Title: Association Between Proteinuria Changes and Colorectal Cancer Incidence: Evidence
from a Nationwide Cohort Study
Version: 1 Date: 23 Feb 2025
Reviewer's report:
This study leverages a large nationwide cohort to explore the relationship between proteinuria
(PU) dynamics and colorectal cancer (CRC) risk, offering valuable insights into PU as
a potential biomarker. However, major revisions are required to address methodological
limitations, strengthen causal inference, and clarify clinical implications. Below are specific
recommendations:
1.The absence of model performance metrics (e.g., Cstatistic, AUC) limits assessment of
predictive utility. Include discrimination metrics (e.g., Harrell’s Cindex) and calibration plots to
quantify how well PU status predicts CRC risk. Clarify whether the Cox models were validated
internally (e.g., bootstrapping).
2.Dipstick urinalysis is semiquantitative and prone to variability. Discuss potential
misclassification bias (e.g., false negatives/positives) and its impact on risk estimates. Compare
findings to studies using quantitative methods (e.g., urine albumintocreatinine ratio).
3.The conclusion implies PU is a modifiable risk factor, but observational data cannot establish
causality. Reframe claims to highlight associations (e.g., “PU may serve as a marker” rather
than “modifiable factor”). Propose interventional studies to test causality.
4.Despite adjusting for CKD and diabetes, residual confounding (e.g., undiagnosed metabolic
disorders) may persist. Perform sensitivity analyses excluding participants with comorbidities
or adjust for additional confounders (e.g., inflammatory markers, medication adherence).
5.The discussion loosely links PU to inflammation/endothelial dysfunction without tying
mechanisms to CRC. Integrate literature on PUassociated biomarkers (e.g., cytokines, VEGF)
and their role in colorectal carcinogenesis. Discuss shared pathways (e.g., NF#B activation).
6.The cohort is ethnically homogeneous (Korean), limiting extrapolation. Compare findings to
diverse populations (e.g., Western cohorts) and discuss whether PUCRC associations may vary
by ethnicity or healthcare access.
Title: Association Between Proteinuria Changes and Colorectal Cancer Incidence: Evidence
from a Nationwide Cohort Study
Version: 1 Date: 23 Feb 2025
Reviewer's report:
This study leverages a large nationwide cohort to explore the relationship between proteinuria
(PU) dynamics and colorectal cancer (CRC) risk, offering valuable insights into PU as
a potential biomarker. However, major revisions are required to address methodological
limitations, strengthen causal inference, and clarify clinical implications. Below are specific
recommendations:
1.The absence of model performance metrics (e.g., Cstatistic, AUC) limits assessment of
predictive utility. Include discrimination metrics (e.g., Harrell’s Cindex) and calibration plots to
quantify how well PU status predicts CRC risk. Clarify whether the Cox models were validated
internally (e.g., bootstrapping).
2.Dipstick urinalysis is semiquantitative and prone to variability. Discuss potential
misclassification bias (e.g., false negatives/positives) and its impact on risk estimates. Compare
findings to studies using quantitative methods (e.g., urine albumintocreatinine ratio).
3.The conclusion implies PU is a modifiable risk factor, but observational data cannot establish
causality. Reframe claims to highlight associations (e.g., “PU may serve as a marker” rather
than “modifiable factor”). Propose interventional studies to test causality.
4.Despite adjusting for CKD and diabetes, residual confounding (e.g., undiagnosed metabolic
disorders) may persist. Perform sensitivity analyses excluding participants with comorbidities
or adjust for additional confounders (e.g., inflammatory markers, medication adherence).
5.The discussion loosely links PU to inflammation/endothelial dysfunction without tying
mechanisms to CRC. Integrate literature on PUassociated biomarkers (e.g., cytokines, VEGF)
and their role in colorectal carcinogenesis. Discuss shared pathways (e.g., NF#B activation).
6.The cohort is ethnically homogeneous (Korean), limiting extrapolation. Compare findings to
diverse populations (e.g., Western cohorts) and discuss whether PUCRC associations may vary
by ethnicity or healthcare access.
Please review this paper.
user
Title: Association Between Proteinuria Changes and Colorectal Cancer Incidence: Evidence
from a Nationwide Cohort Study
Version: 1 Date: 23 Feb 2025
Reviewer's report:
This study leverages a large nationwide cohort to explore the relationship between proteinuria
(PU) dynamics and colorectal cancer (CRC) risk, offering valuable insights into PU as
a potential biomarker. However, major revisions are required to address methodological
limitations, strengthen causal inference, and clarify clinical implications. Below are specific
recommendations:
1.The absence of model performance metrics (e.g., Cstatistic, AUC) limits assessment of
predictive utility. Include discrimination metrics (e.g., Harrell’s Cindex) and calibration plots to
quantify how well PU status predicts CRC risk. Clarify whether the Cox models were validated
internally (e.g., bootstrapping).
2.Dipstick urinalysis is semiquantitative and prone to variability. Discuss potential
misclassification bias (e.g., false negatives/positives) and its impact on risk estimates. Compare
findings to studies using quantitative methods (e.g., urine albumintocreatinine ratio).
3.The conclusion implies PU is a modifiable risk factor, but observational data cannot establish
causality. Reframe claims to highlight associations (e.g., “PU may serve as a marker” rather
than “modifiable factor”). Propose interventional studies to test causality.
4.Despite adjusting for CKD and diabetes, residual confounding (e.g., undiagnosed metabolic
disorders) may persist. Perform sensitivity analyses excluding participants with comorbidities
or adjust for additional confounders (e.g., inflammatory markers, medication adherence).
5.The discussion loosely links PU to inflammation/endothelial dysfunction without tying
mechanisms to CRC. Integrate literature on PUassociated biomarkers (e.g., cytokines, VEGF)
and their role in colorectal carcinogenesis. Discuss shared pathways (e.g., NF#B activation).
6.The cohort is ethnically homogeneous (Korean), limiting extrapolation. Compare findings to
diverse populations (e.g., Western cohorts) and discuss whether PUCRC associations may vary
by ethnicity or healthcare access.
assistant