Sircuța Alexandru Florin, Grosu Iulia Dana, Schiller Adalbert, Petrica Ligia, Ivan Viviana, Schiller Oana, Bodea Madalina, Mircea Monica-Nicoleta, Goleț Ionuţ, Bob Flaviu
Department of Internal Medicine II-Nephrology University Clinic, "Victor Babeș" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timișoara, Romania.
Centre for Molecular Research in Nephrology and Vascular Disease, Faculty of Medicine, "Victor Babes" University of Medicine and Pharmacy, Eftimie Murgu Sq. No. 2, 300041 Timișoara, Romania.
Biomedicines. 2024 Aug 20;12(8):1903. doi: 10.3390/biomedicines12081903.
The importance of identifying mortality biomarkers in chronic kidney disease (CKD), and especially in patients treated with hemodialysis (HD), has become evident. In addition to being a marker of tubulointerstitial injury, plasma kidney injury molecule-1 (KIM-1) has been mentioned in regard to HD patients as a risk marker for cardiovascular (CV) mortality and coronary artery calcification. The aim of this study was to assess the level of plasma KIM-1 as a marker of cardiovascular disease (CVD) and mortality in CKD5-HD patients (patients with CKD stage G5D treated with hemodialysis).
We conducted a prospective case-control study that included 63 CKD5-HD patients (HD for 1-5 years) followed up for 48 months and a control group consisting of 52 non-dialysis patients diagnosed with CKD stages G1-G5 (ND-CKD). All patients had a CVD baseline assessment including medical history, echocardiography, and electrocardiography (ECG). Circulating plasma KIM-1 levels were determined with single-molecule counting immunoassay technology using an enzyme-linked immunosorbent assay. We obtained the following parameters: serum creatinine and urea; the inflammation markers CRP (C-reactive protein) and IL-6 (interleukin-6); and the anemia markers complete blood count, serum ferritin, and transferrin saturation (TSAT).
The mean plasma KIM-1 level was 403.8 ± 546.8 pg/mL, showing a statistically significant correlation with inflammation (CRP, R = 0.28, = 0.02; IL-6, R = 0.36, = 0.005) and with anemia (hematocrit, R = -0.5, = -0.0316; hemoglobin (Hb), R = -0.5, = 0.02). We found that patients with left ventricular hypertrophy (LVH) on echocardiography (59.7%) had significantly lower mean levels of plasma KIM-1 than patients from the control group (155.51 vs. 432.12 pg/mL; = 0.026). Regarding the patients' follow-up, we assessed all-cause mortality as an endpoint. After 24 months of follow-up, we found a mortality rate of 22.23%, while after 48 months, the mortality rate was 50.73%. A plasma KIM-1 level < 82.98 pg/mL was significantly associated with decreased survival in hemodialysis patients ( < 0.001).
In patients treated with hemodialysis, low levels of plasma KIM-1 were associated with cardiovascular changes and an increased risk of mortality. Plasma KIM-1 levels were significantly higher in HD patients compared to ND-CKD patients.
在慢性肾脏病（CKD），尤其是接受血液透析（HD）治疗的患者中，识别死亡生物标志物的重要性已变得显而易见。血浆肾损伤分子-1（KIM-1）除作为肾小管间质损伤的标志物外，在HD患者中还被提及是心血管（CV）死亡和冠状动脉钙化的风险标志物。本研究的目的是评估血浆KIM-1水平作为CKD5-HD患者（接受血液透析治疗的CKD G5D期患者）心血管疾病（CVD）和死亡的标志物。
我们进行了一项前瞻性病例对照研究，纳入63例CKD5-HD患者（血液透析1 - 5年），随访48个月，并设立一个由52例诊断为CKD G1 - G5期的非透析患者组成的对照组（ND-CKD）。所有患者均进行了CVD基线评估，包括病史、超声心动图和心电图（ECG）。采用酶联免疫吸附测定的单分子计数免疫测定技术测定循环血浆KIM-1水平。我们获取了以下参数：血清肌酐和尿素；炎症标志物C反应蛋白（CRP）和白细胞介素-6（IL-6）；以及贫血标志物全血细胞计数、血清铁蛋白和转铁蛋白饱和度（TSAT）。
血浆KIM-1平均水平为403.8±546.8 pg/mL，与炎症（CRP，R = 0.28，P = 0.02；IL-6，R = 0.36，P = 0.005）和贫血（血细胞比容，R = -0.5，P = -0.0316；血红蛋白（Hb），R = -0.5，P = 0.02）呈显著统计学相关性。我们发现，超声心动图显示有左心室肥厚（LVH）的患者（59.7%）血浆KIM-1平均水平显著低于对照组患者（155.51 vs. 432.12 pg/mL；P = 0.026）。关于患者的随访，我们将全因死亡率作为终点进行评估。随访24个月后，我们发现死亡率为22.23%，而随访48个月后，死亡率为50.73%。血浆KIM-1水平<82.98 pg/mL与血液透析患者生存率降低显著相关（P < 0.001）。
在接受血液透析治疗的患者中，血浆KIM-1水平低与心血管改变及死亡风险增加相关。与ND-CKD患者相比，HD患者的血浆KIM-1水平显著更高。
