Scholarlink

Background <p>Renal transplantation (RT) triggers metabolic and immunological shifts intrinsically linked to circadian rhythms. These responses oscillate via the circadian clock (CC), governed by core activators circadian locomotor output cycles kaput (CLOCK) and brain and muscle Arnt-like protein 1 (BMAL1), and repressors like PERIOD (PER) and Cryptochromes (CRY).</p> Objective <p>To determine whether serum concentrations of the circadian clock proteins BMAL1 and PER2 correlate with the pathogenesis of chronic allograft dysfunction (CAD) and subsequent metabolic sequelae in renal transplant recipients.</p> Methods <p>A total of 63 individuals were recruited for this study: 18 healthy controls and 45 renal transplant recipients (RTRs). The transplant cohort was further stratified based on renal functions into stable function (<i>n</i> = 21) and chronic dysfunction (<i>n</i> = 24) subgroups. Utilizing the ELISA method, we quantified the serum levels of hsCRP alongside the molecular clock proteins (PER2 and BMAL1). Clinical assessments included anthropometrics, renal function, lipid profiles, and insulin resistance (HOMA-IR). Renal interstitial fibrosis (IF) severity was histologically graded from renal biopsies.</p> Results <p>Post-RT circadian regulator concentrations were significantly altered. BMAL1 was markedly lower in stable RTRs (2850.73 ± 963.56 pg/ml) and CAD patients (1551.97 ± 142.15 pg/ml) compared to controls (10872.30 ± 2799.39 pg/ml; <i>p</i> &lt; 0.001). Furthermore, CAD patients exhibited significantly lower BMAL1 than stable recipients. Similarly, median (interquartile range [IQR]) PER2 was highest in controls (2532.50 [1005] pg/ml), followed by stable RT recipients (1467.00 [384.50] pg/ml) and CAD groups (1032.50 [304.00] pg/ml; <i>p</i> &lt; 0.001). Serum BMAL1 and PER2 correlated positively with each other (<i>p</i> &lt; 0.05). In both groups of RTRs, both biomarkers correlated inversely with body mass index (BMI), waist-to-hip ratio (WHR), renal impairment, dyslipidemia, HOMA-IR, and hsCRP. Additionally, they negatively correlated with IF severity in the CAD subgroup. Receiver operating characteristic (ROC) analysis demonstrated that BMAL1 and PER2 possessed superior discriminatory capacity over hsCRP for distinguishing CAD from stable renal function (area under the curve [AUC] = 0.964 and 0.951 vs. 0.680, respectively).Furthermore multivariate linear regression (adjusted R2 = 0.824) demonstrated that higher expression of the core clock proteins BMAL1 and PERIOD2 (<i>p</i> = 0.024*, <i>p</i> = 0.041* respectively) independently protects against chronic allograft dysfunction.</p> Conclusion <p>Dysregulation of circadian clock proteins is strongly correlated with the development of CAD and subsequent metabolic complications following renal transplantation.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Serum concentrations of BMAL1 and PERIOD2 as potential indicators of renal graft function

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月15日

查看全文
  • Hayam Abdel Meguid El Aggan,
  • Sabah Abdel Hady Mahmoud,
  • Aya Hassan Okasha,
  • Rasha Ibrahim Gawish

摘要

Background

Renal transplantation (RT) triggers metabolic and immunological shifts intrinsically linked to circadian rhythms. These responses oscillate via the circadian clock (CC), governed by core activators circadian locomotor output cycles kaput (CLOCK) and brain and muscle Arnt-like protein 1 (BMAL1), and repressors like PERIOD (PER) and Cryptochromes (CRY).

Objective

To determine whether serum concentrations of the circadian clock proteins BMAL1 and PER2 correlate with the pathogenesis of chronic allograft dysfunction (CAD) and subsequent metabolic sequelae in renal transplant recipients.

Methods

A total of 63 individuals were recruited for this study: 18 healthy controls and 45 renal transplant recipients (RTRs). The transplant cohort was further stratified based on renal functions into stable function (n = 21) and chronic dysfunction (n = 24) subgroups. Utilizing the ELISA method, we quantified the serum levels of hsCRP alongside the molecular clock proteins (PER2 and BMAL1). Clinical assessments included anthropometrics, renal function, lipid profiles, and insulin resistance (HOMA-IR). Renal interstitial fibrosis (IF) severity was histologically graded from renal biopsies.

Results

Post-RT circadian regulator concentrations were significantly altered. BMAL1 was markedly lower in stable RTRs (2850.73 ± 963.56 pg/ml) and CAD patients (1551.97 ± 142.15 pg/ml) compared to controls (10872.30 ± 2799.39 pg/ml; p < 0.001). Furthermore, CAD patients exhibited significantly lower BMAL1 than stable recipients. Similarly, median (interquartile range [IQR]) PER2 was highest in controls (2532.50 [1005] pg/ml), followed by stable RT recipients (1467.00 [384.50] pg/ml) and CAD groups (1032.50 [304.00] pg/ml; p < 0.001). Serum BMAL1 and PER2 correlated positively with each other (p < 0.05). In both groups of RTRs, both biomarkers correlated inversely with body mass index (BMI), waist-to-hip ratio (WHR), renal impairment, dyslipidemia, HOMA-IR, and hsCRP. Additionally, they negatively correlated with IF severity in the CAD subgroup. Receiver operating characteristic (ROC) analysis demonstrated that BMAL1 and PER2 possessed superior discriminatory capacity over hsCRP for distinguishing CAD from stable renal function (area under the curve [AUC] = 0.964 and 0.951 vs. 0.680, respectively).Furthermore multivariate linear regression (adjusted R2 = 0.824) demonstrated that higher expression of the core clock proteins BMAL1 and PERIOD2 (p = 0.024*, p = 0.041* respectively) independently protects against chronic allograft dysfunction.

Conclusion

Dysregulation of circadian clock proteins is strongly correlated with the development of CAD and subsequent metabolic complications following renal transplantation.