Renal gene and protein expression signatures for prediction of kidney disease progression

Wenjun Ju, Felix Eichinger, Markus Bitzer, Jun Oh, Shannon McWeeney, Celine C. Berthier, Kerby Shedden, Clemens D. Cohen, Anna Henger, Stefanie Krick, Jeffrey B. Kopp, Christian J. Stoeckert, Steven Dikman, Bernd Schröppel, David Thomas, Detlef Schlondorff, Matthias Kretzler, Erwin P. Böttinger

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44 Scopus citations

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-β1 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 (R2 = 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.

Original languageEnglish
Pages (from-to)2073-2085
Number of pages13
JournalAmerican Journal of Pathology
Volume174
Issue number6
DOIs
StatePublished - Jun 1 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Ju, W., Eichinger, F., Bitzer, M., Oh, J., McWeeney, S., Berthier, C. C., Shedden, K., Cohen, C. D., Henger, A., Krick, S., Kopp, J. B., Stoeckert, C. J., Dikman, S., Schröppel, B., Thomas, D., Schlondorff, D., Kretzler, M., & Böttinger, E. P. (2009). Renal gene and protein expression signatures for prediction of kidney disease progression. American Journal of Pathology, 174(6), 2073-2085. https://doi.org/10.2353/ajpath.2009.080888