Matrix Gla Protein (MGP) and Long-Term Cardiovascular and Renal Outcomes in Kidney Transplant Recipients: A Retrospective Study

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Matrix Gla Protein (MGP) and Long-Term Cardiovascular and Renal Outcomes in Kidney Transplant Recipients: A Retrospective Study

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Co-author 1

Sara Abdallah saraabdallah.710.sa@gmail.com LAU Medical Center-Rizk Hospital Internal Medicine Beirut Lebanon -

Co-author 2

Georges Choueiry georges.choueiry@lau.edu.lb Lebanese American University School of Medicine Byblos Lebanon -

Co-author 3

Hicham Cheikh Hassan hicham.cheikhhassan@lau.edu.lb Lebanese American University School of Medicine Byblos Lebanon -

Co-author 4

Hala Kilani hala.kilani@lau.edu.lb Lebanese American University School of Medicine Byblos Lebanon -

Co-author 5

Siba Kallab siba.kallab@lau.edu.lb Lebanese American University School of Medicine Byblos Lebanon -

Co-author 6

Sola Aoun Bahous sola.bahous@lau.edu.lb Lebanese American University School of Medicine Byblos Lebanon *

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Introduction

Vitamin K deficiency, reflected by elevated plasma levels of dephosphorylated-uncarboxylated MGP (dp-ucMGP), is common among kidney transplant recipients (KTRs) and has been associated with higher risks of death and transplant failure mostly in European cohorts. However, its effects on long-term cardiovascular (CV) and renal events, particularly in Middle Eastern populations, remain unclear. This study examines whether baseline dp-ucMGP levels independently predict long-term CV and renal complications in a Middle Eastern KTR cohort with extended follow-up.

Methods

We conducted a retrospective chart review of 58 adult KTRs who participated in the KING trial (Vitamin K2 In reNal Graft) at the Lebanese American University Medical Center-Rizk Hospital between April 2015 and May 2016. Baseline dp-ucMGP levels, along with demographic, clinical, and laboratory data were collected. Subjects were followed until January 2025 (mean follow-up 6.7 years; range 0.2-9.8 years).

The primary outcome was the time to the first CV or renal event. CV events included coronary artery disease, heart failure, arrhythmias, carotid stenosis, peripheral vascular disease, and aortic aneurysm. Renal events included doubling of baseline serum creatinine or development of end-stage kidney disease.

Time-to-event analyses for the combined CV and renal outcomes were performed using bivariate and multivariable Cox proportional hazards models, adjusting for age, sex, dialysis duration, rejection episodes, prior CV disease, and diabetes. dp-ucMGP was analyzed both as a continuous and categorical variable (highest quartile, middle 50%, and lowest quartile). Kaplan–Meier curves compared event-free survival between dp-ucMGP groups, and model discrimination at 5 years was assessed using the area under the ROC curve (AUC).

Results

Mean baseline dp-ucMGP level was 574 pmol/L (SD = 357), with 52% of subjects having vitamin K insufficiency (dp-ucMGP>500 pmol/L). During follow-up, 26 subjects (45%) experienced the primary composite outcome.

In multivariable analysis, each 100pmol/L increase in dp-ucMGP was associated with 23% higher risk of CV or renal events (HR 1.23, 95% CI 1.09-1.38, p<0.01; AUC 80.6%). Patients in the highest dp-ucMGP quartile (>790 pmol/L) had reduced 5-year event-free survival compared to the lowest quartile (<306 pmol/L): 36% vs. 93% (log-rank p<0.01), representing a nearly 3-fold difference in event rates. Male sex was associated with lower event risk (HR 0.34, 95% CI 0.14-0.82, p=0.02).

Table 1 - Multivariable model results

Predictor	Hazard ratio	p-value	Lower 95% CI	Upper 95% CI
Male	0.34	0.02*	0.14	0.82
Age	1.02	0.29	0.98	1.06
dp-ucMGP	1.23	< 0.01*	1.09	1.38
Dialysis duration (months)	1.01	0.06	1.00	1.03
Acute rejection episodes	1.75	0.25	0.67	4.55
Cardiovascular history	1.51	0.45	0.51	4.44
Diabetes at baseline	0.79	0.70	0.23	2.64

Conclusion

In this Middle Eastern KTR cohort with nearly 7 years of follow-up, higher baseline dp-ucMGP levels independently predict long-term CV and renal events. This supports the role of vitamin K in vascular and renal health after transplantation, although causality remains to be confirmed.

Kewords