Sirolimus induced phosphaturia is not caused by inhibition of renal apical sodium phosphate cotransporters.

M. Haller(1,2,3), S. Amatschek(1), J. Wilflingseder(1), A. Kainz(1), B. Bielesz(1), I. Pavik(2), A. Serra(2), N. Mohebbi(2), J. Bieber(2), C. A. Wagner(2), R. Oberbauer(1,3,4)

1- Department of Nephrology, Medical University of Vienna, Vienna, Austria

2- Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland

3- Department of Nephrology and Transplantation, KH Elisabethinen Linz, Austria

4- Austrian Dialysis and Transplant Registry, Austria

 

// Tables
// Figures

Table S1:
Table S1:

Primers and Probes used. List of sequences of primers and probes used in these study.

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Figure S1:
Figure S1:

Unsupervised hierarchical clustering. Unsupervised hierarchical clustering, 21131 transcripts, sirolimus treatment day 7 (pearson correlation, complete linkage)

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Table S2:
Table S2:

Summary of major results.

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Figure S2:
Figure S2:

Dendrogram of gene expression profiles. Dendrogram derived by unsupervised hierarchical clustering of gene expression profiles characterizing the sirolimus group (red bar) and the vehicle group (green bar). Red spots ndicate up-regulated transcripts, whereas green spots indicate down-regulated transcripts relative to the other group.

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Table S3a:
Table S3a:

a: Effect of Sirolimus on electrolyte concentration in the urine. P-values of mixed linear models of Glucose, Calcium, Magensium, Sodium, Chloride, Potassium and Phosphate in the Urine. Group refers to the sirolimus effect, day refers to the time effect over seven days and interaction describes effect modification. With the exception of magnesium and sodium, no adjusted group effect could be observed.

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Table S3b:
Table S3b:

b: Correlation of urinary electrolyte concentration with phosphate in the urine. Correlation coefficients (corr) of calcium, magnesium, sodium, chloride and potassium (Var) to phosphate (phos) in the Urine. Only calcium showed a somewhat stronger correlation with urinary phosphate excretion.

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Table S4:
Table S4:

Significant differentially expressed genes between sirolimus (S) and vehicle (V) treatment listed by fold change.

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Table S5:
Table S5:

Functional classification of DEGs using PANTHER ontologies. Enriched biological processes separating sirolimus from vehicle group as derived on the level of differential gene expression by SAM. Categories are ranked by the p-value (comparison of expected number of genes and observed number of genes in each biological process) indicating the relevance of a particular process.

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Table S6:
Table S6:

Na+/K+ -ATPase subunits expression levels between sirolimus and vehicle group measured on the GeneChip expression array. None of the polypeptides forming Na+/K+ -ATPases are differentially expressed between the groups.

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SCIENTIFIC COLLABORATIONS