MO924GROWTH DIFFERENTIATION FACTOR 15 PREDICTOR VALUE IS SUPERIOR TO TROPONIN I IN THE EVALUATION OF KIDNEY TRANSPLANT CANDIDATES
Authors: De Cos Gomez Marina , Garcia Unzueta Maria Teresa , Benito Hernandez Adalberto , Perez Arnedo Mario , Aguilera Fernandez Alejandro , Serrano Fernández Marina , Belmar Vega Lara , Valero San Cecilio Rosalía , Ruiz San Millán Juan Carlos , Rodrigo Emilio 
Published: May 2021

Abstract

Background and Aims
Elevation of cardiac troponin has been shown to be a marker of myocardial ischemia and other cardiovascular pathologies frequently present in patients with CKD. Pretransplant cardiac troponin I (cTNI) has demonstrated its predictor value of survival after kidney transplant in previous studies. Growth differentiation factor 15 (GDF-15) is a biomarker induced by oxidative stress currently studied as a predictor of mortality and cardiovascular events (CVE) in multiple scenarios, including patients with chronic kidney disease. The aim of this study is to compare the utility of cTNI and GDF-15 to predict posttransplant mortality and CVE in a cohort of kidney transplant recipients.

Method
We included 359 kidney transplants performed between 2005 and 2015. cTNI and GDF-15 were measured on stored serum samples obtained pretransplant. Information about patients was extracted from the prospectively maintained database of renal transplant recipients at our center.

Results
Receptors had a median age of 54.1 and were 67.4% male. 22% were diabetic before the transplant, whereas 9.5% and 8.1% had prior history of coronary and peripheral artery disease. 16.5% transplants were performed preemptively. Median GDF-15 was 5346.4 (IQR= 4071.83-6786.32) pg/ml and median cTNI was 5.6 (IQR= 3.11-10.67) ng/l. After follow up, 77 (21.45%) patients died. During this period, incidence of cerebrovascular accident, acute coronary syndrome and mayor adverse cardiovascular events (MACE) was 6.38%, 12.68% and 20.56% respectively. Patients were stratified in tertiles according to GDF-15 and cTNT levels. In the univariate analysis, higher levels of GDF-15 significantly related to overall mortality, cardiovascular mortality, cerebrovascular accident, acute coronary syndrome and major adverse cardiovascular events. Higher cTNI related to cardiovascular mortality, acute coronary syndrome and MACE, but not overall mortality (Log Rank p=0.4). (Fig 1).
By multivariate cox regression analysis, including both biomarkers and clinical characteristics (age, diabetes, prior coronary and peripheral artery disease and pretransplant renal replacement therapy), the relation between overall survival and GDF-15 remained significant for the highest tertile (HR 2.2 CI95% (1.2-4.1), p = 0.01). Similarly, GDF-15 relation with cerebrovascular accidents and MACE remained significant after the adjustment by these characteristics [HR 9.7 CI95% (2.2-43.1), p = 0.003 and HR 2.7 CI95% (1.4-5.1), p = 0.002] for the highest risk tertile. On the contrary, posttransplant acute coronary syndrome was only related to cTNI tertiles and previous coronary artery disease in the multivariate model [HR 3.2 CI95% (1.5-7.3), p = 0.003 for the highest cTNI tertile].

Conclusion
Our study highlights the potential utility of GDF-15 as a predictor of mortality and cardiovascular events after kidney transplant and its superiority compared to cTNI. In our study, cardiac troponin showed a stronger relation with acute coronary events, probably due to its specific production in myocardial tissue. Altogether, these two molecules could be used in conjunction with clinical characteristics to create prognostic models to better stratify patient’s risk prior organ allocation, predict mortality and cardiovascular adverse events after transplant and ideally find strategies to minimize them. Large-scale, multicenter validation using these biomarkers would be the next step to prove its utility among kidney transplant candidates.