The acute phase protein group IIA secretory phospholipase A2 (sPLA2-IIA) has proatherosclerotic properties. The present study prospectively investigated whether plasma sPLA2-IIA levels are associated with graft failure, cardiovascular and all-cause mortality in renal transplant recipients (RTRs), patients known to be susceptible to accelerated atherosclerosis, both in the graft and in the systemic vasculature. In 495 RTRs (median follow-up 7.0 years) sPLA2-IIA was determined at baseline and was significantly higher in RTRs than in healthy controls (median 384 ng/dL [range 86-6951] vs. 185 ng/dL [range 104-271], P<0.001), but lower than in end-stage renal disease patients (median 1053 ng/mL [range 458-2599], P<0.001). Kaplan-Meier analysis demonstrated an increased risk for graft failure (P=0.002), cardiovascular (P<0.001) and all-cause mortality (P<0.001) with increasing gender-stratified quartiles of sPLA2-IIA. Cox regression analyses showed a strong association of sPLA2-IIA with increased risks of graft failure (hazard ratio=1.42[1.11-1.83], P=0.006), cardiovascular (hazard ratio=1.48[1.18-1.85], P=0.001) and all-cause mortality (hazard ratio=1.39[1.17-1.64], P<0.001). However, this association was largely explained by parameters of kidney function. Further analyses in RTRs demonstrated that patients with higher baseline sPLA2-IIA levels showed faster decline in renal function during follow-up. In addition, kidney function in human sPLA2-IIA transgenic mice deteriorated more rapid over time as compared with wild-type controls (urinary albumin:creatinine ratio at 48 weeks of age 774±156 vs. 193±60, P<0.01). In summary, this prospective study demonstrates that sPLA2-IIA is a significant predictive biomarker for the occurrence of chronic graft failure, overall and CVD mortality in RTRs dependent on kidney function. This dependency is explained by sPLA2-IIA impacting negatively on kidney function over time in humans and transgenic mice.
A follow up study of cytomegalovirus infection in a group of Turkish renal transplant recipients using molecular assays
