Increased nuclear factor-kappaB and angiotensinogen gene expression in posttransplant recurrent focal segmental glomerulosclerosis.
In an attempt to identify potential markers of steroid-resistance in focal segmental glomerulosclerosis (FSGS) we evaluated intra-graft gene expression of IkappaBalpha, nuclear factor-kappaB (NF-kappaB), and angiotensinogen in 60 biopsies from 27 pediatric renal transplant recipients. Intra-graft NF-kappaB expression was significantly elevated in recurrent FSGS (R-FSGS) (218.3 + 55.6 ag/fg versus NON-FSGS 121.1 + 19.9, P=0.04) but not in acute rejection. NF-kappaB:IkappaBalpha ratios were higher in cadaveric donor versus living related donor recipients (15.7 + 2.8 vs. 8.8 + 1.3, respectively, P=0.015), and in African-American versus Caucasian recipients (15.6 + 2.9 vs. 9.1 + 1.3, respectively, P=0.03). Intra-graft angiotensinogen gene expression was significantly elevated in R-FSGS (30.5 + 8.8 ag/fg R-FSGS vs. 16.0 + 4.7 NON-FSGS, P=0.009). We conclude that increased NF-kappaB and angiotensinogen gene expression are associated with R-FSGS. Increased NF-kappaB:IkappaBalpha ratios are associated with cadaveric donor recipients and African-American race.
Schachter
A D
AD
Harvard Medical School, Department of Pediatrics, Boston, MA 02115, USA.
Strehlau
J
J
Zurakowski
D
D
Vasconcellos
L
L
Kim
Y S
YS
Zheng
X X
XX
Gunshin
Y
Y
Overstreet
S L
SL
Benfield
M R
MR
Tejani
A
A
Harmon
W E
WE
Herrin
J T
JT
Strom
T B
TB
D000293:Adolescent; D000808:Angiotensinogen / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015870:Gene Expression; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects; D016328:NF-kappa B / Q000235:genetics*; D011183:Postoperative Complications / Q000209:etiology / Q000378:metabolism; D012008:Recurrence
D016328:NF-kappa B; D000808:Angiotensinogen