Pretransplant Pregnancy-Associated Plasma Protein-A as a Predictor of Chronic Allograft Nephropathy and Posttransplant Cardiovascular Events

Abstract

Cardiovascular disease and chronic allograft nephropathy (CAN) are two of the main complications observed in patients after renal transplantation. Both appear to be manifestations of the same process, in which inflammation plays a determinate role. Pregnancy-associated plasma protein A (PAPP-A) has been shown to be a marker of acute coronary syndrome and cardiovascular pathology. The objective of this study was to demonstrate whether or not serum concentration of pretransplant PAPP-A is a marker of CAN and a predictor of posttransplant cardiovascular events. In all, 178 renal transplants (65% males; 53+/-12 years of age) followed up over the course of 49.3+/-33.6 months were used in this study. During the follow-up period, 19 patients developed CAN (diagnosed by renal biopsy) and 27 patients had a cardiovascular event. Previous to transplantation, the following were determined: ultrasensitive C-reactive protein (CRP) (nephelometry); interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) (immunofluorimetric automatized method), and ultrasensitive PAPP-A (ELISA). A positive correlation was found between PAPP-A and the inflammatory markers (PAPP-A vs. CRP, r=0.218; P=0.004; PAPP-A vs. IL-6, r=0.235; P<0.001; PAPP-A vs. TNF-alpha, r=0.372; P<0.001). The multiple regression analysis showed PAPP-A (relative risk [RR]: 6.4; 95% confidence interval [CI]:1.24-33.11; P=0.027) and CRP (RR: 6.05; 95% CI:1.21-29.74; P=0.028) to be predictors of posttransplant cardiovascular events and PAPP-A (RR: 4.27; 95% CI: 1.03-17.60; P=0.044) and TNF-alpha (RR: 5.6; 95% CI: 1.43-21.83; P=0.013) to be predictors of CAN. PAPP-A correlated with the inflammatory markers studied (CRP, IL-6 and TNF-alpha). Pretransplant serum concentration of PAPP-A is a predictor of posttransplant cardiovascular events and CAN.