Sirolimus induced phosphaturia

ABSTRACT: Introduction: The kidney is the major arbiter of extracellular phosphate homeostasis. The vast majority of glomerular filtrated phosphate is reabsorbed in the proximal tubule. Posttransplant phosphaturia is common and aggravated by sirolimus immunosuppression. The cause of sirolimus induced phosphaturia however remains elusive. Results: The urine phosphate/creatinine ratio was higher and serum phosphate was lower in sirolimus treated rats, fractional excretion of phosphate was elevated and renal tubular phosphate reabsorption was reduced suggesting a renal cause for hypophosphatemia. PTH was lower in sirolimus treated rats. FGF 23 levels were unchanged at day 2 but lower in sirolimus treated rats after 7 days. Brush border membrane vesicle phosphate uptake was not altered in sirolimus treated groups or by direct incubation with sirolimus. mRNA, protein abundance, and subcellular transporter distribution of NaPi-IIa, Pit-2 and NHE3 were not different between groups but NaPi-IIc mRNA expression was lower at day 7. Transcriptome analyses revealed candidate genes that could be involved in the phosphaturic response. Discussion: Sirolimus caused a selective renal phosphate leakage which was not mediated by NaPi-IIa or NaPi-IIc regulation or localization. We hypothesize that another mechanism such as a basolateral phosphate transporter may be responsible for the sirolimus induced phosphaturia. Male Wistar rats received sirolimus or vehicle for 7 days (1.5mg/kg) and were placed in individual metabolic cages for eight days allowing a 24 hour adaption period to the metabolic cage environment. At the end of the experiments rats were anesthetized by inhalation of Isoflurane/air and blood samples and kidneys were collected.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE35048 | GEO | 2012/09/24

SECONDARY ACCESSION(S): PRJNA150851

REPOSITORIES: GEO