Renal gene and protein expression signatures for prediction of kidney disease
progression.
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, Schröppel 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 19465643
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.


Investigators with authorship
NameInstitution
Erwin BottingerMount Sinai School of Medicine
Matthias KretzlerUniversity of Michigan

Complications









Genes
SymbolDescription
Tgfbr1transforming growth factor, beta receptor I