| Authors |
Ju W, Eichinger F, Bitzer M, Oh J, McWeeney S, Berthier CC, Shedden K, Cohen CD,
Henger A, Krick S, Kopp JB, Stoeckert CJ, Dikman S, Schr枚ppel B, Thomas DB,
Schlondorff D, Kretzler M, Bottinger EP
|
| Submitted By |
Erwin Bottinger on 3/24/2010 |
| Status |
Published |
| Journal |
The American journal of pathology |
| Year |
2009 |
| Date Published |
6/1/2009 |
| Volume : Pages |
174(6) : 2073 - 2085 |
| PubMed Reference |
|
| Abstract |
Although chronic kidney disease (CKD) is common, only a fraction of CKD patients
progress to end-stage renal disease. Molecular predictors to stratify CKD
populations according to their risk of progression remain undiscovered. Here we
applied transcriptional profiling of kidneys from transforming growth
factor-beta1 transgenic (Tg) mice, characterized by heterogeneity of kidney
disease progression, to identify 43 genes that discriminate kidneys by severity
of glomerular apoptosis before the onset of tubulointerstitial fibrosis in
2-week-old animals. Among the genes examined, 19 showed significant correlation
between mRNA expression in uninephrectomized left kidneys at 2 weeks of age and
renal disease severity in right kidneys of Tg mice at 4 weeks of age. Gene
expression profiles of human orthologs of the 43 genes in kidney biopsies were
highly significantly related (R(2) = 0.53; P < 0.001) to the estimated
glomerular filtration rates in patients with CKD stages I to V, and
discriminated groups of CKD stages I/II and III/IV/V with positive and negative
predictive values of 0.8 and 0.83, respectively. Protein expression patterns for
selected genes were successfully validated by immunohistochemistry in kidneys of
Tg mice and kidney biopsies of patients with IgA nephropathy and CKD stages I to
V, respectively. In conclusion, we developed novel mRNA and protein expression
signatures that predict progressive renal fibrosis in mice and may be useful
molecular predictors of CKD progression in humans.
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