Noninvasive detection of renal allograft inflammation by measurements of mRNA for IP-10 and CXCR3 in urine.
BACKGROUND
We explored the hypothesis that measurements of mRNA encoding interferon-inducible protein-10 (IP-10) or the chemokine receptor CXCR3 in urinary cells offer a noninvasive means of elucidating cellular traffic causing acute rejection of human renal allografts.


METHODS
We obtained 63 urine specimens from 58 renal allograft recipients who underwent 63 allograft biopsies to resolve the basis for graft dysfunction, and 27 additional urine samples from 24 other patients with stable allograft function. Twenty-seven of the 63 biopsies were classified as acute rejection, 20 as other, and 16 as chronic allograft nephropathy. We measured the levels of transcripts for IP-10 and CXCR3, and a constitutively expressed gene 18S rRNA in the urine specimens and correlated transcript levels with renal allograft diagnosis.


RESULTS
mRNA levels of IP-10 (P < 0.0001) or CXCR3 (P < 0.0001) but not the levels of 18S rRNA (P= 0.56) predicted intragraft cellular traffic causing acute rejection. Receiver-operating characteristic curve analysis demonstrated that acute rejection can be predicted with a sensitivity of 100% and a specificity of 78% using the (log-transformed) cutoff value of 9.11 copies of IP-10, and with a sensitivity of 63% and a specificity of 83% using the cutoff value of 11.59 copies of CXCR3. Immunohistologic analysis of allograft biopsies showed exuberant expression of IP-10 and CXCR3 during acute rejection whereas both were absent in grafts with stable function.


CONCLUSIONS
Our investigation demonstrates that intragraft cellular events associated with acute rejection of human renal allografts can be noninvasively identified by measurements of mRNA for IP-10 and CXCR3 in urinary cells.
Tatapudi
Ravi Raju
RR
Department of Medicine, Weill Medical College of Cornell University, New York, New York, USA.
Muthukumar
Thangamani
T
Dadhania
Darshana
D
Ding
Ruchuang
R
Li
Baogui
B
Sharma
Vijay K
VK
Lozada-Pastorio
Elizabeth
E
Seetharamu
Nagashree
N
Hartono
Choli
C
Serur
David
D
Seshan
Surya V
SV
Kapur
Sandip
S
Hancock
Wayne W
WW
Suthanthiran
Manikkam
M
D000328:Adult; D001483:Base Sequence; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D006084:Graft Rejection / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000652:urine*; D012372:ROC Curve; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000235:genetics*
C114753:CXCL10 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D012333:RNA, Messenger; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D004247:DNA