Neutrophil gelatinase-associated lipocalin (NGAL) in heart transplant recipients after conversion to everolimus therapy. Issue 4 (October 2015)

• Record Type: Journal Article
• Authors: Stypmann, Jörg; Fobker, Manfred; Rosing, Katharina; Engelen, Markus; Gunia, Stefan; Dell'Aquila, Angelo Maria; Nofer, Jerzy-Roch
• Is Part Of: Journal of cardiology. Volume 66:Issue 4(2015:Oct.)
• Page Start: 347
• Page End: 352
• Publication Date: 2015-10
• Subjects: Cardiology -- Periodicals; 616.12
• DOI: 10.1016/j.jjcc.2014.12.010
• Languages: English
• ISSNs: 0914-5087

Abstract

<abstract abstract-type="author" id="abs0005"> <title id="sect0005">Abstract</title> <sec> <title id="sect0010">Background</title> <p id="spar0005">Due to the lack of nephrotoxic activity, proliferation signal inhibitors (PSI) such as everolimus are recommended for immunosuppression after heart transplantation, but the assessment of renal function in patients receiving PSI has led to conflicting results. We examined renal integrity and function using neutrophil gelatinase-associated lipocalin (NGAL) and conventional markers [plasma creatinine, cystatin C, urine albumin, α<sub>1</sub>-microglobulin (α<sub>1</sub>M)] in heart transplant patients, who underwent conversion to everolimus due to allograft vasculopathy, graft rejection episodes, or renal function deterioration, and in patients maintained on calcineurin inhibitors (CNI).</p> </sec> <sec> <title id="sect0015">Methods</title> <p id="spar0010">This cross-sectional study included 121 consecutive heart transplant recipients: 44 patients received CNI-free immunosuppressive therapy with everolimus and 77 patients received CNI. Renal parameters were determined in plasma and urine samples using standard enzymatic or immunochemical methods.</p> </sec> <sec> <title id="sect0020">Results</title> <p id="spar0015">Heart transplant recipients receiving everolimus therapy had significantly lower NGAL concentrations in plasma [median (95% CI): 128 (97–176) ng/mL vs. 252 (224–283) ng/mL, <italic>p</italic> < 0.001] and urine [median (95% CI): 6.4 (4.5–7.6) ng/g vs. 15.7 (10.2–25.9) ng/g creatinine, <italic>p</italic> < 0.001]. In contrast, no significant differences were observed between everolimus- and CNI-treated groups with regard to creatinine and cystatin C, as well as urine albumin and α<sub>1</sub>M levels. Significant correlations were noted between plasma NGAL and creatinine (<italic>r</italic> = 0.42, <italic>p</italic> < 0.001), cystatin C (<italic>r</italic> = 0.44, <italic>p</italic> < 0.001), N-terminal brain natriuretic propeptide (<italic>r</italic> = 0.31, <italic>p</italic> < 0.01) and indicators of chronic inflammation [lipoprotein-associated phospholipase A<sub>2</sub> (Lp-PLA<sub>2</sub>), <italic>r</italic> = 0.31, <italic>p</italic> < 0.01] and soluble CD40 ligand (sCD40L, <italic>r</italic> = 0.22, <italic>p</italic> < 0.05), and between urinary NGAL and α<sub>1</sub>M (<italic>r</italic> = 0.21, <italic>p</italic> < 0.05). Multiple regression analysis indicated that cystatin C and Lp-PLA<sub>2</sub> were the best predictors of plasma NGAL.</p> </sec> <sec> <title id="sect0025">Conclusion</title> <p id="spar0020">The present study documents reduced plasma and urinary NGAL levels in the absence of differences in conventional renal parameters in patients on CNI-free immunosuppressive therapy with everolimus. These results support favorable effects of everolimus on renal integrity in heart transplant recipients.</p> </sec> </abstract>