Study of mRNA growth factors in urinary cells of kidney transplant recipients as predictors of chronic allograft nephropathy.
BACKGROUND
Chronic allograft nephropathy (CAN) is responsible for a significant proportion of graft loss. Current diagnostic methods for CAN are inadequate, and noninvasive assays for detecting allograft dysfunction/rejection and predicting long-term outcomes are a priority in transplantation.


METHODS
Urine samples were collected from 48 kidney transplant recipients (KTR): 18 recipients with stable graft function (creatinine levels<2.0 mg/dL) and proteinuria of less than 500 mg/24 hr (Group 1); 18 recipients with stable graft function and proteinuria of greater than 500 mg/24 hr (Group 2); and 12 recipients with biopsy confirmed CAN. Urinary cell levels of transforming growth factor-beta1 (TGF-beta1) mRNA or epidermal growth factor (EGF) mRNA were measured using real-time quantitative PCR assay, and levels were correlated with renal allograft status. The integrity of RNA isolated from urine sediments was also assessed using the Agilent 2100 Bioanalyzer.


RESULTS
Urinary cell TGF-beta1 mRNA levels were higher in the CAN group compared to Group 1 (P<0.0001) or Group 2 (P<0.0001). Urinary cell EGF mRNA levels were higher in Group 1 compared to Group 2 (P<0.0001) or the CAN group (P<0.0001). There were no significant differences in the urinary cell levels of EGF mRNA between patients with greater than 500 mg/24 hr proteinuria (Group 2) and the CAN group (P=0.75).


CONCLUSIONS
These results demonstrate that urinary cell TGF-beta1 mRNA levels distinguish CAN patients from long-term transplant patients with stable renal function and varied levels of proteinuria. Urinary cells may be a good resource for the noninvasive diagnosis of CAN.
Mas
Valeria R
VR
Division of Transplant, Department of Surgery, Virginia Commonwealth University, Richmond, VA 23298-0057, USA. vrmas@hsc.vcu.edu
Maluf
Daniel G
DG
Archer
Kellie J
KJ
Yanek
Kenneth
K
King
Anne
A
Cotterell
Adrian
A
Ferreira-Gonzalez
Andrea
A
Rodgers
Cheryl
C
Fisher
Robert A
RA
Posner
Marc
M
D000328:Adult; D003404:Creatinine / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation / Q000473:pathology* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011507:Proteinuria; D012333:RNA, Messenger / Q000652:urine*; D017741:Survivors; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014184:Transplantation, Homologous / Q000473:pathology
D006133:Growth Substances; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003404:Creatinine