Skip to content
DraconiticResearch
Search Sources API
203,203 studies31 sourcesUpdated 38 min ago
Peer-reviewedCC BY 4.0Frontiers in Cardiovascular Medicine

Serial urinary NGAL and CK20 for dynamic cardiovascular risk stratification in non-muscle-invasive bladder cancer: a retrospective clinical cohort study

  • Wang Ma1
  • Yan Liu2
  • Lei Tang1
  • Song Ouyang3
  • Yanjun Ma1,4
  • Zhidong Zhang1,4
  • Qianyue Li1
  • Zhikun Li1
  • Lin Li1,5
  • Yawei Zhao1
5 affiliations
  1. 1Department of Urology, Xinjiang Production and Construction Corps Hospital, The Second Affiliated Hospital, School of Medicine, Shihezi University
  2. 2Department of Intensive, Xinjiang Production and Construction Corps Hospital, The Second Affiliated Hospital, School of Medicine, Shihezi University
  3. 3Department of Urology, The First Affiliated Hospital of Shihezi University
  4. 4Department of Urology, Xinjiang Medical University
  5. 5Department of Urology, Shihezi University
Read full textPDFDOICite

Abstract

Background: Non-muscle-invasive bladder cancer (NMIBC) is commonly managed with intravesical BCG, whereas pembrolizumab is reserved for selected BCG-unresponsive high-risk disease. Cardiovascular adverse events (CVAEs) may occur during cancer therapy, but BCG-related systemic inflammatory effects and immune checkpoint inhibitor (ICI)-mediated cardiovascular immune-related adverse events have distinct pathophysiology and clinical kinetics. We evaluated serial urinary NGAL and CK20 as non-invasive candidate biomarkers for dynamic CVAE risk stratification.

Methods: A retrospective single-center cohort of 215 NMIBC patients (2021–2023) underwent serial urinary NGAL (ELISA) and CK20 mRNA (qRT-PCR) assessment at baseline and 1, 3, 6, and 12 months after TURBT. Biomarker cutoffs were derived in a 70% training split and evaluated in the remaining 30% internal validation split. Cardiovascular surveillance included echocardiography, ECG, BNP, and high-sensitivity troponin I. The primary endpoint was CTCAE-graded CVAE; Cox regression evaluated associations with cardiovascular event-free survival (CVEFS).

Results: CVAEs occurred in 74/215 patients (34.4%). The BCG cohort comprised 112 patients; the pembrolizumab subgroup comprised only 25 patients and is therefore interpreted exploratorily. Four ICI-associated myocarditis cases occurred in the pembrolizumab subgroup (16.0%; exact 95% CI 4.5–36.1%). Baseline urinary NGAL was higher in patients with subsequent CVAEs (128.7 ± 38.9 vs. 69.3 ± 33.7 ng/mL, p < 0.001). Combined NGAL + CK20 yielded an internally validated 6-month AUC of 0.913 (95% CI 0.866–0.960), and dual positivity was associated with CVAE risk (aHR=4.12, 95% CI 2.71–6.26). The reported lead-time analysis suggested earlier NGAL change before echocardiographic LVEF decline; this finding requires prospective confirmation.

Conclusions: Serial urinary NGAL and CK20 are promising candidate markers for CVAE risk stratification in this retrospective NMIBC cohort. The findings are driven principally by the overall cohort and the larger BCG-treated group; ICI-specific observations are hypothesis-generating because only 25 patients received pembrolizumab. The proposed biomarker thresholds and surveillance framework require prospective, multicenter external validation before clinical implementation.

Related

  1. Clinical predictors, species distribution, and machine learning-based risk stratification of invasive candidiasis and in-hospital mortality: a retrospective episode-level cohort analysis.
    Mohan Bilikallahalli Sannathimmappa, Vinod Nambiar, Mohammmed Al Amin Ali Alsharawy +9
    BMC infectious diseasesPeer-reviewedCC BY-NC-NDFull textInfectious diseaseEurope PMCPMC
  2. MetALD in Clinical Practice: Diagnosis, Non-Invasive Risk Stratification, and Management
    Hubert Krzewiński, Oliwier Wątroba, Jarosław Koza
    Journal of clinical medicinePeer-reviewedCC BYFull textGeneral medicineEurope PMC
  3. Clinically Accessible Phenotypes Refine Cardiovascular Risk Stratification Beyond Contemporary Clinical Equations
    H. Yang, J. Guo, X. Shi +6
    medRxivPreprintAll rights reservedFull textEpidemiology & public healthmedRxiv
  4. Research progress and clinical translation prospects of multiple urinary biomarkers in non-invasive diagnosis of urothelial carcinoma
    Shuxin Li, Lei Wang, Baoshan Gao
    Frontiers in OncologyPeer-reviewedCC BY 4.0Full textSurgery & anaesthesiaCrossrefEurope PMC
  5. A machine learning-derived aging index for risk stratification and mortality prediction in cardiovascular-kidney-metabolic syndrome: A retrospective cohort study
    Zhengyang Zhu, Kejun Ren, Dong Wang +4
    PLOS MedicinePeer-reviewedCC BY 4.0Full textCardiovascular medicineEndocrinology & metabolismPLOS

Cite

BibTeXRIS
BibTeX
@article{ma2026serial,
  title = {{Serial urinary NGAL and CK20 for dynamic cardiovascular risk stratification in non-muscle-invasive bladder cancer: a retrospective clinical cohort study}},
  author = {Wang Ma and Yan Liu and Lei Tang and Song Ouyang and Yanjun Ma and Zhidong Zhang and Qianyue Li and Zhikun Li and Lin Li and Yawei Zhao},
  journal = {Frontiers in Cardiovascular Medicine},
  year = {2026},
  month = oct,
  doi = {10.3389/fcvm.2026.1949457},
  url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1949457/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Serial urinary NGAL and CK20 for dynamic cardiovascular risk stratification in non-muscle-invasive bladder cancer: a retrospective clinical cohort study
AU  - Wang Ma
AU  - Yan Liu
AU  - Lei Tang
AU  - Song Ouyang
AU  - Yanjun Ma
AU  - Zhidong Zhang
AU  - Qianyue Li
AU  - Zhikun Li
AU  - Lin Li
AU  - Yawei Zhao
PY  - 2026
DA  - 2026/10/16
JO  - Frontiers in Cardiovascular Medicine
DO  - 10.3389/fcvm.2026.1949457
UR  - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1949457/full
AB  - Background: Non-muscle-invasive bladder cancer (NMIBC) is commonly managed with intravesical BCG, whereas pembrolizumab is reserved for selected BCG-unresponsive high-risk disease. Cardiovascular adverse events (CVAEs) may occur during cancer therapy, but BCG-related systemic inflammatory effects and immune checkpoint inhibitor (ICI)-mediated cardiovascular immune-related adverse events have distinct pathophysiology and clinical kinetics. We evaluated serial urinary NGAL and CK20 as non-invasive candidate biomarkers for dynamic CVAE risk stratification.  Methods: A retrospective single-center cohort of 215 NMIBC patients (2021–2023) underwent serial urinary NGAL (ELISA) and CK20 mRNA (qRT-PCR) assessment at baseline and 1, 3, 6, and 12 months after TURBT. Biomarker cutoffs were derived in a 70% training split and evaluated in the remaining 30% internal validation split. Cardiovascular surveillance included echocardiography, ECG, BNP, and high-sensitivity troponin I. The primary endpoint was CTCAE-graded CVAE; Cox regression evaluated associations with cardiovascular event-free survival (CVEFS).  Results: CVAEs occurred in 74/215 patients (34.4%). The BCG cohort comprised 112 patients; the pembrolizumab subgroup comprised only 25 patients and is therefore interpreted exploratorily. Four ICI-associated myocarditis cases occurred in the pembrolizumab subgroup (16.0%; exact 95% CI 4.5–36.1%). Baseline urinary NGAL was higher in patients with subsequent CVAEs (128.7 ± 38.9 vs. 69.3 ± 33.7 ng/mL, p < 0.001). Combined NGAL + CK20 yielded an internally validated 6-month AUC of 0.913 (95% CI 0.866–0.960), and dual positivity was associated with CVAE risk (aHR=4.12, 95% CI 2.71–6.26). The reported lead-time analysis suggested earlier NGAL change before echocardiographic LVEF decline; this finding requires prospective confirmation.  Conclusions: Serial urinary NGAL and CK20 are promising candidate markers for CVAE risk stratification in this retrospective NMIBC cohort. The findings are driven principally by the overall cohort and the larger BCG-treated group; ICI-specific observations are hypothesis-generating because only 25 patients received pembrolizumab. The proposed biomarker thresholds and surveillance framework require prospective, multicenter external validation before clinical implementation.
SN  - 2297-055X
ER  -