Early prognostic performance of miR155-5p monitoring for the risk of rejection: Logistic regression with a population pharmacokinetic approach in adult kidney transplant patients

被引:10
作者
Quintairos, Luis [1 ,2 ]
Colom, Helena [1 ]
Millan, Olga [2 ,3 ]
Fortuna, Virginia [2 ]
Espinosa, Cristina [2 ]
Guirado, Lluis [4 ]
Budde, Klemens [5 ]
Sommerer, Claudia [6 ]
Lizana, Ana [2 ]
Lopez-Pua, Yolanda [7 ]
Brunet, Merce [2 ,3 ]
机构
[1] Univ Barcelona, Fac Pharm & Food Sci, Dept Pharm Pharmaceut Technol & Phys Chem, Biopharmaceut & Pharmacokinet Unit, Barcelona, Spain
[2] Univ Barcelona, Hosp Clin Barcelona, Biochem & Mol Genet Biomed Diagnost Ctr CDB, Pharmacol & Toxicol Lab, Barcelona, Spain
[3] Inst Salud Carlos III, Biomed Res Ctr Hepat & Digest Dis CIBERehd, Madrid, Spain
[4] Fundacio Puigvert, Renal Transplant Unit, Nephrol Dept, Barcelona, Spain
[5] Charite Univ Med Berlin, Med Klin Mit Schwerpunkt Nephrol, Berlin, Germany
[6] Heidelberg Univ, Univ Hosp Heidelberg & Mannheim, Dept Nephrol, Heidelberg, Germany
[7] Univ Barcelona, Hosp Clin Barcelona, Qual Unit CDB, Barcelona, Spain
来源
PLOS ONE | 2021年 / 16卷 / 01期
关键词
MYCOPHENOLIC-ACID; TACROLIMUS; MODEL; EXPRESSION; IMPLEMENTATION; BIOMARKERS; RECIPIENTS; CLEARANCE; MOFETIL; CXCL10;
D O I
10.1371/journal.pone.0245880
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Previous results from our group and others have shown that urinary pellet expression of miR155-5p and urinary CXCL-10 production could play a key role in the prognosis and diagnosis of acute rejection (AR) in kidney transplantation patients. Here, a logistic regression model was developed using NONMEM to quantify the relationships of miR155-5p urinary expression, CXCL-10 urinary concentration and tacrolimus and mycophenolic acid (MPA) exposure with the probability of AR in adult kidney transplant patients during the early post-transplant period. Owing to the contribution of therapeutic drug monitoring to achieving target exposure, neither tacrolimus nor MPA cumulative exposure was identified as a predictor of AR in the studied population. Even though CXCL-10 urinary concentration showed a trend, its effect on AR was not significant. In contrast, urinary miR155-5p expression was prognostic of clinical outcome. Monitoring miR155-5p urinary pellet expression together with immunosuppressive drug exposure could be very useful during routine clinical practice to identify patients with a potential high risk of rejection at the early stages of the post-transplant period. This early risk assessment would allow for the optimization of treatment and improved prevention of AR.
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页数:20
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