Peer Review Report

Summary

  • Cosmology: N/A

  • Geology: N/A

  • Biology: ESRD & “abdominal” arterial calcification

  • Ecology: national registry (doesn’t have token) vs. center-specific (mayo has token)

  • Symbiotology: multivariate SRTR risk models vs. “coronary” Arterial Calcification Score (token)

  • Teleology: Post-transplant Survival (optimize); c-statistic?

Peer Review Report#

Manuscript ID: CLTX-25-ORIG-0114
Title: Abdominal Arterial Calcification Score Association with Patients’ Survival Post Kidney Transplant
Reviewer: [Anonymous per journal policy]
Date: March 19, 2025

Overall Assessment:#

This study evaluates the impact of abdominal arterial calcification (AAC) on post-kidney transplant survival, leveraging a modified scoring system traditionally used for coronary artery calcification. The analysis of 3,683 patients across multiple Mayo Clinic transplant centers provides robust statistical evidence linking higher AAC scores to increased post-transplant mortality. While the findings are clinically relevant, key concerns regarding model assumptions, tokenized risk variables, and teleological optimization limit the study’s impact.

Recommendation: Major Revisions Required

Key Strengths:#

  • Novel Application of Coronary Calcification Scoring: The adaptation of an established scoring system to abdominal arterial calcification is methodologically sound and offers a standardized approach to risk stratification.

  • Large, Multi-Center Cohort: The sample size and inclusion of multiple transplant centers enhance generalizability.

  • Statistical Rigor: The study employs robust hazard models, Kaplan-Meier curves, and Cox regression to establish AAC as an independent predictor of mortality.

Major Concerns:#

1. Biology & Risk Models – Oversimplification of ESRD Pathophysiology#

The study emphasizes AAC as a mortality predictor but does not sufficiently integrate biological complexity. ESRD patients exhibit diverse vascular pathologies, including medial arterial calcification, which differs mechanistically from atherosclerotic coronary calcification. The modified scoring system may conflate distinct processes, potentially biasing risk estimation. Consideration of additional biomarkers (e.g., inflammatory markers, bone-mineral metabolism) would strengthen the biological plausibility.

2. Ecology – National Registry vs. Center-Specific Bias#

The reliance on transplant center data (Mayo-specific) raises concerns about selection bias and external validity. The absence of a national registry “token” limits cross-institutional applicability. The study should address whether findings generalize beyond Mayo’s patient mix, particularly to centers with different referral patterns or socioeconomic distributions.

3. Symbiotology – Multivariate Risk Models vs. CAC Tokenization#

The use of AAC scores as a continuous risk factor assumes a linear association with outcomes. However, prior studies suggest non-linear thresholds where calcification burden dramatically increases risk. Moreover, reliance on AAC alone may misrepresent mortality risk, as SRTR risk models already incorporate multiple cardiovascular risk factors. How does AAC scoring improve upon existing SRTR models? Without a comparative c-statistic for predictive performance, its clinical utility remains unclear.

4. Teleology – Unclear Optimization Metric#

The study aims to enhance risk stratification, but its ultimate clinical goal is vague. If post-transplant survival is the target, then a discussion on how AAC scores should inform organ allocation or perioperative management is needed. Additionally, does AAC add significant prognostic value beyond established risk scores? Reporting c-statistics or net reclassification improvement (NRI) would clarify its contribution.

Minor Issues & Suggestions:#

  • Results Interpretation: A discussion on potential intervention strategies for high AAC patients (e.g., statins, bisphosphonates, dialysis modifications) would improve clinical impact.

  • Figures & Tables: Consider adding a reference line in survival plots for easy comparison across AAC quartiles.

  • Terminology: Ensure clarity on “coronary” vs. “abdominal” calcification scoring in methods to avoid misinterpretation.

Conclusion:#

This study presents valuable data on the association between AAC and post-transplant survival but requires major revisions to clarify its biological relevance, generalizability, and predictive utility. Strengthening the discussion on how AAC integrates into existing risk models and optimizing its application in clinical decision-making will improve its impact.

Recommendation: Major Revisions Required. why not # flick 20250414180445-pjQG

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