Noninvasive Tim-3 messenger RNA evaluation in renal transplant recipients with graft dysfunction.
BACKGROUND
Renal biopsies are usually needed to elucidate graft dysfunction. In this study, T-cell immunoglobulin domain, mucin domain mRNA expression in the peripheral blood leukocytes (PBL) and urinary cells (UC) were studied as a noninvasive method for the diagnosis of acute rejection (AR) of kidney transplant patients with dysfunction.


METHODS
One hundred sixty biopsies were obtained from 115 patients. Blood and urine samples were collected immediately before the biopsies. Histopathologic diagnoses were acute tubular necrosis with superimposed AR or acute tubular necrosis in patients with delayed graft function (DGF), and (AR), or calcineurin inhibitor nephrotoxicity (CIN), or interstitial fibrosis and tubular atrophy in patients with acute graft dysfunction (AGD). Fifteen protocol biopsies of stable grafts were used as controls. mRNA relative quantification was performed by real-time polymerase chain reaction.


RESULTS
Gene expression in tissue, PBL, and UC was always higher in patients with AR than in patients with the other causes of graft dysfunction (P<0.001). Significant correlations of gene expression in different compartments were observed (P<0.001). The obtained diagnostic parameters were 100% accurate in the DGF group and, respectively, for blood and urine: sensitivity (87% and 84%); specificity (95% and 96%); positive predictive value (87% and 89%); negative predictive value (93% and 94%); and accuracy (91% and 93%) for the group of patients with AGD.


CONCLUSIONS
T-cell immunoglobulin domain, mucin domain mRNA quantification by real-time polymerase chain reaction in PBL and UC of renal transplant patients undergoing DGF or AGD may become a useful tool for an accurate noninvasive diagnosis of AR.
Manfro
Roberto C
RC
Department of Internal Medicine, School of Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. rmanfro@hcpa.ufrgs.br
Aquino-Dias
Esther C
EC
Joelsons
Gabriel
G
Nogare
Aline L
AL
Carpio
Virna N
VN
Gonçalves
Luiz Felipe S
LF
D000328:Adult; D001706:Biopsy; D003404:Creatinine / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000235:genetics; D006680:HLA Antigens / Q000276:immunology; D000072597:Hepatitis A Virus Cellular Receptor 2; D006650:Histocompatibility Testing; D006801:Humans; D016030:Kidney Transplantation / Q000473:pathology* / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D012086:Reoperation / Q000706:statistics & numerical data; D020133:Reverse Transcriptase Polymerase Chain Reaction
C448908:HAVCR2 protein, human; D006680:HLA Antigens; D000072597:Hepatitis A Virus Cellular Receptor 2; D008565:Membrane Proteins; D012333:RNA, Messenger; D003404:Creatinine