Plasma neutrophil gelatinase-associated lipocalin and worsening renal function during everolimus therapy after heart transplantation

Teruhiko Imamura, Koichiro Kinugawa, Kent Doi, Masaru Hatano, Takeo Fujino, Osamu Kinoshita, Kan Nawata, Eisei Noiri, Shunei Kyo, Minoru Ono

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Recently, the mammalian target of rapamycin inhibitor everolimus (EVL) has been introduced as a novel immuno-suppressant 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 fltration 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 signifcant 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; specifcity, 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.

Original languageEnglish
Pages (from-to)73-79
Number of pages7
JournalInternational heart journal
Volume56
Issue number1
DOIs
Publication statusPublished - Jan 1 2015

Fingerprint

Heart Transplantation
Kidney
Therapeutics
Sirolimus
Neutropenia
Proteinuria
ROC Curve
Area Under Curve
Coronary Vessels
Logistic Models
Regression Analysis
Everolimus
Lipocalin-2
Calcineurin Inhibitors

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Plasma neutrophil gelatinase-associated lipocalin and worsening renal function during everolimus therapy after heart transplantation. / Imamura, Teruhiko; Kinugawa, Koichiro; Doi, Kent; Hatano, Masaru; Fujino, Takeo; Kinoshita, Osamu; Nawata, Kan; Noiri, Eisei; Kyo, Shunei; Ono, Minoru.

In: International heart journal, Vol. 56, No. 1, 01.01.2015, p. 73-79.

Research output: Contribution to journalArticle

Imamura, T, Kinugawa, K, Doi, K, Hatano, M, Fujino, T, Kinoshita, O, Nawata, K, Noiri, E, Kyo, S & Ono, M 2015, 'Plasma neutrophil gelatinase-associated lipocalin and worsening renal function during everolimus therapy after heart transplantation', International heart journal, vol. 56, no. 1, pp. 73-79. https://doi.org/10.1536/ihj.14-179
Imamura, Teruhiko ; Kinugawa, Koichiro ; Doi, Kent ; Hatano, Masaru ; Fujino, Takeo ; Kinoshita, Osamu ; Nawata, Kan ; Noiri, Eisei ; Kyo, Shunei ; Ono, Minoru. / Plasma neutrophil gelatinase-associated lipocalin and worsening renal function during everolimus therapy after heart transplantation. In: International heart journal. 2015 ; Vol. 56, No. 1. pp. 73-79.
@article{04c72a03b1e8494ea187ce72c1168c7d,
title = "Plasma neutrophil gelatinase-associated lipocalin and worsening renal function during everolimus therapy after heart transplantation",
abstract = "Recently, the mammalian target of rapamycin inhibitor everolimus (EVL) has been introduced as a novel immuno-suppressant 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 fltration 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 signifcant 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; specifcity, 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.",
author = "Teruhiko Imamura and Koichiro Kinugawa and Kent Doi and Masaru Hatano and Takeo Fujino and Osamu Kinoshita and Kan Nawata and Eisei Noiri and Shunei Kyo and Minoru Ono",
year = "2015",
month = "1",
day = "1",
doi = "10.1536/ihj.14-179",
language = "English",
volume = "56",
pages = "73--79",
journal = "International Heart Journal",
issn = "1349-2365",
publisher = "International Heart Journal Association",
number = "1",

}

TY - JOUR

T1 - Plasma neutrophil gelatinase-associated lipocalin and worsening renal function during everolimus therapy after heart transplantation

AU - Imamura, Teruhiko

AU - Kinugawa, Koichiro

AU - Doi, Kent

AU - Hatano, Masaru

AU - Fujino, Takeo

AU - Kinoshita, Osamu

AU - Nawata, Kan

AU - Noiri, Eisei

AU - Kyo, Shunei

AU - Ono, Minoru

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Recently, the mammalian target of rapamycin inhibitor everolimus (EVL) has been introduced as a novel immuno-suppressant 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 fltration 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 signifcant 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; specifcity, 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.

AB - Recently, the mammalian target of rapamycin inhibitor everolimus (EVL) has been introduced as a novel immuno-suppressant 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 fltration 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 signifcant 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; specifcity, 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.

UR - http://www.scopus.com/inward/record.url?scp=84921889275&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84921889275&partnerID=8YFLogxK

U2 - 10.1536/ihj.14-179

DO - 10.1536/ihj.14-179

M3 - Article

C2 - 25742944

AN - SCOPUS:84921889275

VL - 56

SP - 73

EP - 79

JO - International Heart Journal

JF - International Heart Journal

SN - 1349-2365

IS - 1

ER -