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Polycystic kidney disease

Tolvaptan in ADPKD—TEMPO 3:4 trial results

Nature Reviews Nephrology volume 9, page 1 (2013)Cite this article

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Results of the TEMPO 3:4 study, reported at ASN Kidney Week in San Diego, USA in November and published in the New England Journal of Medicine, have shown that tolvaptan may be useful in reducing increases in total kidney volume and slowing renal function decline in autosomal dominant polycystic kidney disease (ADPKD), but is associated with adverse events. “Whether tolvaptan is a helpful long-term treatment in patients with ADPKD will depend on a balance between benefits and risks,” state the authors.

“The TEMPO 3:4 trial was initiated based on previous basic and translational research,” says corresponding author Vicente Torres. “Studies of animal models showed the importance of cyclic adenosine monophosphate in promoting fluid secretion, cell proliferation and cyst growth in polycystic kidneys. And in 1999, Vince Gattone published an article in Developmental Genetics reporting that a drug that blocks the action of the hormone vasopressin on the vasopressin V2 receptors in the kidney blunted the development of the renal cystic disease in cpk mice. This observation was then confirmed in four rodent models with mutations in the same genes that are associated with human ADPKD (PKD1 and PKD2), autosomal recessive polycystic kidney disease (PKHD1) and nephronophthisis (NPHP3). These preclinical studies provided the basis for phase II trials and then the phase III TEMPO 3:4 trial, which started enrolling patients in January 2007 and was completed in April 2012.”

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References

ORIGINAL RESEARCH PAPER

  1. Torres, V. E. et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N. Engl. J. Med. doi:10.1056/NEJMoa1205511

FURTHER READING

  1. Gattone, V. H. Developmental expression of urine concentration-associated genes and their altered expression in murine infantile-type polycystic kidney disease. Dev. Genet. 24, 309–318 (1999)

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  1. Rebecca Kelsey
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Kelsey, R. Tolvaptan in ADPKD—TEMPO 3:4 trial results. Nat Rev Nephrol 9, 1 (2013). https://doi.org/10.1038/nrneph.2012.236

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