Serum angiotensin converting enzyme-2 activity as a new marker of graft function in kidney transplant patients

María J. Soler¹, Marta Riera¹, Marisa Mir¹, Marta Crespo¹, Josep M. Puig¹, Julio Pascual¹.

¹Department of Nephrology, Hospital del Mar, Fundació IMIM, Barcelona, Spain.

Angiotensin-converting enzyme (ACE)-2 is the only known active homologue of ACE, and its function is to degrade Angiotensin II to Angiotensin 1-7, a vasodilator peptide, and Angiotensin I to Angiotensin 1-9. The role of ACE2 in kidney transplant (KT) function is unknown. We previously showed that serum ACE2 activity is increased in male mice and human. The aim of this study is to investigate whether ACE2 activity is altered in KT patients as compared with control subjects. In addition, we studied the correlation between serum ACE2 activity and age, gender, graft function and analytical cardiovascular risk markers in kidney transplant patients.

ACE2 activity was assessed using a fluorescent assay in 113 KT patients (age 55 ±12 yr, glomerular filtration rate (GFR)-MDRD 44.8± 11.3 mL/min). Chronic kidney disease (CKD)-Stage 3 patients (n=27, age 57±10 yr, GFR-MDRD 41.4±8.6 mL/min) age, gender and MDRD-matched served as controls.

Human serum ACE2 activity using a specific ACE2 Inhibitor (DX 600) nicely correlates with the activity using EDTA (a known carboxipeptidase inhibitor) (r=0.96, p<0.001). Serum ACE2 activity was significantly decreased in KT patients as compared to CKD patients (98 ± 6.5 vs. 138.7 ± 17.9 RFU/mL/h, p < 0.05). In the univariate analysis, serum ACE2 activity was significantly increased in KT patients with ischemic heart disease as compared with KT without ischemic heart disease (105.9 ± 8.7 vs. 97.1 ± 7.05 RFU/mL/h, p < 0.05). In addition, serum ACE2 activity directly correlates with serum creatinine (r=0.27), serum urea (r=0.29), Aspartate transaminase (r=0.39), alanine transaminase (r=0.48) and gamma glutamyl transferase (r=0.52) (p<0.05). In addition, serum ACE2 activity was increased in KT patients with glycosylated hemoglobin > 6% as compared with KT patients with glycosylated hemoglobin =< 6% (117 ± 12.5 vs. 82.5 ± 4.9 RFU/mL/h, p < 0.05). Renin angiotensin system blockade did not influence serum ACE2 activity. In multiple regression analysis, serum creatinine, and serum gamma glutamyl transferase, were independent predictors of serum ACE2 activity (see Table). In conclusion, serum ACE2 activity directly correlates with graft and liver function parameters. Measurement of the enzymatic activity of ACE2 in serum may become an easy tool to detect graft dysfunction in KT patients.