋亡在CKD进展中的潜在作用。未来的研究应侧重于验证这些有前景的初步结果。
