Group IIA Secretory Phospholipase A2 Predicts Graft Failure and Mortality in Renal Transplant Recipients by Mediating Decreased Kidney Function.

Wijtske Annema,Lidiya G Dimova,Arne Dikkers,Jan Freark De Boer,Markus Van Der Giet,Uwe J.F Tietge,Stephan J.L Bakker

doi:10.3390/jcm9051282

Abstract

The acute phase protein group IIA secretory phospholipase A2 (sPLA2-IIA) has intrinsic proatherosclerotic properties. The present prospective cohort study investigated whether plasma sPLA2-IIA associates with graft failure, cardiovascular, and all-cause mortality in renal transplant recipients (RTRs), patients with accelerated atherosclerosis formation both systemically and within the graft. In 511 RTRs from a single academic center with stable graft function >1 year, baseline plasma sPLA2-IIA was determined by ELISA. Primary end points were death-censored graft failure and mortality (median follow-up, 7.0 years). Baseline sPLA2-IIA was higher in RTRs than in healthy controls (median 384 ng/dL (range 86–6951) vs. 185 ng/dL (range 104–271), p < 0.001). Kaplan–Meier analysis demonstrated increased risk for graft failure (p = 0.002), as well as cardiovascular (p < 0.001) and all-cause mortality (p < 0.001), with increasing sPLA2-IIA quartiles. Cox regression showed strong associations of sPLA2-IIA with increased risks of graft failure (hazard ratio (HR) = 1.42 (1.11–1.83), p = 0.006), as well as cardiovascular (HR = 1.48 (1.18−1.85), p = 0.001) and all-cause mortality (HR = 1.39 (1.17−1.64), p < 0.001), dependent on parameters of kidney function. Renal function during follow-up declined faster in RTRs with higher baseline sPLA2-IIA levels. In RTRs, sPLA2-IIA is a significant predictive biomarker for chronic graft failure, as well as overall and cardiovascular disease mortality dependent on kidney function. This dependency is conceivably explained by sPLA2-IIA impacting negatively on kidney function.

Highlights

For end-stage renal disease (ESRD) patients, kidney transplantation is generally accepted to be the treatment modality resulting in the highest gain in quality of life and in the lowest morbidity as well as mortality rates
Kidney transplantation decreases the excessive age-adjusted increase in overall and cardiovascular mortality associated with ESRD, renal transplant recipients (RTRs) still exhibit 4–6-fold higher rates of cardiovascular disease mortality compared with the general population [1]
With respect to RTRs, we carried out a prospective longitudinal cohort study, where every adult RTR patient seen in the nephrological outpatient clinic of the University Medical Center Groningen in the time span August 2001 to July 2003 was in principle eligible to participate when a stable graft function was present for at least one year

Summary

Introduction

For end-stage renal disease (ESRD) patients, kidney transplantation is generally accepted to be the treatment modality resulting in the highest gain in quality of life and in the lowest morbidity as well as mortality rates. Kidney transplantation decreases the excessive age-adjusted increase in overall and cardiovascular mortality associated with ESRD, renal transplant recipients (RTRs) still exhibit 4–6-fold higher rates of cardiovascular disease mortality compared with the general population [1]. Atherosclerosis within the kidney graft resulting in transplant vasculopathy with subsequent chronic graft failure represents a significant clinical problem for RTRs [4,5]. In contrast to the clinical significance of the problem, specific therapeutic options to treat transplant vasculopathy are, limited [4,5]

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Conclusion