INCREASED SERUM NEUTRAL ENDOPEPTIDASE ACTIVITY IN ACUTE RENAL-ALLOGRAFT REJECTION

Neutral endopeptidase (EC 3.4.24.11; NEP), originally isolated from re nal tubular brush border, is a cell surface peptidase identical to the CD 10 antigen (or CALLA; common acute lymphoblastic leukemia antigen) in lymphoid cells. We studied the serum NEP levels daily after transp lantation (Tx) in 19 renal allograft recipients. The NEP activity was determined with a two-step enzymatic assay utilizing a fluorogenic sub strate (Suc-Ala-Ala-Phe-AMC; see text) and related to clinical signs o f graft rejection, to signs of immunoactivation in transplant fine-nee dle aspiration biopsy (FNAB) specimens, to renal function, and to seru m levels of C-reactive protein. The serum NEP levels remained normal ( peak level 10.3 +/- 1.8 mu g/l on days 6-9 after Tx, initial level aft er Tx 7.3 +/- 1.4 mu g/l on day 2; mean values +/- SEM) in patients wh o neither showed clinical signs of rejection nor had findings of immun oactivation in FNAB samples. On the contrary, the serum NEP levels ros e clearly in patients developing acute rejection verified clinically a nd in FNAB samples (peak value 90.4 +/- 18.7 mu g/l on days 6-9 post-T x; p < 0.001 compared with patients without signs of immunoactivation) and even in patients having immunoactivation in FNAB without clinical evidence of rejection (108.2 +/- 22.4 mu g/l, p < 0.001). Serum NEP p eak appeared 2-3 days before clinical diagnosis of rejection and a pos itive finding in FNAB samples. Serum NEP increments did not correlate with changes in serum creatinine, delayed onset of renal excretory fun ction, blood leukocyte count, C-reactive protein level, or infections. Thus, the serum NEP activity was shown to increase after renal allotr ansplantation associated with early phases of immunoactivation and dev elopment of acute graft rejection. Because of the limited number of pa tients studied, the clinical implications of these preliminary observa tions for kidney transplant monitoring clearly need confirmation in la rger studies.