Plasma neutrophil gelatinase-associated lipocalin and worsening renal function during everolimus therapy after heart transplantation.
Recently, the mammalian target of rapamycin inhibitor everolimus (EVL) has been introduced as a novel immunosuppressant for heart transplant (HTx) recipients, and is expected to preserve renal function compared to conventional calcineurin inhibitors (CNIs). However, a considerable number of recipients treated with EVL were not free from worsening renal function regardless of CNI reduction. Data were collected retrospectively from 27 HTx recipients who had received EVL (trough concentration, 3.1-9.2 ng/mL) along with reduced CNIs (%decreases in trough concentration, 27.3 ± 13.0%) because of switching from mycophenolate mophetil due to digestive symptoms or neutropenia, progressive coronary artery vasculopathy, or persistent renal dysfunction, and had been followed over 1 year between August 2008 and January 2013. Estimated glomerular filtration rate (eGFR) decreased in 5 recipients (18.5%) during the study period. Univariate logistic regression analysis demonstrated that a higher plasma neutrophil gelatinase-associated lipocalin (P-NGAL) level was the only significant predictor for a decrease in eGFR over a 1-year EVL treatment period among all baseline parameters (P = 0.008). eGFR and proteinuria worsened almost exclusively in patients with baseline P-NGAL ≥ 85 ng/mL, which was the cutoff value calculated by an ROC analysis (area under the curve, 0.955; sensitivity, 1.000; specificity, 0.955). In conclusion, higher P-NGAL may be a novel predictor for the worsening of renal function after EVL treatment that is resistant to CNI reduction in HTx recipients.
Department of Therapeutic Strategy for Heart Failure, Graduate School of Medicine, University of Tokyo.
Teruhiko
T
Imamura
Koichiro
K
Kinugawa
Kent
K
Doi
Masaru
M
Hatano
Takeo
T
Fujino
Osamu
O
Kinoshita
Kan
K
Nawata
Eisei
E
Noiri
Shunei
S
Kyo
Minoru
M
Ono
D000209:Acute-Phase Proteins; D000328:Adult; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D000068338:Everolimus; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation / Q000009:adverse effects / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects; D007564:Japan; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D011237:Predictive Value of Tests; D011379:Prognosis; D011507:Proteinuria / Q000175:diagnosis / Q000209:etiology; D011518:Proto-Oncogene Proteins / Q000097:blood*; D012372:ROC Curve; D051437:Renal Insufficiency / Q000097:blood / Q000139:chemically induced / Q000175:diagnosis / Q000517:prevention & control; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D000209:Acute-Phase Proteins; D007166:Immunosuppressive Agents; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D000068338:Everolimus; D009173:Mycophenolic Acid; D020123:Sirolimus